Background: Glioblastoma (used to be called glioblastoma multiforme—GBM) is the most common and aggressive brain tumor, having the lowest overall survival rate. Initial focal neurological deficits are primarily attributable to surrounding edema; however, as tumor invasion progresses, these deficits become more pronounced and permanent. The standard treatment for newly diagnosed glioblastoma is represented by cytoreductive neurosurgery followed by the Stupp Protocol. Postoperative recovery of the patient with glioblastoma is a long-term process that should include, for overall more acceptable outcomes, neurorehabilitation. This review aims to bring together evidence from neuro-oncology, neurosurgery, and neurorehabilitation in order to better understand the factors associated with recovery, functional status, and quality of life (QoL) after glioblastoma surgery. Our work also aimed to update the related knowledge base and to attempt to optimize the related protocols in patients with operated cerebral glioblastoma. Methods: For these purposes, we conducted a systematic literature review to assess the current state of research referring to the above-mentioned topic. We have used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA—widely recognized internationally) methodology. We used, in this respect, specific keyword combinations/“syntaxes” for searching literature in the domain, in four international databases. Results: Following PRISMA screening, 14 studies met the predefined eligibility criteria. Additional manual reference screening and complementary searches identified further relevant publications, resulting in a total of 22 included articles. Together, the reviewed work addressed a diverse range of topics relevant to postoperative glioblastoma management, including the potential role of multidisciplinary rehabilitation, cognitive interventions, neuromodulation approaches, and functional assessment strategies in improving postoperative outcomes and QoL in glioblastoma patients, while emphasizing that this interdisciplinary domain warrants more extended approaches. Discussion and Conclusions: Despite the relatively limited and largely exploratory available information, neurorehabilitation may contribute to improved functional outcomes and QoL in patients with glioblastoma.

Hydrogen sulfide (H₂S) is a gaseous signaling molecule and a promising biomarker linking gut microbiota metabolism with brain redox balance and neurodegeneration. In Alzheimer’s disease (AD), declining H₂S levels reflect disturbed microbial activity, oxidative stress, and vascular dysfunction. This paper introduces a simplified mathematical framework and a composite H₂S Index (Iₕ₂ₛ) for evaluating systemic sulfur homeostasis across the microbiota–brain axis. The model combines microbiota production, enzymatic synthesis, transport efficiency, and oxidative consumption using first-order differential equations. Analytical solutions show that moderate (30–40 I_H_2S may complement classical imaging and neuropsychological assessments in detecting Alzheimer’s disease at its earliest, most treatable stages.

BACKGROUND:Post-stroke spasticity is a frequent and disabling consequence of stroke, including when affecting the lower limbs, where it may impair stance, gait, balance, postural control, functional independence and quality of life. Botulinum toxin type A (BoNT-A) is widely used as a focal neuromodulatory treatment for post-stroke spasticity. However, the relationship between BoNT-A-induced reduction in muscle hypertonia, objective changes in spastic muscle's biomechanical properties, and functional outcomes such as mobility and balance remains insufficiently clarified. This systematic review aimed to synthesize recent evidence regarding the non-invasive assessment of spastic muscle properties following BoNT-A administration in post-stroke patients, with emphasis on mobility and balance outcomes. METHODS:A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was performed in international electronic databases and included studies published between 1 January 2023 and 31 December 2025. The search strategy used specific keywords and keyword combinations/syntaxes, contextually, related to the topic of interest. RESULTS:A total of 32 studies met the eligibility criteria and were included in the final data analysis and synthesis, comprising 13 primary clinical studies-6 randomized or controlled interventional studies and 7 observational studies-together with 12 reviews or evidence syntheses, 3 technical or clinical framework papers, and 4 survey, epidemiological, health-services or health-economic studies. Overall, the included articles addressed BoNT-A treatment in post-stroke spasticity, with partial focus on muscle properties, gait, mobility, and functional outcomes. However, only a limited number of studies investigated objective non-invasive assessment methods, and few directly related muscle-property changes in balance and mobility outcomes. Formal risk-of-bias assessment and quantitative synthesis were not performed because of the substantial heterogeneity of the included evidence, with only two studies being potentially suitable for pooling and these addressing different muscle groups, interventions, and outcome domains. DISCUSSION AND CONCLUSIONS:The reviewed literature confirms the clinical relevance of BoNT-A in the management of post-stroke spasticity. However, most studies assess treatment effects mainly through clinical scales, while objective evaluation of muscle stiffness, elasticity, viscoelastic properties, and their relationship with mobility and balance remains limited. Although some studies address gait, functional recovery, or muscle-related changes, the combined use of BoNT-A treatment, myotonometric assessment, and proprioceptive-stabilometric evaluation is largely absent. Therefore, current evidence highlights an important research gap and supports the need for future longitudinal studies integrating non-invasive biomechanical and balance assessment tools to better monitor treatment response and guide individualized neurorehabilitation in post-stroke patients.

