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S0009279719318502 | Adriamycin nephropathy model a rodent model of nephrotic syndrome disease that was caused by the nephrotoxicity of adriamycin has been widely used for pharmacodynamic evaluation of traditional Chinese medicine in the treatment of kidney injury . Although some studies have clearly shown the pathological process of AN the mechanism of kidney injury have not been systematically investigated . The reliability of AN was evaluated by weight urinary protein quantitation serum biochemical and histopathological examination . Transcriptomic sequencing combined with network pharmacology were used to elucidate the molecular mechanism of AN and cell experiment combined with real time quantitative PCR and was used to validate the accuracy of transcriptomic sequencing result and KEGG pathways . Network analysis result showed that Mapk10 and Ptgs2 played important roles in the development of adriamycin induced kidney injury . KEGG pathway analysis showed that the mechanism of kidney injury may be related to the regulation of biosynthesis of unsaturated fatty acids complement and coagulation cascades PPAR signaling pathway and PI3K AKT signaling pathway . These results provide a new insight into the deep research on the mechanism of kidney injury and provide an experimental basis for finding drug targets for the treatment of AN . | Adriamycin nephrotic rat model can imitate human nephrotic syndrome. A value based on topological parameters is to evaluate the importance of target. The key target genes of adriamycin induced renal injury are Mapk10 and Ptgs2. Regulation of biosynthesis of unsaturated fatty acids is involved in kidney injury. |
S0009279719318587 | Inflammatory responses play a remarkable role in the mechanisms of acute and chronic respiratory diseases such as chronic obstructive pulmonary disease asthma pulmonary fibrosis and lung cancer . Currently there is a resurgence in the use of drugs from natural sources for various ailments as potent therapeutics . Berberine an alkaloid prominent in the Chinese traditional system of medicine has been reported to exert therapeutic properties in various diseases . Nevertheless the number of studies focusing on the curative potential of berberine in inflammatory diseases involving the respiratory system is limited . In this review we have attempted to discuss the reported anti inflammatory properties of berberine that function through several pathways such as the NF B ERK1 2 and p38 MAPK pathways which affect several pro inflammatory cytokines in the pathophysiological processes involved in chronic respiratory diseases . This review would serve to provide valuable information to researchers who work in this field and a new direction in the field of drug discovery with respect to respiratory diseases . | Inflammatory responses play a crucial role in chronic respiratory diseases. Berberine functions through the NF kB ERK1 2 and p38 MAPK pathways. Berberine causes a decrease in pro inflammatory cytokine levels. Berberine improves the histological changes in the lung tissue of rat models. Berberine suppresses tumours by increasing the activity of FOXO3a. |
S0009279719318952 | Polycystic Ovary Syndrome as a common endocrine disorder is accompanied by hyperandrogenism insulin resistance ovulation problems and infertility . Various types of off label drugs like metformin have been used for the management of targeted problems caused by PCOS such as insulin resistance and hyperandrogenism . Nicotinamide acts as a substrate of visfatin and Nicotinamide N Methyltransferase leading to the generation of Nicotinamide Adenine Dinucleotide and N1 Methylnicotinamide respectively . MNAM is known as an anti inflammatory anti thrombosis and anti diabetic agent . In this study the effects of NAM and MNAM on metabolic and endocrine abnormalities were evaluated in the adipose and ovarian tissues of a letrozole induced rat model of PCOS . Our results showed that MNAM and NAM reversed abnormal estrous cycle and reduced the serum testosterone levels and CYP17A1 gene expression . Furthermore all therapeutic factors improved HOMA IR after treatment and NAM significantly increased the expression of GLUT4 and decreased the gene expression of visfatin . Also MNAM diminished the gene expression of visfatin and resistin . It is noteworthy that all the therapeutic factors successfully activated the AMPK . In summary this study is the first study reported beneficial effects of NAM and MNAM on the treatment of PCOS . Additionally the alleviative effects of our therapeutic factors may be partially mediated by the AMPK dependent manner due to the contribution of the AMPK in the expression of CYP17A1 visfatin resistin and GLUT4 . Although more studies are required to unravel the exact mode of actions of MNAM and NAM in the PCOS the findings of the current study shed light on an urgent need for discovering novel therapeutic pharmaceuticals regarding the treatment of PCOS . | NAM and MNAM reversed the abnormal estrous cycles of letrozole induced PCOS rats. . NAM and MNAM showed the anti androgenic and insulin sensitizing effects. NAM and MNAM activate AMPK in adipose and ovarian tissues of PCOS rats. |
S0009279719319283 | Ginsenoside Rg1 is an active ingredient extracted from the roots of ginsenoside and an naphthylisothiocyanate induced rat model of intrahepatic cholestasis was used to investigate the protective effect of Rg1 on cholestasis . 48 SD male rats were randomly divided into 6 groups control group model group UDCA group low dose Rg1 group medium dose Rg1 group and high dose Rg1 group . The model group the UDCA group and all the Rg1 group were then intragastrically administered with 80mg kg ANIT and the control group were given equal volume of olive oil . Then the pathological changes in liver tissue were observed the secretion of bile in the bile duct was measured and the biochemical markers in serum were quantified including alanine aminotransferase aspartate aminotransferase alkaline phosphatase glutamyl transfer peptidase and the content of total bilirubin direct bilirubin total bile acid . The contents of inflammatory mediators in serum were quantified including tumor necrosis factor interferon and interleukin 1 . The contents of superoxide dismutase malondialdehyde and glutathione peroxidase in liver homogenate were quantified . Expression of farnesoid X receptor transporters and metabolic enzymes in liver tissue was monitored . Rg1 treatment improved liver tissue pathological damage promoted bile secretion and significantly reduced serum levels of the intrahepatic cholestasis markers ALT AST ALP GTP TBIL DBIL and TBA . Rg1 increased the activity of SOD and GSH Px in liver homogenate while reducing the serum levels of MDA and inflammatory mediators . Rg1 also regulated the expression of FXR bile acid transporters and metabolic enzymes . Overall Rg1 alleviated liver injury by improving secretion of bile and normalizing the activity of enzymes in the serum . The protective mechanism appeared to be related to the activation of FXR and regulation of liver transporters and metabolic enzymes . | Ginsenoside Rg1 can alleviate ANIT induced intrahepatic cholestasis in rats. Ginsenoside Rg1 can activate farnesoid X receptor. Ginsenoside Rg1 can regulate transporters and metabolic enzymes. |
S0009279719319532 | Oxidative stress in cardiac myocytes is an important pathogenesis of cardiac lipotoxicity . Autophagy is a cellular self digestion process that can selectively remove damaged organelles under oxidative stress and thus presents a potential therapeutic target against cardiac lipotoxicity . Globular CTRP9 is a newly identified adiponectin paralog with established metabolic regulatory properties . The aim of this work is to investigate whether autophagy participates the protection effects of gCTRP9 in neonatal rat cardiac myocytes under oxidative stress and the underlying mechanism . NRCMs were treated with PA of various concentrations for indicated time period . Our results showed that PA enhanced intracellular ROS accumulation decreased mitochondrial membrane potential and increased activation of caspases 3 . These changes suggested lipotoxicity due to excessive PA . In addition PA was observed to impair autophagic flux in NRCMs and impaired autophagosome clearance induced by PA contributes to cardiomyocyte death . Besides we found that gCTRP9 increased the ratio of LC3II I and the expression of ATG5 which was vital to the formation of autophagosomes and decreased the level of P62 suggesting enhanced autophagic flux in the absence or presence of PA . The result was further confirmed by the methods of infection with LC3 mRFP GFP lentivirus and blockage of autophagosomelysosome fusion by BafA1 . Moreover gCTRP9 reestablished the loss of mitochondrial membrane potential suppressed ROS generation and reduced PA induced myocyte death . However the protective effect of gCTRP9 on the cardiac lipotoxicity was partly abolished by blockade of autophagy by autophagy related 5 siRNA indicating that the effect of gCTRP9 on cell survival is critically mediated through regulation of autophagy . Autophagy induction by gCTRP9 could be utilized as a potential therapeutic strategy against oxidative stress mediated damage in cardiomyocytes . | Impaired autophagic flux induced by palmitic acid contribute to cytotoxicity in NRCMs. CTRP9 upregulates autophagy in NRCMs in the absence or presence of palmitic acid. CTRP9 alleviated PA induced lipotoxicity in NRCMs. ATG5 knockdown eliminated the protective effect of CTRP9 on the cardiac lipotoxicity. |
S0009279719319581 | Runx2 is a key transcription factor which is associated with osteoblast differentiation and expressed in ER human breast cancer cell lines . Runx2 also participates in mammary gland development . Deregulation of RNA Pol III genes is tightly linked to tumor development while Brf1 specifically regulates these gene transcription . However nothing is known about the effect of Runx2 on Brf1 expression and Pol III gene transcription . Expression of Runx2 Brf1 and Pol III genes from the samples of human breast cancer and cell culture model were determined by the assays of RT qPCR immunoblot luciferase reporter activity immunohistochemistry chromatin immunoprecipitation and Immunofluorescence . High expression of Runx2 is observed in the cases of breast cancer . The patients of high Runx2 expression at early stages display longer survival period whereas the cases of high Runx2 at advanced stages reveal faster recurrence . The identification of signaling pathway indicates that JNK1 and c Jun mediate Runx2 transcription . Repression of Runx2 reduces Brf1 expression and Pol III gene transcription . Further analysis indicates that Runx2 is colocalized with Brf1 in nucleus of breast cancer tissue . Both Runx2 and Brf1 synergistically modulate Pol III gene transcription . These studies indicate that Brf1 overexpression is able to be used as an early diagnosis biomarker of breast cancer while high Runx2 expression indicates long survival period and faster recurrence . Runx2 mediates the deregulation of Brf1 and Pol III genes and its abnormal expression predicts the worse prognosis of breast cancer . | Runx2 was overexpressed in human cases of breast cancer. High Runx2 expression of breast cancer cases display worse prognosis. Alcohol increased Runx2 to elevate Brf1 and Pol III gene transcription. Inhibiting Runx2 repressed Brf1 expression and Pol III gene transcription. Runx2 and Brf1 colocalize in nucleus of tumor tissue of breast cancer to synergistically modulate Pol III gene transcription.. Decreasing Runx2 expression caused phenotypic changes in breast cancer cells. |
S0009279719319647 | Epithelial mesenchymal transformation plays a crucial role in the metastasis of bladder cancer which makes bladder cancer difficult to cure . Bladder cancer is the most common malignancy of the urinary system and distant metastasis is the leading cause of death . Therefore finding a bioactive drug that can specifically inhibit epithelial mesenchymal transformation may be a new direction for bladder cancer treatment in the future . Thymoquinone the major active compound isolated from black seed oil | Thymoquinone inhibits migration and invasion in bladder cancer cells. Thymoquinone suppresses EMT in bladder cancer cells. Thymoquinone inhibits the activation of Wnt catenin signaling pathway. catenin plays a key role in EMT inhibition induced by TQ. Thymoquinone exerts an anti metastasis effect of bladder cancer in vivo. |
S0009279719319854 | Epigenetic variations can play remarkable roles in different normal and abnormal situations . Such variations have been shown to have a direct role in the pathogenesis of various diseases either through inhibition of tumor suppressor genes or increasing the expression of oncogenes . Enzymes involving in epigenetic machinery are the main actors in tuning the epigenetic based controls on gene expressions . Aberrant expression of these enzymes can trigger big chaos in the cellular gene expression networks and finally lead to cancer progression . This situation has been shown in different types of leukemia where high or low levels of an epigenetic enzyme are partly or highly responsible for the involvement or progression of a disease . DNA hypermethylation different histone modifications and aberrant miRNA expressions are three main epigenetic variations which have been shown to play a role in leukemia progression . Epigenetic based treatments now are considered as novel and effective therapies in order to decrease the abnormal epigenetic modifications in patient cells . Different epigenetic based approaches have been developed and tested to inhibit or reverse the unusual expression of epigenetic agents in leukemia . Acute myeloid leukemia the most prevalent acute leukemia in adults is anaggressive hematological malignancy arising in hematopoietic stem and progenitor cells . With the exception of a few specific AML subtypes the mainstays of treatment have not significantly changed over the last 20 years and are still based on standard cytotoxic chemotherapy . In this review we will discuss the recent development of therapeutics specifically targeting these key epigenetic programs in AML describe their mechanism of action and present their current clinical development . Finally we will discuss the opportunities presented by epigenetically targeted therapy in AML and will highlight future challenges ahead for the AML community to ensure that this novel therapeutics are optimally translated into clinical practice and result in clinical improvement for AML patients . | In normal and pathogenic cases epigenetics may play an important role. Epigenetic machinery mutations can have preventive therapeutic potential. This outlines a basis for epigenetic therapies in AML. |
S0009279719319970 | Pyroptosis a form of programmed cell death has garnered increasing attention as it relates to innate immunity and diseases . The discovery of caspase 1 3 4 5 8 11 function in sensing various challenges expands the spectrum of pyroptosis mediators and also reveals that pyroptosis is not cell type specific . Recent studies have identified that pyroptosis has become a new topic in cancer research because it may affect all stages of carcinogenesis . In this mini review we provided a primer on pyroptosis discussed the induction of pyroptosis in cancer and its implications in cancer management . Moreover its two important executioners the gasdermin D and gasdermin E the functions and mechanisms of them involved in the regulation of cancer therapy were focused on . Small molecules mediated pyroptosis were found to effectively inhibit various tumor cells . In brief the findings of pyroptosis dependent cancer progression new drugs and therapeutic targets may lead to a promising novel therapeutic approach for cancer patients . | Pyroptosis is a pro inflammatory form of programmed cell death. Pyroptosis can be mainly induced via the activation of caspase 3 4 5 8 11. Pyroptosis plays crucial roles in the pathogenesis of cancer diseases. Pyroptosis pathway is a potential therapeutic target in cancer diseases. |
