Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05020-6
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can induce immune dysregulation and multi-organ injury; mesenchymal stromal cell (MSC) therapy has shown promise in clinical trials for COVID-19 and may have broader applicability to pneumonia induced by respiratory viruses (e.g., the influenza virus). This meta-analysis synthesized the available comparative clinical evidence on the safety and efficacy of MSCs in patients with moderate to critical COVID-19 and examined the reported outcomes relevant to Long-COVID. Methods We searched the PubMed, Embase, and CNKI databases for original, comparative studies in moderate, severe, or critical COVID-19 published up to September 2, 2024. Twenty-four eligible studies (13 RCTs and 11 non-randomized controlled trials; n=1080) were included in the mortality meta-analysis. Patients were assigned to either the intervention group (MSC therapy plus standard care) or the control group (standard care with or without placebo). The primary efficacy outcome was all-cause mortality, while the primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs). Secondary outcomes included clinical recovery, hospitalization metrics, chest imaging, and inflammatory biomarkers. We performed a pooled meta-analysis on mortality with subgroup analyses (by disease severity, administration route, dosing frequency, and study design), assessment of publication bias (using funnel plots and Egger’s test), and evaluation of the quality of evidence via the GRADE approach. AEs/SAEs were analyzed using meta-analysis and descriptive statistics, while other secondary outcomes were summarized descriptively. Results MSC therapy significantly reduced all-cause mortality (MSC: 26.4% vs control: 31.9%; fixed-effect OR=0.74, 95% CI 0.55–0.99), with low heterogeneity (I2=2.8%, P=0.422[Q-test]) and no publication bias. The quality of evidence
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04148-1
Background The long-term effects and outcomes of human mesenchymal stem cell (MSC) therapy in patients with severe coronavirus disease 2019 (COVID-19) remain poorly understood. This study aimed to evaluate the extended safety and efficacy of MSC treatment in severe patients with COVID-19 who participated in our earlier randomized, double-blind, placebo-controlled clinical trial, with follow-up conducted over 3 years. Methods One hundred patients with severe COVID-19 were randomized to receive either an MSC infusion (n=65, 4×10^7 cells/dose, on days 0, 3, and 6) or a placebo, with both groups receiving the standard of care. At 36 months post-MSC therapy, patients were followed up to long-term safety and efficacy, particularly the effects of MSC therapy on persistent COVID-19 symptoms. Evaluated outcomes included lung imaging results, 6-min walking distance (6-MWD), pulmonary function test results, quality of life scores based on the Short Form-36 (SF-36) health survey, Long COVID symptoms, new-onset comorbidities, tumor marker levels, and rates of COVID-19 reinfection. Results Three years post-treatment, 46.94% (23/49) of patients in the MSC group and 34.48% (10/29) in the placebo group showed normal findings on computed tomography (CT) images (odds ratio [OR]=1.68, 95% confidence interval [CI]: 0.65–4.34). The general health (GH) score from the SF-36 was higher in the MSC group (67.0) compared to the placebo group (50.0), with a difference of 12.86 (95% CI: 1.44–24.28). Both groups showed similar results for total lung severity scores (TSS), 6-MWD, pulmonary function tests, and Long COVID symptoms. No significant differences between groups were observed in new-onset complications (including tumorigenesis) or tumor marker levels. After adjusting for China’s dynamic zero-COVID-19 strategy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection rates were 53.06% (26/49) in the MSC group and 67.86% (19/28) in the placebo group (OR=0.54, 95% CI: 0.20–1.41). Conclusions These findings support the long-term safety of MSC therapy in patients with severe COVID-19 over 3 years. MSC treatment may offer potential benefits for lung recovery and improved quality of life in patients experiencing Long COVID symptoms. Trial registration: ClinicalTrials.gov, NCT04288102. Registered 28 February 2020, https://clinicaltrials.gov/study/NCT04288102.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024171
Ozone (O3), a prevalent atmospheric pollutant, can induce lung injury. However, the molecular mechanisms of O3-induced acute lung inflammatory injury remain unclear. In this study, we investigate the abnormal changes in and molecular mechanism of mitochondrial homeostasis in alveolar macrophages (AMs) in O3-induced acute lung inflammatory injury mice. Mitochondria and mitochondrial reactive oxygen species (mtROS) are labeled with Mito-Tracker® Deep Red and MitoSOX Red, respectively. Mitochondrial DNA (mtDNA) in AMs from the bronchoalveolar lavage fluid (BALF) is detected via real-time PCR, and the expressions of mitochondrial fusion/fission-related and biogenesis-related proteins in AMs are determined via immunofluorescence staining. Our data show that in O3-induced acute lung inflammatory injury mice, the number of AMs and the protein expression of the NLRP3 inflammasome complex in the lung tissue are increased. In AMs from O3-exposed mice, the number of mitochondria, mtROS, and fission-related protein DRP1 are increased, but the levels of Na+-K+-ATPase, fusion-related protein OPA1, biogenesis-related protein NRF1 and mtDNA are significantly decreased. Compared with that in O3-exposed WT mice, lung inflammation is attenuated, especially the indicators of mitochondrial homeostatic imbalance in AMs, which are alleviated in NLRP3‒/‒ and Caspase-1‒/‒ mice after O3 exposure. These findings indicate that the NLRP3 inflammasome-mediated imbalance in mitochondrial homeostasis in AMs contributes to O3-induced acute lung inflammatory injury. This study may provide a new target for the prevention of lung inflammation induced by O3.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261624
