Cellular senescence is linked to aging and tumorigenesis. The senescence of mesenchymal stem cells (MSCs) may influence the tumor growth, metastasis, and angiogenesis by secreting a variety of cytokines and growth factors. The conditioned media of adipose derived MSCs (AD-MSCs) stimulated the proliferation of human LoVo colorectal-cancer cells, and the replicative senescent MSCs had the more obvious effects in comparison to that of premature AD-MSCs. Analysis of the factors secreted in the MSCs culture media determined that senescent MSCs expressed and secreted high levels of galectin-3. Galectin-3 expression correlated with the stimulatory effect of senescent AD-MSCs on LoVo cells proliferation, as knockdown of galectin-3 in senescent AD-MSCs significantly reversed the effect of MSCs–mediated growth stimulation of LoVo cells. Furthermore, the simultaneous addition of recombinant galectin-3 to the co-culture systems partially restored the tumor-promoting effect of the senescent AD-MSCs. Analysis of the mechanisms of senescent MSCs and galectin-3 on LoVo cells signal transduction determined that senescent MSCs and exogenous galectin-3 promoted cell growth by activating the mitogen-activated protein kinase (MAPK) (extracellular signal-regulated kinase [ERK]1/2) pathway. Senescent MSCs may alter the tissue microenvironment and affect nearby malignant cells via cytokine secretion, and galectin-3 is an important mediator of senescent AD-MSC–mediated stimulation of colon cancer cell growth. Therefore, thorough assessment of AD-MSCs prior to their implementation in clinical practice is warranted.

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.

Background: CD19 combined with CD22 or CD20 therapy is a promising immunotherapy approach for the treatment of hematological malignancies. Dual-targeted CD19/CD22 CAR T and CD19/CD22 CAR T-cell therapy are currently being evaluated in clinical trials, and the extent of improvement using CD19 in combination with dual-targeted therapy has not yet been determined. To compare the differences between the two in the treatment of hematological tumors, this study summarized the available evidence. To evaluate and compare the efficacy and safety of CD19-combined CD22 and CD19-combined CD20 CAR T-cell therapy.Methods: Data from 13 clinical studies that included 628 patients with hematological malignancies were extracted and analyzed based on a set of inclusion and exclusion criteria. The primary efficacy outcomes were overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, overall survival (OS) rate and minimal residual disease (MRD)-negative response rate. The safety outcomes were cytokine release syndrome (CRS) rate and immune effector cell-associated neurotoxicity syndrome (ICANS) rate.Results: For CD19 combined with CD22 CAR T-cell therapy, the ORR was 83.7%; CR, 78.0%; PR, 20.7%, OS, 78.7%; MRD-negative response rate, 82.3%; incidence of CRS, 58.2%; ICANS, 7.7%. For CD19 combined with CD20 CAR T-cell therapy, the ORR was 80.3%; CR, 68.2%; PR, 10.9%; OS, 76.8%; incidence of CRS, 54.5%; ICANS, 21%. Subgroup analysis indicated that the PR of CD19 combined with CD22 was significantly greater than that of CD19 combined with CD20, and the incidence of ICANS was significantly lower with the CD19+CD22 CAR-T combination.Conclusion: The data from this study suggest that CD19 combined with CD22 CAR T-cell therapy had a higher partial response rate in the treatment of hematologic malignancies and higher safety profile in the occurrence of ICANS than CD19 combined with CD20. These data provide an important clinical basis for the development of new therapeutic targets and the construction of therapeutic methods for the treatment of hematologic malignancies, and broaden our understanding of CD19 dual-targeted CAR T therapy.

Introduction: Asparagus (Asparagus officinalis) is a perennial flowering plant species. Its main components have tumor-prevention, immune system-enhancement, and anti-inflammation effects. Network pharmacology is a powerful approach that is being applied increasingly to research of herbal medicines. Herb identification, study of compound targets, network construction, and network analysis have been used to elucidate how herbal medicines work. However, the interaction of bioactive substances from asparagus with the targets involved in multiple myeloma (MM) has not been elucidated. We explored the mechanism of action of asparagus in MM through network pharmacology and experimental verification.Methods: The active ingredients and corresponding targets of asparagus were acquired from the Traditional Chinese Medicine System Pharmacology database, followed by identification of MM-related target genes using GeneCards and Online Mendelian Inheritance in Man databases, which were matched with the potential targets of asparagus. Potential targets were identified and a target network of traditional Chinese medicine was constructed. The STRING database and Cytoscape were utilized to create protein–protein interaction (PPI) networks and further screening of core targets.Results: The intersection of target genes and core target genes of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway was enriched, the top-five core target genes were selected, and the binding affinity of corresponding compounds to the top-five core targets was analyzed using molecular docking. Network pharmacology identified nine active components of asparagus from databases based on oral bioavailability and drug similarity, and predicted 157 potential targets related to asparagus. Enrichment analyses showed that “steroid receptor activity” and the “PI3K/AKT signaling pathway” were the most enriched biological process and signaling pathway, respectively. According to the top-10 core genes and targets of the PPI pathway, AKT1, interleukin (IL)-6, vascular endothelial growth factor (VEGF)A, MYC, and epidermal growth factor receptor (EGFR) were selected for molecular docking. The latter showed that five core targets of the PI3K/AKT signaling pathway could bind to quercetin, among which EGFR, IL-6, and MYC showed strong docking, and the diosgenin ligand could bind to VEGFA. Cell experiments showed that asparagus, through the PI3K/AKT/NF-κB pathway, inhibited the proliferation and migration of MM cells, and caused retardation and apoptosis of MM cells in the G0/G1 phase.Discussion: In this study, the anti-cancer activity of asparagus against MM was demonstrated using network pharmacology, and potential pharmacological mechanisms were inferred using in vitro experimental data.

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.