Background: Sarcopenia, which has traditionally been considered to be an exclusively geriatric syndrome, has an increased frequency within the general population and fosters interest in its complex neuromuscular, cardiovascular, and metabolic basis. The current systematic review, adopting the recognized Preferred Reporting Items for Systematic Reviews (PRISMA) methodology, seeks to highlight current evidence on the underlying mechanisms as well as approaches to sarcopenia diagnosis and management. Methods: A comprehensive search of major international databases identified studies published between January 2023 and December 2024, from which 42 articles were retained according to prespecified criteria. To further enrich the present work, eleven additional studies of high relevance were included. Results: The selected literature describes sarcopenia’s multifactorial pathophysiology, including mitochondrial dysfunction, neuromuscular junction (NMJ) degeneration, chronic inflammation, anabolic resistance, endocrine and metabolic dysregulation, altered motor-unit remodeling, and molecular alterations. Diagnostic methods focus on functional assessments, especially muscle strength and physical performance. In addition, imaging techniques and new circulating biomarkers enhance precision in specific situations. Over the years, rehabilitation has proven to be one of the most effective therapeutic approaches. Complementary strategies, ranging from nutritional optimization to pharmacologic modulation of the renin–angiotensin system, show promise in specific patient subsets. Discussion and Conclusions: As supported by the works collected within the current study, future approaches will need to consider sarcopenia as a multifactorial disease that goes beyond aging.

Alcohol use disorder (AUD) is highly comorbid with psychiatric conditions and is increasingly recognized as a modifiable factor associated with cognitive decline and dementia, including Alzheimer's disease (AD). While epidemiological and experimental studies consistently demonstrate that chronic alcohol exposure exacerbates neurodegenerative vulnerability rather than implying a single dominant causal pathway, accumulating evidence supports a multifactorial and context-dependent framework in which alcohol acts as a disease-modifying stressor that perturbs endogenous adaptive and resilience mechanisms. Hydrogen sulfide (H2S), involved in redox regulation, mitochondrial function, neuroinflammatory control, and vascular homeostasis, has emerged as a candidate pathway that may be indirectly affected by alcohol exposure and relevant to neurodegenerative processes. This narrative mechanistic review synthesizes preclinical and clinical data examining alcohol-induced perturbations and H2S-related signaling pathways in the context of AD. We analyzed studies on the effects of acute and chronic alcohol exposure, as well as on cellular processes influenced by H2S bioavailability and signaling. Across experimental models and human studies, alcohol exposure was consistently associated with oxidative and mitochondrial stress, neuroinflammation, and vascular dysfunction-processes that overlap with biological domains normally regulated by H2S. Alcohol-related cognitive impairment frequently occurs in the absence of proportional increases in classical AD pathology, suggesting that alcohol may accelerate disease progression through non-canonical mechanisms. H2S signaling confers resilience against oxidative, inflammatory, and mitochondrial stress, whereas reduced H2S bioavailability or disrupted sulfide-dependent signaling increases neuronal vulnerability and cognitive impairment. However, the available data do not support a unidirectional or exclusive role for H2S as an integrative driver of alcohol-related AD pathology. H2S signaling represents a biologically plausible convergent and modulatory pathway linking alcohol exposure to AD risk.

