Mental health and emotion regulation are central to resilience and quality of life across the lifespan, yet scalable, low-burden strategies that complement clinical care remain limited. Auricular interventions—including auricular acupuncture, auriculotherapy, device-based auricular stimulation, and noninvasive self-care approaches—have attracted increasing interest for stress, mood, sleep, and autonomic regulation. However, the field remains fragmented across point systems, mechanistic models, delivery methods, dosage, reporting practices, and implementation pathways. In this perspective, we propose the EASE Framework—Ear-wide engagement, Acupoint-informed prioritization, Self-administration, and Evaluation of emotional and related outcomes—as a pragmatic model for scalable manual auricular self-care. EASE builds on established auricular medicine while incorporating contemporary afferent-based concepts, including vagal and other auricular afferent pathways, as complementary mechanistic support. We review clinician-delivered, device-based, and self-care auricular methods; identify key translational gaps; and outline a four-step workflow that progresses from Shenmen stimulation to inner-ear stimulation from the cymba to the cavum conchae, front-and-back ear contact, and whole-anterior-ear rubbing. The framework includes three dosage tiers (Short, Moderate, and Long) to accommodate diverse settings and user needs. EASE is presented as a population-oriented mental health and well-being promotion framework and as a complement to, rather than a replacement for, evidence-based clinical care. By emphasizing standardized safety guidance, simplicity, brief training, and repeated home or community practice, EASE may provide a practical foundation for future feasibility, mechanistic, and implementation studies.
Medical knowledge is shaped not only by clinical practice but also by linguistic systems that organize and communicate bodily experience. In traditional East Asian medicine, acupoints are key therapeutic sites, yet the semantic structure of their names, which are rooted in classical Chinese medical terminology, has rarely been examined systematically. In modern research, acupoints are typically identified by standardized alphanumeric codes, which facilitate communication but often obscure the meanings embedded in traditional nomenclature. We conducted a descriptive linguistic analysis of the semantic structure of all 361 standardized acupoint names in the fourteen-meridian system, using character frequency analysis and a rule-guided semantic classification. Landscape metaphors accounted for 40.7% of acupoint names (n = 147), exceeding anatomical references (25.2%, n = 91), whereas the remaining 34.1% (n = 123) were classified as abstract or symbolic terms. Many metaphorical expressions referred to geographical features such as valleys, springs, seas, and ponds. These findings indicate that acupoint nomenclature functions not only as a naming system but also as a culturally structured semantic body map for organizing therapeutic space in contemporary standardized terminology. By showing how landscape metaphors are systematically embedded in acupoint terminology, this study provides a linguistic basis for understanding how traditional East Asian medicine represents the body as a therapeutic landscape. It also generates testable hypotheses about embodied cognition and body representation.
Acupoints have traditionally been regarded as specific loci along meridians for regulating Qi, Blood, and organ function. This review is a clinically oriented narrative review summarizing current evidence on the anatomical, neurophysiological, and clinical characteristics of acupoints. We first reviewed the structural basis of acupoints, including peripheral nerve endings, connective tissue planes, fascia, microvascular components, and immune-related elements. We then discussed how mechanical stimulation by acupuncture may be transformed into electrical, biochemical, and neural signals through mechanisms involving sensory afferents, endogenous opioids, neurotransmitters, adenosine, mast cells, and neuroimmune interactions. The concept of the Neural Acupuncture Unit was introduced as a framework for understanding acupoints as three-dimensional functional interfaces rather than simple surface points. We also examined the relationship between acupoints, Ashi points, myofascial trigger points, Five-Shu Points, Back-Shu Points, De-Qi sensation, needling depth, and acupoint sensitization. Finally, this review proposed that acupoints should be understood as dynamic cutaneous functional windows that reflect local tissue microenvironments and systemic physiological or pathological states. Further studies are needed to refine acupoint localization, safety assessment, and precision acupuncture practice.
