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S0009279718303235 | Juglone and thymoquinone are cytotoxic to pancreatic cancer cells . The aim of this study was to investigate using an analysis of isobolograms the type and degree of interactions between juglone and thymoquinone on MIA PaCa 2 pancreatic cancer cells . Cell viability was evaluated using the MTT assay . Cell death was determined by flow cytometry . The IC | Juglone and thymoquinone are cytotoxic to pancreatic cancer cells. IC. for juglone in combination with thymoquinone was higher than juglone alone. Additive effect occurs at concentration that affects 75 and 90 of the cancer cells. Moderate synergism was seen at 40.90M juglone and 511.19M thymoquinone. |
S0009279719302492 | The monoterpenoid terpinen 4 ol is known to inhibit cell excitability has low toxicity and important pharmacological activities which are likely related to neural excitability such as anti inflammatory antiepileptic and antinociceptive effects . However the pharmacological characteristics and mechanisms underlying the effects of 4TERP on blockade of neural action potential are not completely elucidated . Since Na | 4TERP concentration dependently inhibits voltage dependent Na. channels activation. 4TERP inhibits I. predominantly through the mechanism of channel pore blockade. 4TERP blockade showed sensitivity to use dependence. This effect is coherent with 4TERP induced blockade of neuronal excitability. |
S0009279719302893 | Although rifampicin could have a hepatic toxic effect it has also been shown that this chemical acts as a cellular protectant against oxidative stress . Therefore we wondered whether rifampicin has a beneficial effect such as an anti oxidant in the liver because the efficacy of some drugs sometimes relates with their toxicity as well as protective effects . The present study aimed to investigate the antioxidant effect of rifampicin against arachidonic acid plus iron cotreatment and against acetaminophen induced oxidative stress | Rifampicin inhibited acetaminophen induced liver damage. Rifampicin inhibited oxidative stress and mitochondria damage in hepatocyte. Rifampicin activated AMPK related with LKB1 signals. Rifampicin induced nuclear Nrf2 expression and antioxidant genes. Rifampicin might be a pharmaceutical candidate for hepatic injury. |
S0009279719303771 | 2 3 7 8 Tetrachlorodibenzo p dioxin accumulates in human body probably influencing adipocyte differentiation and causing various toxic effects including wasting syndrome . Recently orientin a phenolic compound abundant in natural health products has been shown to have antioxidant properties . We investigated the protective effects of orientin against TCDD induced adipocyte dysfunction and its underlying mechanisms . In this study orientin suppressed TCDD induced loss of lipid accumulation . Orientin inhibited TCDD driven decreases in the levels of peroxisome proliferator activated receptor and adiponectin . Orientin also reduced TCDD induced prostaglandin E | Orientin suppressed TCDD induced loss of lipid accumulation. Orientin inhibited TCDD driven decreases in the levels of PPAR and adiponectin. Orientin reduced TCDD induced PGE. and cPLA. levels. Orientin increased TCDD inhibited PGC1 alpha levels. Orientin increased TCDD reduced IRS1 GLUT4 and insulin stimulated glucose uptake. |
S0009279719305538 | We investigated the inhibitory effects of 13 organophosphate esters and hydrolytic metabolites on the carboxylesterase activity of rat liver microsomes | We examined carboxylesterase inhibition by organophosphate esters OPEs . 2 Ethylhexyl diphenyl phosphate was the most potent inhibitor among tested OPEs. Aryl OPEs were strong rat liver microsomal carboxylesterase inhibitors. Di or mono substituted derivatives of OPEs showed markedly decreased inhibition. OPEs bearing a bulky substituent showed greater carboxylesterase inhibitory effects. |
S0009279719306568 | Spermatogenic dysfunction is one of the major secondary complications of male diabetes . Salidroside is the important active ingredients isolated from | This study first reported the effects of SAL on BTB integrity in diabetic mice. SAL ameliorates diabetes induced histological and morphological damages of testis in male mice. SAL reverses diabetes induced poor sperm parameters comprising sperm count sperm motility and sperm viability in male mice. The mechanism may be through by inhibiting oxidative stress mediated BTB damage. |
S0009279719307872 | Oleanolic acid is a triterpenoid widely found in plants and possesses antitumor activity in many cancer lines . However cancer cells develop multidrug resistance hindering the effect of anticancer drugs . P glycoprotein is a major cause of mdr . Therefore the cytotoxic effect of OA was evaluated on human breast cancer MDA MB 231 and human liver cancer HepG2 with absence and presence of P gp respectively . OA reduced MDA MB 231 viability in a dose dependent manner whereas no remarkable effect was observed on HepG2 in the same range of concentrations . Moreover cytotoxicity studies were conducted in the presence of verapamil a P gp inhibitor . OA exhibited the same effect on MDA MB 231 in the absence and presence of verapamil . However the cytotoxicity was greatly enhanced for HepG2 cells in the presence of verapamil . The results were then confirmed | Oleanolic acid is found in plants and has antitumor activity in many cancer lines. The cytotoxic effect of oleanolic acid was evaluated on MDA MB 231 and HepG2 cells. Inhibiting P gp by verapamil enhanced the cytotoxic effect of oleanolic acid. In zebrafish embryos oleanolic acid was more toxic in the presence of verapamil. Oleanolic acid could be eliminated from cells by the P gp. |
S0009279719307896 | 4 methylesculetin is a natural antioxidant coumarin with protective effects on the intestinal inflammation in which oxidative stress plays a key role in its aetiology and pathophysiology . Based on this we examined the antioxidant molecular mechanisms involved in the intestinal anti inflammatory activity of the 4ME . For this purpose we investigated the effects of the 4ME on the modulation of gene expression and antioxidant related enzyme activities in TNBS model of intestinal inflammation as well as the molecular interaction between 4ME and glutathione reductase . Our results showed that 4ME modulated glutathione related enzymes mainly increasing glutathione reductase activity . These effects were related to upregulation of glutathione reductase and Nrf2 gene expression . Fluorescence and nuclear magnetic resonance data showed that interaction between 4ME and glutathione reductase is collisional hydrophobic and spontaneous in which C4 methyl group is the second epitope most buried into glutathione reductase . Molecular modelling calculation showed Lys70 B Arg81 A Glu381 B Asp443 A Ser444 A Glu447 B and Ser475 A participated in electrostatic interaction Lys70 B Glu381 B and Arg81 A acted in the hydrophobic interactions and Trp73 Phe377 and Ala446 are responsible for the hydrogen bonds . Based on this our results showed 4ME acted by different mechanisms to control oxidative stress induced by intestinal damage controlling the imbalance between myeloperoxidase activity and glutathione production upregulating the glutathione S transferase and glutathione reductase activities preventing the Nrf2 and glutathione gene expression downregulation with consequent glutathione maintenance . Finally 4ME interacted at molecular level with glutathione reductase stabilizing its enzymatic activity and reducing oxidative stress to take place in intestinal inflammatory process . | 4 methylesculetin 4ME is an antioxidant and intestinal anti inflammatory coumarin. 4ME acts modulating glutathione related enzymes to produce antioxidant properties. 4ME upregulated glutathione reductase GSR activity and gene expression. 4ME upregulated Nrf2 expression leading to GSR regeneration and maintenance. 4ME binding with GSR stabilizing its enzymatic activity and reducing oxidative stress. |
S0009279719308762 | Treatment of breast cancer by paclitaxel often encounters therapeutic failure most likely caused by innate acquired resistance . Cancer stem cells and multidrug resistance complex overexpression are main mechanisms implicated in chemoresistance . Increased aldehyde dehrogenase 1 was previously correlated with the stemness features of CSCs and hence is used as a marker for identification and CSCs targeting . The present study therefore aimed at investigating the effect of both curcumin and vitamin D3 on MDR 1 and ALDH 1 expression and consequently the resistance to PAX both | Combining both curcumin and vitamin D3 to paclitaxel was studied. Paclitaxel alone showed acquired or. resistance both. and. Paclitaxel monotherapy showed increased ALDH 1 and MDR 1 levels. The triple therapy showed the lowest levels of ALDH 1. The triple therapy showed the lowest levels of MDR 1 and tumor size. |
S0009279719308981 | This study evaluates the possible protective effects of gallic acid and ferulic acid against an experimentally induced liver fibrosis by thioacetamide in rats . Animals were divided into Control group GaA group 20mg kg day | Gallic and ferulic acids prevent thioacetamide induced changes in the rat liver. Gallic and ferulic acids inhibit TGF 1 Smad 3 signaling pathway. Gallic and ferulic acids upregulate miR 30 and miR 200 while downregulate miR 21 expressions. |
S0009279719309238 | Diabetes mellitus is a metabolic disorder with hyperglycemia being its hallmark symptom . The secondary symptom of DM is oxidative stress which leads to the generation of free radicals . Diabetic nephropathy and neuropathy is the long term effect of oxidative stress caused in DM which leads to damage of kidneys and neurons respectively . Resveratrol is a phytochemical found to be effective in the treatment of diabetic nephropathy and neuropathy . Due to its antioxidant property it reduces the oxidative stress caused by DM . Dipeptidyl peptidase 4 inhibitors are used for the treatment of type 2 DM . | Study investigated the effect of RES on the pharmacokinetics of DPP 4 inhibitors. and. data depicted that RES altered its pharmacokinetics. The pharmacokinetic parameters were evaluated using WinNonLin software. Dose adjustments are necessary when RES is co administered. |
S000927971930941X | This study aimed to investigate the effects of teaghrelin an active ingredient of Chin shin oolong tea on murine C2C12 myoblast cells . Under high serum conditions teaghrelin inhibited C2C12cell proliferation indicating a cell cycle arrest and cessation of proliferative progression . Teaghrelin promoted pro differentiation of C2C12cells as evidenced by a progressively elongated morphology as well as the induction of muscle specific myogenin myosin heavy chain and MyoD . The formation of multinucleated myotubes and the increase of MHC positive immunoreactivity within the myotubes further reflected a complete differentiation and maturation of the contractile skeletal muscle cells induced by teaghrelin . Like ghrelin teaghrelin attenuated dexamethasone decreased myotube diameter indicating its protective effects against skeletal muscle atrophy . Additionally the expressions of Atrogin 1 and MuRF 1 ubiquitin E3 ligase were reduced . In conclusion the results highlight a possibility of developing teaghrelin as a functional food for the prevention or therapeutic treatment of disease associated skeletal muscle atrophy . | Teaghrelin attenuated C2C12 myoblast cell proliferation. Teaghrelin promoted C2C12cell differentiation and myotube formation. Teaghrelin attenuated dexamethasone induced myotube atrophy. Teaghrelin attenuated dexamethasone induced ubiquitin E3 ligase expression. |
S0009279719309913 | Methylmercury and Ethylmercury are toxic to the central nervous system . Human exposure to MeHg and EtHg results mainly from the consumption of contaminated fish and thimerosal containing vaccines respectively . The mechanisms underlying the toxicity of MeHg and EtHg are still elusive . Here we compared the toxic effects of MeHg and EtHg in | MeHg and EtHg reduced the growth of. in both liquid and solid medium. The yeast exposed to MeHg and EtHg presented increased levels of reactive species. MeHg and EtHg decreased membrane integrity and increased the granularity of cells. Mutants related to antioxidant pathways had their growth affected by both mercurials. In general the strains exhibited higher tolerance and resistance to MeHg than EtHg. |
S0009279719309925 | Alcohol has been classified as carcinogenic to humans by the International Agency for Research on Cancer . Studies have demonstrated that alcohol intake increases the risk of breast cancer and alcohol also stimulates breast cancer cell growth . Deregulation of Pol III genes is tightly associated with tumour development . Transcription factor II B related factor 1 is a transcription factor that specifically regulates Pol III gene transcription . Our | Betaine decreases the rates of breast cancer cell proliferation and colony formation caused by alcohol. The inhibiting role of betaine in alcohol increased the rates of breast cancer cell growth was in a dose dependent manner. Betaine represses Brf1 and Pol III gene transcription resulting in the inhibition of the cell growth and colony formation. |
S0009279719310026 | To investigate the molecular structural and functional impact of aerosols from candidate modified risk tobacco products the Carbon Heated Tobacco Product 1.2 and Tobacco Heating System 2.2 compared with that of mainstream cigarette smoke on the cardiovascular system of ApoE Female ApoE Continuous exposure to cMRTP aerosols did not affect atherosclerosis progression heart function left ventricular structure or the cardiovascular transcriptome . Exposure to 3R4F CS triggered atherosclerosis progression reduced systolic ejection fraction and fractional shortening caused heart LV hypertrophy and initiated significant dysregulation in the transcriptomes of the heart ventricle and thoracic aorta . Importantly the structural functional and molecular changes caused by 3R4F CS were improved in the smoking cessation and switching groups . Exposure to cMRTP aerosols lacked most of the CS exposure related functional structural and molecular effects . Smoking cessation or switching to CHTP 1.2 aerosol caused similar recovery from the 3R4F CS effects in the ApoE | cMRTP aerosols induce less atherosclerotic plaque formation than CS. cMRTP aerosols induce lower molecular changes in the aorta and heart tissues than CS. Smoking cessation reverses gene expression changes in the heart ventricle and aorta. |
