نتائج البحث - "Lactate dehydrogenase"

1

Effect of hydrogen-rich water on the lactic acid level in metformin-treated diabetic rats under hypoxia

المؤلفون: Cheng Cheng, Xiangmei Chen, Chuan Zhao, Ruoxi Wang, Yushu Guo

المصدر: The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology

الوصف: The present study aims to investigate the impact of hydrogen-rich water on the lactic acid level in metformin-treated diabetic rats under hypoxia. Thirty Sprague-Dawley rats were randomly divided into five groups, including normal diet group, and diabetes model (DM) group, DM + metformin treatment (DMM) group, DMM + hypoxia treatment (DMMH) group and DMMH + hydrogen-rich water (DMMHR) group. We found that the levels of lactic acid, pyruvate and lactate dehydrogenase were significantly lower in the blood of DMMHR group than DMMH group. Superoxide dismutase and glutathione levels in liver and heart were significantly higher in DMMH group after hydrogen-rich water treatment, while malondialdehyde and oxidized glutathione levels were decreased in DMMHR group when compared with DMMH group, which indicates that hydrogen-rich water could reduce oxidative stress. qPCR analysis demonstrated that that pro-apoptotic genes Bax/Caspase-3 were upregulated in DM group and metformin treatment suppressed their upregulation (DMM group). However, hypoxic condition reversed the effect of metformin on apoptotic gene expression, and hydrogen-rich water showed little effect on these genes under hypoxia. HE staining showed that hydrogen-rich water prevented myocardial fiber damages under hypoxia. In summary, we conclude that hydrogen-rich water could prevent lactate accumulation and reduce oxidant stress in diabetic rat model to prevent hypoxia-induced damages. It could be served as a potential agent for diabetes patients with metformin treatment to prevent lactic acidosis and reduce myocardial damages under hypoxic conditions.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::00802d57024378e52408583bf3420722Test
https://doi.org/10.4196/kjpp.2021.25.6.517Test

2

Vildagliptin protects hypoxia/reoxygenation-induced injury of cardiac microvascular endothelial cells

المؤلفون: Xiaosheng Fan, Lin Qi, Yan Yang

المصدر: Minerva Medica. 114

مصطلحات موضوعية: medicine.diagnostic_test, Chemistry, p38 mitogen-activated protein kinases, General Medicine, Glutathione, Pharmacology, chemistry.chemical_compound, Downregulation and upregulation, Western blot, Lactate dehydrogenase, medicine, Luciferase, Vildagliptin, Hypoxia reoxygenation, medicine.drug

الوصف: Background To uncover the protective role of Vildagliptin in hypoxia-reoxygenation (H/R)-induced injury of cardiac microvascular endothelial cells (CMECs) and the pharmacological mechanisms. Methods H/R model was constructed in primary CMECs extracted from rats, followed by Vildagliptin treatment. Relative levels of DPP-4 and Nox-4 in CMECs were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Viability, glutathione (GSH) content, lactate dehydrogenase (LDH) release and inflammatory factor levels were examined. Western blot was conducted to detect protein levels of DPP-4, p38, p-p38 and nuclear translocation of p65. The transcriptional activity of nuclear factor-κB (NF-κB) was measured by luciferase assay. Results H/R resulted in upregulation of DPP-4 and Nox-4, as well as increased LDH release in CMECs. In addition, GSH content and viability were declined, and the release of inflammatory factors were stimulated in H/R-induced CMECs. The abovementioned changes were relieved by Vildagliptin treatment. Vildagliptin markedly inhibited the activation of the p38/NF-κB signaling in H/R-induced CMECs. Conclusions Vildagliptin protects CMECs from H/R injury via inactivating the p38/NF-κB signaling.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d73ba78fc52b3d001dacc82b3f8c52aeTest
https://doi.org/10.23736/s0026-4806.20.06682-3Test

3

Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells

المؤلفون: Lanlan Geng, Wanfu Xu, Long Fan, Hongli Wang, Sitang Gong, Junhong Zhao, Peiyu Chen, Zhaohui Xu, Liya Xiong, Huan Chen, Jing Xie