Background There is limited long-term prospective data on post-COVID-19 neuropsychiatric symptoms (NPS), hindering our understanding of symptom progression beyond 12 months. The biological mechanisms behind persistent NPS remain unclear, with most hypotheses based on acute-phase data. This study examined the longitudinal associations of inflammatory, oxidative stress, and neurodegeneration biomarkers with post-COVID-19 NPS. Methods This prospective study followed 232 patients hospitalized for COVID-19 for 24 months post-discharge. Depression, anxiety, fatigue, and cognitive function were assessed using validated clinical scales at 3-6, 12, and 24 months. Serum biomarkers of inflammation, neurodegeneration, and oxidative stress were measured at baseline, 3, 6, and 12 months. K-means clustering was used to identify biomarker profiles at baseline. Linear mixed-effects models examined associations between clusters and longitudinal NPS outcomes, adjusting for age, sex, and ethnicity. Results Neuropsychiatric symptom burden remained high for up to 24 months, with depression more common in females and cognitive impairment in Hispanics. Inflammatory markers were elevated during hospitalization; most normalized over time, except for interferon gamma-induced protein 10 (IP-10) and neurofilament light chain (NfL), which persisted elevated through 12 months. Cluster analysis revealed two distinct baseline biomarker profiles. Mixed-effects models indicated that female sex predicted higher depression, anxiety, and fatigue, while Hispanic ethnicity was associated with lower cognitive function. Conclusions Post-COVID-19 NPS persist for at least 24 months, particularly in female and Hispanic individuals. The persistence of NPS, accompanied by sustained alterations in selected inflammatory and neurodegeneration-related biomarkers, highlights the need for long-term monitoring and further research to clarify their clinical significance.
HIV infection remains a major global health challenge. Although antiretroviral therapy (ART) effectively suppresses viral replication, HIV remains incurable because latent, replication-competent proviruses persist in diverse cellular and tissue reservoirs. This study investigated the effect of Yogaraj Rasāyana (YR), a classical Ayurvedic formulation, in augmenting CD4 + T lymphocyte counts in ART-treated HIV-positive individuals. In a randomized controlled trial (RCT), 52 HIV-positive participants (males/females/transgender: 29/20/3) with respective age (mean ± SD: 30.6 ± 7.9, 34.2 ± 10.3 and 32.0 ± 11.1 years), receiving standard ART, were recruited from Patanjali Ayurved Hospital Haridwar, and All India Institute of Medical Sciences Rishikesh, India. Participants were randomized into an Interventional Group (IG; n = 26) receiving YR (2 g/day orally) and ART, and a Conventional Group (CG; n = 26) receiving ART alone for 90 days. Clinical endpoints included CD4+ T cell counts and hematological/biochemical indices (Hemoglobin: Hb, Erythrocyte Sedimentation Rate: ESR, Random Blood Sugar: RBS, Serum Glutamic Oxaloacetic Transaminase: SGOT, Serum Glutamate Pyruvate Transaminase: SGPT, Blood Urea, Serum Creatinine), assessed at baseline and post-intervention. IG demonstrated a statistically significant increase in CD4 + counts and Hb levels (p < 0.05), with no hepatotoxic or nephrotoxic effects. The observed improvements suggest possible immunomodulatory actions of YR, potentially involving enhanced Regulatory T cell (Treg) activity, cytokine balance, and modulation of transcriptional regulators. YR exhibited potential as a safe, affordable adjunct to ART in HIV management. Future studies employing immunophenotyping, cytokine assays, and epigenetic analyses are recommended to elucidate its mechanistic pathways.
Posttraumatic stress disorder (PTSD) is a mental health condition that can develop following exposure to a traumatic event, often with persistent anxiety and depressive symptoms. Recent research suggests the microbiome-gut-brain axis may play an important role in the etiology and pathophysiology of PTSD. At the same time, retreats incorporating psychedelic-assisted therapies have gained increasing attention as potential treatments for PTSD. However, little is known about how participation in these retreats may affect the gut microbiome. Therefore, we conducted a preliminary observational single-arm pre-post study investigating the diversity and community composition of the gut microbiome pre/post participation in a retreat involving ceremonial ayahuasca use, as well as associations between microbiome features, PTSD symptoms, and personality traits. Participants included U.S. Veterans and non-Veterans with varied PTSD symptoms (N = 22). The international retreat took place over one week and included three ayahuasca ceremonies. PTSD Checklist for the DSM-5 (PCL-5) scores, Five-Factor Model (FFM) personality measures, and fecal samples were collected from participants pre/post retreat. Fecal samples were analyzed using 16S rRNA gene amplicon sequencing to assess gut microbiome diversity and community composition. PCL-5 scores decreased following the retreat, relative to baseline. Openness, Conscientiousness, Extraversion, and Agreeableness increased, while Neuroticism decreased. Measures of gut microbiome alpha diversity did not change. However, beta diversity analyses revealed a within-subjects shift in microbial community composition at the end of the retreat relative to baseline. Post retreat there was an increase in the relative abundances of several short-chain fatty acid-producing bacteria associated with gut health, including Lachnospiraceae UCG-004, Colidextribacter, Oscillospira, and Blautia. Although the study design has limitations and does not establish causality, it highlights within-subjects effects of participation in an ayahuasca retreat on the gut microbiome, effects that should be evaluated further in future large randomized double-blind, placebo-controlled clinical trials.