S0009279719310087 | Usnic acid a dibenzofuran derivative found in many lichen species is reported to have anticancer activity against human gastric cancer . We investigated the molecular alterations associated with anticancer effects of usnic acid against human gastric adenocarcinoma AGS and gastric carcinoma SNU 1cells . Usnic acid treatment to these cells caused a significant increase in mitochondrial membrane depolarization and apoptotic cells . Apoptosis induction was accompanied by an increase in the ratio of Bax Bcl 2 expression and cleaved PARP . Usnic acid increased the comet tail length and tail DNA in alkaline comet assay indicating DNA double strand breaks which was also evidenced by an increase in H2A.X phosphorylation . The expression of DNA damage response proteins including DNA PKcs pATM Chk 2 and p53 were increased . Further N acetyl cysteine a known reactive oxygen species scavenger reversed the effects of usnic acid on expression of DNA damage response proteins and H2A.X phosphorylation . This reversal was also observed in comet assay in a time and dose dependent manner suggesting that usnic acid induced DNA damage was caused by ROS . In addition the non toxic concentrations of usnic acid inhibited colony forming potential of AGS cells indicating its anti proliferation activity . More importantly the concentration of usnic acid that caused significant death in gastric cancer cells did not show any considerable toxicity to normal human embryonic kidney HEK293cells human keratinocyte HaCaT cells and mouse primary gastric cells . Collectively these results for the first time demonstrated the selective apoptotic effect of usnic acid through ROS generation and DNA damage on human gastric cancer cells accompanied with upregulation of H2A.X phosphorylation DNA PKcs and p53 . | Usnic acid inhibited growth and survival of gastric cancer AGS and SNU 1cells. The viability of normal cells including mouse primary gastric cells was unaffected. It increased the Bax Bcl 2 ratio caspase activation and mitochondrial apoptosis. Enhanced ROS formation ROS mediated DNA damage and p H2A.X Ser139 . Increased the activation expression of ATM DNA PKcs Chk2 and p53 in cancer cells. |
S000927971931018X | Cardiovascular disorders constitute the principal cause of deaths worldwide and will continue as the major disease burden by the year 2060 . A significant proportion of heart failures occur because of use and misuse of drugs and most of the investigational agents fail to achieve any clinical relevance . Here we investigated rosuvastatin and retinoic acid for their pharmacological pleiotropy against high dose adrenergic agonist induced acute myocardial insult . Rats were pretreated with rosuvastatin and or retinoic acid for seven days and the myocardial injury was induced by administering isoproterenol on the seventh and eighth day . After induction rats were anaesthetized for electrocardiography then sacrificed and different samples were collected stored for various downstream assays . Myocardial injury with isoproterenol resulted in increased cardiac mass decreased R wave amplitude increased QRS and QT durations elevated levels of cardiac markers like cTnI CK MB ALT and AST increased lipid peroxidation protein carbonylation and tissue nitric oxide levels decreased endogenous antioxidants like SOD CAT GR GST GPx and total antioxidant activity increased inflammatory markers like TNF and IL 6 decreased the mRNA expression of Nrf2 and Bcl 2 increased the mRNA expression of Bax eNOS and iNOS genes . Pretreatment with rosuvastatin and or retinoic acid mitigated many of the above biochemical and pathological alterations . Our results demonstrate that rosuvastatin and retinoic acid exert cardioprotective effects and may act as potential agents in the prevention of adrenergic agonist induced acute myocardial injury in rats . Cardioprotective potential of rosuvastatin and retinoic acid could be attributed to their influence on the redox pathways immunomodulation membrane stability Nrf2 preservation iNOS and Bax expression levels . Thus they may act directly or indirectly at various steps the breakpoints in the pathophysiological cascade responsible for cardiac injury . Our study gives insights about the pharmacological pleiotropism of rosuvastatin and retinoic acid . | Rosuvastatin and retinoic acid diminish myocardial injury induced by isoprenaline in rats. Rosuvastatin and retinoic acid may show pleiotropic action. Have antioxidant properties against isoprenaline induced cardiac stress. Mitigate inflammatory response induced by isoprenaline in cardiac tissue. Affect various factors like TNF Nrf2 Bax and iNOS. |
S0009279719310191 | Environmental pollutant Lead is known to induce neurotoxicity in human . The central nervous system is the most vulnerable to the minute levels of Pb induced toxicity . Pb has been linked to Alzheimer s disease as a probable risk factor as it shows epigenetic and developmental link associated with Alzheimer s disease like pathology . Beta amyloid peptides were considered as the crucial factors in the beta amyloid plaque formation in Alzheimer s disease brain . In this context we investigated the molecular mechanism involved in the development of Pb induced Alzheimer s disease in in vitro . Previous data from our studies have reported that Pb in the presence of beta Amyloid peptide and induces more apoptosis than individual exposures . Here to further evaluate the molecular mechanism underlying Pb induced Alzheimer s disease we focussed on the involvement of calcium signalling in inducing cell death . Our experimental observations suggesting that Pb in the presence of beta amyloid peptide alters intracellular calcium levels which leads to the increased beta secretase activity which further promotes the generation of beta amyloid peptides . It also showed depression in the levels of GAP 43 expression inhibition of PKC activity and altering synaptic activity further leads to cell death . | Depletion in the levels of calcium ions could play a vital role in inducing cell death in Lead involved Alzheimer s disease. Lead enhances the molecular aggregation of beta amyloid peptides invitro. Lead in the presence of amyloid peptides inhibits neuronal outgrowth by inactivating GAP 43. |
S0009279719310555 | Currently few herbal pharmacokinetic parameters have been applied successfully for therapeutic monitoring because of the complexity of consistency when there are multiple chemicals and efficacies . The present study aims to evaluate the herbal PK properties by investigating the PK parameters of the 8 absorbed bioactive compounds which can represent its parent herbal holistic efficacy to achieve a PK therapeutic monitoring of herbs . First we tested the hypothesis that the antidepressant and prokinetic effects and related anti inflammation and anti oxidation activity by Fructus aurantii Magnolia Bark formula are related to 8 compounds according to the absorbable evidence and the determined contents . Subsequently stable and representative APIO from 8ABCs allowed us to develop a sensitive and selective liquid chromatography tandem mass spectrometry method for the simultaneous determination of 8 compounds following the oral administration of FM decoction in rats . Result 8 compounds either including Meranzin hydrate or MH alone almost identically or nearly replicated the parent formula FM in terms of efficacy for inducing APIO . This unifying strategy shows how multi herb formulas pharmacokinetic therapeutic monitoring can be achieved by the method we established . | The activity by Fructus aurantii Magnolia Bark formula are related to 8 compounds. 8 compounds almost replicated the parent formula FM in terms of efficacy. The Pharmacokinetic of the 8 absorbed compounds in rats are studied. |
S0009279719310646 | Hemangioma is one of the commonest benign vascular tumors among children . Propranolol is the first line therapeutic drug for hemangioma . However the effects and mechanisms of propranolol in hemangioma have not been thoroughly elaborated . In this study the effects and mechanisms of propranolol were explored using hemangioma derived endothelial cells . The expression of GLUT1 were determined by immunofluorescence staining . qRT PCR assay was conducted to detect the mRNA expressions of angiopoietin 2 and Tie 2 . Western blot assay was carried out to measure the protein levels of Ang 2 Tie 2 protein kinase B and phospholyrated Akt . Cell proliferation was assessed by Cell Counting Kit 8 assay and Western blot of Ki67 protein level . Cell apoptosis was measured by flow cytometry analysis and Western blot of Bax and Bcl 2 levels . We found that propranolol inhibited proliferation and induced apoptosis in human umbilical vein endothelial cells and HemECs . Moreover propranolol inhibited the expressions of Ang 2 and Tie 2 in HUVECs and HemECs . Functional analysis revealed that Ang 2 attenuated the effects of propranolol on HemEC proliferation and apoptosis . Mechanistical analysis showed that propranolol inhibited the Akt pathway by regulating Ang 2 expression in HemECs . Futhermore inhibition of the Akt pathway attenuated the effects of Ang 2 on proliferation and apoptosis in HemECs . In conclusion propranolol inhibited proliferation and induced apoptosis of HemECs via Akt pathway by down regulating Ang 2 expression which contributes to our understanding on the pathogenesis of hemangioma and promotes the development of therapeutic approaches for hemangioma . | Propranolol inhibited the proliferation and induced apoptosis in HemECs. Propranolol inhibited Ang 2 and Tie 2 expression in HemECs. Propranolol inhibited the Akt pathway by regulating Ang 2 expression. |
S0009279719310968 | Overconsumption of alcohol could lead to severe liver injury that connects with oxidative stress apoptosis and inflammatory response . Previously we proved that p coumaric acid prevents ethanol induced reproductive toxicity however p coumaric acid on ethanol mediated hepatotoxicity has not been examined yet . In our work we sought to study the potential of PCA in contradiction of ethanol induced hepatoxicity which linking with MAPKs apoptosis oxidative stress and Nrf2 signaling . Foremost we found that PCA could protect ethanol induced both L 02 and HepG2 hepatic cells by inhibiting cytotoxicity ROS production mitochondrial depolarization and nuclear fragmentation . Also | PCA protects alcohol induced both L 02 and HepG2 hepatic cells. PCA attenuates ethanol induced oxidative stress by inhibiting MAPKs. PCA also regulates liver regulating biomarkers and antioxidants. PCA prevents alcohol induced apoptosis and depletion of Nrf2 related proteins. PCA can be considered as alternative therapeutics for alcohol related disease. |
S000927971931097X | Cyclo peptide CLP is a marine natural metabolite and well recognized as an antimicrobial and antioxidant agent with limited studies on anticancer activity . The current study aims to determine the effect of CLP on migration and growth of triple negative breast cancer cell lines . The anti growth potential was evaluated by MTT BrdU and TUNEL assays DNA damage by H2AX and Dead green assays antimigration activity by Boyden chamber invasion and wound healing assays . Interaction of CLP with CD151 was resolved by PatchDock . Effect of CLP on the expression of transmembrane CD151 was evaluated by cell based ELISA assay . The interaction between CD151 and EGFR was predicted by using FireDoc Web server . Impact of CLP on the interaction of CD151 with EGFR was evaluated by co immunoprecipitation assay . The effect of CLP on the cell cycle and its controlling proteins was determined by Western blotting . CLP reduced the viability of MDA MB 231 and MDA MB 468 TNBC cell lines but not human breast healthy epithelial cell line similar to eribulin standard . CLP also inhibited proliferation cell cycle and migration . It induced DNA strand breaks DNA damage and cell death . It showed the most favorable interactions with CD151 in | Cyclo L Leucyl L Prolyl treatment induced cytotoxicity and reduced the viability of triple negative breast cancer cells. It also induced the DNA damage and apoptosis in TNBC cells. It inhibited migration and proliferation of TNBC cells. It reduced the cell surface expression of CD151 and its interaction with EGFR. It attenuated the cell cycle of TNBC cells by reducing cyclin D1 CDK4 PAK Rac1 and p27kip1 expression. |
S0009279719311123 | Lithium and cannabinoids can disrupt learning and memory performance . The goal of the present study is to investigate the additive or synergistic effect of lithium and cannabinoid combination doses on spatial learning and memory in rats by isobolographic analyses . Although several studies have suggested synergistic effects of cannabinoids or lithium in response to other compounds in most of them isobolographic analyses were not used Thus there is a need for more detailed studies using isobolographic analyses . In this study spatial memory was evaluated in the Morris Water Maze apparatus by eight trials in the training day and one trial in the test day . Lithium was injected intraperitoneal and ACPA was injected into the dorsal hippocampal region . For the isobolographic analyses the ED50 of lithium and ACPA was measured by linear regression analysis considering the doses were tested in our previous research . The results showed that combinations of low medium and high doses of lithium and ACPA had synergistic but not additive effect on spatial learning and spatial memory . In conclusion we suggest that combination doses of lithium and ACPA have synergistic but not additive effect on spatial learning and memory in the rat s dorsal hippocampal region . | Lithium and ACPA showed synergistic effect on spatial learning and memory. Effect of lithium and ACPA on glutamate transmission may lead to synergistic effect. Effect of lithium and ACPA on calcium signaling may lead to synergistic effect. Effect of lithium and ACPA on GSK 3beta activity may lead to synergistic effect. Effect of lithium and ACPA on motor function may lead to impaired spatial memory. |
S0009279719311238 | Angina pectoris can be used as an early warning for coronary artery disease . Vasodilation is an important mechanism of angina pectoris . Traditional Chinese medicine Compound Danshen Dripping Pill is widely used to improve the symptoms of cardiovascular diseases . To investigate the influence of vasodilation effect and underlying mechanisms of CDDP we determined the vasodilation effect of thoracic aorta ring on rat induced by norepinephrine . Then targets fishing method was used to predict the potential mechanism of CDDP on vasodilation based on the structures of the main components . Then iTRAQ based quantitative proteomics analysis was used for verification of the candidate target proteins and pathways to illustrate the underlying mechanisms . Furthermore the differentially expressed proteins in the enriched pathways were validated by western blotting . In this study we found that CDDP could significantly inhibit NE induced aortic contraction tension and the mechanism may be related to platelet activation cGMP PKG signaling pathway and vascular smooth muscle contraction . The method provides a new way to uncover the vasodilation mechanism of CDDP as well as other multi component herbal medicines . | CDDP can inhibit norepinephrine induced aortic contraction tension. Target fishing combined iTRAQ revealed the mechanism of CDDP on vasodilation. PP1 Ednrb and Rasgrf1 were the regulating proteins of CDDP. |
S0009279719311263 | Cytochrome P450 2E1 is the major P450 enzyme involved in ethanol metabolism . That role is shared with two other enzymes that oxidize ethanol alcohol dehydrogenase and catalase . P450 2E1 is also involved in the bioactivation of a number of low molecular weight cancer suspects as validated | P450 2E1 contributes to ethanol metabolism. P450 2E1 also has a role in the oxidation of some drugs and chemical carcinogens. P450 2E1 does not cause global oxidative stress but it can be local. The kinetic mechanism is unusual and leads to some apparent anomalies. Single nucleotide variations exist but have not been implicated in diseases much. |