المصدر: BMC Pharmacology and Toxicology, Vol 22, Iss 1, Pp 1-9 (2021)
BMC Pharmacology & Toxicology

مصطلحات موضوعية: Male, 0301 basic medicine, Interleukin-1beta, Cell, Anti-Inflammatory Agents, H. pylori infection, chemistry.chemical_compound, 0302 clinical medicine, RA1190-1270, Pharmacology (medical), Child, biology, medicine.diagnostic_test, Interleukin-18, Intracellular Signaling Peptides and Proteins, Pyroptosis, Real-time polymerase chain reaction, medicine.anatomical_structure, Child, Preschool, 030220 oncology & carcinogenesis, Rabeprazole, Cell pyroptosis, Female, medicine.drug, Adolescent, RM1-950, Cell Line, Helicobacter Infections, 03 medical and health sciences, Western blot, NLRP3, Lactate dehydrogenase, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Humans, Secretion, Pharmacology, L-Lactate Dehydrogenase, business.industry, Research, Epithelial Cells, Proton Pump Inhibitors, Phosphate-Binding Proteins, Helicobacter pylori, Anti-Ulcer Agents, biology.organism_classification, Molecular biology, 030104 developmental biology, chemistry, Gastric Mucosa, Toxicology. Poisons, Therapeutics. Pharmacology, GSDMD, business

الوصف: Background Helicobacter pylori (H. pylori) is a common pathogen in development of peptic ulcers with pyroptosis. Rabeprazole, a critical component of standard triple therapy, has been widely used as the first-line regimen for H. pylori infectious treatment. The aim of this study to explore the function of Rabeprazole on cell pyroptosis in vitro. Methods The clinical sample from patients diagnosed with or without H. pylori-infection were collected to analyze by Immunohistochemistry (IHC). Real-time quantitative PCR (qPCR), western blot (WB) and enzyme linked immunosorbent assay (Elisa) were performed to analyze the effect of Rabeprazole on cell pyroptosis, including LDH, IL-1β and IL-18. Results In this study, we showed that Rabeprazole regulated a phenomenon of cell pyroptosis as confirmed by lactate dehydrogenase (LDH) assay. Further results showed that Rabeprazole inhibited cell pyroptosis in gastric epithelial cells by alleviating GSDMD-executed pyroptosis, leading to decrease IL-1β and IL-18 mature and secretion, which is attributed to NLRP3 inflammasome activation inhibition. Further analysis showed that ASC, NLRP3 and Caspase-1, was significantly repressed in response to Rabeprazole stimulation, resulting in decreasing cleaved-caspase-1 expression. Most important, NLRP3 and GSDMD is significantly increased in gastric tissue of patients with H. pylori infection. Conclusion These findings revealed a critical role of Rabeprazole in cell pyroptosis in patients with H. pylori infection, suggesting that targeting cell pyroptosis is an alternative strategy in improving H. pylori treatment.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9eb54a0fff42889a48b2c115f3f7e5acTest
https://doaj.org/article/68a877e5bbc74f65b09b6caccdeadef0Test

4

Refill liquids for electronic cigarettes display peculiar toxicity on human endothelial cells

المؤلفون: Sara De Martin, Daniela Gabbia, Franco Biasioli, Sara Bogialli, Daniela Rainer, Ronald Gstir, Luca Cappellin, Andrea Boschetti

المصدر: Toxicology Reports
Toxicology Reports, Vol 8, Iss, Pp 456-462 (2021)

مصطلحات موضوعية: Health, Toxicology and Mutagenesis, Cytotoxicity, 010501 environmental sciences, Pharmacology, Lung injury, Toxicology, 01 natural sciences, Nicotine, 03 medical and health sciences, 0302 clinical medicine, RA1190-1270, Refill liquids, medicine, EVALI, e-vaping acute lung injury, HUVEC, human umbilical vein endothelial cells, Settore VET/07 - FARMACOLOGIA E TOSSICOLOGIA VETERINARIA, 0105 earth and related environmental sciences, ComputingMethodologies_COMPUTERGRAPHICS, e-Cig, electronic cigarette, LDH - Lactate dehydrogenase, LDH, lactate dehydrogenase, Chemistry, EVALI, Regular Article, ENDS, electronic nicotine delivery systems, Ldh release, Electronic cigarettes, Toxicity, Toxicology. Poisons, 030217 neurology & neurosurgery, medicine.drug

