Alzheimer’s disease (AD) is increasingly recognised as a disorder that extends beyond the brain, with accumulating evidence implicating gut microbiota–derived metabolites in its onset and progression. This narrative review synthesises 92 peer-reviewed animal, human and meta-analytic studies published between 2010 and 2025 that investigated short-chain fatty acids (SCFAs), tryptophan-derived indoles and kynurenines, trimethylamine N-oxide (TMAO) and secondary bile acids in the context of AD. Collectively, the literature shows that SCFAs support blood–brain-barrier integrity, dampen microglial reactivity and enhance synaptic plasticity, yet can paradoxically amplify β-amyloid (Aβ) deposition under germ-free or supraphysiological conditions, highlighting the importance of host status and dosing. Beneficial indole metabolites such as indole-3-propionic acid counter oxidative stress, strengthen intestinal and cerebral barriers and suppress pro-inflammatory cascades, whereas a shift toward neurotoxic kynurenines correlates with cognitive decline. TMAO emerges as a consistently deleterious metabolite that aggravates endothelial dysfunction, neuroinflammation and Aβ aggregation; dietary precursor restriction and microbial enzyme inhibitors are therefore being explored as mitigation strategies. Secondary bile acids and polyphenol derivatives further modulate mitochondrial bioenergetics and NF-κB signalling, broadening the therapeutic landscape. Multi-omics profiling reveals that AD patients typically exhibit reduced SCFAs and indoles but elevated TMAO, changes that scale with Mini-Mental State Examination scores, brain atrophy and cerebrospinal Aβ₄₂ levels. Early probiotic and faecal-microbiota-transplant trials have begun to normalise these metabolite profiles and yield modest cognitive benefits, underscoring translational potential. Altogether, gut-derived metabolites are not passive by-products but active modulators of neural, immune and metabolic circuits along the microbiota–gut–brain axis; their targeted manipulation and standardised metabolomic assessment could enable earlier diagnosis and precision microbiome-based interventions for AD, a promise that now warrants validation in large, longitudinal and mechanistically informed clinical studies.

Introduction: Ferroptosis is a crucial process contributing to neuronal damage following intracerebral hemorrhage (ICH). Didang Tang (DDT), a traditional therapeutic, has been used clinically to manage ICH for many years, yet the molecular mechanisms by which by DDT protects neurons from ferroptosis after ICH remain elusive.Methods: This study utilized high-performance liquid chromatography-based fingerprint analysis to characterize DDT’s chemical composition. An ICH rat model and hemin and erastin-induced PC12 cell ferroptosis models were developed to investigate DDT’s neuroprotective mechanisms. Histological assessments of brain tissue morphology and iron deposition were performed using hematoxylin-eosin, Nissl, and Perl’s blue staining. Neurological function was evaluated using Longa and Berderson scores, while lipid peroxidation was measured using biochemical assays and flow cytometry. Protein expression levels of ferroptosis- and endoplasmic reticulum stress (ERS)-related markers were analyzed via Western blotting and immunofluorescence.Results: Our results demonstrated that DDT reduced hematoma volume, decreased iron deposition, lowered malondialdehyde (MDA) levels, and upregulated glutathione peroxidase (GPX4) and SLC7A11 expression in affected brain regions. Furthermore, DDT downregulated GRP78 expression and inhibited the PERK/eIF2α/ATF4/CHOP/GPX4 pathway, exerting strong neuroprotective effects. The fluorescence staining results of MAP2/GPX4 and MAP2/CHOP suggested that DDT may regulate neuronal ferroptosis and ERs to exert the protective effect. In vitro experiments using hemin- and erastin-induced neuron-derived PC12 cells as neuronal ferroptosis models developed in our laboratory corroborated these in vivo findings, showing increased survival and reduced lipid peroxidation in DDT-treated cells, along with similar inhibitory effects on ferroptosis and ERS. Molecular docking suggested that DDT components, such as sennoside B, amygdalin, rhein, and emodin, interact favorably with PERK/eIF2α/ATF4/CHOP signaling pathway proteins, highlighting their potential role in DDT’s anti-ferroptosis effects.Conclusion: DDT alleviates neuronal ferroptosis after ICH by modulating the PERK/eIF2α/ATF4/CHOP/GPX4 signaling pathway. Overall, this study provides novel insights into DDT’s protective mechanisms against ICH-induced neuronal injury by modulating ferroptosis and ERS pathways, underscoring its potential as an effective therapeutic strategy.