S0009279719311652 | Clopidogrel a clinically used antiplatelet agent can be readily hydrolyzed by human carboxylesterase 1A to release an inactive metabolite clopidogrel carboxylic acid . In this study clopidogrel was used as a tool substrate to investigate the interspecies variation of clopidogrel hydrolysis in hepatic microsomes from various mammals including human and six laboratory animals . The results demonstrated that clopidogrel could be hydrolyzed into CCA by all tested hepatic microsomes from human or other mammals but the hydrolytic rates greatly varied among species . Inhibition assays demonstrated that BNPP strongly inactivated clopidogrel hydrolytic activity in all tested hepatic microsomes suggested that mammalian CES were major contributor responsible for clopidogrel hydrolysis in hepatic preparations from all above mentioned species . By contrast the response of a reversible inhibitor of human CES1A on clopidogrel hydrolysis in these liver preparations varied significantly among different species . Moreover the enzymatic kinetics and the apparent kinetic parameters of clopidogrel hydrolysis in hepatic microsomes from various animal species were evaluated and compared to each other . These findings provide crucial information for deeply understanding the differences in catalytic behaviors of mammalian CES which will be very helpful for choosing suitable laboratory animal for whole tests of CES1A substrate drugs . | Interspecies variation of clopidogrel hydrolysis in liver microsomes from various species was investigated. Mammalian CES are major contributor s responsible for clopidogrel hydrolysis in all tested hepatic microsomes. The response of esterase inhibitors on clopidogrel hydrolysis varied significantly among different species. The kinetic behaviors of clopidogrel hydrolysis in liver microsomes from various species were also different to each other. |
S0009279719311664 | Type 2 diabetes mellitus is a disease with a drastically growing worldwide prevalence . It is usually associated with numerous complications of which diabetic nephropathy is a main complication of microvasculature and more seriously a common cause of end stage renal disease . Unfortunately both the lack of a definitive remedy alongside the economic and the social burden on DN patients enforces considerable impetus for developing alternative therapies . IL 33 is a newly discovered member of the IL 1 cytokine family . IL33 ST2 signaling plays a crucial role in acute and chronic kidney diseases . Calycosin is an isoflavone with reported IL33 signaling inhibitory activity . The present study aimed to investigate if calycosin possess renal protective effect in high fat diet STZ induced T2DM model and to clarify the potential underlying mechanisms . HFD STZ control rats showed functional and structural renal damage confirmed by increased serum creatinine blood urea nitrogen and albuminuria associated with marked renal glomerulosclerosis and interstitial fibrosis . Initiation of inflammation oxidative stress and fibrosis was evident as depicted by elevated renal levels of IL33 ST2 mRNA as well as increased renal NF Bp65 TNF IL 1 MDA and TGF contents with suppressed Nrf2 and TAC . Calycosin treatment markedly improved the aforementioned makers of renal injury and dysfunction modulated IL33 ST2 signaling inflammatory cytokines oxidative stress and fibrotic processes . This was accompanied by improvement of T2DM induced renal ultramicroscopic and histopathological alterations . | IL33 ST2 signaling is activated in T2DM induced renal injury. IL33 ST2 axis is associated with inflammation and fibrosis in diabetic kidney. Calycosin treatment preserved renal structure and function in diabetic rats. |
S0009279719311755 | Graves orbitopathy is a sight threatening ocular disease that occurs in patients with hyperthyroidism and is especially associated with oxidative stress . Polydatin is a major active component of | Graves orbitopathy GO is an ocular disease associated with hyperthyroidism. Plant derived polydatin PD has anti inflammatory and antioxidant properties. We investigated the effects of PD on H. induced oxidative stress in GO. PD reduced ROS and inhibited adipogenesis in orbital fibroblasts. PD attenuated oxidative stress in GO. through the Keap1 Nrf2 ARE pathway. |
S0009279719311767 | Liver fibrosis is a common pathological consequence of liver injury which increases liver failure related morbidity and mortality . Hence anti fibrotic treatment is urgently needed . Oxidative stress plays a pivotal role in the progression of liver fibrosis . Thus targeting ROS may be an effective strategy for liver fibrosis treatment . In this study we investigated four benzoquinones derivatives including 5 isopropyl 2 methyl 1 4 benzoquinone 2 tert butyl 1 4 benzoquinone | Benzoquinone derivatives exhibit anti liver fibrosis activity in TAA induced mice. Having anti oxidant properties to regulate the redox balance of cells. Inhibition of the oxidant stress in LX 2cells. Alleviation of the TLR4 mediated inflammatory response. Showing the ability that inducing the apoptosis of LX 2cells. |
S0009279719311822 | Hyperproliferation and oxidative stress induced by hyperglycemia in mesangial cells plays crucial roles in the pathological process of diabetic nephropathy . Farrerol isolated from rhododendron leaves possesses broad anti oxidative and anti inflammatory properties towards several diseases but its role in diabetic neuropathy remains unclear . The aim of this study was to evaluate the effects of farrerol in high glucose induced mesangial cell injury and to explore underlying molecular mechanisms . Our results showed that high glucose | HG stimulated MC proliferation inflammation ECM deposition and ROS production. FAR dose dependently inhibited HG induced MC proliferation and ECM deposition. FAR exerted anti oxidative effect on HG induced MCs via modulating ROS Nox4 ERK. TGF 1 Smad2 was involved in FAR Nox4 mediated ECM deposition in HG induced MCs. |
S0009279719311883 | The microtubule inhibitor class of chemotherapeutics provide an effective treatment for several different types of cancers however severe chemotherapy induced peripheral neuropathy is a major dose limiting toxicity in patients that limits their use . While CIPN was predicted with MTIs based on histopathology and functional effects in non clinical toxicology studies these investigations often require large numbers of animals and long term studies . As | In vitro MT properties binding and dynamicity have been assessed for many MTIs. MTI s with less severe CIPN have reduced. MT affinity and binding. An MTI with less severe CIPN also had more MT binding in absence of neuronal MTs. In vitro MT properties may be used to develop MTIs with less severe CIPN. |
S0009279719311901 | Trigonelline is a plant alkaloid that has generated interest for its neuroprotective roles in brain pathology . However the protective effect of trigonelline on cerebral ischemia reperfusion injury and the potential mechanism have not been fully evaluated . Our results showed that trigonelline pretreatment ameliorated oxygen glucose deprivation reperfusion induced hippocampal neurons injury . The OGD R caused reactive oxygen species generation and decreased concentrations of superoxide dismutases and glutathione peroxidase were markedly attenuated by trigonelline . In addition the increased levels of TNF IL 6 and IL 1 in OGD R induced hippocampal neurons were significantly decreased by trigonelline pretreatment . Trigonelline also suppressed caspase 3 activity and bax expression and induced bcl 2 expression in OGD R induced hippocampal neurons . Furthermore trigonelline induced the activation of PI3K Akt pathway in hippocampal neurons exposed to OGD R condition . Inhibition of PI3K Akt signaling reversed the protective effects of trigonelline on OGD R induced hippocampal neurons injury . Taken together these findings indicated that trigonelline protected hippocampal neurons from OGD R induced injury which was mediated by the activation of PI3K Akt signaling pathway . | Trigonelline ameliorated OGD R induced hippocampal neurons injury. Trigonelline ameliorated OGD R induced oxidative stress in hippocampal neurons. Trigonelline attenuated OGD R induced inflammatory response in neurons. Trigonelline inhibited OGD R induced cell apoptosis in hippocampal neurons. Trigonelline affected PI3K Akt activation in hippocampal neurons under OGD R. |
S0009279719311986 | Quinolinic acid known as a neuro active metabolite associated with the kynurenine pathway . At high concentrations QA is often involved in the initiation and development of several human neurologic diseases like Alzheimer s disease . Because of the QA action as the NMDA receptor it is considered as a potent excitotoxin | Quinolinic acid QA known as a neuro active metabolite. QA strongly accelerate Tau amyloid oligomerization. Electrostatic interactions accompanied by hydrogen bonding guarantee relatively tight binding of QA to the protein. Regarding elevated concentrations of both QA and Tau it is very likely that QA contribute to the NFT formation. |
S0009279719312001 | The extensive use of silver nanoparticles in manufactured products will inevitably increase environmental exposure highlighting the importance of accurate toxicity assessments . A frequent strategy to estimate AgNP cytotoxicity is to use absorbance or fluorescent based assays . In this study we report that AgNPs with or without surface functionalizations and of different sizes can interfere with the spectrometric quantification of different dyes commonly used in cytotoxicity assays such as 3 2 5 diphenyltetrazolium bromide neutral red Hoechst and Resazurin . Some AgNP types caused more interference than others which was dependent on the assay . Overall most AgNPs caused the direct reduction of MTT as well as Hoechst and NR fluorescence quenching and absorbed light at the same wavelength as NR . None of the AgNPs tested caused the direct reduction of Resazurin however depending on AgNP characteristics and concentration they may still promote fluorescence quenching of this dye . Our results show that AgNPs with different size and coatings can interfere with spectroscopy based assays to different degrees suggesting that their cytotoxicity may be underestimated or overestimated . We suggest that when using any spectroscopy based assay it is essential that each individual nanoparticle formulation be tested first for potential interferences at all intended concentrations . | Most of the AgNPs tested and silver ions caused the direct reduction of MTT. Some AgNPs caused fluorescence quenching of Hoechst and Neutral red dyes. All AgNPs tested showed negligible interference with Resazurin dye. Interference is dependent on the AgNP type and dye. We recommend interference testing of AgNP with spectroscopy based assays. |
S0009279719312190 | Synthetic amorphous silica nanoparticles are used widely in industrial applications . These nanoparticles are not classified for their carcinogenicity in humans . However some data still demonstrate a potential carcinogenic risk of these compounds in humans . The Bhas 42cell line was developed to screen chemicals as tumor initiators or promoters according to their ability to trigger cell to cell transformation in a cell transformation assay . In the present study we performed unsupervised transcriptomic analysis after exposure of Bhas 42cells to NM 203 SAS as well as to positive Min U Sil 5 crystalline silica microparticles and 12 | Synthetic amorphous silica nanomaterials induce transformation of Bhas 42cells. Early modulated signaling pathways are linked to cell adhesion and proliferation. Twelve genes were selected based on their potential role in cell transformation. These genes may serve as early markers of Bhas 42cell transformation induced by SAS. |
S0009279719312220 | Pregnane X receptor is a ligand activated transcription factor and nuclear receptor expressed ubiquitously along gut liver axis . Inflammatory bowel disorders have been reported to implicate PXR in maintaining tight junction integrity and countering inflammation . However the hepatoprotective role of PXR activation in soothing bacterial translocation in liver cirrhosis has not been explored . Ginkgolide A a terpene trilactone from Ginkgo Biloba extract is a natural ligand of rodent and human PXR . This study aims to investigate the effect of GA in activating PXR and improving associated tight junction integrity and reducing bacterial translocation in gut liver axis of CCl Swiss albino mice were administered with CCl When compared to nave mice In conclusion our data supports the hypothesis that GA treatment to CCl | Ginkgolide A attenuates markers of bacterial translocation in cirrhotic mice. Ginkgolide A alleviates liver enzymes liver fibrosis ascites in cirrhotic mice. Ginkgolide A activates Pregnane X Receptor along gut liver axis of cirrhotic mice. Ginkgolide A improves gut tight junctions ZO1 and Occludin in cirrhotic mice. Ginkgolide A counters TLR4 NFB mediated inflammation in cirrhotic mice. |
S0009279719312396 | Di n butyl phthalate is a pollutant that is widely present in the environment . We have previously demonstrated that maternal exposure to DBP resulted in renal fibrosis in offspring but the underlying mechanism was not well elucidated . Therefore the current study aims to understand the underlying molecular mechanisms in these sex specific developmental alterations . Here we used RNA seq analysis to explore the underlying molecular mechanisms of DBP associated renal fibrosis . Pregnant rats received DBP orally at a dose of 850mg kg BW day during gestational days 1418 . Upregulated autophagy in renal tubules in offspring was confirmed in the DBP treated group via accessing LC3 protein expression . Increased expression of the HhIP gene was found in the DBP treated group via RNA seq analysis . Immunohistochemistry staining and Western blot analysis confirmed increased expression of HhIP protein and inhibited hedgehog signaling . Increased HhIP expression further leaded to impaired activation of hedgehog signaling which is critical for normal embryonic development . Additional in vitro experiments on renal tubular cells suggest that inactivation of hedgehog signaling induced autophagy in renal tubular cells . Taken together our findings show that maternal exposure to DBP induced autophagy through regulation of hedgehog signaling via overexpression of HhIP in foetal renal tubular cells which may be essential for renal fibrosis development . | Maternal exposure to DBP resulted in renal fibrosis in offspring involving increased expression of the HhIP gene. DBP related HhIP expression leaded to impaired activation of hedgehog signaling in offspring kidneys. Autophagy and hedgehog signaling may play a role in DBP induced renal fibrosis in offspring. |