S0009279719320046 | Early initiated decontamination is demonstrated to be crucial to avoid systemic effects of highly toxic and low volatile agents exposed on the skin . Skin decontamination can be performed by simple procedures such as washing with soap and water or by using advanced decontamination products containing absorption and agent degradation properties . Reactive Skin Decontamination Lotion has demonstrated high efficacy to remove nerve agents from the skin . However contrary to the current operational recommendations experimental studies have shown that prolonged skin contact time of RSDL is important for efficient decontamination of VX . In the present study several RSDL protocols were evaluated for the efficacy to remove neat VX from human skin | Repeated swabbing and time for RSDL to act on skin is important for VX decontamination. For decontamination of nerve agents water content should be kept low to avoid a wash in effect. Soapy water decontamination significantly increased skin penetration of VX. |
S0009279719320101 | Geraniol like other plant derived natural bioactive compounds has been found to possess antiproliferative properties that are essential to cope with malignant tumors . However the mechanisms of molecular action of GOH are not fully elucidated . The aim of this study was to evaluate the effect of GOH on some oxidative parameters in human tumor cell lines . Cytotoxicity evaluated in cell lines by the MTT assay genotoxicity by the comet assay and lipid peroxidation by the TBARS . The activities of antioxidant the enzymes superoxide dismutase catalase and glutathione S transferase were also analyzed . Additionally intracellular reactive oxygen species nitric oxide and lactate production were determined in HepG2 cells . Both tumor cell lines showed a clear concentration dependent response to GOH in several of the parameters evaluated . Lipids turned out to be more sensitive than DNA to oxidative damage induced by GOH . TBARS levels increased with respect to control | GOH effects on some oxidative parameters in HepG2 and A549 were studied. Lipids were damage but not DNA in both tumor cells. SOD and CAT were more sensitive in HepG2 than in A549 while GST was not affected. ROS and lactate increased but not nitric oxide in HepG2. Oxidative stress could mediate the anti proliferative effects of GOH in tumor cells. |
S0009279719320149 | The review summarizes literature data on the DNA binding DNA protecting and DNA damaging activities of a range of natural human endogenous and exogenous compounds . Small natural organic molecules bind DNA in a site specific mode by arranging tight touch with the structure of the major and minor grooves as well as individual bases in the local duplex DNA . Polyphenols are the best studied exogenous compounds from this point of view . Many of them demonstrate hormetic effects producing both beneficial and damaging effects . An attempt to establish the dependence of DNA damage or DNA protection on the concentration of the compound turned out to be successful for some polyphenols daidzein genistein and resveratrol which were DNA protecting in low concentrations and DNA damaging in high concentrations . There was no evident dependence on concentration for quercetin and kaempferol . Probably the DNA protecting effect is associated with the affinity to DNA . Caffeine and theophylline are DNA binders at the same time they favor DNA repair . Although most alkaloids damage DNA berberine can protect DNA against damage . Among the endogenous compounds hormones belonging to the amine class thyroid and steroid hormones appear to bind DNA and produce some DNA damage . Thus natural compounds continue to reveal beneficial or adverse effects on genome integrity and provide a promising source of therapeutic activities . | Numerous polyphenols and other natural compounds bind DNA. Small organic molecules that bind to DNA can both exogenous and endogenous. The DNA binding compound can damage and protect DNA against other genotoxic agents. Conditions when a compound damages or protects DNA are difficult to elucidate. |
S0009279719320393 | In this study we assessed the efficacy of the Reactive Skin Decontamination Lotion Kit against parathion and aldicarb pesticide dermal exposure in a guinea pig model . The pesticides inhibit acetylcholinesterase leading to signs and symptoms of hyperactivity of organs due to accumulation of acetylcholine . The RSDL Kit has been shown to physically remove and chemically degrade chemical warfare agents . Degradation occurs from a nucleophilic substitution reaction between an active ingredient in the RSDL lotion potassium 2 3 butanedione monoximate with susceptible sites in these compounds . In the present study guinea pigs dermally exposed to parathion and aldicarb were decontaminated with RSDL to mitigate the toxic effects of the pesticides . | Guinea pigs dermally exposed to parathion and aldicarb were decontaminated with RSDL. RSDL Kit is an effective decontaminant against parathion and aldicarb pesticide. Base on the in vivo study the Kit can help mitigate acute exposure from pesticides. |
S0009279719320526 | Phytoestrogens are plant derived substances with a similar structure to 17 beta estradiol which have protective roles in estrogen dependent diseases . Isoflavones the most well known subgroup of phytoestrogens play protective roles against chemicals induced liver injuries through several molecular mechanisms . Hepatoprotective effects of isoflavones are partly associated with their antioxidant anti inflammatory immunomodulatory and anti fibrotic properties . Besides isoflavones can reduce gut derived endotoxins accelerate alcohol metabolism stimulate detoxification of hepatotoxic chemicals suppress the bioactivation of these chemicals inhibit hepatocytes apoptosis and restore autophagy activity during chemicals induced liver diseases . This review provides a summary of the molecular mechanisms underlying the hepatoprotective effects of isoflavones . It seems that further studies are needed to investigate the hepatoprotective potential of isoflavones in patients with different stages of chemicals induced liver injuries . | Isoflavones protect the liver against injury induced by hepatotoxic drugs. Isoflavones exert a protective role against alcoholic liver disease. Isoflavones play a protective role in toxicant induced liver injury. Mechanisms of hepatoprotective roles of isoflavones have been summarized. |
S0009279719320769 | Human scalp hair is a biological matrix that can trap chemical vapours from explosives drugs and chemical weapons . The external contamination of human s hair following exposure to organophosphorus nerve agent was simulated by model compounds triethyl phosphate and diisopropyl fluorophosphate . In this work were exposed strands of hair to vapours of TEP and DFP 3 and 7 ppm | Scalp hair can be used as a passive sensor able to trap organophosphorous agents. Sorption kinetics are best fitted by a bimodal firstorder model. Sorption isotherms follow Freundlich model. Qualitative and quantitative informations can be expected in the field. |
S0009279719321003 | The inhibition of the enzyme acetylcholinesterase is a frequently used therapeutic option to treat Alzheimer s disease . By decreasing the levels of acetylcholine degradation in the synaptic space some cognitive functions of patients suffering from this disease are significantly improved . Rivastigmine is one of the most widely used AChE inhibitors . The objective of this work was to determine the effects of this drug on human erythrocytes which have a type of AChE in the cell membrane . To that end human erythrocytes and molecular models of its membrane constituted by dimyristoylphosphatidylcholine and dimyristoylphosphatidylethanolamine were used . They correspond to classes of phospholipids present in the outer and inner monolayers of the human erythrocyte membrane respectively . The experimental results obtained by X ray diffraction and differential scanning calorimetry indicated that rivastigmine molecules were able to interact with both phospholipids . Fluorescence spectroscopy results showed that rivastigmine produce a slight change in the acyl chain packing order and a weak displacement of the water molecules of the hydrophobic hydrophilic membrane interface . On the other hand observations by scanning electron microscopy showed that the drug changed the normal biconcave shape of erythrocytes in stomatocytes and echinocytes . | XRD and DSC indicated that rivastigmine interacted with DMPC and DMPE bilayers. Rivastigmine induces morphological alterations in human erythrocytes. Rivastigmine molecules locate in both monolayers of the human erythrocyte membrane. |
S0009279719321143 | Acetylcholinesterase terminates cholinergic neurotransmission by hydrolyzing acetylcholine . The collagen tailed AChE tetramer is a product of 2 genes ACHE and ColQ . The AChE tetramer consists of 4 identical AChE subunits and one polyproline rich peptide whose function is to hold the 4 AChE subunits together . Our goal was to determine the amino acid sequence of the polyproline rich peptide in | Trypsin digestion converted collagen tailed AChE to soluble AChE tetramers. Trypsin shortened the collagen tail leaving only polyproline rich peptides. AChE assembles into tetramers by interaction with a polyproline rich peptide. Mass spectrometry identified the polyproline rich peptides in TcAChE tetramers. |
S0009279719321295 | An imbalance between oxidants and antioxidants in favour of oxidants potentially leading to damage is termed oxidative stress . Antioxidants either enzymatic or non enzymatic are the ones that can reduce diverse effects of pro oxidants such as DNA proteins and lipids damage . Chalcones are open chain flavonoids that are widely biosynthesized in plants . Aim of this study was to test antioxidative potency of 15 chalcones in Oxidative stress was induced in serum samples of healthy individuals with 0.25mmol L terc buthyl hydroperoxide and then we monitored the effects of various concentrations of chalcones on oxidative stress parameters total antioxidative status total oxidative status total concentration of sulfhydryl group and prooxidative antioxidative balance and calculated prooxidative score antioxidative score and oxy score . Nonparametric repeated measures ANOVA was used for comparison of antioxidative potency of samples with 15 different chalcones in a native state and upon TBH influence . Spearman s nonparametric correlation analysis was used for estimation of relation between different parameters . Negative Oxy Score values for Chs11 15 showed significantly stronger antioxidative potency compared to other investigated chalcones . Ch11 Ch13 and Ch14 remained with negative OS even after TBH addition whereas OS of Ch12 and Ch15 became positive with small nominal values . Samples with Ch11 and Ch13 showed significant negative correlation between TAS and TOS but in Ch14 sample the negative correlation existed between TAS and PAB . Lower value of OS was noticed in samples with Ch11 Ch15 . Electron donor effects of substituent groups as a structural part of these chalcones could explain its antioxidative capability . Phenolic and methyl groups are responsible for antioxidative ability enhancement of five chalcones with the best activity . | biological model system. The best antioxidative properties showed methyl phenol and nitro chalcones. Further investigation should lead to chalcones use in human medicine. |
S0009279719321301 | Rheumatoid Arthritis affects approximately 1 of the total world population . Despite incessant research and development of new therapeutic agents management of RA is still a troublesome affair . Histone Deacetylase 1 is an epigenetic regulator which play important role in pathogenesis of RA . In present study we hypothesized that Phenethyl isothiocyanate a potent inhibitor of HDAC1 may ameliorate RA . Efficacy of PEITC was evaluated in Complete Freund s Adjuvant induced arthritis model in rats . CFA was injected subplantarly in the left hind paw on day 0 to all the groups except normal control . The administration of test drug PEITC and standard drug Ibuprofen started simultaneously and was continued for 21 days . Paw edema total arthritic index mobility score stair climbing ability behavioral parameters and bone erosion were evaluated . Further radiographic studies TNF alpha as well as HDAC1 levels in synovial tissue homogenate and histological analysis were performed . Prophylactic treatment of PEITC attenuated paw edema total arthritic index mobility score stair climbing ability behavioral parameters and bone erosion in dose dependent manner . Furthermore there was significant decrease in TNF alpha as well as HDAC1 levels in synovial tissue homogenate . Histological analysis revealed no cartilage damage bone erosion hyperplasia at synovial lining as well as infiltration of inflammatory cells in treatment group . Results of this study suggest potent anti rheumatoid arthritis activity of Phenethyl isothiocyanate in CFA induced RA model in rats . | Histone Deacetylase 1 HDAC1 is an epigenetic regulator in pathogenesis of RA. Phenethyl isothiocyanate PEITC is a potent inhibitor of HDAC1. In this study efficacy of PEITC was evaluated against RA in rats. Primary and secondary lesions TNF HDAC1 levels and histology were evaluated. Results suggest potent anti RA activity of Phenethyl isothiocyanate in rats. |
S0009279719321386 | Triple negative breast cancer is the most aggressive form of breast cancer with limited intervention options . Moreover a number of belligerent therapeutic strategies adopted to treat such aggressive forms of cancer have demonstrated detrimental side effects . This necessitates exploration of targeted chemotherapeutics . We assessed the efficacy of a novel indenone derivative N 2 3 dihydro 1 | A novel indenone derivative nID demonstrated anticancer potential in triple negative breast cancer TNBC cells. The nID caused G1 arrest in breast cancer MDA MB 231 cells. It modulated the p53 NF B survivin axis to upregulate p21. in MDA MB 231. The nID induced p53 dependent senescence in TNBC MDA MB 231 and MDA MB 468 not in WRL 68 epithelial like cells. |
S0009279720300041 | In patients with acute kidney injury progressively converting into chronic kidney disease proteinuria and high blood pressure predict progression to end stage renal disease . Although Renin angiotensin aldosterone system regulates blood pressure and kidney disease through both direct and indirect mechanisms . RAAS blockers that act at the level of angiotensin or lower in the cascade can cause compensatory increases in the plasma renin and angiotensin II level . Here in this review article we are exploring the evidence based on RAAS blockade action releases of aldosterone and hypothesizing the molecular mechanism for converting the acute kidney injury into chronic kidney disease to end stage renal disease . | The RAAS is a critical regulator of blood volume and systemic vascular resistance. RAAS inhibitors prevent proteinuria kidney fibrosis and the slow decline of renal function. RAAS inhibitors play a protective role in both the early and end stages of kidney disease. |
