Zobrazení zdroje stránky Jacobsonegelund3527

The lymphatic system is a vascular system comprising modified lymphatic endothelial cells, lymph nodes and other lymphoid organs. The system has diverse, but critical functions in both physiology and pathology, and forms an interface between the blood vascular and immune system. It is increasingly evident that remodelling of the lymphatic system occurs alongside remodelling of the blood microvascular system, which is now considered a hallmark of most pathological conditions as well as being critical for normal development. Much attention has focussed on how the blood endothelium undergoes phenotypic switching in development and disease, resulting in over two decades of research to probe the mechanisms underlying the resulting heterogeneity. The lymphatic system has received less attention, and consequently there are fewer descriptions of functional and molecular heterogeneity, but differential transcription factor activity is likely an important control mechanism. Here we introduce and discuss significant transcription factors of relevance to coordinating cellular responses during lymphatic remodelling as the lymphatic endothelium dynamically changes from quiescence to actively remodelling.[This corrects the article DOI 10.3389/fphar.2021.693982.].Irinotecan (CPT11), a broad-spectrum cytotoxic anticancer agent, induces a series of toxic side-effects. The most conspicuous side-effect is gastrointestinal mucositis, including nausea, vomiting, and diarrhea. A growing body of evidence indicates that bacteria β-glucuronidase (GUS), an enzyme expressed by intestinal microbiota, converts the inactive CPT11 metabolite SN38G to the active metabolite SN38 to ultimately induce intestinal mucositis. We sought to explore the potential efficacy and underlying mechanisms of berberine on CPT11-induced mucositis. Our study showed that berberine (50 mg/kg; i. g.) mitigated the CPT11-induced loss of mucosal architecture, ulceration, and neutrophil infiltration. Meanwhile, berberine improved mucosal barrier function by increasing the number of globlet cells, protecting trans-endothelial electrical resistance (TEER), reducing permeability and increasing tight junction proteins expression. LC-MS analysis showed that berberine decreased the content of SN38 in feces, which correlated with decreases in both GUS activity and GUS-producing bacteria. Further molecular docking and Lineweaver-Burk plots analyses suggested that berberine functions as a potential non-competitive inhibitor against GUS enzyme. Of note, berberine maintained the anti-tumor efficacy of CPT11 in a tumor xenograft model while abrogating the intestinal toxicity of CPT11. Overall, we identified for the first time the remission effects of berberine on intestinal mucositis induced by CPT11 without impairing the anti-colorectal cancer efficacy of CPT11 partially via inhibiting bacterial GUS enzyme.Background The incidence of cerebral ischemia disease leading cause of death in human population worldwide. Treatment of cerebral ischemia remains a clinical challenge for researchers and mechanisms of cerebral ischemia remain unknown. During the cerebral ischemia, inflammatory reaction and oxidative stress plays an important role. The current investigation scrutinized the neuroprotective and anti-inflammatory role of pterostilbene against cerebral ischemia in middle cerebral artery occlusion (MCAO) rodent model and explore the underlying mechanism. Methods The rats were divided into following groups viz., normal, sham, MCAO and MCAO + pterostilbene (25 mg/kg) group, respectively. The groups received the oral administration of pterostilbene for 30 days followed by MCAO induction. The neurological score, brain water content, infarct volume and Evan blue leakage were estimated. Hepatic, renal, heart, inflammatory cytokines and inflammatory mediators were estimated. Results Pterostilbene treatment significantly st cerebral ischemia in rats via anti-inflammatory mechanism.Optic neuropathies are a major cause of visual disabilities worldwide, causing irreversible vision loss through the degeneration of retinal ganglion cell (RGC) axons, which comprise the optic nerve. Chief among these is glaucoma, in which sensitivity to intraocular pressure (IOP) leads to RGC axon dysfunction followed by outright degeneration of the optic projection. Current treatments focus entirely on lowering IOP through topical hypotensive drugs, surgery to facilitate aqueous fluid outflow, or both. Despite this investment in time and resources, many patients continue to lose vision, underscoring the need for new therapeutics that target neurodegeneration directly. One element of progression in glaucoma involves matrix metalloproteinase (MMP) remodeling of the collagen-rich extracellular milieu of RGC axons as they exit the retina through the optic nerve head. Thus, we investigated the ability of collagen mimetic peptides (CMPs) representing various single strand fractions of triple helix human type I collagen to protect RGC axons in an inducible model of glaucoma. First, using dorsal root ganglia maintained in vitro on human type I collagen, we found that multiple CMPs significantly promote neurite outgrowth (+35%) compared to vehicle following MMP-induced fragmentation of the α1(I) and α2(I) chains. We then applied CMP to adult mouse eyes in vivo following microbead occlusion to elevate IOP and determined its influence on anterograde axon transport to the superior colliculus, the primary RGC projection target in rodents. In glaucoma models, sensitivity to IOP causes early degradation in axon function, including anterograde transport from retina to central brain targets. We found that CMP treatment rescued