S0009279719312475 | Non alcoholic steatohepatitis has been associated with fibrosis that may progress to cirrhosis . The purpose of this study was to examine hepatocytes and perisinusoidal cells in liver biopsies of 3 families with non cirrhotic and cirrhotic NASH to determine unique histological changes during a period of 27 years from diagnosis . In this study hepatocytes stellate cells and Kupffer cells were analyzed using light and electron microscopy and immunohistochemistry with specific anti macrophage antibody staining of liver biopsies . Body mass index of all patients was over 28 and all viral metabolic markers were negative . Alcohol consumption was insignificant . In all liver biopsies diffuse non zonal macrovesicular steatosis involved 4070 of liver samples . The lobular hepatocytes showed prominent ballooning hepatocyte degeneration . No Mallory Denk hyaline bodies were observed in three of the patients . MDBs developed in ballooned hepatocytes of four individuals that also presented foci of lobular inflammation . The apoptotic bodies were stained by cytokeratin 18 . The trichrome stain revealed portal to portal bridging fibrosis . In one family there was a three fold increase in relative numbers of perisinusoidal macrophages in the older sister with NASH compared to livers of the younger siblings . The special finding in livers of patients with NASH was accumulation of groups of perisinusoidal macrophages which was not associated with focal necrosis . Perisinusoidal macrophages appear to accumulate in NASH . It is possible that collections of macrophages are a response to chronic portal endotoxemia or lipotoxic activation of immuno mediators . The persistent activation of these macrophages could lead to the chronic release of pro inflammatory cytokines and contribute to chronic inflammation fibrosis and cirrhosis leading to HCC . | Non alcoholic fatty liver disease NAFLD is the liver manifestation of the metabolic syndrome. NAFLD is the leading cause of chronic liver disease. Non alcoholic steatohepatitis NASH leads to cirrhosis and hepatocellular carcinoma HCC . NAFLD leading to HCC was assessed in three families. The histology includes giant lipid droplets fibrosis and perisinusoidal macrophage. |
S0009279719312657 | 1 2 3 triazolium salts are poorly understood regarding their antileishmanial activity . Hence as an effort to identify novel chemical scaffolds as antileishmanial agents a series of 1 2 3 triazolium salts | New triazoles derivatives were synthesized and assayed against. with an iodide anion and a side chain of 10 carbon atoms showed the best selective biological activity. presents itself as 1.5 times more active against intracellular amastigotes of. than miltefosine. The antileishmanial activity is mediated via mitochondrial dysfunction. |
S000927971931275X | Gentamicin induced nephrotoxicity has been well documented although the causing mechanisms and preventative measures need further investigation . The current study aimed to explore the potential protective impacts of celecoxib a selective cyclooxygenase 2 inhibitor on gentamicin induced nephrotoxicity and the potential mechanisms in rats . Rats were randomly divided into four groups as follows group1 normal control group 2 received gentamicin only group 3 concurrently received gentamicin and celecoxib and group 4 received celecoxib . | Celecoxib has an ameliorative effect against gentamicin induced nephrotoxicity. Celecoxib increased urine Cr and CCr serum albumin GSH and SOD. Celecoxib lowered kidney weight RSI proteinuria serum Cr BUN LDH MDA and NOx. Celecoxib decreased NFB p65 TNF P53 and caspase 3 and COX 2 immunoreactivity. Celecoxib suppressed renal MPO improved histological features and decreased HSP70. |
S0009279719312761 | Bone defects caused by cancer surgery or trauma have a strong negative impact on human health . Treatment with cell and material based complexes provides an alternative strategy for the regeneration of damaged bone tissue . The good physical properties and suitable biodegradability of a thermosensitive hydrogel has been shown to act as a valuable scaffold . Platelet derived growth factor BB is mainly secreted by platelets and promotes the migration and angiogenesis of mesenchymal stem cells . Although PDGFBB is known to indirectly enhance bone repair | PDGFBB promoted SCAP cells proliferation. PDGFBB stimulated the expression of osteogenic and angiogenic genes in SCAPs. Thermosensitive hydrogel was suitable for cell 3D culture. Cell and material based complex was found to be a promising therapeutic strategy for bone regeneration. |
S0009279719312955 | Ethanol is a recreationally ingested compound that is both teratogenic and carcinogenic in humans . Because of its abundant consumption worldwide and the vital role of stem cells in the formation of birth defects and cancers delineating the effects of EtOH on stem cell function is currently an active and urgent pursuit of scientific investigation to explicate some of the mechanisms contributing to EtOH toxicity . Stem cells represent a primordial undifferentiated phase of development thus encroachment on normal physiologic processes of differentiation into terminal lineages by EtOH can greatly alter the function of progenitors and terminally differentiated cells leading to pathological consequences that manifest as fetal alcohol spectrum disorders and cancers . In this review we explore the disruptive role of EtOH in differentiation of stem cells . Our primary objective is to elucidate the mechanisms by which EtOH alters differentiation related gene expression and lineage specifications thus modifying stem cells to promote pathological outcomes . We additionally review the effects of a reactive metabolite of EtOH acetaldehyde in causing both differentiation defects in stem cells as well as genomic damage that incites cellular aging and carcinogenesis . | Ethanol alters lineage specification during embryonic stem cell differentiation. Acetaldehyde activates retinoic acid signaling in embryonic stem cells. Acetaldehyde compromises the genomic integrity of hematopoietic stem cells. |
S0009279719313183 | Alcoholism synergizes the development of the hepatocellular carcinoma in patients infected with hepatitis B or C virus . Tumor initiating stem like cells are refractory to therapy and have expression of stemness transcription factors . Leaky gut derived endotoxin stimulates TLR4 NANOG pathway that skews asymmetric cell division and that metabolically reprograms hepatocytes liver progenitor cells leading to self renewal . TICs isolated from mouse HCC models or human HCCs are tumorigenic and have p53 degradation via phosphorylation of the protective protein NUMB and its dissociation from p53 by the oncofetal protein TBC1D15 . Furthermore dysregulation of lncRNA promotes genesis of TICs leading to HCC development . This review describes roles of cell fate decision metabolic reprogramming and lncRNA for TIC genesis and liver oncogenesis . This project was supported by NIH grants 1R01AA018857 01 5R21AA025470 P50AA11999 R24AA012885 and pilot project funding . | Co morbidity of life style factors with viral hepatitis synergizes HCC development. TLR4 NANOG pathway metabolically reprograms drug resistance TICs. HCV mediated mechanisms promote genesis of TICs to synergize oncogenesis. Inactivation of NUMB skews asymmetric cell division to generate TICs. Dysregulated LncRNAs generates TICs to promote HCC development. |
S0009279719313201 | Epidemiological evidence underscores alcohol consumption as a strong risk factor for multiple cancer types with liver cancer being most commonly associated with alcohol intake . While mechanisms linking alcohol consumption to malignant tumor development are not fully understood the likely players in ethanol induced carcinogenesis are genotoxic stress caused by formation of acetaldehyde increased oxidative stress and altered nutrient metabolism including the impairment of methyl transfer reactions . Alterations of sphingolipid metabolism and associated signaling pathways are another potential link between ethanol and cancer development . In particular ceramides are involved in the regulation of cellular proliferation differentiation senescence and apoptosis and are known to function as important regulators of malignant transformation as well as tumor progression . However to date the cross talk between ceramides and alcohol in cancer disease is largely an open question and only limited data are available on this subject . Most studies linking ceramide to cancer considered liver steatosis as the underlying mechanism which is not surprising taking into consideration that ceramide pathways are an integral part of the overall lipid metabolism . This review summarizes the latest studies pointing to ceramide as an important mediator of cancer promoting effects of chronic alcohol consumption and underscores the necessity of understanding the role of sphingolipids and lipid signaling in response to alcohol in order to prevent and or successfully manage diseases caused by alcohol . | Alcohol can induce cancer in heavy drinkers via multiple mechanisms. Sphingolipids emerged as important players in alcohol induced carcinogenesis. Sphingolipid p53 axis could be critical in alcohol induced cancer. Studies of sphingolipid p53 axis could lead to novel cancer prevention strategies. |
S0009279719313298 | Multiple targeting compounds might reduce complex polypharmacy of multifactorial diseases such as diabetes and contribute to the greater therapeutic success . Targeting reactive oxygen species producing enzymes as xanthine oxidase might suppress progression of diabetes associated vascular complications . In this study a small series of benzimidazole derivatives | Two tested benzimidazoles inhibited DPP 4 and XO with IC. value lower than 200M. Binding modes of both dual inhibitors with two target enzymes were predicted. Assayed dual inhibitors were not cytotoxic to a greater extent for Caco 2cells. |
S0009279719313468 | Stearoyl CoA desaturase generates monounsaturated fatty acids which contribute to cell growth survival differentiation metabolic regulation and signal transduction . Overexpression of SCD is evident and implicated in metabolic diseases such as diabetes and non alcoholic fatty liver disease . SCD also stimulates canonical Wnt pathway and YAP activation in support of stemness and tumorigenesis . SCD facilitates metabolic reprogramming in cancer which is mediated at least in part by regulation of AKT AMPK and NF kB via MUFAs . Our research has revealed the novel positive loop to amplify Wnt signaling through stabilization of LRP5 6 in both hepatic stellate cells and liver tumor initiating stem cell like cells . As such this loop is pivotal in promoting liver fibrosis and liver tumor development . This review summarizes the mechanisms of SCD mediated tumor promotion described by recent studies and discusses the future prospect for SCD mediated signaling crosstalk as a potential therapeutic target for cancer . | Stearoyl CoA desaturase which produces monounsaturated fatty acids is increasingly recognized to promote malignancies of different organs and this review article discusses potential mechanisms underlying this link. |
S0009279719313572 | The biotoxin okadaic acid is a lipophilic secondary metabolite of marine microalgae . Therefore OA accumulates in the fatty tissue of various shellfish and may thus enter the food chain . The ingestion of OA via contaminated marine species can lead to the diarrhetic shellfish poisoning syndrome characterized by the occurrence of a series of acute gastrointestinal symptoms in humans . In addition genotoxicity and tumor promoting properties of OA might constitute a long term threat to human health . | HepaRG cells are a suitable. model comparing long vs. short term exposure. Okadaic acid induces presumably intrinsic apoptosis after short term treatment. HepaRG cells compensated OA long term treatment with regard to apoptosis induction. |
S0009279719313584 | Cancer has emerged as the main cause of the highest rate of mortality in the world . Drugs used in cancer although show some beneficial effects on cancerous organs demonstrate side effects on other normal tissues . On the other hand anticancer peptides being effective on target tissues should be safe and less harmful on healthy organs since peptides have several advantages i.e . high activity specificity affinity being less immunogenic and not accumulate in the body . In the present work analogues of Longicalcynin A a naturally occurring anticancer cyclopeptide were synthesized and evaluated their cytotoxicity in order to gain information from structure activity relationships of the such cyclopeptides which may lead to find novel and safer anticancer peptide compound to be used in clinic . Peptides were prepared by the solid phase peptide synthesis method using trityl resin . Peptide cyclization was performed in liquid phase . To study anticancer activity of the peptide analogues of Longicalycinin A several methods including MTT flow cytometry analysis and Lysosomal membrane integrity assay were employed using two cell lines HepG2 and HT 29 . Fibroblast cells were used to control the safety of the synthesized cyclopeptides on normal cells . Two cyclopeptides 11 and 17 with the sequences of cyclo and cyclo respectively were cytotoxic against the colon as well as hepatic cancer cells with safety profile against fibroblast cells probably with the mechanism of apoptosis as lysosomal membrane integrity damaged . These cyclopeptides showed to be more favorable compounds better than Longicalycinin A and good candidates to develop cyclopeptides as anticancer agents . | In this study analogues of Longicalcynin A an anticancer cyclopeptide were synthesized by SPPS method. The cytotoxicity analyses of the peptides were evaluated against HepG2 HT 29 and fibroblast as control cell lines. By these peptides apoptosis was most probably occurred as flow cytometry analysis demonstrated. Apoptosis might be happened through lysosomal membrane damage for some peptides. Considering the amino acid sequences of the peptides cyclopeptides 11 and 17 can be good anticancer candidates. |
S0009279719313626 | Antimicrobial resistance remains a serious problem that results in high mortality and increased healthcare costs globally . One of the major issues is that resistant pathogens decrease the efficacy of conventional antimicrobials . Accordingly development of novel antimicrobial agents and therapeutic strategies is urgently needed to overcome the challenge of antimicrobial resistance . A potential strategy is to kill pathogenic microorganisms via the formation of reactive oxygen species . ROS are defined as a number of highly reactive molecules that comprise molecular oxygen O | Reactive oxygen species ROS could combat antimicrobial resistance. ROS are used as an antimicrobial strategy because of their toxicity to a broad range of microbial pathogens. ROS exert antimicrobial activity via an induction of oxidative stress in microbial cells. Oxidative stress caused by ROS leads to microbial DNA damage and ultimately inducing cell death. |
S0009279719313663 | Bone mesenchymal stem cells are a well known donor graft source due to their potential for self renewal and differentiation into multi lineage cell types including osteoblasts that are critical for fracture healing . Fasudil a Rho kinase inhibitor has been proven to induce the differentiation of bone marrow stem cells into neuron like cells . However its role in the osteogenesis of BMSCs remain uncertain . Herein we for the first time studied the effects of FAS on osteogenic differentiation in a mouse fracture model and further explored the involved mechanisms in mouse BMSCs . The results showed that FAS stimulated bone formation in the fracture mouse model . Additionally at 30M FAS significantly promotes alkaline phosphatase activity mineralization and the expression of osteogenic markers COL 1 RUNX2 and OCN in murine BMSCs . Blocking of P38 by SB202190 significantly reversed the effects of FAS in vitro suggesting that P38 but not ERK or JNK activation is required for FAS induced osteogenesis . Collectively our results indicate that FAS may be a promising agent for promoting fracture healing . | We firstly found that Fasudil can induce the osteogenesis of BMSCs. Fasudil enhances the osteogenic differentiation of BMSCs through the MAPK P38 signaling pathway. Fasudil may be a promising agent for promoting fracture healing in addition to its function on cerebral vasospasms. |
