Lesterkelley3576

Considering the rapidly increasing prevalence of obesity worldwide, the number of weight control drugs is very few. Incretin-based therapies are currently being developed to achieve weight control, and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) are used in incretin-based therapies. This study aimed to investigate the cytotoxicity of exenatide, a GLP-1A, on 3T3-L1 adipocytes and the effect of exenatide on the expression of adipogenesis-related genes, insulin and glucose levels, and apoptosis. Cytotoxic activity of exenatide on 3T3-L1 adipocytes was determined by MTT method. Gene expression levels were determined by qPCR. Apoptosis studies were performed on the Muse Cell Analyzer. C1q/TNF-related protein-3 (CTRP3) expression levels were found to be higher in exenatide treated adipocyte cells than in control cells (p less then 0.001). Adipocyte cells treated with exenatide were found to have lower PPAR-γ gene expression levels when compared to control adipocyte cells (p less then 0.001). Intracellular insulin (p less then 0.001) and glucose levels were higher in 3T3-L1 adipocytes treated with exenatide compared to control adipocyte cells. Total apoptosis increased approximately 1.5 times as a result of exenatide administration. The increase in CTRP3 gene expression, which is thought to be a new biomarker for obesity, and the decrease in PPAR-γ gene expression indicate that exenatide is a promising new pharmacotherapeutic agent in the treatment of obesity by regulating the expression of genes related to adipogenesis and lipogenesis and inducing apoptosis.

Based on extensive research on cytotoxicity of exogenous compounds in vitro, it is essential to develop a cell model that better mimics environment in vivo to explore cytotoxic mechanisms of exogenous compounds.

A co-culture system was established using a transwell system with Beas-2B and U937 cells. Cells were treated with fine particulate matter (PM2.5; 25, 50 and 100μg/mL), nicotine-derived nitrosamine ketone (NNK; 50, 100 and 200μg/mL) and benzo(a)pyrene diol epoxide (BPDE; 0.5, 2 and 8μM) for 24h. Cell proliferation, apoptosis and cell cycle, DNA damage were detected by CCK-8 and EdU, flow cytometry, and comet assay, respectively. Differentially expressed transcript and cytokine concentrations were determined by transcriptome sequencing and Cytokine Array, respectively.

Compared with mono-culture, cell proliferation increased, apoptosis decreased, and DNA damage decreased in a dose-response relationship in co-culture. Gene expression profile was significantly different in co-culture, with significahways, such as TNF signaling pathway. Cytotoxic damage to Beas-2B induced by PM2.5, NNK and BPDE, was significantly reduced in co-culture. The mechanism may be related to changes in expression of cytokines and activation of related pathways. These findings provide new insights into cytotoxicity and experimental basis for safety evaluations of exogenous carcinogens.

The plant Senecio nutans SCh. Bip. is used by Andean communities to treat altitude sickness. Recent evidence suggests it may produce vasodilation and negative cardiac inotropy, though the cellular mechanisms have not been elucidated.

To determinate the mechanisms action of S. nutans on cardiovascular function in normotensive animals.

The effect of the extract on rat blood pressure was measured with a transducer in the carotid artery and intraventricular pressure by a Langendorff system. The effects on sheep ventricular intracellular calcium handling and contractility were evaluated using photometry. Ultra-high-performance liquid-chromatography with diode array detection coupled with heated electrospray-ionization quadrupole-orbitrap mass spectrometric detection (UHPLC-DAD-ESI-Q-OT-MSn) was used for extract chemical characterization.

In normotensive rats, S. nutans (10mg/kg) reduced mean arterial pressure (MAP) by 40% (p<0.05), causing a dose-dependent coronary artery dilation and decreased left venrdio-active phytopharmaceuticals or nutraceuticals.

In normotensive animals, S. nutans partially reduces MAP by decreasing heart rate and cardiac contractility. This negative inotropy is accounted for by decreased SERCA activity and increased NCX activity which reduces SR Ca2+ content. These results highlight the plant's potential as a source of novel cardio-active phytopharmaceuticals or nutraceuticals.

Despite widespread use of herbal remedies for treating arthritis and osteosarcoma, many plants are still not pharmacologically evaluated for their efficacy. Metabolism agonist Contrary to many non-steroidal, immunosuppressants, antibiotics, and antineoplastic drugs that have adverse effects, phytotherapeutic compounds have promising benefits with fewer complications. In this study the unexplored Northeastern India indigenous plant Trevesia palmata (Roxb. ex Lindl.) Vis. used in traditional medicine to cure bone fractures is chosen for studying anti-proliferative and anti-rheumatic properties.

This study designed to explore the polyphenolic composition, antioxidant, anti-inflammatory and anti-arthritic potential of T. palmata leaf extracts. Further, the cellular activity was studied using MG 63 osteoblast cell lines and pharmacologically evaluated using Complete Freund's Adjuvant (CFA) induced arthritic rat model.

In vitro free radical scavenging activity, anti-inflammatory and anti-arthritic activities of extracts were anphases. After acute toxicity studies the doses 250mg/kg and 500mg/kg were fixed and showed better results in CFA-induced arthritic animals. Thus, the extract phytoconstituents may have immense potential against chronic inflammation, joint ailments, bone cancer and arthritis which serves as a phytomedicine contrary to synthetic medications.

The potential treatment of polyphenolic compounds in the T. palmata extract on osteosarcoma and arthritis was demonstrated from this study. Thus, cellular inflammatory infiltrates are significantly reduced in bone and joint tissues as well.