Hydrogen sulfide (H₂S) is an endogenous gasotransmitter increasingly recognized as a biologically active biosignal involved in vascular regulation, redox homeostasis, mitochondrial function, and inflammatory control. Physical exercise is a central intervention in physical and rehabilitation medicine, capable of activating molecular signaling pathways that overlap with hydrogen sulfide–dependent mechanisms. In parallel, sulfurous balneotherapy provides exogenous low-dose hydrogen sulfide exposure and is widely used in rehabilitation practice. However, the role of hydrogen sulfide as a mediator of exercise-induced functional adaptation and its potential modulation through balneotherapy has not been systematically investigated in clinical rehabilitation settings. The primary objective of this study is to evaluate the role of exercise-induced hydrogen sulfide–related biosignaling in functional adaptation during rehabilitation. Secondary objectives include assessing whether the addition of sulfurous balneotherapy enhances functional outcomes and modulates biomarkers related to oxidative stress and inflammation, as surrogate indicators of hydrogen sulfide–dependent signaling pathways. This protocol describes a prospective, controlled, parallel-group clinical trial to be conducted in a balneological rehabilitation center. Approximately 60 adults with chronic musculoskeletal disorders will be recruited and allocated to either a therapeutic exercise–only group or a combined intervention group receiving therapeutic exercise plus sulfurous balneotherapy. The intervention period will last 14 days. Functional outcomes will include validated performance-based and patient-reported measures of physical function and pain. Biological outcomes will include systemic markers of oxidative stress and inflammation assessed at baseline and post-intervention. Statistical analyses will be planned to compare within- and between-group changes and to explore associations between functional and biological outcomes.

This review integrates the biology and clinical translation of hydrogen sulfide (H2S) in balneology. It frames H2S as a gasotransmitters with dual chemical and biological actions and summarizes the H2S/HS− equilibrium as a function of pH, temperature, and oxygenation, which governs bioaccessibility in sulfurous waters. Endogenous and exogenous sources, transport, and mitochondrial catabolism are outlined, together with core cellular mechanisms: protein persulfidation; activation of Nrf2/ARE; modulation of NF-κB; regulation of ion channels; and engagement of PI3K/Akt, MAPK/ERK, and Wnt pathways, plus epigenetic interactions with HDACs and sirtuins. Preclinical and clinical evidence in dermatology, musculoskeletal disease, and respiratory care is synthesized, alongside metabolic, cardiovascular, gastrointestinal, and renal effects. Technical aspects that preserve the bioactive fraction of H2S while meeting environmental safety limits are highlighted. Routes of administration (bathing, peloids, inhalation, and drinking cures) and key operational parameters are described. Overall, the review links physicochemical and molecular foundations with clinical indications for sulfurous waters and derivatives and identifies opportunities for research and development in H2S donors and thermal cosmetics without extrapolating beyond the available data.

Biosignals and motion-derived metrics provide robust, quantitative data critical for en-hancing diagnostic accuracy, therapeutic precision, and monitoring efficacy in physical medicine and rehabilitation. Integrating advanced technologies, including electromyog-raphy (EMG), electrocardiography (ECG), accelerometry, gyroscopy, magnetometry, iner-tial measurement units (IMUs), and diverse wearable sensor platforms, has opened inno-vative avenues for real-time assessment, continuous tracking, and personalized optimiza-tion of patient rehabilitation trajectories. This comprehensive review systematically ex-plores recent advancements in biosignal processing and motion analytics, emphasizing their practical applications within contemporary rehabilitation settings and their syner-gistic integration with natural therapeutic interventions such as hydrotherapy, thermal therapy, and mud-based treatments. Furthermore, it critically discusses existing clinical implementations, evaluates the translational impact of these technologies, and outlines potential future directions aimed at advancing precision medicine, enhancing patient outcomes, and expanding the therapeutic applicability of biosignals and motion analytics in rehabilitation practices.