anterograde transport following a 3-week +50% elevation in IOP. These results suggest that CMPs generally may represent a novel therapeutic to supplement existing treatments or as a neuroprotective option for patients who do not respond to IOP-lowering regimens.Background Tigecycline, a glycylcycline antibiotic, is increasingly used clinically for the treatment of severe infections caused by multidrug-resistant bacteria, but it is also associated with hepatotoxicity. However, the incidence and risk factors of tigecycline-associated drug-induced liver injury (DILI) are unclear. We conducted this study to investigate the incidence, characteristics and risk factors of tigecycline-associated DILI in the real-world clinic setting. Patients and Methods A retrospective analysis was conducted in inpatients who received tigecycline treatment from January 2018 to January 2020. Based on the biochemical criteria of DILI and the causality assessment by Roussel Uclaf Causality Assessment Method (RUCAM) using cases with a probable or highly probable causality grading, two clinical pharmacists and one clinician worked together to screen patients for tigecycline-associated DILI. Then patients with DILI were randomly matched by gender in a ratio of 12 to the remaining patients in theigecycline was associated with liver injury, with a slightly higher incidence (5.7%) than the frequency of "frequent" (5%) defined by the Medical Dictionary for Regulatory Activities. Patients with a high maintenance dose and prolonged tigecycline regimen, as well as concomitant use of multiple hepatotoxic drugs should be paid more attention.Background Polyphenols and flavonoid-rich foods help in arresting reactive oxygen species development and protecting DNA from oxidative damage. Coffee peel (CP) preparations are consumed as beverages, and their total polyphenol or flavonoid content and their effect on oxidative stress-induced human mesenchymal stem cells (hMSCs) are poorly understood. Method We prepared hot water extracts of CP (CPE) and quantified the amount of total polyphenol and flavonoid using HPLC analysis. In addition, CPE have been studied for their α-amylase inhibitory effect and beneficial effects in oxidative stress-induced hMSCs. Results The obtained results show that the availability of chlorogenic acid, vanillin, and salicylic acid levels in CPE is more favorable for enhancing cell growth, nuclear integrity, and mitochondrial efficiency which is confirmed by propidium iodide staining and JC-1 staining. CPE treatment to hMSCs for 48 h reduced oxidative stress by decreasing mRNA expression levels of LPO and NOX-4 and in increasing antioxidant CYP1A, GSH, GSK-3β, and GPX mRNA expressions. Decreased pro-inflammatory (TNF-α, NF-κβ, IL-1β, TLR-4) and increased tumor suppressor genes (except Bcl-2) such as Cdkn2A, p53 expressions have been observed. Conclusions The availability of CGA in CPs effectively reduced mitochondrial oxidative stress, reduced pro-inflammatory cytokines, and increased tumor suppressor genes.Background Therapeutic drug monitoring (TDM) and pharmacogenetic (PGx) testing are widely used as approaches to improve individualized (personalized) pharmacotherapy. Little is known about TDM and PGx testing services in China. This study is aimed to describe the TDM and PGx testing services in northern China, and to lay the foundation for improving these services. Methods We developed an electronic survey using online software and disseminated it to 32 public hospitals in northern China from May to July 2019. The data were analyzed using the Statistical Package for Social Sciences (SPSS) program (Ver.27.0). Results We collected 29 of the 32 questionnaires (90.6% response rate) from public hospitals in seven provinces of northern China. Twenty-two public hospitals (76%) utilized TDM; immune suppressants, antiepileptic drugs and anti-infective drugs were the main drugs monitored. [https://www.selleckchem.com/products/S31-201.html click here] The hospitals that did not provide TDM service were traditional Chinese medicine hospitals and hospitals with a smaller number of hospital beds. Seventeen public hospitals (58.6%) had PGx testing programs. The hospitals that did not offer PGx testing service had a smaller number of hospital beds and had fewer daily outpatients. Conclusion TDM is available in the vast majority of public hospitals in northern China, although mainly in tertiary hospitals. PGx testing, a newer approach, is less widely available. We recommend that more hospitals be encouraged to provide TDM and PGx testing services and more efforts be directed toward quality control, delivery of results and counseling of patients based on those results.Background Although the predominant airway inflammation in chronic obstructive pulmonary disease (COPD) is neutrophilic, approximately 20-40% of COPD patients present with eosinophilic airway inflammation. Compared with non-eosinophilic COPD patients, eosinophilic COPD patients are characterized by a greater number of total exacerbations and higher hospitalization rates. Furthermore, anti-interleukin-5 (IL-5) therapy, consisting of monoclonal antibodies (mAbs) targeting IL-5 or IL-5 receptor α (IL-5Rα), has been proven to be effective in severe eosinophilic asthma. This meta-analysis aimed to determine the efficacy and safety of anti-IL-5 therapy in eosinophilic COPD. Methods We searched the PubMed, Web of Science, Embase, and Cochrane Library databases from inception to August 2020 (updated in June 2021) to identify studies comparing anti-IL-5 therapy (including mepolizumab, benralizumab, and reslizumab) with placebo in eosinophilic COPD patients. Results Anti-IL-5 therapy was associated with a decrease in acute exacerbation rate (RR 0.