Myasthenia gravis (MG) is an acquired autoimmune disease characterized by impaired transmission at the neuromuscular junction, primarily manifesting as fluctuating muscle weakness, fatigability, and partial paralysis. Due to its long disease course, treatment resistance, and frequent relapses, it places a significant burden on patients and their families. In recent years, advances in molecular biology have provided growing evidence that mitochondrial dysfunction impairs muscle function and affects immune cell proliferation and differentiation in patients. Mitochondria, as the cell's energy source, play a critical role in various pathological processes in MG, including oxidative stress, dynamic abnormalities, mitophagy, and mitochondrial metabolism. The role of mitochondrial dysfunction in the pathogenesis of MG has garnered increasing attention. This manuscript primarily explores mitochondrial function and abnormal morphological changes in MG, as well as mitochondrial quality control, metabolic reprogramming, and their potential mechanisms in the pathological changes of the disease. It also reviews the current status of drug therapies aimed at improving mitochondrial function. The goal is to provide novel perspectives and strategies for future mitochondrial-targeted therapies in MG.

Background and Objectives: Multiple sclerosis (MS) significantly impacts adolescents and young adults (aged 15–39 years), causing substantial neurological disability. Despite therapeutic advances, the global burden persists due to disparities in healthcare access and lifestyle factors. This study analyzes global, regional, and national trends and burdens of MS using Global Burden of Disease (GBD) 2021 data, emphasizing the influence of the Socio-demographic Index (SDI). Methods: Using data from the GBD 2021 data, we conducted a secondary analysis. We assessed the prevalence, mortality, and disability-adjusted life years (DALYs) of MS across 204 countries/territories from 1990 to 2021, calculating age-standardized rates. Results: In 2021, global MS prevalence was 489,310 cases, associated with 1,424 deaths and 215,869 disability-adjusted life years (DALYs). The global age-standardized rates per 100,000 were: prevalence 22.2 (19.8 - 24.8), deaths 0.2 (0.2 - 0.2), and DALYs 11.4 (9.8 - 13.2). Compared to 1990, these rates decreased by 0.4%, 12.8%, and 11.0% respectively, while the number of prevalent cases increased by 52.4%. Sweden (161.6), Canada (134.2), and Norway (131.5) had the highest age-standardized prevalence. The UK (71.3) had the highest and Nauru (0.4) the lowest age-standardized DALY rate. Female MS death rates exceeded those of males across all ages, peaking at 20–24 years. Regionally, age-standardized DALY rates showed an inverse V-shaped relationship with the SDI. Discussion: Although the global MS burden among adolescents and young adults (AYAs) decreased, the substantial and rising prevalence demands attention. The burden from premature mortality and stark geographic variations in prevalence and DALYs indicate inadequate disease management, underscoring the need for enhanced awareness and effective interventions. Urgent, targeted healthcare policies are required to address geographical inequities, sex-specific pathophysiology, and modifiable risk factors such as smoking.