Novel targeted therapies have transformed spinal muscular atrophy from a condition with a predictable, severe course into a more heterogeneous disorder with a range of new clinical phenotypes and outcomes. The emergence of new phenotypes in spinal muscular atrophy is a recent development in the field. The introduction of new etiopathogenic pharmacological treatments have significantly altered the natural history of the disease, leading to previously unseen clinical presentations and outcomes. Materials and Methods: We observed a cohort of 104 patients (children and adolescents), considering the number of SMN2 gene copies, the use of respiratory ventilation support devices and gastrointestinal support, and finally, their evolution on clinical-functional scales with physical therapy and rehabilitation interventions. With the increasing availability of effective therapies for spinal muscular atrophy, outcome measurement in clinical practice and research requires highly sensitive and reliable tools. In this study, motor function was systematically evaluated using two validated scales—the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Functional Motor Scale Expanded (HFMSE)—which are specifically designed to capture incremental changes in motor skills across the spectrum of SMA severity and age groups. Results: The median scores on the validated tools steadily increased over the 24 months of follow-up. Starting from 29 at baseline, the scores rose to 36 at 6 months, then to 39 at 12 months, 43 at 18 months, and 44.5 at 24 months. The Friedman test showed that these changes were statistically significant (p < 0.01). Moreover, each follow-up score was significantly higher than both the baseline and the previous time point (all p < 0.01), showing continuous improvement over time. Conclusions: These findings reveal that the development of new SMA phenotypes is closely linked to the stage of disease at which treatment is initiated. Earlier intervention consistently enables patients to acquire previously unattainable motor skills. Consequently, enhancing diagnostic precision and expediting therapy initiation is crucial for maximizing clinical benefits and facilitating optimal functional outcomes.

Frequently, cardiovascular pathologies lead to disability states, affecting the patient’s life quality, having a great socio-economic influence on public health systems. In order to identify the current situation of cardiovascular rehabilitation in Romania, we set out to create a systematic literature review on this subject matter. Aim. We aimed at a structured National protocol for cardiovascular rehabilitation, as for a national electronic register for cardiovascular diseases. Methods. We fulfilled, for the above mentioned purpose, a systematic literature review of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) type. The data query has been achieved in June 2023 and updated in March 2025 using several keyword combinations/ phrases, searched contextually. For this selection, we took into account: open access articles, written in English, published in ISI indexed journals between 01.01.2018 – 31.12.2022, extendend until 31.12.2024. Results. Five eligible articles were identified and operated in order to achieve this systematic literature review. Discussion. Accordingly, we noticed that there is no National electronic register for cardiovascular pathology in Romania, nor a National protocol for cardiovascular rehabilitation – the need for this type of a programme being imperative. Conclusions. Consequently, based on our efforts and given the fact that we approached an insufficiently researched niche, we consider our paper to contribute to such an endeavor.

Oxidative stress plays an essential role in neurodegenerative pathophysiology, acting as both a critical signaling mediator and a driver of neuronal damage. Hydrogen sulfide (H2S), a versatile gasotransmitter, exhibits a similarly “Janus-faced” nature, acting as a potent antioxidant and cytoprotective molecule at physiological concentrations, but becoming detrimental when dysregulated. This review explores the dual roles of oxidative stress and H2S in normal cellular physiology and pathophysiology, focusing on neurodegenerative disease progression. We highlight potential therapeutic opportunities for targeting redox and sulfur-based signaling systems in neurodegenerative diseases by elucidating the intricate balance between these opposing forces.

