Zieglerkirby8253

Polymyxins are last-resort antibiotics re-emerged to treat infections caused by multidrug resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacterial infections. However, polymyxin-associated nephrotoxicity has become the main safety concern. Therefore, we conducted this systematic review and meta-analysis on polymyxin-induced nephrotoxicity and its predictors using studies conducted based on the validated RIFLE (Risk, Injury, Failure, Loss of Function and End-stage renal disease) criteria of acute kidney damage. Literature search was carried out through visiting legitimate databases and indexing services including PubMed, MEDLINE (Ovid®), EMBASE (Ovid®), and Scopus to retrieve relevant studies. Following screening and eligibility evaluation, relevant data were extracted from included studies and analyzed using STATA 15.0 and Rev-Man 5.3. Inverse variance method with random effects pooling model was used for the analysis of outcome measures at 95% confidence interval. Besides, meta-regression.00) were independent risk factors for polymyxin-induced nephrotoxicity. Patients with high serum albumin level were less likely (AOR = 0.69, 95% CI 0.56-0.85] to experience nephrotoxicity compared to those with low albumin level. Despite the resurgence of these antibiotics for the chemotherapy of MDR/XDR-Gram-negative superbugs, the high incidence of nephrotoxicity has become a contemporary clinical concern. Being elderly, high daily dose, having underlying diseases such as diabetes, and use of concomitant nephrotoxic drugs were independent predictors of nephrotoxicity. Therefore, therapeutic drug monitoring should be done to these patients to outweigh the potential benefits of polymyxin therapy from its risk.Glucocorticoids (GCs) plays an irreplaceable role in inflammation and immune responses, fat metabolism and sugar metabolism, it is often used for the treatment of asthma, rheumatoid arthritis and allergic rhinitis clinically, but long-term or high-dose use will produce adverse drug reactions (ADRs). Its biological action is mediated by glucocorticoid receptors (GRs), of which the oligomerization state is closely related to the target gene of which the GRs act. A leading hypothesis is that the beneficial anti-inflammatory effects of GCs occur through the transrepression mechanism mediated by GR monomers, while ADRs may be dependent on the transactivation mechanism mediated by GR dimers. However, in recent years, multiple studies have shown that the transactivation and transrepression functions of the GR dimer also confer anti-inflammatory effects. Furthermore, some studies have shown that some selective glucocorticoid receptor agonists and modulators (SEGRAMs) have good separation characteristics (i.e., preferentially mediate the transrepression of proinflammatory genes or preferentially activate anti-inflammatory target genes). This article reviewed the formation of GR dimers, the role of GR dimers in the inflammation and immune responses, and the progress of SEGRAMs to provide novel ideas for further understanding the anti-inflammatory mechanism of GR and the development of SEGRAMs.Enteropeptidase is a transmembrane serine protease localized in the lumen of the duodenum that acts as a key enzyme for protein digestion. SCO-792 is an orally available enteropeptidase inhibitor that has been reported to have therapeutic effects on obesity and diabetes in mice. However, the mechanism underlying the therapeutic effect of SCO-792 has not yet been fully elucidated. In this study, we evaluated the role of gut microbiota on SCO-792-induced body weight (BW) reduction in high-fat diet-induced obese (DIO) mice. Chronic administration of SCO-792 substantially decreased BW and food intake in DIO mice. While the pair-fed study uncovered food intake-independent mechanisms of BW reduction by SCO-792. Interestingly, antibiotics-induced microbiota elimination in the gut canceled SCO-792-induced BW reduction by nearly half without affecting the anorectic effect, indicating the involvement of gut microbiota in the anti-obesity mechanism that is independent of food intake reduction. Microbiome analysis revealhe therapeutic effects of SCO-792 in obesity.Glioblastomas (GBMs), the most frequent and aggressive human primary brain tumours, have altered cell metabolism, and one of the strongest indicators of malignancy is an increase in choline compounds. Choline is also a selective agonist of some neuronal nicotinic acetylcholine receptor (nAChR) subtypes. As little is known concerning the expression of nAChR in glioblastoma cells, we analysed in U87MG human grade-IV astrocytoma cell line and GBM5 temozolomide-resistant glioblastoma cells selected from a cancer stem cell-enriched culture, molecularly, pharmacologically and functionally which nAChR subtypes are expressed and,whether choline and nicotine can affect GBM cell proliferation. We found that U87MG and GBM5 cells express similar nAChR subtypes, and choline and nicotine increase their proliferation rate and activate the anti-apoptotic AKT and pro-proliferative ERK pathways. These effects are blocked by the presence of non-cell-permeable peptide antagonists selective for α7- and α9-containing nicotinic receptors. siRNA-mediated silencing of α7 or α9 subunit expression also selectively prevents the effects of nicotine and choline on GBM cell proliferation. Our findings indicate that nicotine and choline activate the signalling pathways involved in the proliferation of GBM cells, and that these effects are mediated by α7 and α9-containing nAChRs. Potassium Channel inhibitor This suggests that these nicotinic receptors may contribute to the aggressive behaviour of this tumor and may indicate new therapeutic strategies against high-grade human brain tumours.Drug evoked synaptic plasticity represents "memory traces" in the brain following abuse experiences. Preclinical studies have detailed the myriad changes in mesolimbic and cortical functioning, including alterations in synaptic transmission and plasticity. In humans, recent research advances utilizing a combination of non-invasive brain stimulation and neurophysiological readouts have opened a new avenue for the study cortical plasticity in clinical substance dependence states. These insights, along with findings in psychopathology more generally, uniquely positions brain stimulation as a key tool for understanding cortical function and plasticity in substance dependence.