S0009279719313821 | Relapse and drug resistance is still major challenges in the treatment of leukemia . Promethazine an antihistaminic phenothiazine derivative has been used to prevent chemotherapy induced emesis although there is no report about its antitumor potential . Thus we evaluated the promethazine cytotoxicity against several leukemia cells and the underlying mechanisms were investigated . Promethazine exhibited potent and selective cytotoxicity against all leukemia cell types | Resistance to chemotherapy is a clinical challenge in leukemia therapy. Antiallergic small molecule promethazine is used as antiemetic in cancer patients. Promethazine induced a selective leukemia cell death through autophagy apoptosis. For the first time the antitumor effects of promethazine were described. |
S0009279719313857 | Quaternary ammonium compounds and cetylpyridinium chloride constitute a group of cationic surfactants are widely used for personal hygiene and medical care despite the potential pulmonary toxicity . To examine whether BAC and CPC aerosols deposited in the alveolar region alter pulmonary function we studied the effects on pulmonary surfactant using two step | Deposition of disinfectant on the lung surface alter the alveolar surface activity. Disinfectants change the shape of A isotherm in pulmonary surfactant monolayer. A hydrophobic tail hydrocarbon group of disinfectant interacts with surfactant lipid. Disinfectants result in smaller condensed lipid domain of pulmonary monolayer. Disinfectants cause cell death via caspase 3 dependent apoptotic pathway. |
S0009279719313894 | The incidence and mortality of lung cancer are the highest among cancer related deaths . However the long term use of currently available cytotoxic drugs can increase genetic alterations in cancer cells and cause drug resistance which significantly limits their usage . Since current systemic treatment options are limited effective chemotherapeutic agents are urgently needed for non small cell lung cancer treatment . In this study we demonstrated that ganoderic acid DM could increase apoptosis in A549 and NCIH460 NSCLC cells . GA DM treatment decreased the protein expression levels of Bcl 2 and increased the expression levels of Bax cleaved caspase 3 and cleaved PRAP . Furthermore GA DM could promote autophagic flux and the cytotoxic effect against cancer cells of GA DM was significantly inhibited by targeted suppression of autophagy suggesting that autophagy contributed to GA DM induced cell death in NSCLC . Moreover GA DM clearly induced autophagy by inactivating the PI3K Akt mTOR pathway . When overexpression of Akt reactivated Akt mTOR pathway in A549 or NCIH460cells the increase of autophagy related marker LC3B II and apoptosis related protein cleaved PARP and cleaved caspase 3 and the ration of apoptotic cells by GA DM was reversed suggesting that GA DM promoted autophagy and apoptosis by inhibiting Akt mTOR pathway mediated autophagy induction . In conclusion our study indicated that GA DM can induce autophagic apoptosis in NSCLC by inhibiting Akt mTOR activity . . | Ganoderic acid DM a natural compound induced apoptosis of A549 and NCIH460cells. Ganoderic acid DM promoted autophagic flux which contributed to it induced cell death in NSCLC. Ganoderic acid DM increased autophagy and apoptosis through inhibition of Akt mTOR pathway. |
S0009279719313997 | The isoquinoline 7 fluoro 1 3 diphenylisoquinoline 1 amine has been studied due to its multitarget properties such as modulation of GABAergic and glutamatergic systems antioxidant and anti inflammatory . This study investigated the contribution of oxidative stress nuclear factor like 2 heme oxygenase signaling and the cholinergic system to the anti amnesic action of FDPI in mice . Adult male Swiss mice received FDPI for 5 days the animals received scopolamine from day 35 . The vehicle control group was carried out . Afterward mice performed object recognition tests . Scopolamine induced amnesia and cholinergic dysfunction by increasing the acetylcholinesterase activity and content decreasing the muscarinic M1 receptor levels in the prefrontal cortex and hippocampus of mice . This study reveals that scopolamine altered oxidative stress parameters differently in the prefrontal cortex and hippocampus of mice . Whereas the prefrontal cortex was susceptible to oxidative stress none of the parameters evaluated was altered in the hippocampus of scopolamine treated mice . FDPI at doses of 10 and 25mg kg had an anti amnesic effect in the ORT tests . FDPI 10mg kg reversed the increase in the AChE activity and content oxidative stress parameters and modulated Nrf2 HO 1 signaling in the prefrontal cortex of scopolamine exposed mice . Pearson s correlation analyses reinforced the contribution of the prefrontal cortical cholinergic system oxidative stress as well as Nrf2 HO 1 signaling in the anti amnesic effect of FDPI . Considering FDPI effects on the hippocampus it was effective against the cholinergic dysfunction AChE activity and content and M1 receptor levels which collectively could contribute to its anti amnesic effect . | FDPI treatment was effective against memory impairment induced by scopolamine in mice. FDPI modulated AChE and M1 receptor contents in mice exposed to scopolamine. FDPI reversed oxidative stress induced by scopolamine in prefrontal cortex of mice. Oxidative stress and Nrf2 HO 1 signaling contributed to the action of FDPI. |
S000927971931405X | Acute pancreatitis is a sudden pancreatic inflammation accompanied by an excessive reactive oxygen species production that provokes inflammation . The present study investigated whether carvedilol can protect against | Carvedilol was able to protect against acute pancreatitis induced by. arginine. Carvedilol blocked inflammatory mediators induction and reduced the pancreas injury. Carvedilol could be used as a prophylactic agent or adjuvant therapy for AP. |
S0009279719314061 | Heart failure is an epidemic disease with increased incidence annually . It has been reported that taurine can improve cardiac function . This study investigated the cardioprotective effects of taurine in pressure loaded HF mice and elucidated the possible mechanism . HF models were established by transverse aortic constriction . Animals were treated with either taurine for 9 weeks and or the SIRT1 inhibitor EX527 after TAC operation . Cardiac function and geometry were revealed by echocardiography . Myocardial hypertrophy and fibrosis were assessed using Fluorescent wheat germ agglutinin staining and Masson s trichrome staining . Western blot and RT PCR were performed to elucidate the expression of target proteins and genes respectively . Apoptosis in cardiomyocytes was detected by TUNEL staining . Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase and malonyldialdehyde and reactive oxygen species . Taurine concentrations and NAD Taurine notably relieved cardiac dysfunction after TAC . The mechanisms were attributed to reduced myocyte hypertrophy and fibrosis and alleviated apoptosis and oxidative stress . Meanwhile taurine increased NAD NADH ratiopromoted the expression of SIRT1 and suppressed p53 acetylation . However EX 527 decreased NAD The mechanism responsible for cardiac protective effects of taurine in HF induced by pressure overload is associated with the activation of the SIRT1p53 pathway . | Taurine can improve cardiac function of HF mice. Taurine concentration dependently activated the SIRT1 expression in TAC mice. Taurine inhibited pressure overload induced p53 acetylation via a SIRT1 pathway. |
S000927971931422X | The lack of predictivity of animal s models has increased the failure rate of drug candidates . Thus the reversion of this scenario using preliminary | Pre. assays such as MTT and NR assays can reduce unnecessary mice experiments when used in appropriated framework. RN104 showed low cytotoxicity profile on cell based assays. RN104 proposed metabolites could indicate potential sites for further investigation. |
S000927971931436X | Tebuconazole is a broad spectrum conazole fungicide that has been used in agriculture in the control of foliar and soil borne diseases of many crops . The present study has investigated the adverse effects of subchronic exposure to TEB on the kidney of male rats . Animals were divided into four equal groups and treated with TEB at increasing doses 0.9 9 and 27mg kg body weight for 28 consecutive days . The results showed that TEB induced oxidative stress in the kidney demonstrated by an increase in malondialdehyde protein carbonyl advanced oxidation protein product levels and DNA damage as compared to the controls . Furthermore superoxide dismutase catalase glutathione peroxidase activities were increased in the renal tissue of treated rats . Moreover significant decrease in reduced glutathione content in TEB treated rats was observed while oxidized glutathione levels were increased thus a marked fall in GSH GSSG ratio was registered in the kidney . Glutathione reductase activity showed a significant increase after TEB exposure . Moreover TEB down regulated the expression of Bcl2 and up regulated the expression of Bax and caspase 3 which triggered apoptosis via the Bax Bcl2 and caspase pathway . Also TEB administration resulted in altered biochemical indicators of renal function and varying lesions in the overall histo architecture of renal tissues . Taken together our findings brought into light the renal toxicity induced by TEB which was found to be significant at low doses . | TEB exposure induced oxidative stress in the kidney. TEB exposure increased MDA PC and AOPP levels. TEB treated rats showed modified endogenous antioxidants activity. TEB exposure was associated with biochemical and histopathological changes. TEB exposure induced DNA damage and apoptosis induction. |
S0009279719314383 | Oxidized low density lipoprotein induced endothelial inflammation plays an important role in the development of cardiovascular diseases . G protein coupled receptors are gaining traction as potential treatment targets due to their roles in mediating a wide range of physiological processes . GPR120 is a recently identified omega 3 fatty acid receptor . We hypothesized that agonism of GPR120 might attenuate ox LDL induced endothelial dysfunction . In the present study we tested the effects of two GPR120 agonistsGW9508 and TUG 891in mitigating endothelial insult induced by ox LDL in human aortic endothelial cells . Real time PCR western blot and ELISA analyses were used in our experiments . Our findings demonstrate that GPR120 is downregulated by exposure to ox LDL suggesting a role for GPR120 in mediating ox LDL insult . Furthermore we found that agonism of GPR120 could suppress oxidative stress and inflammation by inhibiting the production of reactive oxygen species and the expression of proinflammatory cytokines . Importantly we show that agonism of GPR120 prevents the attachment of monocytes to endothelial cells by suppressing the expression of VCAM 1 and E selectin . Finally we show that agonism of GPR120 exerts a remarkable atheroprotective effect by elevating the expression level of Krppel like factor 2 . Together our results demonstrate a potential role for specific agonism of GPR120 in the prevention of endothelial damages induced by ox LDL . | Expression of GPR120 is downregulated by ox LDL. GPR120 agonism reduces ox LDL induced oxidative stress. GPR120 agonism reduces ox LDL induced inflammation. GPR120 agonism prevents monocyte attachment to endothelial cells. GPR120 agonism rescues ox LDL induced reduced expression of KLF2. |
S0009279719314395 | Alzheimer s disease the most common form of dementia is a neurodegenerative disease characterized by neuronal atrophy in various brain regions . The expression of miR 107 is down regulated in AD patients and target genes of miR 107 have been shown to directly involved in AD . In this study we aimed to investigate the potential neuroprotective effects of miR 107 . We first assessed brain activity in health controls and patients with AD . Then we examined miR 107 expression in SH SY5Y and PC12cells treated with 6 hydroxydopamine and investigated its function in cytotoxicity induced by 6 OHDA . We predicted a potential miR 107 target and assessed its role in miR 107 mediated effects and explored the intracellular signaling pathways downstream of miR 107 . Finally we assessed the function of miR 107 in the mouse model insulted by 6 OHDA . We found that 6 OHDA suppressed miR 107 expression and miR 107 played neuroprotective effects against 6 OHDA mediated cytotoxicity . We showed that miR 107 targeted programmed cell death 10 . MiR 107 suppressed PDCD10 expression and exogenous expression of PDCD10 inhibited miR 107 mediated neuroprotection . Additionally we found that Notch signal pathway was downstream of miR 107 PDCD10 . Finally we found that 6 OHDA treatment suppressed miR 107 in mice and restoration of miR 107 alleviated motor disorder in the mouse model . Our study shows that miR 107 plays important neuroprotective roles against neurotoxicity both in vitro and in vivo by inhibiting PDCD10 . Our findings confirm that miR 107 may be involved in AD pathogenesis and may be a therapeutic target for the treatment of AD related impairments . | miR 107 targets programmed cell death 10. miR 107 overexpression inhibits 6 OHDA induced neurotoxicity. miR 107 may be a therapeutic target for AD treatment. |
S0009279719314474 | Type II diabetes is recognized as a major risk factor for death due to cardiovascular complications such as coronary heart disease but the complex interplay between these two diseases remains poorly understood . Suppression of oxidative stress apoptosis and inflammation of endothelial cells is a valuable treatment strategy to prevent or halt the progression of CHD . In the present study we used real time polymerase chain reaction Western blot analysis and enzyme linked immunosorbent assay to investigate the effects of saxagliptin on hypoxia inducible factors . Our findings demonstrate that saxagliptin can significantly improve cell viability in H9c2 cells as well as reduce hypoxia induced oxidative damage and loss of mitochondrial membrane potential . Saxagliptin reduced hypoxia induced NADPH oxidase 4 . We also show that saxagliptin can reduce the expression of matrix metallopeptidase 2 and matrix metallopeptidase 9 two important degradative enzymes . Saxagliptin also suppressed hypoxia induced expression of high mobility group box 1 protein a key inflammatory cytokine . Finally we show that saxagliptin can exert atheroprotective effects by reducing the expression of myeloid differential protein 88 and increasing the expression of nuclear factor erythroid 2 related factor 2 and heme oxygenase 1 . Thus saxagliptin shows promise as a treatment against diabetes associated CHD . | Saxagliptin improves cell viability. m and oxidative stress in H9c2 cells. Saxagliptin leads to downregulation of MMP 2 and MMP 9 induced by hypoxia. Saxagliptin attenuates upregulation of HMGB1 and MyD88 induced by hypoxia. The cardioprotective effects of saxagliptin are mediated by Nrf2 HO 1. |