Age-related oxidative stress is a critical factor in vascular dysfunction, contributing to hypertension and atherosclerosis. Smooth muscle cells and endothelial cells are particularly susceptible to oxidative damage, which exacerbates vascular aging through cellular senescence, chronic inflammation, and arterial stiffness. Gasotransmitters—hydrogen sulfide (H2S), nitric oxide (NO), and carbon monoxide (CO)—are emerging as promising therapeutic agents for counteracting these processes. This review synthesizes findings from recent studies focusing on the mechanisms by which H2S, NO, and CO influence vascular smooth muscle and endothelial cell function. Therapeutic strategies involving exogenous gasotransmitter delivery systems and combination therapies were analyzed. H2S enhances mitochondrial bioenergetics, scavenges ROS, and activates antioxidant pathways. NO improves endothelial function, promotes vasodilation, and inhibits platelet aggregation. CO exhibits cytoprotective and anti-inflammatory effects by modulating heme oxygenase activity and ROS production. In preclinical studies, gasotransmitter-releasing molecules (e.g., NaHS, SNAP, CORMs) and targeted delivery systems show significant promise. Synergistic effects with lifestyle modifications and antioxidant therapies further enhance their therapeutic potential. In conclusion, gasotransmitters hold significant promise as therapeutic agents to combat age-related oxidative stress in vascular cells. Their multifaceted mechanisms and innovative delivery approaches make them potential candidates for treating vascular dysfunction and promoting healthy vascular aging. Further research is needed to translate these findings into clinical applications.

“Sola dosis facit venenum” (Paracelsus). Essential trace elements, crucial for maintaining neuronal function, have their dysregulation increasingly correlated with neurodegenerative disorders, particularly Parkinson’s disease (PD). This systematic review aims to synthesize recent high-quality evidence regarding the involvement of essential trace elements, such as iron, zinc, copper, manganese, and selenium, in the pathogenesis and, consequently, as potential therapeutic targets of PD. A comprehensive literature search was conducted for articles published between 1 January 2023 and 31 December 2024. Out of an initial pool of 1231 identified studies, 63 met the methodological eligibility criteria according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. All potentially eligible interventional and observational studies were initially assessed using the Physiotherapy Evidence Database (PEDro) scale, which is commonly employed for evaluating the internal validity and statistical interpretability of clinical trials and rehabilitation-focused studies. Following the qualitative assessment using the PEDro scale, 18 studies were ultimately selected based on their scientific relevance and methodological rigor. To supplement the PEDro scoring, which is designed primarily for individual trials, we applied the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) checklist for the evaluation of the included systematic reviews or meta-analyses. The included studies employed a variety of clinical, postmortem, and experimental models to investigate trace-element concentrations and their mechanistic roles in PD. The findings revealed consistent patterns of iron accumulation in the substantia nigra, zinc’s bidirectional effects on oxidative stress and autophagy, copper-induced α-synuclein aggregation, and the neuroprotective role of selenium via antioxidant pathways. Manganese was associated with mitochondrial dysfunction and neuroinflammation. Essential trace-element disturbances contribute to PD pathology through interconnected mechanisms involving redox imbalance, protein misfolding, and impaired cellular homeostasis. These elements may serve as both biomarkers and potential therapeutic tools, warranting further investigation into personalized metal-based interventions for PD.