Psychoneuroimmunology (PNI) offers a cohesive model explaining the interrelationships among psychological phenomena and the nervous, endocrine, and immune systems. While the fundamental principles of PNI are well documented, translating these multidimensional interactions into actionable experimental frameworks remains a challenge. This paper advances the current PNI literature by proposing a refined bio-psycho-social framework rooted in systems biology. By structurally mapping physiological mechanisms, from molecular cytokines to systemic neuroendocrine responses to environmental and psychological factors, this perspective bridges theoretical PNI and personalized healthcare routine. This review article contributes towards providing better understanding of these bidirectional pathways which clarifies the necessity for a multi-targeted, individualized healthcare system that integrates pharmacological interventions, evidence-based lifestyle changes, and mind-body therapies, ultimately improving experimental efficacy and holistic health outcomes.
Depression is a prevalent mood disorder characterized by persistent dysphoria, anhedonia, feelings of guilt, fatigue, and a spectrum of concomitant emotional and somatic symptoms. As a major public health burden, depression is responsive to both pharmacological and non-pharmacological interventions; however, the clinical utility of these therapeutic strategies is largely undermined by adverse effects and significant interindividual heterogeneity in treatment response. Furthermore, monotherapy with pharmacological agents fails to guarantee adequate clinical efficacy in all patients—a shortcoming that may erode the fragile sense of optimism and motivational drive inherent to this patient population, who are inherently prone to hopelessness due to the core pathophysiological features of depression. Non-pharmacological interventions for depression refer to a set of therapeutic approaches designed to ameliorate the disease, relieve symptoms, alleviate pain, improve function, prolong survival, and facilitate overall health recovery in affected individuals. These interventions, including psychological interventions, medicated food homology-based regimens, dietary therapy, music therapy, acupuncture, and traditional Chinese medicine (TCM) modalities, exert antidepressant effects through multiple mechanistic pathways, such as the attenuation of neuroinflammation, modulation of neurotransmitter release and metabolism, enhancement of neuronal plasticity, and regulation of the gut-brain axis. In light of the aforementioned challenges and potential of non-pharmacological interventions, this review systematically summarizes their clinical applications and mechanistic underpinnings to provide an objective evidence-based evaluation, and further explores the therapeutic efficacy of different non-pharmacological interventions in mitigating depressive symptomatology.
Major Depressive Disorder (MDD) is a common mental illness, for which current western pharmacotherapies often suffer from limited targets, delayed onset of action, and high relapse rates. Traditional chinese medicine (TCM) have potentials in multi-target regulation for improving the treatment outcome. A great number of classic TCM herbal formulas such as Yueju Pill and Chaihu Shugan San, as well as their active ingredients, can alleviate depressive symptoms via mechanisms such as neuroplasticity, inflammatory response, and tryptophan metabolism. The TCM "liver" organ is more functional and integrative, with "dispersing and discharging" characteristic. It is proposed that stagnation due to liver's dispersing and discharging dysfunction may lead to depression, and thus "soothing the liver and relieving stagnation" is critical for the treatment. Previous studies have shown the involvement of liver regulation of metabolism of tryptophan or bile acid, immunity in depression. An increasing number of evidence indicates the important role of epigenetics in depression, which is contingent on the metabolic products by liver. Here the research progress on liver-brain epigenetic axis and its connection with immune system for the development and treatment of depression is reviewed. Epigenetic mechanisms include DNA/RNA methylation, histone modification, and non-coding RNA regulation. The metabolic products by liver, including factors such as S-adenosylmethionine (SAM), provide the doner for epigenetic modification. Immune system is profoundly involved for the liver-brain epigenetic axis. Emerging studies of TCM treatment of depression start to investigate the mechanism. Further exploration of the liver-brain epigenetic axis and its interaction to immune systems in regulation of depression are discussed.