S0009279720300168 | A growing body of evidence indicates that exposure to nonylphenol a typical persistent organic pollutant in early life results in the impairment of the central nervous system but the underlying mechanism still remains to be elucidated . High levels of pro inflammatory cytokines in the brain have been implicated in the CNS damages . The animal model of exposure to NP in early life was established by maternal gavage during the pregnancy and lactation in the present study . We found that exposure to NP in early life increased the levels of pro inflammatory cytokines in the rat prefrontal cortex . Interestingly the levels of pro inflammatory cytokines in the intestine as well as in the serum were also increased by NP exposure . Furthermore the increased permeability of intestinal barrier and blood brain barrier two critical barriers in the gut to brain communication was observed in the rats exposed to NP in early lives . The decreased expression of zonula occludens 1 and claudin 1 tight junction proteins that responsible for maintaining the permeability of intestinal barrier and BBB was found which may underlie these increases in permeability . Taken together these results suggested that the disturbed gut brain communication may contribute to the increased levels of pro inflammatory cytokines in the prefrontal cortex caused by NP exposure in early life . | NP exposure in early life increased pro inflammatory cytokines in prefrontal cortex. NP exposure in early life also increased these cytokines in intestine and serum. Gut brain communication may contribute to increased cytokines in prefrontal cortex. |
S0009279720300326 | Montelukast is a cysteinyl leukotriene receptor antagonist with efficacy against a variety of diseases including asthma and inflammation related conditions . However various neuropsychiatric events suspected to be related to montelukast have been reported recently with limited understanding on their association and underlying mechanisms . This study aimed to investigate whether montelukast can induce neuroinflammation and neurotoxicity in microglial HAPI cells and neural SH SY5Y cells . The present study also compared the effects of montelukast with a 5 lipoxygenase inhibitor and a cyclooxygenase 2 inhibitor to better understand modulation of related pathways . HAPI or SH SY5Y cells were treated with the indicated drugs for 24h to investigate drug induced neuroinflammation and neurotoxicity . Montelukast induced cytotoxicity in HAPI cells accompanied with caspase 3 7 activation prostaglandin E | This study provides the first. evidence on Montelukast toxicity to microglial and neuronal cells. Provides evidence that this toxicity may be mediated by inflammatory response. Suggests that the inflammatory response and toxicity may contribute to neuropsychiatric events seen with montelukast use. |
S0009279720300478 | Reactive oxygen species is mainly produced as a by product from electron transport chain of mitochondria and effectively eliminated by cellular antioxidants . However 2 chloroethyl ethyl sulfide exposure to keratinocytes declined antioxidant capacity and increased accumulation of ROS triggered alteration of mitochondrial activity and apoptosis is lacking . Our findings demonstrated that the electron leakage from the impaired ETC leading to the accumulation of ROS was gradually elevating with increasing concentration of CEES exposure which decline the activity of superoxide dismutase manganese SOD and copper zinc SOD in keratinocytes . Further excess accumulation of ROS decreased the mitochondrial membrane potential and increased the mitochondrial mass with increasing dose of CEES . CEES exposure provoked the decrease in expression of transcription factor A mitochondrial augmented mitochondrial DNA damage and altered the mtDNA encoded oxidative phosphorylation subunits . Moreover fragmented mtDNA translocated into cytosol where it activated cGAS STING and interferon regulatory factor3 coinciding with the increased expression of inflammatory mediators and alteration of cell to cell communication markers . Pre treatment of N acetyl | CEES exposure enhance electron leakage from mitochondria leading to ROS accumulation and decline the antioxidants activity. Accumulated ROD due to CEES exposure augments decrease in m and increased in mitochondrial mass. CEES exposure provoked mitochondrial dysfunctions in keratinocytes. Fragmented mtDNA due to CEES exposure translocated into cytosol and activate signalling cascades. Pre treatment of ROS or ERK1 2 or PI3K Akt inhibitors significantly restored the CEES effect. |
S0009279720300545 | Non small cell lung cancer is one of the common malignant tumors and multidrug resistance and tumor metastasis limit the anticancer effect of NSCLC . Therefore it is necessary to develop new anticancer drug that can inhibit MDR and metastasis of NSCLC . In the present study we found that 5 4 piperazine 1 carbonyl 2 | MAY inhibits microtubule polymerization in A549 and A549 Taxol cells. MAY induces apoptosis in A549cells and A549 Taxol cells. MAY inhibits P gp expression and function in A549 Taxol cells. MAY inhibits EMT by targeting Twist1 in A549 Taxol cells. |
S0009279720300636 | UDP glucuronosyltransferases are a family of phase II drug metabolizing enzymes that catalyze glucuronidation of numerous endogenous and exogenous substrates . Carbon tetrachloride CCl | Dysregulation of UGTs in CCl. induced liver injury rats is isoform specific. CCl. dysregulated UGTs in rats depending on the exposure time. CCl. induced liver injuries could inhibited the enzyme activities of rat UGTs. UGTs dysregulation was accompanied by the diversity of nuclear receptors expression. |
S0009279720300661 | The mortality rates for acute myeloid leukemia are very high necessitating the search for novel chemotherapeutic candidates . Herein we investigated the anticancer potential of a new synthetic compound 2 ethyl 3 methyliden 1 tosyl 2 3 dihydroquinolin 4 1 | Anticancer potential of a new quinolinone analog was assessed. AJ 374 was highly cytotoxic for HL 60cells but not for healthy HUVEC cells. AJ 374 induced apoptosis by intrinsic and extrinsic pathway without ROS generation. The compound promoted the cell cycle arrest in the subG0 G1 phase. |
S0009279720300703 | Ketamine is gaining ground as a potential treating depression because it has a distinct mode of action than typical drugs that influence monoamine neurotransmitters including noradrenaline dopamine or serotonin . Ketamine is thought to act by blocking N methyl | Ketamine is thought to act by blocking N methyl. aspartate NMDA receptors in the brain. Ketamine is an arylcycloalkylamine that is structurally related to phencyclidine PCP . This review exploring the molecular targets for the treatment and psychomimetic phenomena of the ketamine. |
S0009279720300788 | Oxidative stress induced apoptosis of retinal ganglion cells contributes to the development and progression of glaucoma . Sestrin2 a stress inducible protein has a potent antioxidant capacity that can provide cytoprotection against various noxious stimuli . However whether Sesn2 is involved in protecting RGCs from oxidative stress remains unexplored . The purpose of this study was to evaluate the role of Sesn2 in regulating hydrogen peroxide H | Sesn2 expression is induced by in H. exposure in RGCs. Sesn2 overexpression alleviated H. induced injury in RGCs. Sesn2 enhances Nrf2 activation by inhibiting Keap1. Sesn2 exerts cytoprotective effect by enhancing Nrf2 activation. |
S0009279720301216 | Ulcerative colitis is a chronic idiopathic and inflammatory disease of the rectal and colonic mucosa . Studies have shown that Toll like receptors 4 and Signal Transducer and Activator of Transcription 3 mediated the decline in immune function and inflammatory infiltration are potential pathomechanism of UC occurrence and development . In this study the anti inflammation of Erianin a natural bibenzyl compound with the antioxidant antitumor and anti inflammatory activities was investigated in a dextran sodium sulphate induced UC mouse model . Three week Erianin administration resulted in the increment on the body weight and colon length and the reduction on the activity index score of UC mice . Liver spleen and renal organ indexes and pathological observations confirmed that Erianin was not cytotoxic and had an effect of improving immune organ function . The haematoxylin and eosin staining sections of colon tissue show Erianin s effect of reversing inflammation in the mucosal laye . Proteomic analysis and enzyme linked immunosorbent assay indicated that Erianin regulated the levels of inflammatory and oxidative stress related factors and immunochemokines in serum and colon tissues thereby reducing cell peroxidative damage and reducing immune inflammatory responses . Further data obtained by Western Blotting confirmed that Erianin s anti UC activity was mediated by inhibiting the TLR4 and STAT3 signaling . | Mice model with UC are established via dextran sodium sulphate administration. Erianin has anti ulcerative colitis UC activity in mice with UC. Erianin shows anti inflammatory and antioxidant function in mice with UC. Erianin s anti UC activity is collaboratively mediated by TLR4 and STAT3. |
S0009279720301228 | Increasing studies have well documented the involvement of numerous lncRNAs in regulating the malignant phenotypes of various tumors including non small cell lung cancer cells . However up to date the effects and mechanism of lncRNA amine oxidase copper containing 4 pseudogene in NSCLC progression remain undefined . AOC4P expression in NSCLC cells was detected by qRT PCR . The protein levels of Wnt catenin pathway related proteins matrix metallopeptidase 2 and MMP 9 were examined by Western blot . The effects of AOC4P or combined with Wnt agonist BML 284 on the malignant phenotypes in NSCLC cells were explored by CCK 8 Transwell invasion assay flow cytometry analysis and caspase 3 7 activity . AOC4P was lowly expressed in NSCLC samples and cells . Overexpression of AOC4P inhibited viability the expression of MMP 2 and MMP 9 and invasion of NSCLC cells . Apoptosis and caspase 3 7 activity were suppressed in response to AOC4P overexpression in NSCLC cells . AOC4P overexpression suppressed tumor growth in a xenograft mouse model . | AOC4P was lowly expressed in NSCLC cells. AOC4P overexpression inhibited the proliferation and the Wnt catenin pathway in NSCLC cells. AOC4P overexpression suppressed the invasion and induced apoptosis of NSCLC cells. AOC4P overexpression suppressed tumor growth in a xenograft mouse model. |
S000927972030137X | Apple polyphenols have attracted much attention due to their various bioactivities . In this study the protective effect of AP against chronic ethanol exposure induced neural injury as well as the possible mechanisms were investigated . Body weight daily average food intake and daily average fluid intake were measured and daily average ethanol consumption was calculated . The influences of AP on motor behavior and memory were detected by locomotor activity test rotarod test beam walking test and Y maze test and novel object recognition test respectively . The changes of blood ethanol concentration and the oxidative stress were also measured . | Apple polyphenols improved chronic ethanol exposure induced inhibition of body weight and daily average food intake. Motor activity and motor coordination were not influenced after chronic ethanol exposure under our experimental protocol. Apple polyphenols improved chronic ethanol induced memory impairments in the Y maze test and novel object recognition test. Apple polyphenols improved chronic ethanol induced morphological damage to hippocampal CA1 neurons. Memory impairmentsameliorated by apple polyphenols were associated with inhibition of oxidative stress and activation of antioxidant defense systems. |
S0009279720301381 | Herbal medicines and their bioactive compounds are increasingly being recognized as useful drugs for cancer treatments . The parasitic fungus Cordyceps militaris is an attractive anticancer herbal since it shows very powerful anticancer activity due to its phytocompound cordycepin . We previously discovered and reported that a high amount of xylitol is present in Cordyceps militaris extract and that xylitol unexpectedly showed anticancer activity in a cancer selective manner . We thus hypothesized that xylitol could become a useful supplement to help prevent various cancers if we can clarify the specific machinery by which xylitol induces cancer cell death . It is also unclear whether xylitol acts on cancer suppression | Xylitol induces selective cancer death through oxidative stress caused by the induced CHAC1. Xylitol mediated CHAC1 induction is required for the ER stress. Xylitol efficiently sensitized cancer cells to chemotherapeutic drugs. as well as |
S0009279720301496 | In the present study eighteen inhibitors of the hydrolytic enzymes of the endocannabinoid system were investigated for antioxidant activity using lipid peroxidation method . Among the assayed compounds ten belong to carbamates with phenyl 3 ylcarbamate | antioxidant activity was evaluated using lipid peroxidation LP method. activity of the most potent compound. was comparable with standard antioxidants. Theoretical calculations were involved in order to clarify a possible mechanism of action. Appropriate models for HAT SET and SPLET mechanisms of the antioxidant activity are proposed. |
S0009279720301629 | The debilitating nature of cognitive impairment in epilepsy and the potential of some traditional antiepileptics to further deteriorate cognitive function are areas of growing concern . Glucagon like peptide 1 deficiency has been linked to reduced seizure threshold as well as cognitive dysfunction . Here we tested whether sitagliptin by virtue of its neuroprotective properties could alleviate both epilepsy and associated cognitive dysfunction in a rat model of kindling epilepsy . Chemical kindling was induced by subconvulsive doses of pentylenetetrazol . SITA was administered 1h before PTZ injections . SITA conceivably attenuated PTZ hippocampal histological insult preserved neuronal integrity and amended neurotransmitter perturbations in rat hippocampi paralleled with enhanced hippocampal GLP 1 levels as well as the downstream cAMP content and protein kinase A activity . Moreover SITA improved cognitive functioning of rats in the Morris water maze which was coupled with hampered hippocampal p Ser | PTZ kindling is associated with diminished hippocampal GLP 1. SITA protected against PTZ induced seizures and cognitive deficits in rats. SITA improves cognitive function in kindled rats evidenced by lowered A and p tau as well as increased Ach levels. SITA corrects glutamate GABA imbalance in kindled rats possibly via GSK 3 MMP9 BDNF modulation. SITA attenuated hippocampal RAGE and BACE1levels in kindled rats. |
S0009279720301800 | Till now monocrotophos has been addressed as a neurotoxic stressor . Limited studies investigate its aftermath on bone pathologies . Given the fact that MCP is a propensely used insecticide in developing countries this study investigates its potential to mirror osteoporotic features and bone loss incurred in a rodent model . Briefly Swiss albino mice were orally gavaged daily with varying doses of MCP for 8 weeks . Musculoskeletal changes were analyzed through micro computed tomography and histology . A series of | Oral gavaging of MCP to Swiss albino mice mimic human trabecular bone loss. MCP induced loss of bone mass is due to increased osteoclastogenesis. This model can be used for osteoporotic preclinical therapeutic investigations. |
S0009279720302398 | Human butyrylcholinesterase is a stoichiometric bioscavenger that protects from the toxicity of nerve agents . Non human primates are suitable models for toxicity studies that can not be performed in humans . We evaluated the biochemical properties of native macaque tetramers compared to recombinant MaBChE monomers PEGylated recombinant MaBChE tetramers and monomers and native HuBChE tetramers . | Macaque and human butyrylcholinesterase have similar catalytic properties. Biochemical properties of monomeric and tetrameric BChE forms are identical. 2 PAM reactivates DFP inhibited HuBChE 300 fold faster than DFP Macaque BChE. Proline 285 in HuBChE has a major role in fast reactivation by 2 PAM. |