S000927971931453X | Grape seed proanthocyanidin extract has been reported to exhibit a variety of protective effects such as antioxidant anti atherosclerosis and other pharmacological effects . As a member of the complement system complement component 3 deposition in the glomerulus is recognized as an important causative mediator of various kidney diseases . In this study we aimed to identify the effect of GSPE on C3 in the chronic kidney fibrosis and evaluate the possible mechanism . We observed that administration of GSPE relieves inflammation and chronic renal fibrosis in mouse models of UUO . GSPE inhibited C3 secreted by macrophages to relieve renal interstitial inflammation . In vitro we found that C3 stimulated HMGB1 translocation form nucleus to cytoplasm and promote the expression of pro inflammatory cytokines including TGF 1 in primary renal tubular epithelial cells which could be inhibited by GSPE . Meanwhile GSPE could also decreased HMGB1 induced EMT of PTEC through suppresses the HMGB1 TLR4 p65 TGF 1 pathway . In addition the myofibroblast activation was inhibited by GSPE via TGF 1 Smad2 3 signaling pathways in normal rat kidney fibroblast cells . Overall these observations provide that GSPE alleviates renal fibrosis by inhibiting the C3 HMGB1 TGF 1 pathway and could thus lead to find the potential therapy for the suppression of renal fibrosis . | GSPE mitigates the release of C3 to renal interstitium by macrophages in UUO. Secretion of C3 appears to promote HMGB1 translocation that is inhibited by GSPE. GSPE suppressed HMGB1 TLR4 p65 pathway thereby inhibiting production of TGF 1. |
S0009279719314553 | The toxic effects of poly based polymeric nanoparticles must be analyzed before their biomedical applications as drug delivery systems . The aim of the study was to characterize and evaluate the toxicity for its biocompatibility of a newly synthesized | glutamic acid g poly HEMA was synthesized successfully. The characterization of nanoparticle was determined. The toxicity of the. glutamic acid g poly HEMA was determined on in vitro assays. glutamic acid g poly HEMA has a potential for use as drug delivery systems. |
S0009279719314607 | Tripartite motif protein family is a group of proteins which belongs to RING family of ubiquitin E3 ligases . TRIM proteins are involved in oncogenesis while the roles in different cancers are controversial . However the expression pattern and biological functions of TRIM47 in breast cancer remain unclear . In the present study we aimed to investigate the function of TRIM47 in the progression and metastasis of breast cancer . TRIM47 was found to be significantly up regulated in breast cancer tissues and cell lines . TRIM47 knockdown in breast cancer cell lines significantly inhibited cell proliferation migration and invasion . Besides TRIM47 knockdown regulated the expressions of the epithelial mesenchymal transition related markers including increase in E cadherin and decrease in N cadherin vimentin and Snail . Xenograft tumor assay proved that TRIM47 knockdown also suppressed tumor growth | TRIM47 was significantly up regulated in breast cancer tissues and cell lines. TRIM47 knockdown inhibited the proliferation and invasion of breast cancer cells. TRIM47 knockdown suppressed tumor growth. TRIM47 knockdown inhibited the activation of PI3K Akt pathway in breast cancer cells. |
S0009279719314759 | Zebrafish inflammation models were used to evaluate the anti inflammatory activity of isoniazid and preliminarily investigate the underlying mechanism . Local acute and systemic zebrafish inflammation models were established by tail cutting copper sulfate CuSO Compared to those observed in the control inflammation model group the numbers of migrated and accumulated inflammatory cells in zebrafish in the INH treated group significantly decreased . INH significantly decreased the ROS content induced by LPS . Compared to that observed in the LPS model group INH at 1 and 2mM significantly increased the expression of PPAR and inhibited the expression of NF B iba and AP 1 as well as the inflammatory factors TNF TGF IL 1b and COX 2 . In this study different zebrafish inflammation models were used to confirm that INH has anti inflammatory activity . The associated mechanism may occur through the inhibition of ROS release activation of PPAR expression inhibition of the transcriptional regulatory activity of NF B and AP 1 and reduction of INH inflammatory factor expression to relieve inflammation . The results of this study provide references for the clinical application of INH . | INH exhibited a notable anti inflammatory effect. INH mediated decrease in ROS production. INH resulted in the activation of PPAR expression. INH leaded to the inhibition of the transcriptional activity of NF B and AP 1. INH inhibited the expression of related inflammatory factors. |
S0009279719314875 | Chondrocytes in joints are responsible for the formation and remodeling of articular cartilage . The accumulation of advanced glycation end products in cartilage is detrimental to the survival of chondrocytes . Linagliptin is one of the most commonly used anti diabetes agents and recent work indicates that it exerts an anti inflammatory effect in different cell types . In this study we showed that Linagliptin had a protective role in AGEs induced chondrocyte injury . The presence of Linagliptin ameliorated AGEs induced reactive oxygen species induction and reduced cellular protein carboxyl content . Linagliptin mitigated AGEs induced mitochondrial membrane potential | Linagliptin reduced AGEs induced increase in ROS and protein carboxyl. Linagliptin protected ATDC5 cells against AGEs induced mitochondrial dysfunction. Linagliptin reduced AGEs induced expression of NOX 4 HMGB 1 and MMP 2 9. Linagliptin prevented AGEs induced apoptosis in a mitochondria dependent pathway. |
S0009279719314899 | Irinotecan is a chemotherapeutic drug used in the treatment of advanced colorectal cancer and elevated blood concentrations of its active metabolite SN 38 leads to increased gastrointestinal toxicity and diarrhea in patients . In this study we investigated the effects of inflammation on the pharmacokinetics of irinotecan and its active metabolite SN 38 . Mice were i.p . injected with either saline or lipopolysaccharide to induce inflammation . After 16h irinotecan was administered orally . Blood was collected from the tail vein of mice from 0 to 24h after dosing . Concentrations of irinotecan SN 38 and SN 38G were analyzed using LC MS MS . The AUC C | The Effects of Inflammation on Irinotecan CPT 11 PK were investigated. SN 38 blood concentrations and AUC were increased in mice with inflammation. Entero hepatic recycling EHR was found to increase SN 38 exposure. A best fit PK model was developed with irinotecan SN 38 and EHR compartments. The developed model predicts the PK of Irinotecan and SN 38 during inflammation. |
S0009279719314917 | Pulmonary hypertension is distal pulmonary arterial remodelling and is mainly due to the abnormal proliferation and apoptosis resistance of pulmonary artery smooth muscle cells . Apigenin a natural dietary flavonoid is a promising PH preventive agent that inhibits PASMC proliferation and induces apoptosis . In this study we investigated the biological effects of apigenin on PH . PH was induced in male Sprague Dawley rats by chronic hypoxia exposure . Administration of apigenin prevented the development of PH hypoxia induced right ventricular hypertrophy and pulmonary arterial remodelling and prevented the progression of established PH in this model . Moreover treatment with apigenin induced mitochondria dependent apoptosis . To explore the underlying mechanisms the mitochondrial membrane potential and the mitochondria dependent apoptosis factors cytochrome C BAX Bcl 2 cleaved caspase 3 and cleaved caspase 9 were analysed . These results confirmed that apigenin induces mitochondria dependent apoptosis in hypoxic PASMCs to protect against PH . In addition treatment with apigenin reversed hypoxia induced inhibition of KV1.5 expression both | Apigenin ameliorate hypoxia induced PAH and pulmonary arterial remodelling. Apigenin induced mitochondria dependent apoptosis. Apigenin attenuates PH via inhibiting the HIF 1 KV1.5 channel pathway. |
S0009279719315030 | mTOR inhibitors are considered today to be one of the most promising anticancer drugs . Here to study the mechanism of the acquired resistance of MCF 7 breast cancer cells to mTOR inhibitors two different models of the cell resistance were used rapamycin resistant MCF 7 Rap subline developed under long term rapamycin treatment and metformin resistant MCF 7 M subline obtained by long term metformin treatment . We have found that both resistant sublines were characterized by common features increased expression of mTOR interacting Raptor protein increased phosphorylation of Akt and activation of growth related transcriptional factor AP 1 . Cell response to mTOR inhibitors was partially restored under treatment with PI3K inhibitor wortmannin supporting the direct connection between Akt activation and poor cell response to therapeutic drugs . | Novel cell sublines with resistance to mTOR inhibitors were developed. Activation of mTOR interacting Raptor protein Akt and AP 1 factor are associated with resistance. Wortmannin restores cell sensitivity to mTOR inhibitors. mir 181c is involved in the cell resistance to mTOR inhibitors. |
S0009279719315078 | Osteoarthritis is one of the most prevalent degenerative joint diseases and the risk of developing OA significantly increases with age as well as with concomitant diseases such as diabetes . Advanced glycation end products accumulate in the body over time and are associated with increased expression of various molecules involved in the pathophysiology of OA . Prostaglandin E | AGEs reduces the expression of GLP 1R in human SW1353 chondrocytes. Dulaglutide ameliorates AGEs induced degradation of type II collagen and aggrecan. Dulaglutide inhibits the expressions of MMP 3 MMP 13 ADAMTS 4 and ADAMTS 5. Dulaglutide reduces AGEs induced expressions of IL 6 IL 8 MCP 1 COX 2 PGE. The effects of dulaglutide in SW1353 chondrocytes are mediated through NF B. |
S0009279719315200 | Carbon monoxide is an inorganic chemical compound that can bind with hemoglobin with highly toxic effects . In living organisms it is produced endogenously during the degradation of heme by oxygenase which occurs in three isoforms HO 1 HO 2 and HO 3 . CO can play an important role in the regulation of many physiological functions . Carbon Oxide Releasing Molecules are a novel group of chemical compounds capable of controlled CO release directly in tissues or organs . This release depends on concentration pH solvent type and temperature . The biological role and the therapeutic potential of different CORMs is not always well demonstrated . However this mini review summarizes the various function of these compounds . | CO is an inorganic chemical compound that can bind with hemoglobin. It is produced endogenously during the degradation of heme by oxygenase. CO can play an important role in the regulation of many physiological functions. CORMs are group of chemical compounds capable of controlled CO. |
S0009279719315443 | The aim of this study was the synthesis of ion doped silica based nanoparticles and the evaluation of their toxic effect on erythrocytes . Their synthesis was performed using the sol gel method by the progressive addition of calcium magnesium and copper ions on pure silica nanoparticles . The toxicity evaluation was based on hemolysis lipid peroxidation ROS H The addition of Mg and Cu in the SNs presented better hemocompatibility by protecting erythrocytes from oxidative stress . Ion doping with magnesium in the investigated calcium silicate system induces a protective effect in erythrocyte membrane in compare with pure silica nanoparticles . | Addition of Mg and Cu in SNs improved their hemocompatibility. All SNs concentrations lower than 0.125mg mL are hemocompatible. Ion doping in SNs protected erythrocytes from oxidative stress. Higher amount of H. species detected by LC MS have been generated in un doped SNs. |
S0009279719315637 | Mineral oils are widely applied in food production and processing and may contain polycyclic aromatic hydrocarbons . The PAHs that may be present in mineral oils are typically alkylated and have been barely studied . Metabolic oxidation of the aromatic ring is a key step to form DNA reactive PAH metabolites but may be less prominent for alkylated PAHs since alkyl substituents would facilitate side chain oxidation as an alternative . The current study investigates this hypothesis of preferential side chain oxidation at the cost of aromatic oxidation using naphthalene and a series of its alkyl substituted analogues as model compounds . The metabolism was assessed by measuring metabolite formation in rat and human liver microsomal incubations using UPLC and GC MS MS . The presence of an alkyl side chain markedly reduced aromatic oxidation for all alkyl substituted naphthalenes that were converted . 1 n Dodecyl naphthalene was not metabolized under the experimental conditions applied . With rat liver microsomes for 1 methyl 2 methyl 1 ethyl and 2 ethyl naphthalene alkyl side chain oxidation was preferred over aromatic oxidation . With human liver microsomes this was the case for 2 methyl and 2 ethyl naphthalene . It is concluded that addition of an alkyl substituent in naphthalene shifts metabolism in favor of alkyl side chain oxidation at the cost of aromatic ring oxidation . Furthermore alkyl side chains of 6 or more carbon atoms appeared to seriously hamper and reduce overall metabolism metabolic conversion being no longer observed with the C12 alkyl side chain . In summary alkylation of PAHs likely reduces their chances of aromatic oxidation and bioactivation . | Alkyl substitution of naphthalene shifts metabolism in favor of alkyl side chain oxidation at the cost of aromatic ring oxidation. Metabolism and bioactivation of naphthalene is hampered when the alkyl substituent contains over 6 carbon atoms. Alkylation of PAHs likely reduces their chances on aromatic oxidation and potential bioactivation. |
S0009279719315893 | Stroke has been considered the second leading cause of death worldwide and ischemic stroke accounts for the vast majority of stroke cases . Some of the main features of ischemic stroke are increased brain permeability ischemia reperfusion injury oxidative stress and acute inflammation . Antagonism of cysLT1R has been shown to provide cardiovascular and neural benefits . In the present study we investigated the effects of the cysLT1R antagonist zafirlukast both | Zafirlukast protected against MCAO induced brain infarction and neurological deficit. Zafirlukast protected against MCAO induced increase in brain permeability and reduction of occludin and ZO 1. Zafirlukast suppressed OGD R induced endothelial monolayer permeability. Zafirlukast prevented OGD R induced MMP 2 and MMP 9 expression and NF B activation. |
S0009279719315947 | Exposure to mycotoxins is mostly by ingestion but also occurs by the dermal and inhalation routes . The present study for the first time demonstrated that mycotoxin Deoxynivalenol permeates through | Deoxynivalenol DON a trichothecene mycotoxin penetrates through mice skin. Protein Kinase C is involved in DON induced upregulation of COX2 and iNOS proteins. Celecoxib reduces DON induced epidermal inflammation and cell proliferation. Skin Permeation potential of Celecoxib is lower as compared to the oral route. Celecoxib can effectively ameliorate mycotoxin induced skin inflammatory disorders. |