الوصف: Graphical abstract
Highlights • The vapors obtained from different refill liquids for e-cigarettes exert different extent of cytotoxicity. • The condensates obtained from traditional cigarettes are always highly cytotoxic in the same experimental conditions. • Accurate evaluations for refill liquids will help to correlate toxicity to chemical composition.
The electronic cigarettes mimic combustible cigarettes through a heating technology that vaporizes a refill liquid consisting of solvents, flavors, and nicotine. E-cigarettes are sometimes still used as a support for smoking cessation, even if in 2019 an acute lung injury outbreak occurred in the USA, affecting mainly adolescents and young adults, and was correlated to eCigs. Therefore, due to the lack of a definite knowledge about the mechanism(s) of refill liquid toxicity and considering that previous investigations gave controversial results, the aim of the present study was the cytotoxicity assessment of different refill liquids on human endothelial cells, evaluated by means of two different in vitro approaches, i.e. the resazurin and the LDH release assays. Our results clearly demonstrated that different refill liquids (6 samples) display different levels of cytotoxicity in our cellular model, although their cytotoxicity was always lower than that observed for the condensate obtained from traditional cigarettes (3 samples). These results suggest that accurate evaluations should be provided for refill liquids, in particular to correlate their toxicity to their chemical composition, with the final aim of obtaining useful information for the agencies involved in the regulation of their components.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bbddc929f4c1ea0d46cf52ba9a1190eaTest
http://europepmc.org/articles/PMC7933715Test

5

Artemisinin and artemisinin derivatives as anti-fibrotic therapeutics

المؤلفون: Tanja Dominko, Pamela J. Weathers, David Dolivo

المصدر: Acta Pharmaceutica Sinica B, Vol 11, Iss 2, Pp 322-339 (2021)
Acta Pharmaceutica Sinica. B

مصطلحات موضوعية: BUN, blood urea nitrogen, Artesunate, Review, Pharmacology, Col I, type I collagen, LAP, latency-associated peptide, chemistry.chemical_compound, 0302 clinical medicine, Scar, HUVEC, human umbilical vein endothelial cell, Fibrosis, CCl4, carbon tetrachloride, NAG, N-acetyl-β-d-glucosaminidase, General Pharmacology, Toxicology and Pharmaceutics, Artemisinin, HA, hyaluronic acid, 0303 health sciences, LDH, lactate dehydrogenase, LDH - Lactate dehydrogenase, mTOR, mechanistic target of rapamycin, TGF, β-transforming growth factor-β, DLA, dried leaf Artemisia, i.p., intraperitoneal, HSC, hepatic stellate cell, ALP - Alkaline phosphatase, DHA, dihydroartemisinin, ECM, extracellular matrix, MMP, matrix metalloproteinase, Alt alanine aminotransferase, 030220 oncology & carcinogenesis, MI, myocardial infarction, Fibroblast, TIMP, tissue inhibitor of metalloproteinase, medicine.drug, TGF-β, Anti fibrotic, ASP, aspartate aminotransferase, PCNA, proliferating cell nuclear antigen, BDL, bile duct ligation, FLS, fibroblast-like synoviocyte, STZ, streptozotocin, PHN, passive heymann nephritis, CTGF, connective tissue growth factor, 03 medical and health sciences, ROS, reactive oxygen species, ALT, alanine aminotransferase, parasitic diseases, medicine, BAD, BCL-2-associated agonist of cell death, sCr, serum creatinine, NICD, Notch intracellular domain, UUO, unilateral ureteral obstruction, 030304 developmental biology, Myofibroblast, ALP, alkaline phosphatase, business.industry, lcsh:RM1-950, medicine.disease, AMPK, AMP-activated protein kinase, lcsh:Therapeutics. Pharmacology, Artemisia, chemistry, Tissue fibrosis, BSA, bovine serum albumin, α-SMA, smooth muscle α-actin, business, EMT, epithelial-to-mesenchymal transition, MAPK, mitogen-activated protein kinase