S0009279720302489 | Oncogenic alterations in the BRAF gene are identified in an estimate of 50 of melanomas and cause melanoma development . BRAF kinase inhibitors including vemurafenib and dabrafenib were discovered and used in the clinical treatment of BRAF mutant metastatic melanoma . Though BRAFi s therapeutic advantages are short term and short lived associated with drug resistance . Although a few pathways of developed BRAFi resistance have also been established in approximately 40 of melanomas the cause for inherited resistance remains unclear . Recognizing a new process of developed BRAFi resistance might provide new possibilities to successfully treat BRAF mutant melanoma . In this study we are exploring the compensatory alternative pathway followed by BRAFi MEKi treated resistant cell for maintaining the long term integrity and survival . | BRAFi were used in the clinical treatment of BRAF mutant metastatic melanoma. BRAFi s therapeutic advantages are short term associated with drug resistance. Rho regulated gene transcription is a promising therapeutic approach to restore sensitivity to BRAFi resistant tumors. |
S0009279720302556 | The prenylated flavonoid icaritin is currently undergoing phase 3 clinical trial for the treatment of advanced hepatocellular carcinoma based on a solid array of preclinical and clinical data . The antitumor activity originates from the capacity of the drug to modulate several signaling effectors in cancer cells mainly the estrogen receptor splice variant ER36 the transcription factors STAT3 and NFB and the chemokine receptor CXCR4 . Recent studies have implicated additional components including different microRNAs the generation of reactive oxygen species and the targeting of sphingosine kinase 1 . ICT also engages the RAGE HMGB1 signaling route and modulates the apoptosis autophagy crosstalk to promote its anticancer activity . In addition ICT exerts profound changes on the tumor microenvironment to favor an immune response . Collectively these multiple biochemical and cellular characteristics confer to ICT a robust activity profile which can be exploited to treat HCC as well as other cancers including glioblastoma and onco hematological diseases such as chronic myeloid leukemia . This review provides an update of the pharmacological properties of ICT and its metabolic characteristics . It also addresses the design of derivatives including both natural products and synthetic molecules such as SNG1153 also in clinical trial . The prenylated flavonoid ICT deserves attention as a multifunctional natural product potentially useful to improve the treatment of advanced hepatocellular carcinoma . | The prenyl flavonoid icaritin is in clinical trial for the treatment of hepatocellular carcinoma. The estrogen receptor ER36 and sphingosine kinase 1 are icaritin targets. The drug modulates multiple cellular pathways contributing to the anticancer activity. The drug displays immune modulatory effects that reinforce the antitumor activity. Structural analogs of icaritin have been designed such as SNG1153 in clinical trials. |
S0009279720302878 | Despite advances in cancer treatment modalities DNA still stands as one of the targets for anticancer agents . DNA minor groove binders represent an important investigational chemotherapeutic class with promising cytotoxic capacity . Herein this study reports the potent cytotoxic effect of a series of repurposed flexible bis imidamides | In vitro cytotoxicity of flexible triaryl guanidines and imidamides against breast cancer. Flow cytometric cell cycle and apoptosis analysis of MCF 7cells treated with imidamide. Imidamide. induces significant increase of p53 PUMA and Bax gene expression and reduction of Bcl 2. In vivo anticancer effect on treated EAC bearing mice. Reduction in oxidative stress and elevation of antioxidant parameters. |
S000927972030301X | Osteoarthritis is a common degenerative joint disease that is closely associated with inflammation . Stachydrine is a bioactive alkaloid with anti inflammatory activity . However the role of STA in OA remains unknown . This study aimed to explore the effects of STA on OA chondrocytes in the presence of IL 1 . Primary human OA chondrocytes were pretreated with various concentrations of STA for 2h and then stimulated with IL 1 for 24h . Inflammatory mediators and cytokines including NO PGE2 TNF and IL 6 in chondrocytes were detected to reflect inflammation status . Production of extracellular matrix degrading enzymes including MMP 3 MMP 13 ADAMTS 4 and ADAMTS 5 in chondrocytes was measured using ELISA . The expression levels of iNOS COX 2 p65 p p65 p IB and IB were detected by Western blot analysis . Our results showed that STA significantly suppressed IL 1 induced inflammation with decreased levels of inflammatory mediators and cytokines including NO PGE2 iNOS COX 2 TNF and IL 6 . Treatment with STA suppressed the production of ECM degrading enzymes including MMP 3 MMP 13 ADAMTS 4 and ADAMTS 5 in IL 1 induced chondrocytes . Furthermore STA blocked the IL 1 mediated potentiation of NF B pathway in chondrocytes . In conclusion these findings demonstrated that STA protected chondrocytes from IL 1 induced inflammation through the NF B signaling pathway . | STA inhibits IL 1 induced production of NO and PGE2 in chondrocytes. STA decreases IL 1 induced expression of iNOS and COX 2 in chondrocytes. STA suppresses IL 1 induced production of TNF and IL 6 in chondrocytes. STA inhibits IL 1 induced production of ECM degrading enzymes in chondrocytes. STA prevents IL 1 induced NF B activation in chondrocytes. |
S0009279720303264 | A previous study demonstrated that glutathione produces specific antidepressant like effect in the forced swimming test a predictive test of antidepressant activity . The present study investigated the involvement of multiple cellular targets implicated in the antidepressant like effect of GSH in the FST . The antidepressant like effect of GSH 300 nmol site | GSH produces synergistic antidepressant effect when combined with antidepressants. NMDAR NOS pathway inhibition is implicated in the antidepressant effect of GSH. GABA receptors are involved in the antidepressant like effect of GSH. 1 adrenoceptor activation is associated to GSH antidepressant effect. Redox mediated signaling on the membrane receptors could be new antidepressant target. |
S000927972030346X | The sepsis is considered as serious clinic pathological condition related with high rate of morbidity and mortality in critical care settings . In the proposed study the hydrazides derivatives | The NCHDH and NTHDH treatment markedly improved the survival rate and biochemical parameters. The NCHDH and NTHDH treatment markedly improved the histological parameters compared to LPS control. The NCHDH and NTHDH treated group showed significant reduction in the oxidative stress and enhanced the anti oxidants enzymes. The NCHDH and NTHDH markedly induced the Nrf2 HO 1 proteins expression while attenuated the Keap1 and TRPV1 expression. |
S0009279720303768 | Cardiac inflammation plays a critical role in the development of heart failure . Inflammation induced oxidative stress contributes to aberrant cardiac metabolism and mitochondrial function . GLP 1 receptor agonists are a type of blood glucose lowering agent typically used in the treatment of type 2 diabetes . Recent studies have convincingly shown that GLP 1 RAs possess beneficial effects in diabetes related cardiovascular complications . Liraglutide is a commonly used long acting agonist that shows promising cardioprotective benefits . In this study we investigated the protective role of Liraglutide in cultured cardiomyocytes . We found that HL 1 cardiomyocytes moderately expressed the GLP 1 receptor and co treatment with Liraglutide ameliorated IL 1 induced cellular ROS production and NADPH oxidase 4 expression . Furthermore we found that Liraglutide protected cardiomyocytes from IL 1 induced decreased mitochondrial membrane potential and reduced ATP production . Seahorse analysis revealed that Liraglutide mitigated IL 1 induced reduced basal and maximum respiration rates as well as spare respiration capacity . Additionally we found that Liraglutide alleviated IL 1 induced aberrant triglyceride accumulation and adiponectin secretion . Mechanistically we showed that Liraglutide ameliorated IL 1 induced phosphorylation of AMPK and ACC as well as the reduction in PGC 1 CPT 1 and DGAT1 . Finally through the study we demonstrated that the blockage of AMPK activity by Compound C abolished the ameliorative effect of Liraglutide on IL 1 induced repressed ATP production and triglyceride accumulation indicating that the action of Liraglutide was dependent on AMPK activation . In conclusion this study revealed the molecular mechanism of Liraglutide protection in cultured cardiomyocytes . The GLP 1 RA Liraglutide could have therapeutic implications by modulating cardiac inflammation . | Cardiac inflammation plays a significant role in heart failure. Liraglutide ameliorates IL 1 induced mitochondrial dysfunction and metabolic disturbance. AMPK activation is required for the action of Liraglutide. |
S000927972030404X | Inhibition of mouse double minute 2 homolog p53 interaction and reactivation of p53 signaling have been explored as effective anticancer therapeutic strategy . The potent and specific antitumor activity shown by Nutlins first class of MDM2 p53 inhibitors discovered has made these compounds potential antitumor candidates . To this end we synthesized Nutlin 1 and Nutlin 2 analogs through molecular simplification and selected the compound with the most efficient antitumoral activity . Cytotoxicity of Nutlin 2 analog LQFM126 on B16F10 melanoma cells induced intense cytoplasmic vacuolization reduction of cell size chromatin condensation cytoplasmic degeneration and nuclear fragmentation . LQFM126 antiproliferative effects mediated cell cycle retention in G | A new piperazine compound was obtained through molecular simplification of Nutlins. LQFM126 prototype promoted cell cycle arrest and apoptosis in melanoma cells. LQFM126 has shown low estimated toxicity and. antiangiogenic activity. |
S000927972030418X | Doxorubicin administration decreases cardiac soluble guanylate cyclase activity . We hypothesized that bypassing impaired NO sGC cGMP pathway resulting from the activation of oxidized and heme free soluble guanylate cyclase could be a therapeutic target for DOX mediated cardiomyopathy . The present study investigated the therapeutic roles and mechanism of BAY60 2770 an activator of oxidized sGC in alleviating DOX CM . H9c2 cardiomyocytes were pretreated with BAY60 2770 followed by DOX . Cell viability and intracellular reactive oxygen species were subsequently measured . To determine the role BAY60 2770 in mitochondrial ROS generation and mitochondrial membrane potential we examined mitoSOX RED and TMRE fluorescence under DOX exposure . As animal experiments rats were orally administered with 5mg kg of BAY60 2770at 1h prior to every DOX treatment and then assessed by echocardiography and apoptotic marker and autophagy . BAY60 2770 ameliorated cell viability and DOX induced oxidative stress in H9c2 cells which was mediated by PKG activation . Mitochondrial ROS and TMRE fluorescence were attenuated by BAY60 2770 in DOX treated H9c2 cells . DOX induced caspase 3 activation decreased after pretreatment with BAY60 2770 BAY60 2770 appears to mitigate DOX induced mitochondrial ROS membrane potential loss autophagy and subsequent apoptosis leading to protection of myocardial injury and dysfunction . These novel results highlighted the therapeutic potential of BAY60 2770 in preventing DOX CM . | Doxorubicin directly induces oxidative stress in the mitochondria. Doxorubicin reduces cardiac soluble guanylate cyclase and reduces sGC activity. sGC pathway activation could be a therapeutic target for DOX mediated cardiotoxicity. BAY60 2770 a sGC activator may relieve cardiotoxicity caused by doxorubicin. |
S0009279720304361 | Embryonic studies have demonstrated the neurotoxic teratogenic and neurobehavioral toxicity of ethanol . Although multiple mechanisms may contribute to these effects oxidative stress has been described as the major damage pathway . In this regard natural antioxidants have the potential to counteract oxidative stress induced cellular damage . Therefore the present study aimed to investigate the potential protective role of 24 epibrassinolide a natural brassinosteroid with proved antioxidant properties in EtOH induced teratogenic effects during early zebrafish development . Embryos were exposed to 1 EtOH co exposed to 24 EPI and to 24 EPI alone for 24h . Following exposure biochemical evaluations were made at 26 hpf developmental analysis was made throughout the embryo larval period and behavioural responses were evaluated at 120 hpf . Exposure to 1 EtOH caused an increase in the number of malformations which were diminished by 24 EPI . In addition EtOH induced an accumulation of GSSG and consequent reduction of GSH GSSG ratio indicating the involvement of oxidative mechanisms in the EtOH induced effects . These were reverted by 24 EPI as proved by the GSSG levels and GSH GSSG ratio that returned to control values . Furthermore exposure to EtOH resulted in behavioural deficits at 120 hpf as observed by the disrupted response to an aversive stimulus suggesting the involvement of neurotoxic mechanisms . 24 EPI restored the behavioural deficits observed in a dose dependent manner . The absence of effects in the embryos exposed solely to 24 EPI showed its safety during the exposure period . In conclusion EtOH caused developmental teratogenicity and behavioural toxicity by inducing glutathione changes which were prevented by 24 EPI . | Zebrafish embryos were co exposed to 1 EtOH and 24 EPI at 2 hpf for 24 h. Embryonic exposure to EtOH resulted in malformations which were ameliorated by 24 EPI. EtOH exposure resulted in an increased accumulation of GSSG that was overturned by 24 EPI. Exposure to EtOH resulted in aversive behaviour disruption of 5 dpf larvae which were restored by 24 EPI. |
S0009279720304415 | Acacetin is a natural flavonoid that is widely distributed in plants and possesses numerous pharmacological activities . The aim of the present study was to investigate the effects of acacetin on the activities of the cytochrome P450 family members CYP1A2 CYP2B1 CYP2C11 CYP2D1 CYP2E1 and CYP3A2 in rat liver microsomes | We investigated effects of acacetin on activities of cytochrome P450 family members. UPLC MS MS method developed for simultaneous detection of substrates and metabolites. CYP2B1 CYP2C11 CYP2E1 CYP1A2 and CYP3A2 were inhibited by acacetin. AUC CL and C. of drug substrates differed significantly with acacetin. Acacetin could cause toxicity and drug interactions via cytochrome P450 inhibition. |
S0009279720304749 | Alzheimer s disease is a common neurodegenerative disease and its pathogenesis is closely related to amyloid peptide . The deposition of A in the brain due to impaired A clearance is considered as an important cause of AD . The decrease in A clearance is closely related to the autophagy dysfunction in brains of AD patients . It is feasible to treat AD by increasing the autophagy level of cells such as microglia and neurons to accelerate A clearance . In this article we explored the ability of graphene oxide to clear A through activating autophagy . Our work demonstrated that GO could inhibit the mTOR signaling pathway by activating AMPK to induce the autophagy of microglial and neurons . As expected with the improvement of autophagy ability of microglia GO promoted microglia mediated A phagocytosis . Under the conditions of co culture of microglia and neurons GO induced the autophagy of microglia and neurons especially the autophagy of microglia thereby promoting the clearance of A and ultimately achieved the effect of protecting neurons . Moreover GO was not only non cytotoxic to microglia and neurons but also able to reduce the toxicity of A to neurons through its clearance . These results have shown the potential of GO in treating Alzheimer s disease . | Graphene oxide GO protected neurons in pathological conditions. Microglia and neurons were co cultured to simulate pathological environment. GO promoted the clearance of A in pathological conditions. GO induced autophagy of microglia and neurons through the AMPK mTOR pathway. |
