Cheekrao2284

There are technical obstacles in the safety evaluation of traditional Chinese medicine (TCM) injections due to their complex chemical nature and the lack of rapid and accurate in vitro methods. Here, we established a dual in vitro mitochondrial toxicity approach combing the conventional "glucose/galactose" assay in HepG2 cells with the cytotoxic assay in mitochondrial respiration deficient cells. Using this dual in vitro approach, for the first time, we systematically assessed the mitochondrial toxicity of TCM injections. Four of the 35 TCM injections, including Xiyanping, Dengzhanhuasu, Shuanghuanglian, and Yinzhihuang, significantly reduced cellular ATP production in galactose medium in the first assay, and presented less cytotoxic in the respiration deficient cells in the second assay, indicating that they have mitochondrial toxicity. Furthermore, we identified scutellarin, rutin, phillyrin, and baicalin could be the potential mitochondrial toxic ingredients in the 4 TCM injections by combining molecular docking analysis with experimental validation. Collectively, the dual in vitro approach is worth applying to the safety evaluation of more TCM products, and mitochondrial toxic TCM injections and ingredients found in this study deserve more attention.[This corrects the article DOI 10.3389/fphar.2017.00558.].Bladder cancer (BC) is the most frequent type of urinary system cancer. The prognosis of BC is poor due to high metastasis rates and multidrug resistance. Hence, development of novel therapies targeting BC cell death is urgently needed. As a novel cell death type with strong antitumor potential, ferroptosis has been investigated by many groups for its potential in BC treatment. As an iron-dependent cell death process, ferroptosis is characterized by excessive oxidative phospholipids. The molecular mechanisms of ferroptosis include iron overload and the system Xc-GSH-GPX4 signaling pathway. A recent study revealed that ferroptosis is involved in the metastasis, treatment, and prognosis of BC. Herein, in this review, we comprehensively summarize the mechanism of ferroptosis, address newly identified targets involved in ferroptosis, and discuss the potential of new clinical therapies targeting ferroptosis in BC.Cannabidiol, a non-psychoactive component extracted from the plant cannabis sativa, has gained growing focus in recent years since its extensive pharmacology effects have been founded. The purpose of this study intends to reveal the hot spots and frontiers of cannabidiol research using bibliometrics and data visualization methods. A total of 3,555 publications with 106,793 citations from 2004 to 2021 related to cannabidiol were retrieved in the Web of Science database, and the co-authorships, research categories, keyword burst, and reference citations in the cannabidiol field were analyzed and visualized by VOSviewer and Citespace software. Great importance has been attached to the pharmacology or pharmacy values of cannabidiol, especially in the treatment of neuropsychiatric disorders, such as epilepsy, anxiety, and schizophrenia. The mechanisms or targets of the cannabidiol have attracted the extreme interest of the researchers, a variety of receptors including cannabinoids type 1, cannabinoids type 2, 5-hydroxytriptamine1A, and G protein-coupled receptor 55 were involved in the pharmacology effects of cannabidiol. Moreover, the latest developed topic has focused on the positive effects of cannabidiol on substance use disorders. In conclusion, this study reveals the development and transformation of knowledge structures and research hotspots in the cannabidiol field from a bibliometrics perspective, exploring the possible directions of future research.For many years, the primary focus has been on finding effective treatments for Alzheimer's disease (AD), which has led to the identification of promising therapeutic targets. The necessity for AD stage-dependent optimal settings necessitated a herbal therapy strategy. The plant species Areca Catechu L. (AC) was selected based on the traditional uses against CNS-related diseases. learn more AC leaf extract were prepared using a Soxhlet extraction method and hydroxyapatite nanoparticles (HAp-NPs) were synthesized from the same (AC-HAp-NPs). Powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED) and fourier transform infrared spectroscopy (FTIR) were used to confirm the structure and morphology of the as-prepared AC-HAp-NPs. The crystalline character of the AC-HAp-NPs was visible in the XRD pattern. The synthesized material was found to be nanoflake, with an average diameter of 15-20 nm, according to SEM analysis. The TEM and goal of studying their bioactivity.Objectives Tumours remain a serious threat to human life. Following rapid progress in oncology research, tyrosine kinase inhibitors have been used to treat multiple tumour types. Given the great influence of kidneys on pharmacokinetics, renal toxicities associated with TKIs have attracted attention. However, the TKIs with the lowest risks of renal impairment are unclear. In this study, we conducted a Bayesian network meta-analysis to compare the incidence of renal impairment among different TKIs in patients with tumours. Methods and analysis Six databases (PubMed, EMBASE, The Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Data, and China Biomedical Literature Database) were electronically searched from inception to 1 November 2021 to identify randomized controlled trials on the incidence of renal impairment for different TKIs in patients with tumours. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Then, a pairwise meta-analysis was conducted using Stata version 13, and network meta-analysis within the Bayesian framework was conducted using R software version 3.5.3 with the package "gemtc 0.8-2" recalling JAGS (version 4.3.0). Results Overall, 34 randomized controlled trials were included in this study. Although renal toxicity was common among patients receiving TKIs, the incidence and severity greatly differed among the drugs and studies. Elevated creatinine and protein levels were the most common nephrotoxic events, whereas haematuria was relatively rare. Among TKIs, nintedanib and ripretinib carried the lowest risks of renal impairment. Conclusion TKIs displayed different profiles of renal toxicity because of their different targets and underlying mechanisms. Clinicians should be aware of the risks of renal impairment to select the optimal treatment and improve patient adherence to treatment. Systematic Review Registration [www.crd.york.ac.uk/prospero/], identifier [CRD42022295853].[This corrects the article DOI 10.3389/fphar.2022.945565.].Introduction With the widespread application of Immune checkpoint inhibitors (ICIs), it is important to explore the association between ICIs and cardiac arrhythmias and to characterize the clinical features of ICI-associated cardiac arrhythmias in real-world studies. Objective The purpose of this study was to characterize the main features of ICI-related cardiac arrhythmias. Methods From January 2017 to June 2021, data in the Food and Drug Administration Adverse Event Reporting System (FAERS) database were retrieved to conduct the disproportionality analysis. For the ICI-related cardiac arrhythmia detection, signals were detected by reporting odds ratio (ROR) and information component (IC), calculated using two-by-two contingency tables The clinical characteristics of patients reported with ICI-related cardiac arrhythmias were compared between fatal and non-fatal groups, and the time to onset (TTO) following different ICI regimens was further investigated. Multivariate logistic regression was used to evaluate of ICI-associated arrhythmias were associated with other concurrent cardiotoxicity, including cardiac failure [ROR 2.61 (2.20-3.09)], coronary artery disorders [ROR 2.28 (1.83-2.85)], myocardial disorders [ROR 5.25 (4.44-6.22)], pericardial disorders [ROR 2.76 (2.09-3.64)] and cardiac valve disorders [ROR 3.21 (1.34-7.68)]. Conclusion ICI monotherapy and combination therapy can lead to cardiac arrhythmias that can result in serious outcomes and tend to occur early. Our findings underscore the importance of early recognition and management of ICI-related cardiac arrhythmias.5-Fluorouracil (5-FU) chemoresistance is a persistent impediment to the efficient treatment of many types of cancer, yet the molecular mechanisms underlying such resistance remain incompletely understood. Here we found CRC patients resistant to 5-FU treatment exhibited increased extracellular matrix protein 1 (ECM1) expression compared to CRC patients sensitive to this chemotherapeutic agent, and higher levels of ECM1 expression were correlated significantly with shorter overall survival and disease-free survival. 5-FU resistant HCT15 (HCT15/FU) cells expressed significantly higher levels of ECM1 relative to parental HCT15 cells. Changes in ECM1 expression altered the ability of both parental and HCT15/FU cells to tolerate the medication in vitro and in vivo via processes associated with apoptosis and EMT induction. From a mechanistic perspective, knocking down and overexpressing ECM1 in HCT15/FU and HCT15 cell lines inhibited and activated PI3K/AKT/GSK3β signaling, respectively. Accordingly, 5-FU-induced apoptotic activity and EMT phenotype changes were affected by treatment with PI3K/AKT agonists and inhibitors. Together, these data support a model wherein ECM1 regulates CRC resistance to 5-FU via PI3K/AKT/GSK3β pathway-mediated modulation of apoptotic resistance and EMT induction, highlighting ECM1 as a promising target for therapeutic intervention for efforts aimed at overcoming chemoresistance in CRC patients.Background Aortic stenosis (AS) increases left ventricular afterload, leading to cardiac damage and heart failure (HF). Transcatheter aortic valve replacement (TAVR) is an effective therapy for AS. No inotropic agents including levosimendan have been evaluated in patients undergoing TAVR. Methods A total of 285 patients underwent TAVR between 2014 and 2019; 210 were included in the matched analysis and 105 received 0.1 μg/kg body weight/min levosimendan immediately after the prosthesis had been successfully implanted. Medical history, laboratory tests, and echocardiography results were analyzed. Endpoints including 2-year all-cause mortality, stroke, or HF-related hospitalization, and a combination of the above were analyzed by Cox proportional hazard models. Results The levosimendan group had no difference in 2-year mortality compared with the control group (hazard ratio [HR] 0.603, 95% confidence interval [CI] 0.197-1.844; p = 0.375). However, levosimendan reduced stroke or HF-related hospitalization (HR 0.346; 95% CI 0.135-0.884; p = 0.027) and the combined endpoint (HR 0.459, 95% CI 0.215-0.980; p = 0.044). After adjusting for multiple variants, levosimendan still reduced stroke or HF-related hospitalization (HR 0.346, 95% CI 0.134-0.944; p = 0.038). Conclusion Prophylactic levosimendan administration immediately after valve implantation in patients undergoing TAVR can reduce stroke or HF-related hospitalization but does not lower all-cause mortality.