Cancer-related fatigue (CRF) is one of the most prevalent and debilitating symptoms experienced by cancer patients, significantly affecting treatment adherence and quality of life. Its pathogenesis is multifaceted, involving inflammatory responses, hypothalamic-pituitary-adrenal (HPA) axis dysfunction, and mitochondrial energy metabolism disorders. To date, the therapeutic outcomes of CRF have not met clinical needs, and no pharmacological or non-pharmacological approach has been specifically approved for CRF. This review examines the current understanding of CRF mechanisms, discusses the limitations of current therapeutic modalities, and highlights the unique potential advantages of traditional Chinese medicine (TCM) interventions for CRF. Existing evidence indicates that TCM, with its advantages of holistic regulation and multi-targeted intervention, may have clinical value in alleviating symptoms, improving quality of life, and mitigating adverse reactions associated with Western medical treatments in patients with CRF. These beneficial effects may be closely associated with anti-inflammatory activity, restoration of HPA axis homeostasis, and improvement of mitochondrial energy metabolism. In this review, classic Chinese herbal formulas used for CRF management are briefly summarized. As increasing studies have investigated active components from individual herbs, particularly those with both medicinal and food properties, recent progress regarding these active components, including oil compounds, flavonoids, polysaccharides, and saponins, is reviewed in greater detail. Future studies focusing on therapeutic efficacy, novel and specific mechanisms, and interactions among active compounds in TCM treatment of CRF may help establish more effective and safer therapeutic strategies.
Chronic stress is a major risk factor for the development and persistence of chronic pain and is frequently associated with psychiatric comorbidities such as depression and post-traumatic stress disorder. However, the mechanisms linking stress exposure to pain chronification remain poorly integrated across peripheral and central levels. In this review, we examine chronic pain as a consequence of stress-driven brain–periphery–immune interactions, with a specific focus on primary sensory neurons as key integrators of immune, neuroendocrine, and neural signals. We discuss evidence showing that chronic stress reshapes immune function and promotes a pro-inflammatory milieu that directly targets nociceptors, increasing their excitability and susceptibility to peripheral sensitization. We then address how sustained nociceptive signaling and stress-related neuroimmune activation facilitate central sensitization within the spinal cord and limbic circuits, contributing to widespread pain and psychiatric vulnerability. By integrating findings from clinical and preclinical studies, this review highlights sensory neurons as a critical interface linking stress, immune dysregulation, and maladaptive pain processing across peripheral and central nervous system levels.
Postoperative depression in breast cancer (PDC) is a clinically consequential condition that can adversely affect treatment adherence, functional recovery, symptom burden, and overall quality of life. Emerging evidence indicates that the development and persistence of PDC are driven by dynamic interactions among psychological stress, endocrine dysregulation, autonomic imbalance, and immune-inflammatory activation. Within this context, the neuro-endocrine-immune (NEI) network offers a biologically and clinically informative framework for elucidating both the pathophysiological basis of PDC and the mechanistic underpinnings of non-pharmacological interventions (NPIs).In this mechanism-oriented integrative review, the pathogenesis of PDC is synthesized across three interconnected NEI domains: neural dysregulation, endocrine disturbance, and immune-inflammatory activation. In parallel, the review critically evaluates current evidence for major NPIs, including cognitive behavioral therapy, mindfulness- and acceptance-based approaches, relaxation training, physical exercise, traditional mind–body practices, music- and art-based interventions, acupuncture, and dietary strategies.Available evidence suggests that NPIs may ameliorate depressive symptoms and associated psychological distress through partially convergent mechanisms involving stress appraisal, emotional regulation, sleep and fatigue modulation, hypothalamic–pituitary–adrenal (HPA) axis functioning, autonomic nervous system balance, inflammatory signaling, oxidative stress, and immunometabolic regulation. Nevertheless, the robustness and mechanistic specificity of existing evidence vary considerably across intervention modalities. In general, evidence supporting clinical efficacy exceeds that for direct biological mechanisms, and many hypothesized NEI pathways remain insufficiently validated in populations specifically affected by PDC.Future research should prioritize the integration of clinical outcomes with NEI-related biomarkers and advance symptom- and mechanism-informed intervention models to facilitate more precise and individualized supportive care in breast cancer rehabilitation.