S0009279720304750 | Hydroxychloroquine is frequently used medications for many auto immunity diseases . However HCQ induced retinal toxicity which might result in irreversible retinopathy is one of the most important complications of HCQ . However the molecular mechanism underlying the HCQ retinal toxicity is still not well known . Retinal pigment epithelium in which HCQ is highly enriched due to the tissue specific affinity of HCQ is considered to play important role in HCQ retinopathy . Herein we used a metabolomics approach based on liquid chromatography mass spectrometry to investigate the metabolic changes in retinal pigment epithelial cells with HCQ exposure at 6h and 24h . ARPE 19cells were treated with HCQ at sub lethal concentration 20 which was determined with MTT assay . Untargeted metabolic profiling revealed 9 and 15 metabolites that were significantly different between control group and HCQ exposure group at 6h and 24h respectively . Enrichment and pathway analysis highlighted ascorbate and aldarate metabolism | Explore the biomarker of Hydroxychloroquine induced retinal toxicity. Investigate the disturbed metabolic pathways in retinal pigment epithelial cells by HCQ exposure. Provide new clues to the pathogenesis of HCQ induced retinopathy. |
S0009279720304841 | Lung cancer is one of the leading causes of cancer related death worldwide . It has aggressive manifestation high ability to promote metastasis and late diagnosis . In the present study we investigated the cytotoxic effect of 3 3 5 5 tetramethoxybiphenyl 4 4diol against the A549 human non small cell lung carcinoma lineage . The A549cell line was treated for 72h with TMBP with and subsequently defined the 50 inhibitory concentration from which tests were performed to determine the viability volume and regulation of the cell cycle . Finally we investigated the death mechanisms involved in the action of the treatments by flow cytometry and fluorimetry . The TMBP treatment of primary cells peritoneal macrophages and sheep erythrocytes did not reduce the viability of these cells . On the other hand TMBP was able to reduce the viability of the investigated cell line by cytotoxic action and to promote the reduction of cell size . Subsequently we found that TMBP treatment was able to increase the production of reactive oxygen species cause mitochondrial depolarization induce cell cycle arrest in G2 M phase and lead to death by direct apoptosis . Thus this study revealed that TMBP could be a promising candidate for the development of antitumor drugs targeting lung cancer . | predictions showed good drug likeness potential for TMBP. TMBP promotes cytotoxic action and changes in cell size in A549cells. TMBP increases the production of ROS and disrupts the cell cycle in G2 M. TMBP alters the m and. promotes formation of droplets lipid in A549. Treatment with TMBP induces apoptosis in tumor cells. |
S0009279720304865 | The apparent predicament of the representative chemotherapy for managing respiratory distress calls for an obligatory deliberation for identifying the pharmaceuticals that effectively counter the contemporary intricacies associated with target disease . Multiple complex regulatory pathways manifest chronic pulmonary disorders which require chemotherapeutics that produce composite inhibitory effect . The cost effective natural product based molecules hold a high fervor to meet the prospects posed by current respiratory distress therapy by sparing the tedious drug design and development archetypes present a robust standing for the possible replacement of the fading practice of poly pharmacology and ensure the subversion of a potential disease relapse . This study summarizes the experimental evidences on natural products moieties and their components that illustrates therapeutic efficacy on respiratory disorders . | Plant derived therapeutics for managing chronic respiratory disorders. Activity of natural product based molecules on key regulatory pathways of COPD. Preclinical evidence for the efficacy of natural product moieties. Clinical significance of plant derived molecules in pulmonary distress. |
S0009279720304889 | The present study analyzed whether melatonin could mediate the expression of VEGF IL 6 and TNF as well as the apoptotic index in rats with diabetic retinopathy . Fifty Wistar albino rats were divided into the following groups GC rats without induction of diabetes by streptozotocin GD rats induced to diabetes by streptozotocin and treated with placebo GDM rats induced to diabetes by streptozotocin and after confirmation treated with melatonin at a dose of 10mg kg for 20 days GDMS rats induced to diabetes by streptozotocin and treated simultaneously with melatonin at a dosage of 10mg kg for 20 days GDI rats induced to diabetes by streptozotocin and after confirmation treated with insulin for 20 days . Diabetes was induced by intraperitoneal injections of streptozotocin and insulin was administered subcutaneously . For apoptosis TUNEL was used while for the analysis of VEGF IL 6 and TNF . The results showed that the groups that were treated with melatonin decreased the expression of cytokines and VEGF in addition to apoptosis . Thus it is concluded that melatonin can regulate the expression of these factors by improving the condition of the retina in diabetic retinopathy . | Melatonin mitigates the adverse effects of diabetic retinopathy. Melatonin reduced inflammatory cytokines in the retina of rats with diabetes. Melatonin is a good alternative in the treatment of diabetic retinopathy. |
S0009279720304890 | Altered intracellular distribution of weak base anticancer drugs owing to lysosomal sequestration is one purported mechanism contributing to chemotherapy resistance . This has often been demonstrated with the example of daunorubicin chemotherapy with its characteristic red fluorescence used to trace it in cellular compartments . | Image analysis cannot provide a real picture of DNR distribution in cells. There is a complex relationship between DNR fluorescence and its concentration in different compartments. LC MS MS analysis of cell extracts can provide reliable picture about lysosomal accumulation of DNR. Lysosomal sequestration of DNR is not sufficient to significantly reduce its concentration at target sites. Therefore lysosomal sequestration of DNR can hardly contribute to drug resistance |
S0009279720304920 | The renin angiotensin aldosterone system is a hormonal system that has a critical role in maintaining the normotensive state and electrolyte balance of the organism . The RAAS also has an important influence in the development of various pathophysiological conditions especially those concerning the renal system cardiovascular system and hypertension . One of the consequences of the RAAS system is an increase in the generation of the reactive oxygen species that causes an increase in oxidative stress which may play a role in the development or exacerbation of such pathological conditions . Blocking this system at multiple points has been advantageous in the clinical management of these disorders . The key blockers that had gained predominant clinical use for such manifestations were angiotensin receptor blockers and angiotensin converting enzyme inhibitors . However their prolonged use caused a compensatory increase in renin and angiotensin I levels . The blocking of the system at the initial stages by blocking renin was of advantage to overcome such compensation . Such a renin blocker that gained widespread use was aliskiren . It is the first oral renin inhibitor that was approved for use in 2007 . Although the opinions are varied about the use and future of renin inhibitors as antihypertensive agents aliskiren has been well documented to have antioxidant effects . Aliskiren functions as an antioxidant by lowering the increase in ROS that are produced by the RAAS system at doses independent of decreasing the blood pressure . In the present review we discuss the antioxidant properties of aliskiren independent of its blood pressure lowering property . | RAAS may contribute to disease development through generation of oxidative stress. Blocking RAAS can prevent such RAAS generated ROS. Aliskiren is an antihypertensive agent that blocks RAAS. RAAS blockage by aliskiren prevents ROS generation so reducing severity of disease. Aliskiren may be used as antioxidant independent of its antihypertensive action. |
S0009279720304956 | Glutathione S transferases are a key enzyme superfamily involved in the detoxification and cytoprotection of a wide variety of xenobiotics such as carcinogens anticancer drugs environmental toxicants and endogenously produced free radicals . In the liver the hGSTA1 isoenzyme is the most abundant and catalyzes the glutathione conjugation of a wide range of electrophiles and has been the principal GST responsible for xenobiotic detoxification . Given the critical role of this enzyme in several cellular processes particularly cell detoxification understanding the molecular mechanisms underlying the regulation of | NF treatment resulted in increased hGSTA1 activity in HepG2 cells. NFmediated induction of hGSTA1 expression is at transcriptional level. NFmediated induction of hGSTA1 is AHR dependent. AHR activation promotes its recruitment to the. gene promoter. |
S000927972030507X | To avoid being preyed organisms must be able to identify predatory threats by sensing molecules released by predators and to employ effective strategies to prevent detection by predators . Furthermore in the wild organisms are also exposed to chemicals that may alter their behavioral traits such as neuroactive pharmaceuticals . Considering the co occurrence of both types of chemicals their possible interaction needs to be studied . To address this topic the aim of this study was to verify the effects of fish kairomone and chlorpromazine isolated and in combination in different functional endpoints of | Chlorpromazine CPZ and Fish kairomone FK caused functional alteration in. Feeding rate was decreased in all treatment conditions. Oxygen consumption was only affected in the mixture treatment CPZ FK . For life history traits and phototactic behavior the effects of FK dominated those of CPZ. |
S0009279720305159 | Activation of Notch signaling is associated with tumor aggressiveness poor clinical outcome and drug resistance in breast cancer patients . Targeting Notch signaling with small molecule inhibitors may be a better strategy for anticancer drug development . We identified 3 O p Coumaroylbetulinic acid as a lead compound and potent inhibitor of Notch signaling pathway . Treatment of human breast cancer MBA MD 231 and T47D cells with CB resulted in a dose and time dependent inhibition of cell viability and G0 G1 phase cell cycle arrest . This effect was associated with a marked decrease in the expression of cyclin D1 and its activating partner cyclin dependent kinase 2 with concomitant increase in cyclin kinase inhibitor p21 operative in G1 phase of the cell cycle . CB treatment induced early apoptosis in breast cancer cells as evident by increase in cleaved caspase 3 decrease in Bcl2 and survivin surge in reactive oxygen species and disruption of mitochondrial membrane potential . CB treatment altered Notch target genes | 3 O E p Coumaroyl betulinic acid induces apoptosis in breast cancer cells. 3 O E p Coumaroyl betulinic acid arrest cell cycle in breast cancer cells. 3 O E p Coumaroyl betulinic acid down regulate Notch signaling pathway. 3 O E p Coumaroyl betulinic acid suppress stemness markers in mammosphere. |
S0009279720305391 | Hetero mononuclear rhenium metal complexes using different substituted indole pyrazoline based ligands were synthesized and characterized by spectroscopic and analytical methods . The binding of the rhenium complexes to Herring sperm DNA was monitored by UV spectroscopy viscosity measurements and molecular docking studies groove binding was suggested as the most possible mode and the DNA binding constants of the complexes were evaluated . | Synthesis and characterization of pyrazoline indole based Re I carbonyls. Cell anti proliferation activity on MCF 7 HCT116 and A549cell lines. Complexes have potent anticancer activity than standard drugs carboplatin and oxaliplatin. DNA interaction antibacterial. and. cytotoxicity studies. |
S0009279720305494 | Currently whether nod like receptor family pyrin domain containing 3 inflammasome activation contributes to neuropathy induced by 2 5 Hexanedione the toxic metabolite of | HD induces NLRP3 inflammasome activation in sciatic nerve of rats. NLRP3 inflammasome inhibitor glybenclamide protects against HD induced toxicity. Glybenclamide inhibits HD induced macrophage infiltration and M1 activation. |
S0009279720305676 | Although physiological levels of iron are essential for numerous biological processes excess iron causes critical tissue injury . Under iron overload conditions non chelated iron generates reactive oxygen species that mediate iron induced tissue injury with subsequent induction of apoptosis necrosis and inflammatory responses . Because liver is a central player in iron metabolism and storage it is vulnerable to iron induced tissue injury . Taxifolin is naturally occurring compound that has shown potent antioxidant and potential iron chelation competency . The aim of the current study was to investigate the potential protective effects of taxifolin against iron induced hepatocellular injury and to elucidate the underlining mechanisms using rats as a mammalian model . The results of the current work indicated that taxifolin inhibited iron induced apoptosis and enhanced hepatocellular survival as demonstrated by decreased activity of caspase 3 and activation of the pro survival signaling PI3K AKT respectively . Western blotting analysis revealed that taxifolin enhanced liver regeneration as indicated by increased PCNA protein abundance . Taxifolin mitigated the iron induced histopathological aberration and reduced serum activity of liver enzymes highlighting enhanced liver cell integrity . Mechanistically taxifolin modulated the redox sensitive MAPK signaling and improved redox status of the liver tissues as indicated by decreased lipid peroxidation and protein oxidation along with enhanced total antioxidant capacity . Interestingly it decreased liver iron content and down regulated the pro inflammatory cytokines TNF IL 6 and IL 1 . Collectively these data highlight for the first time the ameliorating effects of taxifolin against iron overload induced hepatocellular injury that is potentially mediated through anti inflammatory antioxidant and potential iron chelation activities . | Taxifolin ameliorates iron overload induced hepatocellular apoptosis. Taxifolin enhances hepatocellular survival under iron overload conditions. Taxifolin improves hepatocellular regeneration under iron overload conditions. Taxifolin down regulates iron overload induced inflammatory responses. Taxifolin modulates iron overload induced oxidative stress. |
S000927972030569X | Hundreds of millions of people worldwide are exposed to unacceptable levels of carcinogenic inorganic arsenic . Animal models have shown that selenium and arsenic are mutually protective through the formation and elimination of the seleno bis | Selenide but not selenite efficiently protected human HepG2 cells against arsenite. Selenide accumulated to a greater extent than selenite in HepG2 cells. Intracellular selenium availability is important for protection against arsenite. Selenite is likely converted to selenide. for antagonism of arsenic toxicity. Selenium chemical form critical for. arsenic selenium interaction studies. |