Introduction:Considering the extensive development of artificial intelligence (AI) facilities, like Generative Pre-Trained Transformer (ChatGPT) 4.o and ChatGPT Scholar, we explored their abilities to conduct a systematic literature review. Using as a specific domain, an attempt to frame/methodize clinical assessment instruments used to evaluate neuro-functional deficits in Parkinson's disease (PD) - including framed through the ICF(-DH) paradigm - for the above-mentioned comparison between human intelligence (HI) and AI, this paper is as well, a follow-up regarding the most actual subject matter of the AI's capabilities evolution in this respect. As well-known clinical-/paraclinical-/functional evaluations, using assessment quantitative (as much as possible) instruments, are basic endeavors for rehabilitation, as they enable setting of appropriate and realistic therapeutic-rehabilitative specific goals. Methods:Within the actual work, we have first achieved a narrative synthesis of the main molecular mechanisms involved in PD pathophysiology, underpinning its clinical appearance and evolution. To fundament our knowledge on an up-to-date information regarding the clinical-functional evaluation tools practiced in PD, we systematically reviewed the literature in this domain, published in the last 6 years, through a PRISMA type method for filtering/selecting the related bibliographic resources. The same keywords combinations/syntaxes have been used contextually, also to dialogize with ChatGPT4.o and ChatGPT. Results:Scholar Applying PRISMA type methodology (HI achieved), we have selected, matching the filtering criteria, 24 articles. Interrogating the two AI above-mentioned models, we obtained quite difficult to be availed/useful - comparative to our HI obtained - outcomes. Thus, when interrogating ChatGPT4.o, ChatGPT Scholar repeatedly, they provided - partially diverse - inappropriate related answers, including ones pending on the interrogator's IP, although they claimed to have this capacity. Discussion:We consider, regarding their capabilities to achieve systematic literature reviews, that neither ChatGPT 4.o nor ChatGPT Scholar still cannot succeed this (yet, they keep improving lately). Additionally, we have consistently extended, including within a narrative related literature review, our 'dialogue" with these two AI facilities regarding their availability to enhance the related evaluation instruments accuracy on neurofunctional assessments within biomarker-based frameworks. So, our research aimed basically to emphasize the main topical data regarding these two important paradigms of knowledge (based on HI and on AI) acquirements - considering the impetuous development of the latter - and thus, possibly to contribute inclusively at improving the actual performances to achieve Systematic Literature Reviews through the PRISMA type method - for the moment still better served by HI.

[This corrects the article DOI: 10.3389/fmed.2025.1565275.].

Hydrogen sulfide (H2S) has emerged as a pivotal gaseous transmitter in the central nervous system, influencing synaptic plasticity, learning, and memory by modulating various molecular pathways. This review examines recent evidence regarding how H2S regulates NMDA receptor function and neurotransmitter release in neuronal circuits. By synthesizing findings from animal and cellular models, we investigate the impacts of enzymatic H2S production and exogenous H2S on excitatory synaptic currents, long-term potentiation, and intracellular calcium signaling. Data suggest that H2S interacts directly with NMDA receptor subunits, altering receptor function and modulating neuronal excitability. Simultaneously, H2S promotes the release of neurotransmitters such as glutamate and GABA, shaping synaptic dynamics and plasticity. Furthermore, reports indicate that disruptions in H2S metabolism contribute to cognitive impairments and neurodegenerative disorders, underscoring the potential therapeutic value of targeting H2S-mediated pathways. Although the precise mechanisms of H2S-induced changes in synaptic strength remain elusive, a growing body of evidence positions H2S as a significant regulator of memory formation processes. This review calls for more rigorous exploration into the molecular underpinnings of H2S in synaptic plasticity, paving the way for novel pharmacological interventions in cognitive dysfunction.

Intermittent hypoxic–hyperoxic exposure therapy (IHHT) has become a promising approach in adaptive training that may stimulate mitochondrial biogenesis, improve redox homeostasis, and enhance cardiopulmonary efficiency. However, standardized clinical protocols and safety validation in healthy populations are still insufficient. Objective: This prospective pilot study assessed the feasibility, safety, and physiological tolerance of the IHHT using the CellOxy intelligent system in healthy volunteers. The study was conducted at the Teaching Emergency Hospital “Bagdasar-Arseni” (SCUBA), with approval from the institution’s Bioethics Committee. Healthy adult volunteers underwent structured IHHT consisting of 4 cycles of hypoxia [Fraction of Inspired Oxygen (FiO2) 9–16%, titrated in order to reach a target oxygen saturation (SpO2) ~ 85%], alternating with 3–4 cycles of hyperoxia (FiO2 33–37%), each hypoxic cycle lasting 4 minutes and each hyperoxic phase 2 minutes; one session lasted approximately 30 minutes. Sessions were repeated 2–3 times per week for one month. Cardiopulmonary exercise testing (CPET) and complete blood count (CBC) analyses were performed at baseline and after the intervention. All participants completed the intervention without any adverse events. Preliminary data indicate improved exercise tolerance and stable hematological parameters, consistent with good physiological adaptability. The CellOxy-based IHHT protocol was safe and well-tolerated in healthy volunteers. This adjunctive therapy may be applicable in neuro- and cardiopulmonary rehabilitation. Further controlled studies with extended biomarker assessment are necessary.