The antidepressant efficacy exhibits significant individual variation influenced by genetic factors. Traditional Chinese Medicine (TCM) as a personalized medicine is intrinsically contributed by genetic variation, but experimental investigation remains scarce. This study investigated the genetic impacts of the antidepressant effects of Yueju Pill (YJ), a classic TCM formula, using Balb/c and C57BL/6 J mouse strains, and the underlying electrophysiological and molecular mechanisms. We found that the same dose of YJ induced immediate and sustained antidepressant-like effects exclusively in Balb/c mice, accompanied by a specific enhancement of long-term potentiation (LTP) in the hippocampus. These effects were absent in C57BL/6 J mice. Further pharmacological validation confirmed the key role of the PKA-CREB pathway: treatment with a PKA signaling inhibitor H-89, administered either before or after YJ, completely blocked its antidepressant effects, indicating that this pathway is essential for both the initiation and maintenance of its efficacy. Notably, a comparative analysis with ketamine revealed mechanistic differences between the two: PKA activation was not required for the initiation of ketamine's antidepressant effect, and PKA signaling was only responsible for the early but short maintenance stage of ketamine's antidepressant effects. Furthermore, in the LPS-induced inflammatory depression model using Balb/c mice, YJ demonstrated antidepressant effects 24 h after a single administration and western blot analysis of hippocampal tissue revealed that YJ treatment significantly down‑regulated the protein expression of phospho‑NF‑κB (p‑NF‑κB) and the microglial marker Iba1, indicating a suppression of neuroinflammatory activation. In summary, differences in genetic background influenced the behavioral and electrophysiological effects of YJ. The activation of PKA signaling is required for both the initiation and early maintenance of its antidepressant actions, and attenuation of neuroinflammation may also contribute to the maintainence of its antidepressant effects.
Hypoxia, a critical pathological driver in conditions ranging from inflammatory diseases to cancer, profoundly disrupts the homeostatic interplay between neutrophils and endothelial cells. This review synthesizes current knowledge on the multifaceted mechanisms through which hypoxia, largely via the hypoxia-inducible factor (HIF) signaling axis, reprograms both cell types to create a self-perpetuating cycle of inflammation and vascular injury. We delineate how hypoxia induces a hyperactivated state in neutrophils, characterized by metabolic shifts, enhanced adhesion, a heightened secretory profile, and the release of neutrophil extracellular traps (NETs). Concurrently, hypoxia compromises endothelial barrier integrity, increases permeability, and promotes a pro-adhesive phenotype through the upregulation of adhesion molecules like E-selectin, ICAM-1, and VCAM-1. The crosstalk between these activated cells is further mediated through emerging pathways including ferroptosis and extracellular vesicle signaling. This synergistic interaction culminates in microvascular dysfunction, characterized by leukocyte stasis, capillary occlusion, and impaired tissue perfusion. By examining specific disease models—including cerebral ischemia-reperfusion injury, acute lung injury, high-altitude pulmonary edema, venous thrombosis, and neurodegenerative diseases—we highlight the central role of this dysregulated axis in disease pathogenesis. Finally, we discuss the translational implications of these findings, proposing that targeting key nodes of this interaction, such as specific adhesion cascades, NETs formation, or novel cell death pathways, offers promising therapeutic strategies for a spectrum of hypoxia-related disorders.
The pathological progression of neurodegenerative diseases is tightly linked to microglia-mediated immune dysregulation. Immunometabolism reprogramming in microglia exerts a pivotal influence on their polarization toward pro-inflammatory or anti-inflammatory phenotypes, wherein imbalanced metabolic remodeling and immunometabolism disorders perpetuate a vicious cycle that perturbs immune homeostasis and exacerbates neuropathology. Dysregulated microglial immunometabolism is increasingly recognized as a central driver of neurodegenerative diseases, rendering microglia a prime therapeutic target. Recent advances have demonstrated that traditional Chinese medicine (TCM), with its inherent merits of multi-component and multi-target actions, confers substantial efficacy in mitigating neurological disorders by targeting microglial metabolic pathways. Notably, TCM exhibits unique potential in orchestrating the crosstalk between microglial metabolism and immunity; however, a systematic synthesis of these findings is still lacking. This review compiles TCM-based immunomodulators, including monomers, single herbs, and compound formulations, which alleviate metabolism-associated neuroinflammation by targeting key microglial metabolic cascades, such as aberrant glycolytic hyperactivation, impaired mitochondrial oxidative phosphorylation, and dysregulated glutamine and lipid metabolism. We aim to delineate the metabolic regulation of immunity, dissect microglial metabolic perturbations in neurodegenerative diseases, and summarize the salutary effects of TCM on microglial immunometabolism, thereby providing novel insights into the prevention and therapeutic intervention of neurodegenerative diseases.
