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.

Background. The application of virtual reality (VR) in clinical settings is growing rapidly, with encouraging results. As VR has been introduced into complementary and alternative medicine (CAM), a systematic review must be undertaken to understand its current status. Aim. This review aims to evaluate and summarize the current applications of VR in CAM, as well as to explore potential directions for future research and development. Methods. After a brief description of VR technology, we discuss the past 20 years of clinical VR applications in the medical field. Then, we discuss the theoretical basis of the combination of VR technology and CAM, the research thus far, and practical factors regarding usability, etc., from the following three main aspects: clinical application, teaching, and scientific research. Finally, we summarize and propose hypotheses on the application of VR in CAM and its limitations. Results. Our review of the theoretical underpinnings and research findings to date leads to the prediction that VR and CAM will have a significant impact on future research and practice. Conclusion. Although there is still much research needed to advance the science in this area, we strongly believe that VR applications will become indispensable tools in the toolbox of CAM researchers and practitioners and will only grow in relevance and popularity in the era of digital health.

Ethnopharmacological Relevance. Mineral medicines are widely used traditional Chinese medicines with curative effects. These medicines are used for many refractory diseases. Aim of the Review. In this review, cinnabar (HgS) and realgar (AsS) serve as examples of mineral medicines, and their pharmacology, therapeutic toxicity, use in traditional medicine mixtures, and research perspectives are discussed. Materials and Methods. A search was performed for the literature on cinnabar and realgar in PubMed, the Chinese Pharmacopeia, Google, and other sources. The search included studies using single herbs, traditional formulations, or novel dosage forms. Results. Cinnabar and cinnabar formulas exhibit good efficacy for sedation, sleep improvement, anxiety alleviation, and brain protection. However, previous studies on neurotransmitters have reached different conclusions, and detailed pharmacological mechanisms are lacking. Realgar and its formulas exert promising antitumor activity through regulation of cell cycle arrest, intrinsic and extrinsic apoptosis, induction of differentiation, autophagy, metabolic reprogramming, matrix metalloproteinase-9 (MMP-9) signaling, and reactive oxygen species (ROS) generation. In addition, realgar can be used to treat a variety of refractory diseases by regulating immunity and exerting antibacterial, antiviral, and other effects. However, the existing pharmacological research on the use of realgar for epidemic prevention is insufficient, and animal experiments and research at the cellular level are lacking. Inappropriate applications of cinnabar and realgar can cause toxicity, including neurotoxicity, liver toxicity, kidney toxicity, and genotoxicity. The toxicological mechanism is complex, and molecular-level research is limited. For clinical applications, theory and clinical experience must be combined to guide scientific and rational drug use and to achieve reduced toxicity and increased efficacy through the use of modern preparation methods or combined drugs. Notably, when cinnabar and realgar are used to treat targeted diseases, these agents have a bidirectional effect of treatment and toxicity on the central nervous system in pathological and normal states. The pharmacological and toxicological mechanisms need to be elucidated in greater detail in the future. Overall, systematic research is needed to provide a basis for better promotion of the rational use of cinnabar and realgar in the clinic. Conclusion. Mineral medicines are multicomponent, multiactivity, and multitargeted substances. The pharmacology and mechanisms of the toxicity and action of realgar and cinnabar are extremely complex. A number of Chinese medicinal preparations of realgar and cinnabar have demonstrated unique efficacy in the treatment of refractory diseases.

Currently, the existing evidence on the correlation between serum total bilirubin (STB) and Parkinson's disease (PD) is insufficient. The objective of this study was to clarify the relationship between STB levels and PD within the US (United States) population. A cross-sectional analysis was conducted using data from 25,637 participants in the National Health and Nutrition Examination Survey (NHANES) 1999–2018. Weighted logistic regression, smooth curve fitting, subgroup analysis, and sensitivity analyses were employed to validate the research objectives. Among all eligible subjects, the mean age was 57.11 ± 11.78 years. The prevalence of PD was 1.18 % overall, with 47.86 % in males. After adjusting for multiple variables, the odds ratio [OR] (95 % confidence interval [CI]) for PD associated with STB levels in T2 and T3 were 0.59 (95 % CI = 0.40–0.85, p = 0.006) and 0.67 (95 % CI = 0.45–0.99, p = 0.045), respectively, when compared to STB levels in T1. The analysis using restricted cubic splines (RCS) indicated an L-shaped relationship between STB levels and the prevalence of PD (p for nonlinearity = 0.004), with the lowest risk observed at 10.84 μmol/L. Comparable patterns of association were noted in subgroup analyses. Furthermore, consistent findings were derived from additional sensitivity analyses. Our study findings indicated that the level of STB is significantly negatively correlated with the prevalence of PD. Therefore, more prospective studies need to be designed to prove the causal relationship between them.