الوصف: Fibrosis is a pathological reparative process that can occur in most organs and is responsible for nearly half of deaths in the developed world. Despite considerable research, few therapies have proven effective and been approved clinically for treatment of fibrosis. Artemisinin compounds are best known as antimalarial therapeutics, but they also demonstrate antiparasitic, antibacterial, anticancer, and anti-fibrotic effects. Here we summarize literature describing anti-fibrotic effects of artemisinin compounds in in vivo and in vitro models of tissue fibrosis, and we describe the likely mechanisms by which artemisinin compounds appear to inhibit cellular and tissue processes that lead to fibrosis. To consider alternative routes of administration of artemisinin for treatment of internal organ fibrosis, we also discuss the potential for more direct oral delivery of Artemisia plant material to enhance bioavailability and efficacy of artemisinin compared to administration of purified artemisinin drugs at comparable doses. It is our hope that greater understanding of the broad anti-fibrotic effects of artemisinin drugs will enable and promote their use as therapeutics for treatment of fibrotic diseases.
Graphical abstract Artemisinin drugs, isolated from Artemisia, effectively prevent or treat multiple types of tissue fibrosis when administered to several preclinical animal models of varied etiologies.Image 1

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b31e277e49b3a3364e9726d531259ad4Test
https://doi.org/10.1016/j.apsb.2020.09.001Test

6

GC–MS and HPLC analysis of antiglycogenolytic and glycogenic compounds in kaempferol 3–O–gentiobioside containing Senna alata L leaves in experimental rats

المؤلفون: N. Rangarajan, M. Pennarasi, S. Mohanasundaram, K. Porkodi, V. Sampath

المصدر: Translational Metabolic Syndrome Research. 4:10-17

مصطلحات موضوعية: biology, Glycogen, Pharmacology, biology.organism_classification, medicine.disease, Glibenclamide, chemistry.chemical_compound, Glycogen phosphorylase, chemistry, Diabetes mellitus, Lactate dehydrogenase, medicine, Senna alata, biology.protein, Kaempferol, Glycogen synthase, medicine.drug

الوصف: Background Medicinal herbs have received attention as an alternative to prescription medications. Diabetes mellitus is a chronic disease that affects the normal metabolic pathways in several organs. The purpose of this study was to determine the metabolites responsible for the antiglycogenolytic and glycogenic effects of a hydroethanolic extract of Senna alata L in an experimental model of diabetes mellitus; the male albino Wister rat treated with streptozotocin. Results The therapeutic effects of Glibenclamide (0.6 mg/kg body weight) and S. alata L (400 mg/kg body weight) extracts were compared. The oral administration of this extract to diabetic rats resulted in a significant decrease in the levels of glycogenolytic factors that included: glycogen phosphorylase, glucose 6 phosphatase, glycosylated haemoglobin, and lactate dehydrogenase, and a significant increase in the levels of glycogenic factors such as plasma insulin, glycogen synthase, liver glycogen, hexokinase, pyruvate kinase After administration of the plant extract, the observed changes in the activities of these factors were found to be statistically significant and returned to near-normal levels. Additionally, the S. alata extract increased muscle and liver glycogen levels, demonstrating S. alata L's anti-diabetic properties. HPLC analysis identified Kaempferol 3–O–gentiobioside, while GCMS analysis showed the presence of phytol, stigmasterol, sitosterol, dimethyl derivatives, methyl esters, and octanoic acid derivatives. Conclusion This work provides experimental evidence for the anti-diabetic potential of S. alata extract, which may result from the existence of beneficial bioactive chemicals. The aberrant metabolic enzymes in streptozotocin-induced diabetic rats' livers were restored following regular treatment with S. alata extract. As a result, S. alata leaves can affect blood glucose levels.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::725ecf322c46c0419f76d4537962a4dfTest
https://doi.org/10.1016/j.tmsr.2021.07.001Test

7

Neomenthol prevents the proliferation of skin cancer cells by restraining tubulin polymerization and hyaluronidase activity