Background Brain–immune interactions are increasingly implicated in depression, anxiety, sleep disturbance, cognitive impairment, and neurodegenerative neuropsychiatric syndromes. Ayurvedic botanical medicinal plants are studied for mental functions, and their effects may plausibly be underpinned by neuroimmune mechanisms. Methods This narrative review synthesizes human clinical evidence for 22 Ayurvedic botanical medicinal plants across (A) general mental properties, (B) well‑being/prevention, and (C) psychiatric/neuropsychiatric disorders, and incorporates a targeted mechanistic search to identify brain–immune pathways relevant to these Ayurvedic medicinal plants. PubMed and the AYUSH Research Portal were searched through 4 January 2026. Clinical certainty was graded using a modified GRADE‑informed rubric; mechanistic evidence is integrated narratively. Results The strongest clinical signals are observed with Withania somnifera for stress/anxiety and sleep, Bacopa monnieri for selected cognitive outcomes, Crocus sativus for depressive/anxiety symptoms, and curcumin preparations for depressive symptoms. The brain–immune synthesis indicates that the reviewed Ayurvedic botanical medicinal plants converge most plausibly on a limited set of pathways: peripheral cytokine-to-brain signaling, microglial and astroglial activation, NF‑κB and NLRP3 inflammasome signaling, oxidative stress–immune coupling, hypothalamic–pituitary–adrenal axis regulation, blood–brain/gut–brain barrier signaling, and tryptophan–kynurenine metabolism. Representative examples include Bacopa‑mediated suppression of microglial TNF‑α/IL‑6 release, saffron‑related modulation of immune-driven kynurenine and monoamine disruption, glycyrrhizic acid targeting HMGB1/kynurenine signaling, Tinospora‑associated suppression of glial activation in Parkinsonian models, and anti‑neuroinflammatory signaling described for Withania, Centella, tulsi, jatamansi, and mucuna. For many Ayurvedic medicinal plants, mechanistic support is broader than the human efficacy evidence and remains mainly preclinical. Conclusions Ayurvedic botanical medicinal plants with the strongest mental‑health signals also show biologically plausible links to brain–immune pathways, but clinical translation is constrained by limited biomarker-enriched trials, formulation heterogeneity, botanical ambiguity, and safety/quality concerns. Future studies should directly test cytokines, inflammasome activity, kynurenine metabolites, stress-hormone indices, and glial/immune biomarkers alongside psychiatric and cognitive outcomes.
The prevalence of obesity is increasing in modern urban societies, resulting in a significant burden on public health systems globally. The current review explores research supporting the premise that chronic consumption of a Western diet alters the diversity and community composition of the gut microbiome, promotes “leaky gut”, systemic low-grade inflammation, and neuroinflammation, enhancing risk for obesity and stress-related psychiatric disorders. Specifically, consumption of a Western diet promotes metabolic endotoxemia by altering the gut microbiome, disrupting the mucus layer, and increasing permeability of the mucosal barrier. Specifically, increased permeability of the mucosal barrier leads to translocation of gut contents, including bacteria and bacterial metabolites, across the mucosal barrier. Translocation of gram-negative bacteria or lipopolysaccharide (LPS) can promote metabolic endotoxemia, heightened inflammation, and disruption of physiological function, leading to metabolic diseases. The review explores a novel approach to counteracting the metabolic effects of the Western diet by utilizing “Old Friends”, i.e., anti-inflammatory, immunoregulatory microbes that humans co-evolved with, but are reduced or absent in modern urban societies. Particularly, Mycobacterium vaccae ATCC 15483, one of these “Old Friends”, has showcased promising results by protecting against Western diet-induced systemic inflammation, obesity, and anxiety-like defensive behavioral responses associated with stress-related psychiatric disorders. Furthermore, M. vaccae ATCC 15483 decreases biomarkers of hippocampal microglial priming, suggesting a potential mechanism underlying stress resilience effects. While more research is warranted, harnessing the therapeutic potential of “Old Friends” like Mycobacterium vaccae ATCC 15483 may offer a novel strategy to combat modern diseases associated with consumption of a Western diet.