The bHLH transcription factor family in Forsythia suspensa was systematically identified and characterized using genomic data, yielding 170 members with complete HLH conserved domains distributed across 14 chromosomes. Protein lengths ranged from 67 to 885 amino acids, with relative molecular masses of 7,910.58 to 98,854.78 and theoretical isoelectric points of 4.71 to 10.44. Phylogenetic analysis classified these factors into 13 subfamilies, with subfamily III being the largest. Cis-acting element analysis revealed multiple light-, hormone-, and stress-responsive elements. Exogenous methyl jasmonate (MeJA) treatment of F. suspensa leaves followed by qRT-PCR within 48 h and correlation with phillygenin content identified FsbHLH26 and FsbHLH139 as likely key regulators of phillygenin biosynthesis and accumulation. These findings provide a foundation for elucidating the molecular mechanisms underlying phillygenin biosynthesis.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05020-6
Background: SARS-CoV-2 infection induces immune dysregulation and multi-organ injury. Mesenchymal stromal cell (MSC) therapy has shown promise in COVID-19 trials, with potential applicability to other viral pneumonias. This meta-analysis synthesized comparative clinical evidence on MSC safety and efficacy in moderate to critical COVID-19, including Long-COVID outcomes. Methods: PubMed, Embase, and CNKI were searched for comparative studies published up to September 2, 2024. Twenty-four studies (13 RCTs, 11 non-randomized; n=1080) were included. Patients received MSC therapy plus standard care (intervention) or standard care with/without placebo (control). Primary efficacy outcome: all-cause mortality. Primary safety outcomes: adverse events (AEs) and serious adverse events (SAEs). Secondary outcomes: clinical recovery, hospitalization metrics, chest imaging, inflammatory biomarkers. Meta-analysis with subgroup analyses (disease severity, administration route, dosing frequency, study design), publication bias assessment (funnel plots, Egger's test), and GRADE evaluation were performed. Results: MSC therapy significantly reduced all-cause mortality (26.4% vs 31.9%; fixed-effect OR=0.74, 95% CI 0.55–0.99), with low heterogeneity (I2=2.8%, P=0.422) and no publication bias. Evidence quality was moderate. AEs/SAEs were comparable between groups. Secondary outcomes favored MSC therapy in severe/critical subgroups. Conclusion: MSC therapy reduces mortality and improves clinical outcomes in severe/critical COVID-19 with a favorable safety profile. Efficacy in moderate illness remains inconclusive. Early signals suggest benefit in Long-COVID recovery. Standardized protocols and long-term follow-up are needed.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21271
BACKGROUND: As the population ages, research on gut microbiota in the elderly is gaining attention. However, bibliometric analysis in this field is still lacking. OBJECTIVE: To comprehensively analyze literature on gut microbiota in older adults from multiple databases, identify current research hotspots, predict future trends, and provide potential directions for subsequent research. METHODS: CNKI was searched using the subject terms “gut microbiota in older adults,” “gut microecology in older adults,” and “intestinal flora in older adults.” The Web of Science database was searched using the search strategy of “TS=(elderly gut microbe OR elderly gut microbiome OR elderly gut microbiota OR elderly intestinal microbiome OR elderly intestinal microbiota).” Bibliometric tools VOSviewer and CiteSpace were employed to systematically analyze publication years, country distribution, research institutions, authors, and keywords in the retrieved literature. RESULTS AND CONCLUSION: A total of 250 and 604 eligible articles were obtained from the CNKI and Web of Science databases, respectively. From 2014 to 2023, the global publication volume in the field of gut microbiota in older adults showed a steady upward trend. Research interest and discussions in this field have increased significantly worldwide, with expanding depth and breadth through interdisciplinary collaboration. Notably, COVID-19, oxidative stress, depression, and cognitive impairment emerged as prominent keywords in the past 2 years. This bibliometric analysis visually demonstrated the research status and development trends in the field of gut microbiota in the elderly over the past decade. The field is currently in a rising phase, and further exploration of the mechanisms of gut microbiota and intervention strategies for related diseases is still needed.