The potential treatment of polyphenolic compounds in the T. palmata extract on osteosarcoma and arthritis was demonstrated from this study. Thus, cellular inflammatory infiltrates are significantly reduced in bone and joint tissues as well.

The flowers of Trollius chinensis Bunge (Ranunculaceae) is a traditional Chinese medicine used to treat various inflammatory diseases, including upper respiratory infections, chronic tonsillitis, and pharyngitis. Recently, there has been growing research on the antiviral role of the flowers of T. chinensis Bunge. However, little is known about its anti-influenza virus effects and the underlying mechanisms.

This study aims to evaluate the therapeutic effects of the crude extract from the flowers of T. chinensis Bunge (CEFTC) on mice infected with influenza virus. We further explored its mechanism by detecting the expression of vital proteins (TLR3, TBK1, TAK1, IKKα, IRF3, and IFN-β) related to TLR3 signaling pathway.

Mice were infected with influenza A virus (H1N1) through the nasal cavity and were intragastrically administered CEFTC at the dose of 0.2mg/g once daily. The therapeutic effects of CEFTC were evaluated by blood cell count, lung index, spleen index, alveolar lavage fluid testing, and HE stainl cells after virus infection.

These results suggested that different doses of influenza virus could cause varying infection symptoms in mice. Moreover, CEFTC could exert anti-influenza virus effects by regulating the expression of TLR3, IRF3, IFN-β, TAK1, and TBK1 in the TLR3 signaling pathway.

These results suggested that different doses of influenza virus could cause varying infection symptoms in mice. Moreover, CEFTC could exert anti-influenza virus effects by regulating the expression of TLR3, IRF3, IFN-β, TAK1, and TBK1 in the TLR3 signaling pathway.Peripheral immune markers are widely used to predict risk for inflammatory disease. However, whether single assessments of inflammatory biomarkers represent stable individual differences remains unclear. We reviewed 50 studies (N = 48,674; 57 % male; mean age 54 (range 13-79) years) that assessed markers of inflammation on >1 occasion, with time between measures ranging from 24 h to 7+ years. Separate random effects meta-analyses were conducted for each inflammatory marker and time interval. Markers that had broad coverage across most time intervals included C-reactive protein (CRP; k = 37), interleukin (IL)-6 (k = 22), TNF-α (k = 10), and fibrinogen (Fg; k = 9). For CRP, IL-6, and TNF-α, stability estimates generally decreased with time, with strong to moderate stability over intervals 3 years to reliably identify stable individual differences in health risk. These findings are consistent with stability estimates and clinical recommendations for repeated measurement of other cardiovascular measures of risk (e.g., blood lipids, blood pressure).Muscle stem cells (MuSCs) are indispensable for muscle regeneration. A multitude of extracellular stimuli direct MuSC fate decisions from quiescent progenitors to differentiated myocytes. The activity of these signals is modulated by coreceptors such as syndecan-3 (SDC3). We investigated the global landscape of SDC3-mediated regulation of myogenesis using a phosphoproteomics approach which revealed, with the precision level of individual phosphosites, the large-scale extent of SDC3-mediated regulation of signal transduction in MuSCs. We then focused on INSR/AKT/mTOR as a key pathway regulated by SDC3 during myogenesis and mechanistically dissected SDC3-mediated inhibition of insulin receptor signaling in MuSCs. SDC3 interacts with INSR ultimately limiting signal transduction via AKT/mTOR. Both knockdown of INSR and inhibition of AKT restore Sdc3-/- MuSC differentiation to wild type levels. Since SDC3 is rapidly downregulated at the onset of differentiation, our study suggests that SDC3 acts a timekeeper to restrain proliferating MuSC response and prevent premature differentiation.There is substantial inter-individual variation in alcohol metabolism and response that are likely due to sex and age; however, these are not well understood. We investigated age and sex influences on alcohol elimination rate (AER) and subjective responses following intravenous (IV) administration in nondependent drinkers. Participants underwent a 2-session study where they received IV alcohol (target level 0.05 g%) and placebo in counter-balanced order. AER was higher in males than in females across age groups. These differences were partly explained by sex differences in lean body mass and liver volume. Alcohol significantly increased peak feelings of high, intoxication, drug-effects, liking-effects, and wanting-more, with no major sex differences. There were no age-related differences in feelings of high and intoxication; however, the older group reported significantly lower peak liking-effects and stimulation responses than the younger group. These findings highlight the significant impact of sex and age as sources of variability in the clinical pharmacology of alcohol.

Sarcopenia has been reported to be a prognostic factor for chronic obstructive pulmonary disease (COPD). However, the relationship between the ratio of blood urea nitrogen to creatinine (BUN/Cr) and sarcopenia in patients with COPD remain unclear. Therefore, the purpose of this study is to explore whether the ratio can be used as a predictor of sarcopenia in hospitalized COPD patients.

The skeletal muscle area index (SMI) at the level of the 12th thoracic vertebra (T12) was used to assess the risk of sarcopenia in patients. This single center cross-sectional study was conducted by analyzing the clinical parameters and identifying the T12 skeletal muscle area (SMA) and density (SMD) on chest CT images of COPD hospitalized patients admitted to the respiratory department of our hospital from March 2018 to August 2021. The study enrolled 265 hospitalized patients. Based on the different statistical properties of the above variables, differences between groups were measured by independent sample Student t-tests, Mann-Whitney U tests, or Chi-Square tests.