Background: This meta-analysis was first conducted to evaluate the efficacy and safety of transplantation of mesenchymal stem cells in the treatment of type 1 and type 2 diabetes mellitus (T1DM and T2DM). Methods: We systematically searched PubMed, ScienceDirect, Google Scholar, CNKI, EMBASE, Web of Science, MEDLINE, and the Cochrane Library for studies published from the establishment of the databases to November 2020. Two researchers independently screened the identified studies, based on inclusion and exclusion criteria. The combined standard mean difference (SMD) and 95% confidence interval (CI) of data from the included studies were calculated using fixed- or random-effects models. Results: We included 10 studies in our meta-analysis (4 studies on T1DM and 6 on T2DM, with 239 participants) to examine the efficacy of mesenchymal stem cells (MSCs) therapy in the treatment of diabetes mellitus. According to the pooled estimates, the glycated hemoglobin (HbA1c) level of the MSC-treated group was significantly lower than it was at baseline (mean difference (MD) = −1.51, 95% CI −2.42 to −0.60, P = 0.001). The fasting C-peptide level of the MSC-treated group with T1DM was higher than that of the control group (SMD = 0.89, 95% CI 0.36 to 1.42, P = 0.001), and their insulin requirement was significantly lower than it was at baseline (SMD = −1.14, 95% CI −1.52 to −0.77, P < 0.00001). Conclusion: Transplantation of mesenchymal stem cells has beneficial effects on diabetes mellitus, especially T1DM, and no obvious adverse reactions.

This meta-analysis systematically evaluated the effects of water improvement and defluoridation on fluorosis-endemic areas in North and South China. The study used PubMed, Embase, China National Knowledge Infrastructure, and Wanfang to retrieve relevant research studies published between January 2000 and October 2019. The data included water fluoride levels, dental fluorosis prevalence in children 8-15 years of age, urinary fluoride levels in children and adults, and skeletal fluorosis prevalence in adults. Fixed-effects and random-effects models were used in the meta-analysis. A total of 17 research articles met the inclusion criteria and had an average water improvement period of 15.8 years. With water improvement, water fluoride levels decreased from 2.72 mg/L to 0.54 mg/L (95% confidence intervals: -2.75, -1.58), which was below the standard for drinking water (1.5 mg/L). Additionally, after water improvement, the prevalence of dental fluorosis decreased from 54.5% to 36.2% (95% confidence intervals: 0.12, 0.31) in children, and the prevalence of skeletal fluorosis decreased from 13.7% to 4.2% (95% confidence intervals: 0.16, 0.40) in adults. Urinary fluoride levels decreased from 3.06 mg/L to 1.70 mg/L (OR = -2.03, 95% confidence intervals: -2.77, -1.30) in children and from 2.29 mg/L to 1.72 mg/L (OR = -0.57, 95% confidence intervals: 0.65, -0.49) in adults. The results showed that the prevalence of dental fluorosis and skeletal fluorosis and urinary fluoride levels were significantly reduced by water improvement. This study findings revealed that the effects of water improvement and defluoridation were greater in South China than in North China, and it is obviously related to the time of water improvement and reducing fluoride.

Anti-CD19 chimeric antigen receptor (CAR) T cell therapy is a common, yet highly efficient, cellular immunotherapy for lymphoma. However, many recent studies have reported on its cardiovascular (CV) toxicity. This study analyzes the cardiotoxicity of CD19 CAR T cell therapy in the treatment of lymphoma for providing a more valuable reference for clinicians. The PubMed, Embase, Cochrane library, and Web of Science databases were comprehensively searched from the time of their establishment to May 2024. The ClinicalTrials.gov English database is a comprehensive repository of the original studies of CD19 CAR T cell therapy and associated adverse outcomes, such as arrhythmia, CV events, and hypotension, in patients with lymphoma. The Cochrane Collaboration tool and the Newcastle–Ottawa Scale (NOS) were used to assess the quality of the included original studies. For RCTs, the Cochrane Collaboration tool was used to assess the risk of bias. For non-randomized studies, the risk of bias was assessed using the NOS quality assessment scale. A risk analysis of two randomized controlled trials and nine cohort studies, totaling 1379 patients with lymphoma receiving CD19 CAR-T, is conducted. The incidences for all-cause mortality, CV events, and hypotension were found to be 17.8%, 17.8%, and 52.8%, respectively. Additionally, the incidences of heart failure (HF), cardiomyopathy, cardiac arrest, and other CV events are 3%, 0.6%, 1.3%, and 2.5%, respectively. In addition to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) as adverse events, patients treated with CD19 CAR T cells are also at risk of CV events. The most common CV events are arrhythmia and HF. Our further analysis showed that the incidence of CV events was 28.7% in the elderly and 13.5% in adults. The incidence of CV events in the elderly was higher than that in adults, and it was statistically significant. Furthermore, the incidence of CV events and hypotension is strongly associated with patients with CRS. Therefore, clinicians should pay close attention to the occurrence of such CV events and take timely prevention and intervention measures to further improve the safety of CD19 CAR T cell therapy.