S0009279720305755 | Oxidative stress provides a major contribution to the pathogenesis of glaucoma and may induce retinal ganglion cell damage . Transforming growth factor has appeared as a neuroprotective protein in various indignities . However the TGF mechanism of protective effects against oxidative stress damage in RGCs still undetermined . In our research we investigated the regulatory mechanisms and potential effects of TGF 1 TGF 2 in hydrogen peroxide H | TGF 1 protected RGCs from H2O2 induced oxidative stress. ALDH3A1 upregulation may defend RGCs against oxidative injury. TGF 1 enhanced the activation of Nrf2 HO 1 HIF 1 signal transduction. Pathway characterization of hydrogen peroxide induced oxidative stress on RGCs. |
S0009279720305937 | This study was aimed to investigate the cytotoxic potential of a natural compound progenin III on a broad range of cancer cell lines including various sensitive and drug resistant phenotypes . The cytotoxicity progenin III induced autophagic ferroptotic and necroptotic cell death were evaluated by the resazurin reduction assay . Spectrophotometric analysis of caspases activity was performed using caspase Glo assay . Flow cytometry was applied for cell cycle analysis apoptosis mitochondrial membrane potential and reactive oxygen species H | The cytotoxicity of a naturally occuring spirostanol saponin progenin III was evaluated. Progenin III exerted cytotoxic effects towards the 18 cancer cell lines tested including animal and human cell lines. Progenin III induced apoptosis autophagy and necroptosis in CCRF CEM cells. |
S0009279720306244 | The capsaicin receptor TRPV1 is a heat activated cation channel modulated by inflammatory mediators and contributes to acute and chronic pain . TRPV1 channel is one of the most researched and targeted mechanisms for the development of novel analgesics . Over the years natural products have contributed enormously to the development of important therapeutic drugs used currently in modern medicine . A literature review was conducted using Medline Google Scholar and PubMed . Searching the literature resulted in listing 136 natural compounds that interacted with TRPV1 channel . These compounds were phytochemicals that belong to different chemical groups including vanilloids flavonoids alkaloids terpenoids terpenyl phenols fatty acids cannabinoids sulfur containing compounds etc . Other natural TRPV1 modulators were of animal fungal or bacterial origin . Some natural products were small agonists or antagonists of TRPV1 . Others were protein venoms . Most in vitro studies utilized electrophysiological or calcium imaging techniques to study calcium flow through the channel using primary cultures of rat dorsal root and trigeminal ganglia . Other studies used hTRPV1 or rTRPV1 expressed in HEK239 CHO cells or | Searching the literature resulted in listing at least 136 natural modulators of TRPV1 channel. Natural TRPV1 modulators were of plant animal fungal or bacterial origin. Some natural products were small agonists or antagonists of TRPV1. Others were protein venoms. Many gaps in natural product research are present in distinguishing modality specific from polymodal antagonists. Species specific differences in TRPV1 functionality must be taken into account in any future study. |
S0009279720306372 | A series of novel pyrrolopyrimidine urea derivatives were synthesized and evaluated for their anticancer activity against colon cancer cell lines . Compounds showed the remarkable cytotoxic activity on HCT 116 wt cell line . The most potent compound | Novel pyrrolopyrimidines were designed and synthesized. is the most potent compound against HCT 116wt cell with IC. value of 0.14M. induced apoptosis in HCT 116wt and HCT 116 p53 cells. increase the levels of casp 3 and casp 9 in HCT 116wt and HCT 116 p53 cells. induced p53 independent apoptosis via the mitochondrial pathway in colon cancer. |
S0009279720306402 | The aim of the study was to synthesize a new series of benzimidazole derivatives and to investigate the underlying molecular mechanisms of the potential cell cycle inhibition and apoptotic effects against a panel of selected human cancer cell lines along with HEK 293 human embryonic kidney cells . MTT assay was used to evaluate cytotoxic effects . Muse Cell Analyzer was used to assess cell cycle progression . Annexin V PI staining assay was used for detecting apoptosis . All the synthesized compounds showed a significant cytotoxic effect against cancer cells with the IC | New benzimidazole derivatives 15 were cytotoxic to a panel of human cancer cells. HEK 293 embriyonic kidney cells were much less susceptible to compound 5. Bromo derivatived compound 5 induced apoptosis in all tested cancer cells. Compound 5 induced G. M arrest which was modulated by a p53 independent mechanism. |
S0009279720306451 | Testicular damage contributes to cyclosporine A induced male infertility . However the exact underlying molecular mediators involved in CsA induced testis disorder remains unclear . The present study aimed to characterize the role of mir 34a sirt 1 in CsA induced testicular injury alone or in combination with curcumin . A total of twenty eight male Wistar rats were subdivided into four groups control sham cyclosporine A cyclosporineA curcumin . The animals received cyclosporine A and curcumin for 28 days by oral gavage . At the end of the experiment CsA administration signicantly resulted in a decrease in testis weight and testis coefficient . The molecular analysis demonstrated that CsA exposure increased 8 OHdg and Nox4 protein contents in the testis tissue . TUNEL staining indicated that CsA caused the number of apoptotic cells to increase in the testes of male rats . In addition exposure to CsA resulted in an increased expression of Bax and a decreased expresion in that of Bcl 2 with a concomitant up regulation of the Bax Bcl 2 c Caspase 3 p Caspase 3 ratio and cytochrome | Cyclosporine A increased oxidative stress manifestations in testis of rats. Cyclosporine A increased apoptotic cells by mitochondrial apoptotic pathway in testis of rats. Cyclosporine A increased the expression of mir 34a and decreased sirt 1 sirtuin 1 protein level in the testis tissue. Curcumin alleviated genes and protein expression alterations in testis of rats. |
S0009279720306505 | The development of fast acting antidepressants is crucial considering that conventional antidepressants require a long period to elicit therapeutic effects . Creatine an ergogenic guanidine like compound stands out as a candidate to exert fast antidepressant like responses . The present study investigated whether a single dose of creatine elicits a fast response in mice submitted to the novelty suppressed feeding test a paradigm that may assess depression like and anxiety like behaviors . Ketamine an NMDA receptor antagonist that has rapid antidepressant effects and conventional antidepressants were also tested . The involvement of the mTORC1 signaling pathway in the behavioral responses was also investigated . Biochemical analyses included hippocampal BDNF level and total and phospho mTORC1 Ser | Conventional antidepressants did not show fast behavioral effect in the NSF test. Creatine and ketamine presented rapid behavioral effect in the NSF test via mTORC1. The increase on BDNF levels evoked by creatine and ketamine is dependent on mTORC1. Ketamine promoted mTORC1 dependent hippocampal synaptic protein translation. |
S0009279720306530 | Excessive osteoclast leads to the imbalance in bone reconstruction and results in osteolytic diseases such as osteoporosis and rheumatic arthritis . Integrin | Tablysin 15 inhibits the formation and bone resorption of osteoclast. Tablysin 15 inhibits the. None. FAK NF B MAPK and Akt NFATc1 signaling pathways. In vivo Tablysin 15 inhibits LPS induced bone loss. |
S0009279720306566 | Triple negative breast cancer is highly metastatic and lacks effective therapeutic targets among several subtypes of breast cancer . Cancer metastasis promotes the malignancy of TNBC and is closely related to the poor prognosis of the TNBC patients . We aim to explore novel agents that effectively inhibit cancer metastasis to treat TNBC . In our study 2 Methoxy 5seleninyl phenol a CA 4 analogue could inhibit cell motility and invasion in MDA MB 231cells and the mechanism is closely associated to the inhibition of epithelial to mesenchymal transition . Meanwhile SQ significantly inhibited the expression and secretion of vascular endothelial growth factor in MDA MB 231cells . Moreover the conditioned medium from SQ treated MDA MB 231cells significantly inhibited the motility and invasion of human umbilical vein endothelial cells which was correlated with the inhibition of EMT process in HUVECs . In addition exogenous application of VEGF reversed the occurrence of EMT in HUVECs which stimulated by conditioned medium from SQ treated cells . Furthermore SQ inhibited vasculogenic mimicry formation in MDA MB 231cells which was associated with VE cadherin and EphA2 down regulation . This study indicates that SQ inhibits MDA MB 231cell metastasis through suppressing EMT and VEGF thereby implicating this compound might be a potential therapeutic agent against metastatic TNBC . | SQ a CA 4 analogue inhibits triple negative breast cancer cell metastasis. SQ suppresses EMT process and MMP 9 expression. SQ decreases VEGF expression and secretion. SQ inhibits endothelial cell metastasis by down regulating VEGF secretion. SQ attenuates vasculogenic mimicry formation. |
S0009279720306608 | This study investigated the enantioselective metabolism of benoxacor an ingredient of herbicide formulations in microsomes or cytosol prepared from female or male rat livers . Benoxacor was incubated for 30min with microsomes or cytosol and its enantioselective depletion was measured using gas chromatographic methods . Benoxacor was depleted in incubations with active microsomes in the presence and absence of NADPH suggesting its metabolism by hepatic cytochrome P450 enzymes and microsomal carboxylesterases . Benoxacor was depleted in cytosolic incubations in the presence of glutathione consistent with its metabolism by glutathione S transferases . The depletion of benoxacor was faster in incubations with cytosol from male than female rats whereas no statistically significant sex differences were observed in microsomal incubations . The consumption of benoxacor was inhibited by the CYP inhibitor 1 aminobenzotriazole the CES inhibitor benzil and the GST inhibitor ethacrynic acid . Estimates of the intrinsic clearance of benoxacor suggest that CYPs are the primary metabolic enzyme responsible for benoxacor metabolism in rats . Microsomal incubations showed an enrichment of the first eluting benoxacor enantiomer E | Benoxacor is metabolized by rat the hepatic cytochrome P450 system and carboxylesterases. Benoxacor is metabolized by hepatic glutathione S transferases. The. metabolism of benoxacor is sex dependent in rats. Benoxacor is enantioselectively metabolized by different drug metabolizing enzymes. |
S0009279720306633 | Since several decades oximes have been used as part of treatment of nerve agent intoxication with the aim to restore the biological function of the enzyme acetylcholinesterase after its covalent inhibition by organophosphorus compounds such as pesticides and nerve agents . Recent findings have illustrated that besides oximes certain Mannich phenols can reactivate the inhibited enzyme very effectively and may therefore represent an attractive complementary class of reactivators . In this paper we further probe the effect of structural variation on the in vitro efficacy of Mannich phenol based reactivators . Thus we present the synthesis of 14 compounds that are close variants of the previously reported 4 amino 2 phenol a very effective non oxime reactivator and 3 dimeric Mannich phenols . All compounds were assessed for their ability to reactivate human acetylcholinesterase inhibited by the nerve agents VX tabun sarin cyclosarin and paraoxon in vitro . It was confirmed that the potency of the compounds is highly sensitive to small structural changes leading to diminished reactivation potency in many cases . However the presence of 4 substituted alkylamine substituents was tolerated . More surprisingly the dimeric compounds demonstrated non typical behavior and displayed some reactivation potency as well . Both findings may open up new avenues for designing more effective non oxime reactivators . | Synthesis of new Mannich phenol non oxime derivatives. New 4 N alkylamine derivatives of PADOC show reactivation potential. Mannich phenol dimers show surprising reactivation potential. The results point at potential new avenues for design of non oximes. |
S0009279720306682 | The caseinate and glycated caseinate generated from the transglutaminase catalyzed reaction of caseinate and oligochitosan were digested using pepsin and trypsin and the activity of the resultant digests was measured in rat intestinal epithelial cell line using several biological responses as indicators . Compared with the caseinate digest the glycated caseinate digest had similar contents in 17 amino acids but less reactable NH | IEC 6cells show responses to both glycated caseinate digest and caseinate digest. They promote cell growth and accumulate cell cycle progression at the S phase. They also possess apoptosis prevention and differentiation activity to the cells. Glycated caseinate digest has enhanced activity due to the TGase type glycation. The enhanced activity is regulated via the Wnt catenin signaling pathway. |
S0009279720306724 | Since its inception in 1969 Chemico Biological Interactions has persistently published high quality research articles . As part of the journal s golden anniversary we performed an electronic search on Scopus to get all publications details . Based on citescore ranking percentile CBI holds 21st position in the top 113 relevant journals . CBI also completed publications of 8005 manuscripts in March 2020 . The highest documents were articles followed by conference papers and reviews . The maximum number of publications was recorded in 2019 followed by 366 and 336 in 2016 . Furthermore details of the top 50 countries top 50 authors and top 20 institutes with total publications h index total citations and without selfcitations are provided . USA China and United Kingdom are the top three countries O Brien P.J Maser E. and Lockridge O. are the top three authors and Karolinska Institutet Stockholm University Ministry of Education China are the top three institutes involved in research publications . More than eighty four thousand 84 000 | The 1st bibliometric study of chemico biological interactions. The data about top authors universities and countries are provided. The top 200 articles reviews and conference papers were analyzed by Vosviewer. |