Neurodegenerative diseases encompass a spectrum of disorders marked by the progressive degeneration of the structure and function of the nervous system. These conditions, including Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS), often lead to severe cognitive and motor deficits. A critical component of neurodegenerative disease pathologies is the imbalance between pro-oxidant and antioxidant mechanisms, culminating in oxidative stress. The brain’s high oxygen consumption and lipid-rich environment make it particularly vulnerable to oxidative damage. Pro-oxidants such as reactive nitrogen species (RNS) and reactive oxygen species (ROS) are continuously generated during normal metabolism, counteracted by enzymatic and non-enzymatic antioxidant defenses. In neurodegenerative diseases, this balance is disrupted, leading to neuronal damage. This systematic review explores the roles of oxidative stress, gut microbiota, and epigenetic modifications in neurodegenerative diseases, aiming to elucidate the interplay between these factors and identify potential therapeutic strategies. We conducted a comprehensive search of articles published in 2024 across major databases, focusing on studies examining the relationships between redox homeostasis, gut microbiota, and epigenetic changes in neurodegeneration. A total of 161 studies were included, comprising clinical trials, observational studies, and experimental research. Our findings reveal that oxidative stress plays a central role in the pathogenesis of neurodegenerative diseases, with gut microbiota composition and epigenetic modifications significantly influencing redox balance. Specific bacterial taxa and epigenetic markers were identified as potential modulators of oxidative stress, suggesting novel avenues for therapeutic intervention. Moreover, recent evidence from human and animal studies supports the emerging concept of targeting redox homeostasis through microbiota and epigenetic therapies. Future research should focus on validating these targets in clinical settings and exploring the potential for personalized medicine strategies based on individual microbiota and epigenetic profiles.

Recent studies underscore the role of gut and oral microbiota in influencing neuroinflammation through the microbiota-gut-brain axis, including in Alzheimer's disease (AD). This review aims to provide a comprehensive synthesis of recent findings on the involvement of gut and oral microbiota in the neuroinflammatory processes associated with AD, emphasizing novel insights and therapeutic implications. This review reveals that dysbiosis in AD patients' gut and oral microbiota is linked to heightened peripheral and central inflammatory responses. Specific bacterial taxa, such as Bacteroides and Firmicutes in the gut, as well as Porphyromonas gingivalis in the oral cavity, are notably altered in AD, leading to significant changes in microglial activation and cytokine production. Gut microbiota alterations are associated with increased intestinal permeability, facilitating the translocation of endotoxins like lipopolysaccharides (LPS) into the bloodstream and exacerbating neuroinflammation by activating the brain's toll-like receptor 4 (TLR4) pathways. Furthermore, microbiota-derived metabolites, including short-chain fatty acids (SCFAs) and amyloid peptides, can cross the blood-brain barrier and modulate neuroinflammatory responses. While microbial amyloids may contribute to amyloid-beta aggregation in the brain, certain SCFAs like butyrate exhibit anti-inflammatory properties, suggesting a potential therapeutic avenue to mitigate neuroinflammation. This review not only highlights the critical role of microbiota in AD pathology but also offers a ray of hope by suggesting that modulating gut and oral microbiota could represent a novel therapeutic strategy for reducing neuroinflammation and slowing disease progression.