المؤلفون: Kaneez Fatima, Abha Meena, Suaib Luqman, Nusrat Masood, Zahoor Ahmad Wani

المصدر: Journal of Advanced Research

مصطلحات موضوعية: TRIG, Triglyceraldehyde, Skin Neoplasms, Cell, DOXO, Doxorubicin, Hyaluronidase, Pharmacology, NaOH, Sodium hydroxide, Polymerization, MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Mice, 0302 clinical medicine, BIL, Bilirubin total & direct, Neomenthol, PEP A, pepstatin A, Cancer biomarker, MEF, Mean erythrocyte fragility, HYAL, Hyaluronidase, PBS, Phosphate buffer saline, CM-H2DCFDA, Chloromethyl derivative of dichloro fluorescin diacetate, HA, Hyaluronic acid, Epidermoid carcinoma, Human epidermoid carcinoma, 030220 oncology & carcinogenesis, RBC, Red blood cell, DMEM, Dulbecco’s minimal essential media, SRB, Sulphorhodamine B, BUN, Blood urea nitrogen, FACS, Fluorescence-Activated Cell Sorting, AKLP, Alkaline phosphatase, Hyaluronoglucosaminidase, NADPH, Nicotinamide adenine dinucleotide phosphate hydrogen, TMPD, N,N,N′,N′-tetramethyl-p-phenylenediamine, Article, 03 medical and health sciences, In vivo, Ehrlich Ascites Carcinoma, BE, Binding energy, Humans, CATD, Cathepsin D, LDH, Lactate dehydrogenase, COX-2, Cyclooxygenase 2, FOX, Ferrous oxidation-xylenol orange, DMSO, Dimethyl sulfoxide, mTOR, Mammalian target of rapamycin, In vitro, Ab/Am, Antibiotic/antimycotic, NRU, Neutral red uptake, EC50, Half maximal effective concentration, 030104 developmental biology, IC50, Half maximal inhibitory concentration, EAC, Ehlrich Ascites Carcinoma, RPMI, Roswell park memorial institute, ROS, Reactive oxygen species, 0301 basic medicine, HDL, High density lipoprotein, TNBS, Trinitrobenzenesulphonic acid, PI3K, Phosphotidyl inositol-3 kinase, URIC, Uric acid, DNA, Deoxyribonucleic acid, GAPDH, Glyceraldehyde 3-phosphate dehydrogenase, HEPES, N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid, Tubulin, OECD, Organization for Economic Co-operation and Development, SGPT, Alanine aminotransferase, LOX-5, Lipoxygenase-5, DFMO, α-difluoro methyl ornithine, Multidisciplinary, WBC, White blood cell, Chemistry, ELISA, enzyme-linked immunosorbent assay, PKB/Akt, Protein kinase B, AA, Arachidonic acid, RNase A, Ribonuclease A, TPR, Total protein, Molecular Docking Simulation, medicine.anatomical_structure, TCA, Tricarboxylic acid, CHOL, Cholesterol, Ki, Inhibitory constant, medicine.drug, ODC, Ornithine decarboxylase, DHFR, Dihydrofolatereductase, BSA, Bovine serum albumin, PDB, Protein Data Bank, medicine, Animals, MMP, Mitochondrial membrane potential, DCFDA, 2′,7′ dichloro fluorescin diacetate, RNA, Ribonucleic acid, RIPA, Radio immune precipitation assay buffer, EDTA, Ethylene diamine tetra acetic acid, IC50, TPA, 12-O-Tetradecanoylphorbol-13-acetate, ComputingMethodologies_COMPUTERGRAPHICS, TRPM8, Transient receptor potential member 8, Cell Proliferation, HDAC, Histone deacetylase, MTX, Methotrexate, OF, Osmotic fragility, PI, Propidium iodide, FDA, Food and Drug Administration, HEK293 Cells, PDT, Podophyllotoxin, Cell culture, NAC, N-acetyl cysteine, SGOT, Aspartate aminotransferase, CRTN, Creatinine, FBS, Fetal bovine serum, PCR, Polymerase chain reaction, Rh123, Rhodamine 123, Ex vivo, IDT, Integrated DNA Technologies