S0009279720307286 | The present study was undertaken to assess the effect of imatinib mesylate a tyrosine kinase inhibitor and a well known anticancer with numerous medical benefits on blood sugar levels insulin and glucagon secretion in an experimental model of STZ induced diabetes mellitus . Type 1 diabetes mellitus was induced by a single I.P . injection of Streptozotocin in male Sprague Dawley rats . Daily oral imatinib and for 4 weeks induced a significant attenuation in signs of DM in rats reflected in their assessed lab values . Biomarkers of cell injury tissue necrosis and apoptosis caspase 3 were significantly reduced with imatinib treatment . Furthermore pancreatic antioxidants defenses of which superoxide dismutase and catalase activities reduced glutathione concentration and total antioxidant capacity have significantly improved with a simultaneous reduction in malondialdehyde content . Histopathologically imatinib treatment was associated with a minimal pancreatic injury and marked restoration of insulin content in cells . Moreover imatinib treatment revealed a significant reduction in the infiltration of macrophages in cells . Imatinib s ameliorative impact on DM may be attributed to it s mediated protection and preservation of pancreatic cells function and the improvement in serum insulin levels and hence the improvement of blood glucose and overall glycemic control . | Imatinib improved DM indices in an experimental model of STZ induced T1DM. Imatinib showed preservation of morphological characteristics of pancreatic cells. Imatinib alleviated oxidative stress associating T1DM. Imatinib exerted anti inflammatory and anti apoptotic properties. |
S000927972030747X | Cigarette smoke is a complex mixture capable of triggering inflammation and oxidative damage in animals at pulmonary and systemic levels . Tempol reduces tissue injury associated with inflammation | Cigarette smoke exposure promotes inflammation and injury in lung parenchyma. Leukocytes release inflammatory mediators under acutely cigarette smoke exposure. Tempol attenuates inflammation and oxidative damage caused by cigarette smoke. Tempol activates Nrf2 pathway and reduces chemotaxis into inflammatory site. |
S0009279720307493 | A liquid chromatograpy nanoelectrospray ionization high resolution tandem mass spectrometry method was developed for quantitation of the DNA adducts 7 guanine and | We developed a LCNSIHRMS MS method for carboxyethylguanines in leukocyte DNA. Levels of. 1 CEG were 10 times higher than those of 7 2 CEG in human DNA. There was no difference in DNA adduct levels between smokers and non smokers. |
S0009279720307560 | Extensive application of methylene blue for therapeutic and diagnostic purposes and reports for unwanted side effects demand better understanding of the mechanisms of biological action of this thiazine dye . Because MB is redox active its biological activities have been attributed to transfer of electrons generation of reactive oxygen species and antioxidant action . Results of this study show that MB is more toxic to a superoxide dismutase deficient | SOD deficient mutants are hypersensitive to methylene blue. Methylene blue induces enzymes controlled by the. regulon. Induction of enzymes depended on. protein synthesis. Methylene blue activates the. regulon by intracellular redox cycling. |
S0009279720307572 | Alcoholic liver disease is a progressively aggravated liver disease with high incidence in alcoholics . Ethanol induced fat accumulation and the subsequent lipopolysaccharide driven inflammation bring liver from reversible steatosis to irreversible hepatitis fibrosis cirrhosis and even hepatocellular carcinoma . Peroxisome proliferator activated receptor is a member of the nuclear receptor superfamily of ligand activated transcription factors and plays pivotal roles in the regulation of fatty acid homeostasis as well as the inflammation control in the liver . It has been well documented that PPAR activity and or expression are downregulated in liver of mice exposed to ethanol which is thought to be one of the prime contributors to ethanol induced steatosis hepatitis and fibrosis . This article summarizes the current evidences from | PPAR plays pivotal roles in regulation of fatty acid homeostasis in liver. PPAR activity and or expression in liver is downregulated after ethanol exposure. The expression of PPAR in human liver may be similar to that in mice liver. PPAR expression is decreased in the liver of patients with NAFLD. |
S0009279720307663 | Many natural products are prodrugs which are biotransformed and activated after oral administration . The investigation of gastrointestinal and hepatic biotransformation can be facilitated by | Comparison of S9 and microsomal cytosolic fractions for. liver biotransformation. Aim Identifying differences in biotransformation of medicagenic acid. 13 biotransformation products were identified 4 are reported for the first time. Similar qualitative metabolic profile with minor quantitative differences. Both protocols can be used to study. human liver biotransformation. |
S0009279720307742 | General anaesthetics are some of the most widely used and essential therapeutic agents . However despite over a century of research the molecular mechanisms of general anaesthesia in the central nervous system remain elusive . Ketamine has been approved for use in general anaesthesia either alone or in combination with other medications . It is a superb drug for use in short term medical procedures that do not require skeletal muscle relaxation and it has approval for the induction of general anaesthesia as a pre anaesthetic to other general anaesthetic agents . However Several questions remain unsolved including the exact identification of the neural substrate of consciousness and its components the pharmacodynamic interactions between anaesthetic agents the mechanisms of cognitive alterations that follow an anaesthetic procedure the identification of an eventual unitary mechanism of anaesthesia induced alteration of consciousness the relationship between network effects and the biochemical targets of anaesthetic agents leading to difficulties in between studies comparisons . Thus the glutamate and dopamine systems play distinct roles in terms of neuronal signalling yet both have proposed to contribute significantly to the pathophysiology of neuropsychiatric diseases . Imaging of the glutamate system and other aspects of research on the dopamine system have produced less consistent findings potentially due to methodological limitations and the heterogeneity of the disorder . In this review we discuss the neural circuits through which the two systems interact and how their disruption may cause psychotic symptoms . We also summarize from a molecular perspective of mechanisms of action of ketamine as general anaesthetics on ligand gated ion channels mediated modulation of dopamine in the brain region . | General anaesthetics are some of the most widely used and essential therapeutic agents. However despite over a century of research the molecular mechanisms of general anaesthesia in the CNS remain elusive. Ketamine has been approved for use in general anaesthesia either alone or in combination with other medications. |
S0009279720307791 | Cancer metastasis and resistance for chemotherapeutic agent correlate with epithelial mesenchymal transition while ROS production also involves in the EMT process However how autophagy mediated ROS production affects EMT remains unclear . Previous study showed that DpdtC could induce ferritinophagy in HepG2 cell . To insight into more details that how ferritinophagy affects cellular feature the SGC 7901and BGC 823 gastric cancer cell lines were used . Interestingly DpdtC treatment resulted in EMT inhibition and was ROS dependent . Similar situation occurred in TGF 1 induced EMT model supporting that DpdtC was able to inhibit EMT . Next the ability of DpdtC in ferritinophagy induction was further evaluated . As expected DpdtC induced ferritinophagy in the absence and presence of TGF 1 . The correlation analysis revealed that an enhanced ferritinophagic flux contributed to the EMT inhibition . In addition ferritinophagy triggers Fenton reaction resulting in ROS production which give rise of p53 response thus the role of p53 was further investigated . DpdtC treatment resulted in upregulation of p53 but the addition of p53 inhibitor PFT could significantly neutralize the action of DpdtC on ferritinophagy induction and EMT inhibition . Furthermore autophagy inhibitors or NAC could counteract the action of DpdtC indicating that ferrtinophagy mediated ROS played an important role in the cellular events . In addition to upregulation of p53 its down stream targets AKT mTor were also downregulated supporting that DpdtC induced EMT inhibition was achieved through ferritinophagy ROS vicious cycle mediated p53 AKT mTor pathway . And the activation of ferritinophagic flux was the dominant driving force in action of DpdtC in gastric cancer cells . | Iron chelator DpdtC induced EMT inhibition. DpdtC induced occurrence of ferritinophagy. Creating vicious cycle between ferritinophagy and ROS production contributed to EMT inhibition. DpdtbA induced p53 response resulted in downregulation of targeted genes and the EMT inhibition. |
S0009279720307948 | In terms of public health the 21st century has been characterized by coronavirus pandemics in 2002 03 the virus SARS CoV caused SARS in 2012 MERS CoV emerged and in 2019 a new human betacoronavirus strain called SARS CoV 2 caused the unprecedented COVID 19 outbreak . During the course of the current epidemic medical challenges to save lives and scientific research aimed to reveal the genetic evolution and the biochemistry of the vital cycle of the new pathogen could lead to new preventive and therapeutic strategies against SARS CoV 2 . Up to now there is no cure for COVID 19 and waiting for an efficacious vaccine the development of savage protocols based on old anti inflammatory and anti viral drugs represents a valid and alternative therapeutic approach . As an alternative or additional therapeutic preventive option different in silico and | Flavonoids can inhibit key proteins involved in coronavirus infective cycle. SARS CoV proteases PL. and 3CL. can be inhibited by flavonoids. NTPase helicase and N protein of SARS CoV can be inhibited by flavonoids. |
S0009279720308103 | Presence of Simple Sequence Repeats both in genic and intergenic regions have been widely studied in eukaryotes prokaryotes and viruses . In the current study we undertook a survey to analyze the frequency and distribution of microsatellites or SSRs in multiple genomes of | 919 SSRs were found across 55 members of the Coronaviridae family. Genomes exhibit under representation of SSRs. Commonly 1213nt long hexanucleotide repeats occupying the genic region. Identified genic SSRs in SARS CoV 2 are under selection pressure against mutations. 29 of the total bases covered by SSRs in SARS CoV 2 were found to be variants. |
S0009279720308231 | Ischemia reperfusion injury causes oxidative stress leading to severe cardiac dysfunction . Thus biologically active compounds with antioxidant properties may be viewed as a promising therapeutic strategy against oxidative related cardiac disorders . Usnic acid a natural antioxidant was complexed with cyclodextrin to improve its bioavailability . Wistar male rats were orally treated with the free form of UA or the inclusion complex UA CD for seven consecutive days . Afterward hearts were subjected to I R injury and the cardiac contractility rhythmicity infarct size and antioxidant enzyme activities were evaluated . Here we show that neither UA nor UA CD treatments developed signs of toxicity . After I R injury animals treated with UA CD showed improved post ischemic cardiac functional recovery while the release of cell injury biomarkers decreased . Following reduced cardiac damage a lower incidence of ventricular arrhythmias and smaller myocardial infarct size were associated with reduced lipid peroxidation along with preserved activity of antioxidant enzymes compared to untreated rats . Surprisingly uncomplexed UA did not protect hearts against IR injury . Altogether our results indicate that the inclusion complex UA CD is a critical determining factor responsible for the cardioprotection action of UA suggesting the involvement of an antioxidant dependent mechanisms . Moreover our findings support that UA CD is a structurally engineered compound with active cardioprotective properties . | UA CD inclusion complex enhances the aqueous solubility of UA. Uncomplexed UA has no cardioprotective properties. UA CD inclusion complex protects hearts against myocardial IR injury. UA CD is a structurally engineered compound with active cardioprotective properties. |
S0009279720308553 | Cisplatin induces acute renal failure in humans and mice.Tubular apoptosis necrosis and inflammation are the primary pathogenesis of cisplatin induced acute kidney injury . We previously reported that the depletion of Numb from proximal tubules exacerbates tubular cells apoptosis in cisplatin induced AKI however the role of Numb in tubular necrosis and renal inflammation in cisplatin induced AKI remains unclear . A mouse model of AKI was produced by cisplatin intraperitoneally injection in mice from proximal tubule specific depletion of Numb and their wild type littermates respectively . Renal Numb expression was determined by Western blotting . Renal morphological damage was examined by hematoxylin and eosin staining . Tubular necrosis was evaluated by histological study and the protein level of renal Mixed lineage kinase domain like protein which is a molecular marker of necrosis . Leukocyte infiltration and pro inflammatory cytokines was determined by immunostaining and quantitative real time PCR respectively.The protein level of Numb was dramatically decreased in kidneys of PT Nb KO mice compared with PT Nb WT mice . After cisplatin injection a significant increase of tubular injury score and the protein level of renal MLKL were detected in PT Nb KO mice compared with those in PT Nb WT . In addition the number of F4 80 positve and CD3 positive cells markers for macrophages and neutraphils respectively showed significantly increased in kidneys from PT Nb KO mice compared with those in PT Nb WT mice . Consistently the gene expression of pro inflammatory cytokines including TNF and MCP 1 in the kidneys was higher in PT Nb KO mice than those in PT Nb WT mice . Numb play additional protective role in cisplatin induced AKI through ameliorating tubular necrosis and renal inflammation besides attenuating cisplatin induced tubular apoptosis . | Cisplatin induces Acute kidney injury. Necrosis and Inflammation are involved in Acute kidney injury. Numb ameliorates Necrosis and Inflammation. |
S0009279720308723 | Hepatic ischemia reperfusion injury is not only one of the pathophysiological process involving the liver but also a complex systemic process affecting multiple tissues and organs . IRI after liver transplant occurs due to in major resections and occlusion of vessels or during the perioperative period leads to acute liver failure which shows the dynamic process that involves two interrelated phases of local ischemic insult and inflammation mediated reperfusion injury and has an impact on morbidity and mortality . The renin angiotensin aldosterone system is activated locally in the injured cells by the occurrence of I R which plays an essential role in the fate of the damaged tissue . However a preclinical study explores the protective role of RAAS inhibitor in acute liver injury in a model of inflammation caused by ischemia and reperfusion . In addition to RAAS blockers in monotherapy does not effectively block the complete pathway . Thus the present study is designed to explore the effect of combined folic acid with RAAS blockers in combination produce a synergistic effect . Moreover in this review we will describe the understanding of the possible incidence of downregulatory molecular mechanisms associated with renin angiotensin aldosterone system and the significance outcome of the combination of folic acid and RAAS blockers in liver injury due to ischemia reperfusion . | The ischemia reperfusion damage represents a severe problem in the clinical practice due to several reasons. RAAS is activated locally in the injured cells by the occurrence of I R. ROS generation causes cell damage and leads to cell death via autophagy necrosis necroptosis and apoptosis. |