S0009279719315984 | Ferroptosis is recently identified form of regulated cell death which differs from previously identified cell death in a way that it is driven by iron dependent lipid peroxide accumulation . Morphologically cell volume shrinkage and increased mitochondrial membrane density are main features which characterize this form of cell death . Molecular mechanism of ferroptosis induction involved suppression of the phospholipid glutathione peroxidase 4 and further intracellular accumulation of lipid reactive oxygen species a process in which iron is involved either via inhibition of system Xc or direct inhibition of GPX4 . Several other pathways like RAS MAPK and NRF2 are found to be involved in ferroptosis regulation . However the precise mechanism of ferroptosis induction is not revealed till date . Like other regulated cell deaths ferroptosis plays important role in tumor suppression and progression as revealed by several scientific reports . This review summarizes basic information about discovery of this novel cell death mechanism including molecular mechanism of its induction and further explains the roles of ferroptosis in human cancers . | Ferroptosis a newly discovered iron dependent programmed cell death. Ferroptosis activation a promising strategy for diagnosis and therapeutic intervention in cancer. Ferroptosis inducing agents as an attractive therapeutic strategy. Ferroptosis induction involved suppression of the phospholipid GPX4. |
S0009279719316023 | Endemic fluorosis is a serious problem in public health affecting thousands of people . Abnormal proliferation and activation of osteoblasts in skeletal fluorosis lesions play a leading role and osteoblast proliferation is finely regulated by the cell cycle . There are a few reports on fluoride induced DNA methylation . However the role of DNA methylation of the cyclin cyclin dependent kinase cyclin dependent kinase inhibitor regulatory network in skeletal fluorosis has not been investigated . We used a population study and | Fluoride exposure induced up regulation of. down regulation of. No changes in methylation status of. were found in fluoride exposure. Down regulation of. induced by fluoride is attributable to its hypermethylation. Hypermethylation of the. gene can serve as a potential biomarker for fluorosis. |
S0009279719316114 | Osteoarthritis is one of the most common degenerative joint diseases in aging people . The activation of chondrocytes and their dysregulation are closely related to the pathogenesis of OA . GPR55 is an unique orphan G receptor which binds to cannabinoids . In this study we explored the role of GPR55 in advanced glycation end productions induced chondrocytes activation in cultured cells . We showed that AGEs dose dependently induced GPR55 expression in ATDC5 chondrocytes . The blockage of GPR55 by its newly discovered antagonist CID16020046 mitigated AGEs induced increase in cellular ROS and decrease in antioxidant NRF2 . Moreover CID16020046 showed a dose response suppressive effect on AGEs induced expression of the major inflammatory mediators including COX 2 and iNOS and the production of NO and PGE | AGEs increased the expression of GPR55 in human ATDC5 chondrocytes. CID16020046 ameliorated AGEs induced ROS production and Nrf2 reduction. CID16020046 reduced AGEs induced COX 2 iNOS expression and PGE. and NO production. CID16020046 inhibited AGEs induced MMP 3 MMP 13 and degradation of type collagen. CID16020046 suppressed AGEs induced activation of IB NF B. |
S0009279719316151 | The transmission of T 2 toxin and its metabolites into the edible tissues of poultry has potential effects on human health . The bile acid and xenobiotic system composes an intricate physiological network of chemoprotective and transporter related functions which ensures the detoxification and removal of harmful xenobiotic and endobiotic compounds from the body . This study revealed that cholic acid as one of the bile acids promoted the metabolism of T 2 toxin | Bile acid increases the expression of the xenobiotic enzymes. Bile Acid enhances metabolism of T 2 toxin. Bile Acid attenuates oxidative stress. |
S0009279719316163 | Type 2 diabetes is associated with oxidative stress and low grade inflammation resulting in endothelial dysfunction . This study determined to explore the protective effects of berry derived anthocyanins with potent antioxidant and anti inflammatory activities in human diabetic endothelial cells upon oxidative and inflammatory stressors . Cultured healthy human aortic endothelial cells and diabetic human aortic endothelial cells exposed to oxidative stress by hydrogen peroxide H | T2DM is associated with oxidative stress and inflammation resulting in ED. Anthocyanins AC decreased H. induced cytotoxicity in both HAEC D HAEC. AC reduced LPSinduced IL6 production in the diabetic endothelial cell line. AC treatment inhibited LPSinduced caspase 1 activation in D HEAC. AC protected D HAECs via anti inflammatory mechanisms to prevent diabetic ED. |
S0009279719316369 | Pulpal infection is one of the most common causes of dental emergency admission . Tooth pain due to infection caused by gram negative bacteria is the main manifestation of this sort of dental problem . The GPR173 signaling pathway is a highly conserved G protein coupled receptor that mediates neurological and reproductive function . In this study we found that GPR173 was fairly expressed in isolated human dental pulp cells and its expression was reduced in response to pro inflammatory lipopolysaccharide treatment . The activation of GPR173 by its ligand Phoenixin 20 reduced LPS induced cytotoxicity as revealed by a reduction in the release of LDH . Additionally Phoenixin 20 suppressed LPS induced release of pro inflammatory cytokines and inflammatory mediators including IL 6 MCP 1 VCAM 1 and ICAM 1 as well as MMP 2 and MMP 9 . Mechanistically we showed the suppressive action of Phoenixin 20 on LPS induced activation of TLR 4 and Myd88 as well as the activation of the NF B pathway . Collectively our study demonstrates that the GPR173 signaling pathway is an important mediator of LPS induced inflammation and the activation of GPR173 by its natural ligand Phoenixin 20 exhibits robust anti inflammatory effects in dental pulp cells suggesting that GPR173 is an interesting target molecule in the development of pulp cell based therapies . | LPS reduced the expression of GPR173 in human dental pulp cells hDPCs . Phoenixin 20 reduced LPS induced release of LDH in hDPCs. Phoenixin 20 reduced LPS induced IL 6 MCP 1 VCAM 1 ICAM 1 MMP 2 and MMP 9. Phoenixin 20 abolished LPS induced activation of TLR4 Myd 88 NF kB in hDPCs. |
S0009279719316497 | As one of the main active ingredients of Chinese herbal medicine A rat model of rheumatoid arthritis was induced by subcutaneous injection of complete Freund s adjuvant in the footpad . The model was established 14 days after induction . The treatment was performed from 14th day to 35th day with different doses of andrographolide and positive control methotrexate . The medium and high dose andrographolide group declined the levels of tumor necrosis factor interleukin 6 and CXC chemokine ligand2 articular elastase and myeloperoxidase and increased the levels of antioxidant enzymes superoxide dismutase catalase and glutathione . The activity of malondialdehyde and nitrite nitrate in andrographolide group was weakened than the model group . The degree of swelling and arthritis score of andrographolide group was lower than the model group . The results of hot plate test showed that high dose of andrographolide significantly improved the anti injury ability of rats Radiological and histological results showed that the joint osteoporosis inflammatory cell infiltration synovial hyperplasia and other phenomena in the andrographolide group were significantly improved . Andrographolide acts as a protective agent for the treatment of complete freund s adjuvant induced rheumatoid arthritis by inhibiting lipid peroxidation and nitrite nitrate levels in a dose dependent manner enhancing antioxidant enzyme activity reducing levels of chemokines and inflammatory factors preventing neutrophil accumulation and infiltration . | Andrographolide inhibits neutrophil elastase and myeloperoxidase activity in arthritic rats. Andrographolide reduces neutrophil aggregation in joint inflammation by affecting neutrophil chemotactic factors. Andrographolide reduces arthritis oxidative stress levels and inhibits inflammation. |
S000927971931659X | Methylmercury is a neurotoxicant that poses risk to human health and the environment while glutamate homeostasis is necessary for the proper functioning of the brain . We have previously shown an increase in oxidative stress after cockroach exposure to diet containing monosodium glutamate both separately and combined with a low dose of methylmercury . We herein seek to corroborate these findings by quantifying the expression levels of certain antioxidant genes in | MeHg alone downregulated mRNA levels of. and. 5 in experimental cockroaches. MeHg MSG upregulated downregulated mRNA levels of. and. 5 in exposed cockroaches. MeHg NaCl and MeHg MSG upregulated G. and. T in cockroaches. ICP AES analysis showed an increase in mercury Hg levels in the MeHg treated groups in the heads of cockroaches. |
S0009279719316643 | Over the years the attention of researchers in the field of modern drug discovery and development has become further intense on the identification of active compounds from plant sources and traditional remedies as they exhibit higher therapeutic efficacies and improved toxicological profiles . Among the large diversity of plant extracts that have been discovered and explored for their potential therapeutic benefits asperuloside an iridoid glycoside has been proven to provide promising effects as a therapeutic agent for several diseases . Although this potent substance exists in several genera it is primarily found in plants belonging to the genus | Asperuloside have potent medicinal properties including antiobesity and anti inflammatory. Asperuloside inhibited the increase in body weight and visceral fat weight. The anti inflammatory mechanism of Asperuloside was demonstrated in LPS induced RAW 264.7cells. The anticancer activity of Asperuloside was comparable with antimycin A. Asperuloside also demonstrated moderate antibacterial effects on several known microbes. |
S0009279719316771 | Fatty liver is the hepatic consequence of chronic insulin resistance and related syndromes . It is mostly accompanied by inflammatory and oxidative molecules . Increased activity of xanthine oxidase exerts both inflammatory and oxidative effects and has been implicated in metabolic derangements including non alcoholic fatty liver disease . Short chain fatty acids elicit beneficial metabolic alterations in IR and related syndromes . In the present study we evaluated the preventive effects of a SCFA acetate on nicotine induced dysmetabolism and fatty liver . Twenty four male Wistar rats vehicle treatment | Nicotine exposure induces excess hepatic lipid. Nicotine increases XO activity. Acetate protects against hepatic effects of nicotine. Acetate suppresses XO in nicotine treated rats. |
S0009279719316825 | Endocrine therapies targeting estrogen action are effective in decreasing mortality of breast cancer . However their efficacy is limited by intrinsic and acquired resistance . Our previous study demonstrated that overexpression of a histone methyltransferase NSD2 drives tamoxifen resistance in breast cancer cells and that NSD2 is a potential biomarker of tamoxifen resistant breast cancer . Here we found that DZNep an indirect inhibitor of histone methyltransferases potently induces the degradation of NSD2 protein and inhibits the expression of NSD2 target genes involved in the pentose phosphate pathway . DZNep treatment of tamoxifen resistant breast cancer cells and xenograft tumors also strongly inhibits tumor growth and the cancer cell survival through decreasing cell production of NADPH and glutathione and invoking elevated ROS to cause apoptosis . These findings suggest that DZNep like agents can be developed to target NSD2 histone methyltransferase for effective treatment of tamoxifen resistant breast cancer . | DZNep potently induces the degradation of NSD2 protein. DZNep inhibits the expression of NSD2 target genes HK2 G6PD GLUT1 and TIGAR involved in the pentose phosphate pathway. DZNep decreases cell production of NADPH and glutathione GSH and elevated ROS. DZNep inhibits TamR breast cancer cell growth in vitro and in vivo |
S0009279719316904 | Homeodomain interacting protein kinase 2 has emerged as a crucial stress responsive kinase that plays a critical role in regulating cell survival and apoptosis . However whether HIPK2 participates in regulating cardiomyocyte survival during myocardial ischemia reperfusion injury remains unclear . Here we investigated the regulatory effect of HIPK2 on hypoxia reoxygenation induced cardiomyocyte injury and its potential underlying molecular mechanism . We found that HIPK2 expression was induced in response to H R exposure . HIPK2 depletion by small interfering RNA mediated gene silencing significantly decreased the viability and exacerbated H R induced apoptosis and reactive oxygen species production in cardiomyocytes . Comparatively HIPK2 overexpression effectively rescued H R impaired viability and repressed H R induced apoptosis and ROS production in cardiomyocytes . HIPK2 overexpression significantly increased the nuclear expression of nuclear factor like 2 and enhanced Nrf2 mediated transcriptional activity . Moreover HIPK2 overexpression significantly increased the transcription of Nrf2 ARE target genes . Additionally Nrf2 inhibition partially reversed the HIPK2 mediated protective effect . Overall these results demonstrate that HIPK2 overexpression protects cardiomyocytes from H R induced injury by enhancing Nrf2 ARE antioxidant signaling data that suggest HIPK2 is a potential target for cardioprotection . | HIPK2 expression was induced by H R in cardiomyocytes. Loss of HIPK2 enhances the sensitivity of cardiomyocytes to H R injury. HIPK2 overexpression protects cardiomyocytes from H R injury. HIPK2 regulates H R injury through Nrf2 ARE signaling. |
S000927971931703X | Excess weight and obesity increase the risk of developing major risk factors for chronic kidney disease . Lignin comprises 20 30 of the global plant biomass however it is not well utilized because of its resistance to chemical and biological degradation . We investigated whether low molecular weight oxidized lignophenol a lignin derivative could alter inflammation and fibrosis in the kidneys of a high fat diet fed mice . Male mice were divided into three treatment groups HFD HFD 0.3 LOLP and HFD 0.6 LOLP . The control mice were fed a low fat diet . Macrophage kinetics the degree of fibrosis the extent of phosphorylation of AMP activated protein kinase and mRNA expression of proinflammatory mediators in the kidneys were examined . The number of macrophages the percentage of fibrotic area and the mRNA expression of proinflammatory markers TNF and Ccl2 and a marker of fibrosis TGF were significantly higher in the kidneys of mice in the HFD group than those in the Cont group . Conversely treatment with 0.6 LOLP for 8 weeks significantly suppressed the degree of macrophage infiltration interstitial fibrotic area and the increased mRNA expression of proinflammatory and fibrosis markers induced by HFD . In conclusion LOLP suppressed macrophage infiltration and the increase in fibrotic area and upregulated AMPK phosphorylation in the kidneys of HFD fed mice thus it may ameliorate HFD induced kidney injury . | Obesity increases the risk of major risk factors for chronic kidney disease. Low molecular weight oxidized lignophenol LOLP a lignin derivative was prepared. LOLP suppressed macrophage infiltration and the increase in fibrotic area in the kidneys of a high fat diet HFD fed mice. LOLP upregulated AMP activated protein kinase phosphorylation in the kidneys of HFD fed mice. LOLP may exert beneficial effects through the improvement of obesity induced kidney injury. |