الوصف: Graphical abstract
Introduction Neomenthol, a cyclic monoterpenoid, is a stereoisomer of menthol present in the essential oil of Mentha spp. It is used in food as a flavoring agent, in cosmetics and medicines because of its cooling effects. However, neomenthol has not been much explored for its anticancer potential. Additionally, targeting hyaluronidase, Cathepsin-D, and ODC by phytochemicals is amongst the efficient approach for cancer prevention and/or treatment. Objectives To investigate the molecular and cell target-based antiproliferative potential of neomenthol on human cancer (A431, PC-3, K562, A549, FaDu, MDA-MB-231, COLO-205, MCF-7, and WRL-68) and normal (HEK-293) cell lines. Methods The potency of neomenthol was evaluated on human cancer and normal cell line using SRB, NRU and MTT assays. The molecular target based study of neomenthol was carried out in cell-free and cell-based test systems. Further, the potency of neomenthol was confirmed by quantitative real-time PCR analysis and molecular docking studies. The in vivo anticancer potential of neomenthol was performed on mice EAC model and the toxicity examination was accomplished through in silico, ex vivo and in vivo approaches. Results Neomenthol exhibits a promising activity (IC50 17.3 ± 6.49 μM) against human epidermoid carcinoma (A431) cells by arresting the G2/M phase and increasing the number of sub-diploid cells. It significantly inhibits hyaluronidase activity (IC50 12.81 ± 0.01 μM) and affects the tubulin polymerization. The expression analysis and molecular docking studies support the in vitro molecular and cell target based results. Neomenthol prevents EAC tumor formation by 58.84% and inhibits hyaluronidase activity up to 10% at 75 mg/kg bw, i.p. dose. The oral dose of 1000 mg/kg bw was found safe in acute oral toxicity studies. Conclusion Neomenthol delayed the growth of skin carcinoma cells by inhibiting the tubulin polymerization and hyaluronidase activity, which are responsible for tumor growth, metastasis, and angiogenesis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7618e7dc6e2d535e1930d5f8c2bf7d7eTest
https://doi.org/10.1016/j.jare.2021.06.003Test

8

Conjugation to PEG as a Strategy to Limit the Uptake of Drugs by the Placenta: Potential Applications for Drug Administration in Pregnancy

المؤلفون: Gianfranco Pasut, Frances Beards, Francesca Greco, Abbie Dodd, Az Alddien Natfji, Antonella Grigoletto, Lewis Renshall, Lynda K. Harris, Helen M. I. Osborn, Angelos Evangelinos

المصدر: Molecular Pharmaceutics. 19:345-353

الوصف: Here, we evaluated the feasibility of non-prodrug PEG-drug conjugates to decrease the accumulation of drugs within the placental tissues. The results showed that PEG was biocompatible with the human placenta with no alteration of the basal rate of proliferation or apoptosis in term placental explants. No significant changes in the released levels of lactate dehydrogenase and the human chorionic gonadotropin were observed after PEG treatment. The cellular uptake studies revealed that conjugating Cy5.5 and haloperidol to PEG significantly reduced (by up to ∼40-fold) their uptake by the placenta. These findings highlight the viability of novel non-prodrug polymer-drug conjugates to avoid the accumulation of drugs within the placenta.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2666a0c847581476cb6e3b341d4656e7Test
https://doi.org/10.1021/acs.molpharmaceut.1c00498Test

9

Ramelteon Mitigates Free Fatty Acid (FFA)–Induced Attachment of Monocytes to Brain Vascular Endothelial Cells