S0009279720308747 | Ellagic acid is a naturally occurring polyphenolic compound that has been shown to exhibit diverse beneficial pharmacological activities including anti osteoclastogenesis effect . However the molecular mechanism by which EA inhibits osteoclastogenesis remains to be elucidated . The protein protein interaction between receptor activator of nuclear factor B ligand and its receptor RANK contributes to osteoclast differentiation and activation in bone remodeling and is regarded as an important therapeutic target for the treatment of osteoporosis . The current study is focused on investigating whether EA can directly bind to RANKL and or RANK and block the interaction between RANKL and RANK thereby inhibiting downstream signaling pathways . Interestingly we found that EA had strong affinities to RANK and RANKL with the estimated equilibrium dissociation constants | Ellagic acid EA inhibited RANKL induced osteoclast differentiation and F actin ring formation. EA directly bound to RANK and RANKL with strong affinities and blocked RANKLRANK interaction. EA suppressed canonical RANK signaling pathways in osteoclast precursors. EA downregulated master transcriptional factors and osteoclast specific genes and proteins expression. |
S000927972030884X | The lack of tissue selectivity of anticancer drugs generates intense collateral and adverse effects of cancer patients making the incorporation of vitamins or micronutrients into the diet of individuals to reduce side or adverse effects of antineoplastics . The study aimed to evaluate the effects of retinol palmitate on the toxicogenic damages induced by cyclophosphamide doxorubicin and its association with the AC protocol in Sarcoma 180 tumor cell line using the micronuclei test with a block of cytokinesis and in non tumor cells derived from Mus musculus using the comet assay . The results suggest that CPA DOX and AC protocol induced significant toxicogenic damages on the S 180cells by induction of micronuclei cytoplasmic bridges nuclear buds apoptosis and cell necrosis proving their antitumor effects and significant damage to the genetic material of peripheral blood cells of healthy mice proving the genotoxic potential of these drugs . However RP modulated the toxicogenic effects of antineoplastic tested both in the CBMN test at the concentrations of 1 10 and 100 IU mL as in the comet assay at the concentration of 100 IU kg for the index and frequency of genotoxic damage . The accumulated results suggest that RP reduced the action of antineoplastics in non tumor cells as well as the cytotoxic mutagenic and cell death in neoplastic cells . | Toxicogenetic modulation by retinol palmitate. Reduced antineoplactic action in non tumour cells. Modulatory cytotoxic mutagenic and cell death in neoplastic cells. |
S0009279720309030 | Obesity is characterized by the deposition of excessive body fat and is caused by energy imbalance especially when consuming fat rich diets . High fat diet associated obesity is greatly common in patients with non alcoholic fatty liver disease that is emerging as one of the most universal causes of liver disease worldwide especially in Western countries . In spite of its high prevalence only a small proportion of affected individuals will become inflamed followed by fibrosis and chronic liver diseases and most patients only show simple steatosis . In this case the full comprehension of the mechanisms underlying the progression of NAFLD is of extreme significance in spite of progress in this field awareness on the development of NAFLD is still incomplete . Traditionally liver steatosis is commonly connected with HFD obesity and insulin resistance . Recently various possible mechanisms have been put forward for liver damage including endoplasmic reticulum stress perturbation of autophagy mitochondrial dysfunction hepatocellular apoptosis gut microbiota imbalance dysregulation of microRNAs and genetic epigenetic risk factors as well as an increase in inflammatory responses among many others . Collectively these proposed mechanisms allow for a variety of hits acting together on subjects to mediated NAFLD and will offer a more accurate explanation for progression of NAFLD . Therefore this review summarizes the present information concerning NAFLD after HFD exposure as well as discusses possible mechanisms through which it may arise . | High fat diet HFD is a crucial contributory factor affecting NAFLD progression. HFD triggered possible mechanisms are posited to explain NAFLD pathogenesis. Currently effective therapeutic options for NAFLD remain lifestyle interventions. |
S0009279720309157 | Hyperuricosuria is associated with kidney stone disease especially uric acid and calcium oxalate types . Nevertheless detailed mechanisms of hyperuricosuria induced kidney stone formation remained unclear . This study examined changes in cellular proteome and function of renal tubular cells after treatment with high dose UA for 48 h. Quantitative proteomics using 2 DE followed by nanoLC ESI ETD MS MS tandem mass spectrometry revealed significant changes in levels of 22 proteins in the UA treated cells . These proteomic data could be confirmed by Western blotting . Functional assays revealed an increase in intracellular ATP level and enhancement of tissue repairing capability in the UA treated cells . Interestingly levels of HSP70 and HSP90 were increased in apical membranes of the UA treated cells . CaOx crystal cell adhesion assay revealed significant increase in CaOx binding capability of the UA treated cells whereas neutralization of the surface HSP70 and or HSP90 using their specific monoclonal antibodies caused significant reduction in such binding capability . These findings highlighted changes in renal tubular cells in response to high dose UA that may at least in part explain the pathogenic mechanisms of hyperuricosuria induced mixed kidney stone disease . | Proteomics revealed altered levels of 22 proteins in UA treated renal tubular cells. Intracellular ATP level was increased in UA treated renal tubular cells. Tissue repairing capability was enhanced in UA treated renal tubular cells. HSP70 HSP90 known CaOx crystal receptors were increased in apical membranes. CaOx binding capability was increased in UA treated renal tubular cells. |
S0009279720309625 | Colorectal cancer represents one of the commonest malignancies around the world . PP9 a natural steroidal saponin was firstly isolated from the rhizomes of | PP9 a natural steroidal saponin suppresses proliferation and induces cell cycle arrest and apoptosis in CRC. PP9 exerts antitumor effects in xenografted mouse models. PP9 inhibits PI3K Akt GSK3 signaling in CRC cells. |
S0009279720309704 | Flavonoids are natural products widely recognized for their plurality of applications such as antiviral antiproliferative antitumor activities and antioxidant properties . The flavanone naringenin is presented in citrus fruits and has been studied to combat recurrent diseases that still lack effective treatment . Research groups have been investing efforts to the development of new safe and active candidates to combat these agents or conditions and despite good results recently reported against the Zika virus and tumor cells the use of citrus naringenin is limited due to its low bioavailability . Structural exchanges through functionalization for example attaching lipophilic groups instead of hydroxyl groups can further enhance biological properties . | Synthesis and characterization of both lipophilic ethers and esters of the citrus naringenin a natural product. Regioselective preparation of 7. alkyl ethers. Inhibitory activities against Zika virus and proliferative cells of Melanoma and breast cancer cells. The lipophilic ethers present the ability to inhibit selectively ZIKV replication in human cells and inhibitions. Modifications in flavonoid molecules could be further explore in the future development of specific anti ZIKV compounds. |
S0009279720309820 | Kinetic modeling of the behavior of complex chemical and biochemical systems is an effective approach to study of the mechanisms of the process . A kinetic model of coronaviral infection development with a description of the dynamic behavior of the main variables including the concentration of viral particles affected cells and pathogenic microflora is proposed . Changes in the concentration of hydrogen ions in the lungs and the pH dependence of carbonic anhydrase activity are critical . A significant result is the demonstration of an acute bifurcation transition that determines life or system collapse . This transition is connected with exponential growth of concentrations of the process participants and with functioning of the key enzyme carbonic anhydrase in development of toxic effects . Physical and chemical interpretations of the therapeutic effects of the body temperature rise and the potential therapeutic effect of thermoheliox are given . The phenomenon of thermovaccination is predicted which involves stimulation of the immune response by thermoheliox . | The proposed kinetic model describes the dynamics of coronaviral infection development. Acidification and pH dependence of key enzymes is discussed as a basis of viral toxicity. An acute bifurcation transition of the system to collapse is demonstrated. The theory and experimental facts of thermoheliox therapy are discussed. Thermovaccination by thermoheliox is predicted. |
S0009279720309844 | The use of 3D models in various scientific applications is becoming more popular to replace traditional monolayers models . In this work we used a three dimensional in house model of epidermis using HaCaT immortalized cells to evaluate the dermal toxicity induced by Basic Blue 99 and Basic Red 51 both present in commercial hair dye formulations . Our data show that cells cultured in the 3D model respond differently to those cultured in monolayer . Basic Red 51 dye induces apoptosis an DNA breaks in both models however these effects is more pronounced in cells cultured in monolayer . The toxic mode of action of Basic Blue 99 seems to be the induction of cell death without genotoxic effects but while the necrotic pathway is observed in HaCaT monolayer cell culture was apoptosis seen in the Equivalent Human Epidermis model . We could also confirm that cells in EHE model an environment that could better mimic human effects react differently to chemical stressors than the cells cultivated in 2D . | The hair dyes can cause some toxic effects in the body. The 3R s principle encourages the development and use of alternative methods to use of animals. The 3D model is an alternative method capable of mimicking dermal exposure. |
S000927972030987X | The 2 aminothiazole functionality has long been established as a privileged structural feature and therefore frequently exploited in the process of drug discovery and development . It has been introduced into numerous compounds due to its capacity for targeting a wide range of therapeutic target proteins . On the other hand the aminothiazole group has also been classified as a toxicophore susceptible to metabolic activation and the ensuing reactive metabolite formation hence caution is warranted when used in drug design . This review is divided into three parts entailing | The advantages of the 2 aminothiazole group in medicinal chemistry were detailed. 2 aminothiazoles were studied as toxicophores that form reactive metabolites. Chemical strategies that reduce the intrinsic hepatotoxicity were highlighted. |
S0009279720309911 | Only in the last decade the long term consequences of sepsis started to be studied and even less attention has been given to the treatment of psychological symptoms of sepsis survivors . It is estimated that 60 of sepsis survivors have psychological disturbances including depression anxiety and cognitive impairment . Although the causative factors remain largely poorly understood blood brain barrier disturbances neuroinflammation and oxidative stress have been investigated . Therefore we sought to explore if the immunomodulatory and antioxidant selenocompound 3 selanyl 1 methyl 1H indole would be able to ameliorate long term behavioral and biochemical alterations in sepsis survivors male | CMI ameliorated long lasting behavioral alterations in sepsis survivor mice. CMI modulated peripheral cell count and oxidative stress in sepsis survivor mice. CMI reduced plasma markers of liver and kidney dysfunction induced by sepsis. CMI ameliorated BBB dysfunction induced by sepsis. CMI reduced inflammation and oxidative stress in the brain of post septic mice. |
S0009279720310231 | Cancer continues to be one of the most challenging diseases to be treated and is one of the leading causes of deaths around the globe . Cancers account for 13 of all deaths each year with cancer related mortality expected to rise to 13.1 million by the year 2030 . Although we now have a large library of chemotherapeutic agents the problem of non selectivity remains the biggest drawback as these substances are toxic not only to cancerous cells but also to other healthy cells in the body . The limitations with chemotherapy and radiation have led to the discovery and development of novel strategies for safe and effective treatment strategies to manage the menace of cancer . Researchers have long justified and have shed light on the emergence of nanotechnology as a potential area for cancer therapy and diagnostics whereby nanomaterials are used primarily as nanocarriers or as delivery agents for anticancer drugs due to their tumor targeting properties . Furthermore nanocarriers loaded with chemotherapeutic agents also overcome biological barriers such as renal and hepatic clearances thus improving therapeutic efficacy with lowered morbidity . Theranostics which is the combination of rationally designed nanomaterials with cancer targeting moieties along with protective polymers and imaging agents has become one of the core keywords in cancer research . In this review we have highlighted the potential of various nanomaterials for their application in cancer therapy and imaging including their current state and clinical prospects . Theranostics has successfully paved a path to a new era of drug design and development in which nanomaterials and imaging contribute to a large variety of cancer therapies and provide a promising future in the effective management of various cancers . However in order to meet the therapeutic needs theranostic nanomaterials must be designed in such a way that take into account the pharmacokinetic and pharmacodynamics properties of the drug for the development of effective carcinogenic therapy . | Cancer is one of the leading cause of death around the globe. Theranostics is a customised approach to cancer diagnosis. These nanomaterials can address cancer treatment issues and diagnostic challenges. |
S0009279720310322 | Caffeic acid is a phenolic compound widely found in commonly consumed foods such as pears apples and coffee and is pharmacologically known for its antioxidant anti inflammatory and anti asthmatic properties . However its relaxant activity in the aorta uterus and ileum smooth muscle has not been investigated . This study aimed to comparatively evaluate the effect of caffeic acid on smooth muscle from different organs and the contractions of this different organ were induced by different agonists . The organ bath technique was used where the organs were placed in different cuvettes with 10mL of Tyrode solution for 1h to stabilize then myometrial intestinal strip and aortic ring contractions were evoked using different contractile agonists KCl 60mM PHE 0.1 M OT 10 2 IU mL CCh 10 | Caffeic acid has a muscle relaxant effect on vascular smooth muscle myometrial and intestinal. Caffeic acid had an antispasmogenic effect on different organs aorta uterus and ileum of rats in the presence of K . The relaxing effect of caffeic acid is partially dependent on the calcium channels operated by type L voltage. Caffeic acid can be used as a therapeutic substance. |
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