S0009279719317193 | Cantharidin is a traditional Chinese medicine that shows an anticancer effects in multiple types of cancer cells . However the mechanism of CTD anti cancer function in gastric cancer is still unclear . The aim of the present study was to investigate the underlying mechanism that CTD inhibits proliferation and migration through suppression of the PI3K Akt signaling . CTD induced GC cell apoptosis and inhibited metastasis measured by CCK8 assays as well as wound healing assays and transwell assays . Mechanistic investigations suggested that CTD modulated the PI3K Akt signaling via western blot and quantitative q PCR . In addition we identified and confirmed CCAT1 as a novel direct target of CTD inhibited PI3K AKt signaling expression . In conclusion our results provide new point into the critical role of CTD in suppressing PI3K Akt signaling via down regulation of CCAT1 resulting in suppression GC cell growth and migration invasion . | Cantharidin suppressed MGC803 and BGC823cell metastasis by inhibiting PI3K Akt signal pathway in vitro. Down regulated CCAT1 by cantharidin may inhibit gastric cancer metastasis. CCAT1 may regulate PI3K Akt signal pathway in gastric cancer cell. |
S0009279719317259 | Heroin is a highly addictive opioid drug synthesized from morphine . The use of heroin and incidence of heroin associated overdose death has increased sharply in the US . Heroin is primarily metabolized via deacetylation forming the active metabolites 6 monoacetylmorphine and morphine . A diminution in heroin hydrolysis is likely to cause higher drug effects and toxicities . In this study we sought to determine the contribution of the major hepatic hydrolase carboxylesterase 1 to heroin metabolism in the liver as well as the potential influence of one of its known genetic variants G143E . Furthermore given the potential therapeutic application of cannabidiol for heroin addiction and the frequent co abuse of cannabis and heroin we also assessed the effects of CBD on heroin metabolism . | Hepatic carboxylesterase 1 contributes to 3.66 of heroin hydrolysis in the liver. Carboxylesterase 1 G143E variant unlikely to clinically impact heroin metabolism. Cannabidiol is a potent in vitro inhibitor of the two step hydrolysis of heroin. Cannabidiol can potentially interact with heroin in various clinical settings. |
S0009279719317260 | Heart rhythm disturbances have been widely recognized as major triggers of cardiovascular mortality in chronic kidney disease patients . Connexin 43 composed gap junctions are essential in cardiomyocyte synchronization and may be involved in the pathological response to uremic toxins . Indoxyl sulfate is one of the most dominant uremic toxins that contribute to CKD related cardiovascular diseases . In primary cultures of rat neonatal cardiomyocytes we demonstrated that IS treatment decreased spontaneous contraction without impairing viability . In addition there was disruption of gap junction intercellular communication between cardiomyocytes after 30min of IS stimulation . IS caused time and dose dependent Cx43 redistribution and the patterns of Cx43 immunostaining returned to baseline while IS stimulation was removed . Furthermore IS exposure downregulated Cx43 protein and mRNA levels . Elevated JNK1 and JNK2 phosphorylation was further identified after IS exposure in both rat cardiomyocytes and H9c2 cells . The above changes as well as GJIC and Cx43 suppression were reversed by pretreatment with a JNK inhibitor . Inhibition of p JNK attenuated IS mediated downward trends in Cx43 transcription and translation . In cardiac muscle from nephrectomy induced CKD mice an alteration in Cx43 level was identified at intercalated discs . Our findings disclosed that JNK activation might participate in the remodeling of gap junction and Cx43 expression by uremic toxin IS both in vitro and | IS restrained spontaneous contraction in cardiomyocytes with gap junction disruption. Cx43 protein and mRNA level were reduced under IS exposure with time and dose dependent effect. The inhibition of JNK ameliorated IS induced Cx43 composed gap junction reassembly in cardiomyocytes. |
S000927971931734X | Epidemiological studies have shown that cigarette smoking is beneficial in ulcerative colitis and that nicotine may be responsible for this effect . However the mechanism remains unclear . In a previous study nicotine was found to induce autophagy in intestinal cells . Here we evaluated the effect of nicotine induced autophagy in a dextran sodium sulfate induced colitis mouse model . C57BL 6 adult male mice drank DSS water solution freely for seven consecutive days and then tap water was administered . The effect of nicotine treatment was examined in the DSS model including colon length disease severity histology of the colon tissue and inflammation levels . Moreover autophagy levels were detected by Western blot analysis . The levels of DSS induced colitis were significantly decreased following nicotine treatment . The disease activity score body weight histologic damage scores and the level of colonic inflammatory factors of nicotine treated mice all decreased compared to those of the control mice . Additionally nicotine enhanced the expression of LC3II LC3I and beclin 1 but decreased the p62 protein level . Inhibiting autophagy by 3 MA attenuated the protective effects of nicotine on colitis . Additionally both in vitro and in vivo experiments showed changes in AMPK mTOR P70S6K during this process . These results suggest that nicotine improved colitis by regulating autophagy and provided a protective effect against DSS induced colitis . | Cigarette smoking is beneficial in ulcerative colitis and nicotine may be responsible for this effect. Nicotine ameliorated DSS induced colitis and enhanced the autophagy. Blockade of autophagy attenuates the protective effect of nicotine. Nicotine enhanced autophagy was regulated by the AMPK mTOR pathway. |
S0009279719317399 | Eugenol a phenylpropanoid predominantly found in clove is a very common spice in daily cuisine . It already reported to have anti breast cancer activity . In this study the effect of eugenol on CSC markers and its main regulator catenin both | Establishing catenin as a novel druggable target of eugenol on cancer cell lines. Restriction of catenin nuclear translocation upon eugenol treatment. Increased N terminal phosphorylation hence degradation of catenin by eugenol. Downregulation of related CSC markers in stemness enriched spheroid culture. |
S0009279719317454 | Cisplatin and other platinum based antineoplastic drugs are highly effective and widely used in the treatment of solid tumors in both pediatric and adult patients . Although considered to be life saving as a cancer treatment Pt based drugs frequently result in dose limiting toxicities such as chemotherapy induced peripheral neuropathies . Specifically irreversible damage to outer hair cells and injury of sensory neurons are linked to profound sensorineural hearing loss which complicates tumor management and can lead to a poor clinical prognosis . Given the severity of CIPN substantial effort has been devoted to the development of neuroprotective compounds regardless clinical results have been underwhelming . It is noteworthy that Pt is a highly reactive electrophile that causes toxicity by forming adducts with nucleophilic targets on macromolecules . In this regard we have discovered a series of carbon based enol nucleophiles e.g . N 2 oxocytclopentane 1 carboxamide that can prevent neurotoxicity by scavenging the platinum ion . The chemistry of enol compounds is well understood and mechanistic research has demonstrated the role of this chemistry in cytoprotection . Our cell derived data were corroborated by calculations of hard and soft acids and bases parameters that describe the electronic character of interacting electrophiles and nucleophiles . Together these observations indicate that the respective mechanisms of Pt neurotoxicity and antitumor activity are separable and can therefore be affected independently . | Carbon based enol nucleophiles scavenge the platinum ion. Enolate forming compounds provide protection against platinum induced ototoxicity. CisPt associated neurotoxicity and antitumor activity mechanisms are independent. |
S0009279719317478 | Reactive oxygen species cause cell damage and death . To reverse these effects cells produce substances such as reduced glutathione that serve as substrates for antioxidant enzymes . One way to combat microbial resistance includes nullifying the effect of glutathione in microbial cells causing them to die from oxidative stress . The compound 2 methylene | Thiophene thiosemicarbazone derivative L10 causes interference in the redox balance of. Thiophene thiosemicarbazone derivative L10 causes death by apoptosis in. L10 causes an increase in reactive oxygen species by binding to reduced glutathione in |
S0009279719317545 | Head and neck squamous cell carcinoma is one of the most common lethal tumors with a high recurrence rate and low survival rate . Therefore an urgent need exists for novel and effective treatment strategies for HNSCC patients . Osthole a natural ingredient extracted from Our findings show that the anti proliferation effect of osthole might function through induction of cell cycle arrest and apoptosis in HNSCC . Osthole could also down regulating the protein level of cell cycle and apoptosis related proteins such as Bcl 2 PARP1 Survivin CyclinB1 and Cdc2 while up regulating expression of Cleaved Caspase3 9 Cleaved PARP1 and Bax . Similarly osthole suppressed the in vivo growth of FaDu cells in a subcutaneous tumor model . In terms of mechanism our data show that osthole can suppress the PI3K AKT pathway . In the current study our in vitro and in vivo assay showed the suppressive effect of Osthole on HNSCC cells through induce cell cycle arrest and apoptosis . Moreover the action mechanisms of Osthole on proliferation related signaling pathways was disclosed . Our present study suggests that osthole might be used as an effective therapeutic agent for patients with HNSCC . | Osthole suppresses proliferation and induces apoptosis in HNSCC cells. Osthole inhibits HNSCC tumorigenicity in mice. Osthole suppresses the PI3K AKT pathway in HNSCC cells. |
S0009279719317569 | Protein kinases play an indispensable role in signaling pathways that regulate tumor cell functions which represent potent therapeutic targets in cancers . Dual specificity tyrosine phosphorylation regulated kinase 1A as a serine threonine kinase has recently been reported to be upregulated in pancreatic ductal adenocarcinoma and show protumorigenic effect . By activity guided phytochemical investigation of the extracts from | Licocoumarone potentially targets to DYRK1A revealed by molecular docking. The binding affinity to DYRK1A was validated by MST and DARTS experiments. Licocoumarone suppressed BxPC 3cell proliferation by inhibiting DYRK1A |
S0009279719318010 | Evidence has shown that sevoflurane plays a protective role in acute lung injury due to its anti inflammatory and apoptotic regulating activity . Nevertheless the mechanism of sevoflurane is still not completely understood . This study intends to discuss the mechanism of sevoflurane on ALI and the possible mechanisms involved . ALI model of rats was established through intravenous injection of endotoxin lipopolysaccharide . microRNA 34a 3p and signal transducers and activators of transcription 1 expression in lung tissues of ALI rats were detected . The optimal inhaled concentration of sevoflurane was screened and then the modeled rats were injected with miR 34a 3p inhibitors overexpressed STAT1 and inhaled 1.0 Minimum Alveolar Concentration sevoflurane to determine mean arterial pressure of rats wet weight dry weight ratio and myeloperoxidase activity oxidative stress and inflammation related factors in lung tissues of rats along with lung cell viability and apoptosis . MiR 34a 3p was downregulated while STAT1 was upregulated in ALI rats . Sevoflurane of 1.0 MAC was selected as the optimal inhalation concentration . Sevoflurane increased MAP at T3 and reduced MPO activity alleviated pathological damage suppressed apoptosis oxidative stress and inflammation and induced cell viability in lung tissues of ALI rats . Down regulated miR 34a 3p or up regulated STAT reversed the functions of sevoflurane on ALI rats . Collectively we demonstrate that sevoflurane reduces inflammatory factor expression increases lung cell viability and inhibits lung cell apoptosis in ALI through upregulation of miR 34a 3p and downregulation of STAT1 which provides new clues for ALI treatment . | MiR 34a 3p was downregulated while STAT1 was upregulated in ALI rats. Sevoflurane elevates miR 34a 3p and downregulates STAT1 in lung tissues of ALI rats. Sevoflurane reduces MDA level and elevates SOD activity in lung tissues of ALI rats. Sevoflurane reduces inflammatory factor expression in ALI. Sevoflurane inhibits lung cell apoptosis in ALI by regulating miR 34a 3p and STAT1. |
S0009279719318186 | High dietary iron intake is a risk factor for the development of colorectal cancer . However how iron subsequently impacts the proliferation of colorectal cancer cells remains unclear . This study determined the expression of six iron regulatory genes in twenty one human colorectal cancer biopsies and matched normal colonic tissue . The results show that only | Colorectal cancer biopsies showed dysregulated iron metabolism gene expression. Iron depletion or loading affected colorectal cancer cell growth. The response to iron loading or depletion was cell type specific. |
S0009279719318228 | Huntington s disease is an autosomal dominant neurodegenerative disorder caused by polyglutamine expansion in the Huntingtin levels reduced transglutaminase activity increased aconitase activity with increased tricarboxylic acid generated reducing equivalents and mitochondrial oxidative phosphorylation complexes activity . Mitochondrial function was strengthened by increases in glycolysis pyruvate dehydrogenase activity and anaplerosis component represented by pyruvate carboxylase . These changes in mitochondrial function were associated with improved motor performance on the rotarod test . These findings suggest that exercise may have beneficial effects on motor behavior by reversing deficits in mitochondrial function in a rodent model of HD . | Treadmill running is associated increases of nitric oxide in brain homogenates. Increases in nitric oxide result in inhibition of brain transglutaminase 2. Inhibition of transglutaminase 2 results in increased glycolytic activity. Inhibition of transglutaminase 2 results in increased bioenergetics. Increased bioenergetics is associated with improved motor performance. |
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