Myasthenia gravis (MG) is a chronic autoimmune disorder affecting the neuromuscular junction. The emergence of molecular therapies, such as monoclonal antibodies, B-cell-depleting agents, and chimeric antigen receptor T-cell-based therapies, has the potential to transform the treatment landscape for myasthenia gravis. The clinical efficacy of novel biologics in the treatment of individuals with myasthenia gravis is still a subject of debate. The objective was to compare and rank the efficacy and acceptability of novel biologics in the treatment of individuals with MG through a network meta-analysis. This systematic review and network meta-analysis (NMA) involved a comprehensive search for published randomized controlled trials (RCTs) across several databases, including PubMed, Web of Science, Embase, Cochrane Library, SinoMed, CNKI, Wanfang, and VIP, covering articles published from inception until July 3, 2024. We included randomized controlled trials involving patients with myasthenia gravis. The main outcome was the overall symptomatology. Random-effects pairwise meta-analyses and network meta-analyses (NMAs) were conducted to compute standardized mean differences (SMDs) or risk ratios with 95% confidence intervals (CIs). The research process did not include individuals with lived experience. The studies’ quality was evaluated utilizing the risk-of-bias assessment tool created by the Cochrane Collaboration. Network meta-analysis was performed utilizing Stata 16 and R4.2.3. Eleven RCTs including 840 participants with myasthenia gravis were eligible. Belimumab improvement of the MG-ADL score is compared to placebo (MD = − 3.29, 95% CI (− 5.78, − 0.80), P < 0.05). Compared to placebo, batoclimab enhanced the QMG score (MD = − 4.46, 95% CI (− 7.57, − 1.35), P < 0.05) and the MGC score (MD = − 3.58, 95% CI (− 6.68, − 0.47), P < 0.05). Eculizumab improvement of the MG-QoL 15r score is compared to placebo (MD = − 7.10, 95% CI (− 12.20, − 2.00), P < 0.05). Regarding adverse reactions, we found no difference in the network comparison of novel biologics compared to placebo, but this conclusion requires further validation through rigorous research. This study provides an updated, relative rank-order efficacy of novel biologics therapies for myasthenia gravis. These data may help inform the design and sample size calculation of future clinical trials and assist selection of combination therapy. PROSPERO CRD42024559757. • When compared to placebo, various novel biologics demonstrate distinct benefits in enhancing clinical outcomes. • Batoclimab and eculizumab exhibit marginal advantages, with batoclimab effectively improving both QMG and MGC scores. • Belimumab shows significant efficacy in enhancing the MG-ADL score while minimizing adverse reactions. • Regarding adverse reactions, we found no difference in the network comparison of novel biologics compared to placebo, but this conclusion requires further validation through rigorous research.

Background: Myasthenia gravis (MG) is a rare autoimmune disorder characterized by fluctuating muscle weakness due to impaired neuromuscular transmission. Vaccination remains a cornerstone of infectious disease prevention, yet concerns persist regarding potential autoimmune exacerbation in susceptible individuals. This systematic review and meta-analysis aimed to synthesize available evidence on the association between vaccination and MG, evaluating both vaccine effectiveness and safety in this population. Methods: Observational studies in cohort or case-control formats were identified through systematic searches of PubMed, Web of Science, Embase, Cochrane Library, SinoMed, CNKI, Wanfang, and VIP databases from inception to June 24, 2025. Study quality was assessed using the Newcastle–Ottawa Scale (NOS). Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using fixed- or random-effects models based on heterogeneity. Publication bias was assessed using funnel plots and Egger’s test. Results: Five studies encompassing 27,193 participants (22,618 vaccinated and 4,575 unvaccinated) met inclusion criteria. Meta-analysis demonstrated a significant protective effect of vaccination against COVID-19 infection (fixed-effects model: OR = 0.23, 95% CI [0.20–0.26], P < 0.001). Conversely, vaccination was not associated with a statistically significant increase in MG exacerbation (random-effects model: OR = 0.67, 95% CI [0.10–4.54], P = 0.68). Conclusions: This study provides quantitative evidence that COVID-19 vaccination effectively reduces infection risk without significantly increasing MG exacerbation. These findings support the safety and clinical utility of vaccination in MG patients, emphasizing the need for individualized risk–benefit assessment and ongoing pharmacovigilance in this population. Systematic review registration: https://www.crd.york.ac.uk/prospero/ , identifier CRD420251078995.