المؤلفون: Yang Liu, Chun-Feng Liu, Yu Li, Fang Tian, Guijie Wang

المصدر: Neurotoxicity Research. 39:1937-1945

الوصف: Acute ischemic stroke is a challenging disease that threatens the life of older people. Dysfunction of brain endothelial cells is reported to be involved in the pathogenesis of acute ischemic stroke. Ramelteon is a novel agonist of melatonin receptor developed for the treatment of insomnia. Recently, the promising protective effect of Ramelteon on brain injury has been widely reported. The present study aims to investigate the protective effect of Ramelteon against free fatty acid (FFA)-induced damages in brain vascular endothelial cells and the underlying mechanism. Firstly, we discovered that Ramelteon administration remarkably reversed the decreased cell viability, increased LDH release, activated oxidative stress, and excessive released inflammatory factors caused by FFAs. Secondly, Ramelteon extensively suppressed the attachment of U937 monocytes to bEnd.3 brain endothelial cells induced by FFAs. In addition, the elevated expression of E-selectin and the reduced expression of KLF2 induced by FFAs were pronouncedly alleviated by Ramelteon. Lastly, silencing of KLF2 abolished the protective effects of Ramelteon against FFA-induced expression of E-selectin and the attachment of U937 monocytes to bEnd.3 brain endothelial cells. In conclusion, Ramelteon mitigated FFA-induced attachment of monocytes to brain vascular endothelial cells by increasing the expression of KLF2 and reducing the expression of E-selectin.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::54bc78c9ec7e5811f6a4960a76d3de15Test
https://doi.org/10.1007/s12640-021-00422-1Test

10

Antiproliferative and Pro-Apoptotic Effects of Thiazolo[3,2–b][1,2,4]triazoles in Breast and Cervical Cancer Cells

المؤلفون: Aliya Ibrar, Sumera Zaib, Mohsin Javed, Imtiaz Khan, Faisal Rashid, Jamshed Iqbal

المصدر: Anti-Cancer Agents in Medicinal Chemistry. 21:2181-2191

الوصف: Background and Objectives: Cancer is one of the leading causes of death in the world affecting millions of people. The commercially available anticancer drugs lack the selectivity and show several undue side effects during the biologically targeted therapy, thus calling for the exploration of wider chemical space to furnish new structural leads with promising anticancer potential. In this endeavor, we synthesized a series of coumarinyl thiazolotriazoles with diverse functional group tolerance and will be tested for their anticancer properties against cancer cell lines (HeLa and MCF-7) and a normal cell line (BHK-21). Materials and Methods: To overcome such complications, in the current study, we evaluated the cytotoxic effects of coumarinyl thiazolotriazole hybrids on human breast adenocarcinoma (MCF-7), cervical adenocarcinoma (HeLa) cells and normal cells i.e., Baby Hamster Kidney cells (BHK-21) using MTT (dimethyl-2-thiazolyl- 2,5-diphenyl-2H-tetrazolium bromide) assay. DNA binding studies of compound 6c was performed on Herring- Sperm DNA (HS-DNA) and docking studies were also carried out. The mechanistic studies were performed on potent compounds by fluorescent microscopic studies, release of Lactate Dehydrogenase (LDH) and mitochondrial membrane potential, activation of caspase-9 and -3 and flow cytometric analysis. Results: As revealed by MTT assay, compounds 6m and 6c were identified as the most potent derivatives among the tested series with IC50 values of 5.64 and 29.1 μM against HeLa and MCF cells, respectively as compared to cisplatin which gave IC50 values of 11.3 and 6.20 μM, respectively. DNA binding studies of compound 6c showed the binding of compound in DNA with Gibbs free energy of ‒17 KJ/mol and docking studies validated the DNA binding studies. Fluorescent microscopic studies using 4′,6-diamidino-2-phenylindole (DAPI) and Propidium Iodide (PI) staining confirmed the occurrence of apoptosis in HeLa cells treated with the most active compound 6m. Moreover, compounds 6m and 6c also triggered the release of Lactate Dehydrogenase (LDH) in treated HeLa and MCF-7 cells while a luminescence assay displayed a remarkable increase in the activity of caspase-9 and -3. Moreover, flow cytometric results revealed that compound 6m caused G0 /G1 arrest in the treated HeLa cells. Conclusion: Our results suggested that the compound possesses chemotherapeutic properties against breast cancer and cervical adenocarcinoma cells, thus warranting further research to test the anticancer efficacy of this compound at clinical level.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f8450d5735646f6b2e7dbf08d941bc2Test
https://doi.org/10.2174/1871520621666210126092303Test

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