Asparagus officinalis (ASP) has antioxidation, anti‐inflammatory, antiaging, and immune system‐enhancing effects. We explored the preventive and therapeutic consequences of ASP on the brain damage elicited by fluorosis through network pharmacology and in vivo experimental validation. We ascertained the pharmaceutically active ingredients and drug targets of ASP from the Traditional Chinese Medicine Systems Pharmacology database, predicted the disease targets of fluorosis‐induced brain injury using GeneCards and Online Mendelian Inheritance in Man databases, obtained target protein–protein interaction networks in the Search Tool for the Retrieval of Interacting Genes/Proteins database, used Cytoscape to obtain key targets and active ingredients, and conducted enrichment analyses of key targets in the Database for Annotation, Visualization and Integrated Discovery. Enrichment analyses showed that “mitogen‐activated protein kinase” (MAPK), “phosphoinositide 3‐kinase/protein kinase B” (PI3K‐Akt), “nuclear factor‐kappa B” (NF‐κB), and the “neurotrophin signaling pathway” were the most enriched biological processes and signaling pathways. ASP could alleviate fluorosis‐based injury, improve brain‐tissue damage, increase urinary fluoride content, and improve oxidation levels and inflammatory‐factor levels in the body. ASP could also reduce dental fluorosis, bone damage, fluoride concentrations in blood and bone, and accumulation of lipid peroxide. Upon ASP treatment, expression of silent information regulator (SIRT)1, brain‐derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), MAPK, NF‐κB, PI3K, Akt, and B‐cell lymphoma‐2 in rat brain tissue increased gradually, whereas that of Bax, caspase‐3, and p53 decreased gradually. We demonstrated that ASP could regulate the brain damage caused by fluorosis through the SIRT1/BDNF/TrkB signaling pathway, and reported the possible part played by ASP in preventing and treating fluorosis.

Fluoride (F), an environmental contaminant, is known to induce cardiotoxicity, although the precise molecular mechanisms remain unclear. This study aimed to investigate the role of the SIRT1/PI3K/AKT signaling pathway in F-induced cardiotoxicity and explore the potential protective effects of SIRT1 activation. Human AC16 cardiomyocytes and zebrafish embryos were exposed to increasing concentrations of sodium NaF. Cellular assays were used to assess viability, apoptosis, cell cycle distribution, and oxidative stress. Expression levels of oxidative and inflammatory markers, as well as components of the SIRT1/PI3K/AKT pathway, were analyzed by western blotting, immunofluorescence, and real-time PCR. Zebrafish were evaluated for cardiac developmental abnormalities, apoptosis, and oxidative stress. The SIRT1 agonist SRT1720 was used to evaluate the protective effects of SIRT1 activation. Statistical analysis was performed using SPSS 23 Software and GraphPad Prism7 software, with significant differences evaluated by one-way analysis of variance (ANOVA) and Dunnett's test (p < 0.05). NaF exposure significantly inhibited AC16 cell proliferation, induced G1 phase arrest, and increased apoptosis in a dose-dependent manner. Reactive oxygen species levels were elevated, accompanied by downregulation of antioxidant proteins and upregulation of inflammatory cytokines. NaF markedly suppressed SIRT1, PI3K, and AKT expression while activating FOXO1a. Zebrafish embryos exhibited dose-dependent cardiac malformations, increased apoptosis, and elevated oxidative stress markers. Treatment with SRT1720 restored SIRT1/PI3K/AKT pathway activity, enhanced cell proliferation, reduced apoptosis, and alleviated oxidative and inflammatory responses in both cell and zebrafish models. This study demonstrates that F induces cardiotoxicity by disrupting the SIRT1/PI3K/AKT signaling pathway, leading to increased oxidative stress, inflammation, and apoptosis. Activation of SIRT1 by SRT1720 mitigates these effects, highlighting the protective role of this pathway in F-related cardiac injury. These findings provide mechanistic insights and identify potential molecular targets for the prevention and treatment of fluorosis-associated cardiovascular toxicity.