Cerebral ischemic injury, a major cause of mortality and disability, results from reduced or interrupted blood flow to the brain, most commonly in ischemic stroke. Insufficient oxygen and nutrient supply disrupts cellular metabolism, leading to neuronal death, neurological dysfunction, and lasting impairments. Current therapeutic strategies, including thrombolysis, mechanical thrombectomy, and anticoagulation, primarily aim to restore perfusion and provide neuroprotection by preserving the ischemic penumbra. While these interventions can partially rescue viable tissue in the acute phase, their effectiveness is constrained by narrow therapeutic windows, low recanalization rates, and contraindications, leaving significant unmet clinical needs. Consequently, the search for novel, targeted approaches has become a central focus of ischemic stroke research. Recent discoveries have identified lactylation, a newly recognized post-translational modification derived from lactate, as a key regulator of gene expression, protein function, and metabolic reprogramming. Once regarded as a simple glycolytic byproduct, lactate is now known to act as both an alternative energy substrate and a signaling molecule, influencing neuronal metabolism, antioxidant defense, and inflammatory responses. In ischemic brain injury, lactylation modifications of histone and non-histone proteins may either protect neurons—by supporting energy homeostasis, regulating stress-responsive genes, and suppressing apoptosis—or exacerbate injury through neuroinflammation, excitotoxicity, and immune evasion. Evidence indicates that the outcomes of lactylation depend on lactate concentration, timing of accumulation, cell type, and the balance between “writer” and “eraser” enzymes. Therefore, lactylation emerges as a promising yet complex therapeutic target in cerebral ischemia. Modulating lactate metabolism and its downstream modifications offers new opportunities to expand the therapeutic window, attenuate neuronal injury, and improve recovery. This review summarizes the molecular mechanisms linking lactate and lactylation to ischemic injury, highlights current contradictions in experimental findings, and explores the potential of targeting lactylation pathways for innovative treatment strategies.

Background: The existing evidence concerning the correlation between dietary β-carotene intake and Parkinson’s disease (PD) is currently deemed insufficient. Thus, this research aims to investigate the relationship between dietary β-carotene intake and both the prevalence of PD and all-cause mortality within the US (United States) population.Methods: The research employed cross-sectional analysis and cohort studies utilizing data from 16,852 participants in the National Health and Nutrition Examination Survey (NHANES) spanning from 2001 to 2018. Weighted logistic regression, weighted cox regression, restricted cubic splines (RCS), subgroup analysis, and sensitivity analyses were employed to validate the research objectives.Results: Among all eligible subjects, the mean age was 59.62 ± 11.77 years, with a prevalence of PD at 1.82% overall, with 43.88% in males. In the fully adjusted model, dietary β-carotene intake exhibited a negative association with PD prevalence [odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.90 ~ 0.997; p = 0.040]. Utilizing RCS analysis, a negative linear correlation between dietary β-carotene intake and PD prevalence was observed (non-linear p = 0.857). Furthermore, after controlling for multiple variables, dietary β-carotene intake was inversely associated with all-cause mortality [Hazard ratios (HR) = 0.98; 95% CI: 0.97 ~ 0.99; p = 0.002], with RCS curves indicating a negative linear relationship (nonlinear: p = 0.082). Comparable patterns of association were noted in subgroup analyses, and consistent findings were derived from additional sensitivity analyses.Conclusion: The cross-sectional and cohort study reveals a significant negative correlation between dietary β-carotene intake and both the prevalence of PD and all-cause mortality in the general population. This suggested that supplementing with dietary β-carotene might have certain benefits for reducing the prevalence of PD and all-cause mortality. However, further rigorously designed expected studies are needed to establish the causal relationship between them.