Adiponectin, an adipokine abundantly produced by adipose tissue, is a well-established regulator of energy metabolism and insulin sensitivity. Beyond these metabolic roles, a growing body of evidence characterizes adiponectin as a potent immunoregulatory factor. This mini-review provides a brief overview of adiponectin's anti-inflammatory functions in both the peripheral and central nervous systems. We discuss its role in modulating innate and adaptive immunity, including suppressing pro-inflammatory cytokine production, promoting anti-inflammatory M2 macrophage polarization, and regulating T-cell function. Additionally, we discuss how adiponectin signaling through its receptors (AdipoR1 and AdipoR2) in microglia and astrocytes can counteract neuroinflammation, with relevance to neurological and behavioral conditions. Given the challenges in pharmacologically targeting the adiponectin signaling system, we explore physical exercise as a feasible therapeutic strategy to increase adiponectin levels. We highlight evidence that exercise-induced increases in adiponectin mediate significant anti-inflammatory effects, underscoring the potential of lifestyle interventions to modulate immune responses via adiponectin.
Traumatic Brain Injury (TBI) is a leading global cause of mortality and disability. Its pathophysiology encompasses two distinct phases: primary and secondary injury. The secondary injury phase, which involves complex mechanisms such as neuroinflammation, oxidative stress, and apoptosis, is a critical contributor to neurological deterioration. Traditionally, TBI has been considered an isolated event of the central nervous system (CNS), with therapeutic strategies focusing primarily on intracranial targets. However, recent research has revealed that TBI triggers a potent systemic immune and inflammatory response. The spleen, as the body's largest secondary lymphoid organ, plays a pivotal dual role in this process, acting as both an “amplifier” and a “regulator”. This narrative review aims to comprehensively elucidate the dual role of the spleen (pro-inflammatory and anti-inflammatory) in the pathological progression following TBI. It will provide an in-depth analysis of the regulatory mechanisms involving spleen-derived immune cells (particularly macrophages and T cells), inflammatory factors, and the signaling pathways of the “brain-spleen” axis (such as the cholinergic anti-inflammatory pathway, the sympathetic nervous pathway, and the HPA axis). Building on this foundation, this article will critically summarize recent advances in spleen-targeted therapeutic strategies, including splenectomy, pharmacological modulation of splenic function, neurostimulation to modulate the brain-spleen axis, and stem cell therapy. Furthermore, it will discuss the challenges associated with clinical translation and outline future directions, thereby providing a theoretical framework and novel perspectives for developing new immunomodulatory interventions for TBI.
This article explores areas of conceptual alignment and functional similarity between Traditional Chinese Medicine (TCM) and contemporary neuroscience, particularly the models of allostasis and the predictive mind, by comparing different theoretical frameworks to highlight heuristic analogies in the understanding of the human mind as a dynamic, embodied, and regulatory process. In TCM, Qi represents the vital energy that animates and connects physiological and psychological functions; in predictive neuroscience, mental activity emerges from the continuous interaction between predictive models and sensory signals, integrating perceptions, emotions, and bodily states to promote flexible and proactive adaptation to the environment. Both perspectives propose a systemic view in which mind and body co-emerge from the dynamic interaction between the individual and the environment. In the predictive mind model, persistent prediction errors can consolidate into dysfunctional patterns and contribute to the accumulation of allostatic load, thereby compromising multisystem regulation and promoting the development of chronic conditions; a functional analogy emerges in TCM, where imbalances in Qi reflect states of altered adaptation. In both views, illness arises from a dysfunction of regulatory processes. Healing aims to restore the dynamic balance of the mind-body-environment system, intervening before chronicity sets in. Mind-body practices are interpreted in light of contemporary neurobiology as tools for regulating communication between the brain and internal organs, reducing the allostatic load caused by chronic stress, and fostering adaptive psychophysiological balance.
