{"title":"Xathine unveiled: Bridging CD4+ T cell and stress-induced disorders through purine metabolism","authors":"Li Zhang , Jia-xin Dong , Yi-yuan Li , Jin Jin","doi":"10.1016/j.bbii.2025.100113","DOIUrl":"10.1016/j.bbii.2025.100113","url":null,"abstract":"<div><div>Neuroimmunology, a field exploring the intricate interplay between the nervous and immune systems, has long focused on the regulatory effects of stress on immune function. Chronic stress activates the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal-medullary system, leading to glucocorticoid and catecholamine release, which modulate T cell activity. Clinical studies reveal that chronic stress dysregulates peripheral T cells, particularly reducing CD4<sup>+</sup> T cell counts, which are implicated in anxiety and obsessive-compulsive disorders. The current research demonstrates that chronic stress depletes peripheral CD4<sup>+</sup> T cells, and their depletion protects against stress-induced anxiety-like behaviors. Furthermore, adoptive transfer of CD4<sup>+</sup> T cells from anxious mice induces anxiety in recipient mice, highlighting the pivotal role of these cells in stress-related disorders. This finding uncovers a novel mechanism where stress triggers purine metabolism dysregulation in CD4<sup>+</sup> T cells, leading to elevated xanthine and adenine levels. Xanthine enhances amygdala neuronal activity, contributing to anxiety-like behaviors, while adenine suppresses it. Stress-induced leukotriene B4 promotes mitochondrial fission in CD4<sup>+</sup> T cells, enhancing IRF1 nuclear accumulation and upregulating purine synthesis enzymes, resulting in xanthine overproduction. This metabolic shift links mitochondrial dysfunction to stress-induced anxiety. Purines exert their effects via adenosine receptors, with A1 in oligodendrocytes mediating xanthine-induced neuronal activation in the brain. In the gut, stress-induced xanthine elevation activates A2B receptors, driving exosome biogenesis and contributing to irritable bowel syndrome pathogenesis. These findings identify dysregulated purine metabolism in CD4<sup>+</sup> T cells as a hallmark of stress-related disorders, offering novel therapeutic targets. Purine synthesis inhibitors and adenosine receptor antagonists show promise in alleviating anxiety and IBS symptoms, paving the way for innovative treatments for stress-induced diseases. This research bridges neuroimmunology and metabolism, providing a comprehensive understanding of stress-related disorders and their therapeutic potential.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"10 ","pages":"Article 100113"},"PeriodicalIF":0.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A case report of chronic abdominal pain caused by non digestive or psychological disorders","authors":"Jianchang Wei, Yonglong Bao, Ping Yang, Shanqi Zeng, Jie Cao, Tong Zhang","doi":"10.1016/j.bbii.2025.100114","DOIUrl":"10.1016/j.bbii.2025.100114","url":null,"abstract":"<div><h3>Background</h3><div>Chronic abdominal pain (CAP) is defined as ongoing or recurring abdominal pain that lasts for three months or longer, presenting a complex medical challenge due to its wide range of possible causes. Here, we report a case of CAP caused by a non-digestive and non-psychological disorder.</div></div><div><h3>Case presentation</h3><div>A 49-year-old man began experiencing intermittent upper abdominal pain three months ago. Gastroenteroscopy revealed chronic non-atrophic gastritis with erosion and multiple colon polyps. He received treatment including proton pump inhibitors (PPIs), Chinese medicine, painkillers, and psychological therapy, but his symptoms did not improve. One day ago, his abdominal pain worsened along with fever of 38.5 °C. Computed tomography (CT) scan showed a foreign body (FB) and pneumoperitoneum. Urgent laparoscopic exploration was performed, revealing a 3.5 cm fishbone penetrating the left lobe of the liver. The fishbone was successfully removed, and his abdominal pain finally disappeared.</div></div><div><h3>Conclusion</h3><div>CAP is a complex condition with significant diagnostic challenges. Hepatic foreign bodies are very rare and are frequently overlooked in gastroenteroscopic evaluations, which can lead to delayed diagnoses. CT scanning is a crucial diagnostic tool for identifying FBs. Laparoscopic minimally invasive extraction is a viable option for FB removal when indicated. This case underscores the necessity of addressing both physical and psychological factors when managing CAP.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"10 ","pages":"Article 100114"},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anxiolytic efficacy of Sphaeranthus indicus Linn Ghana Vati in Generalized Anxiety Disorder: A randomized, placebo-controlled trial","authors":"Sumedh Joshi , Bhargav Vijay Bhide , Shivani Ghildiyal , Tanuja Manoj Nesari","doi":"10.1016/j.bbii.2025.100110","DOIUrl":"10.1016/j.bbii.2025.100110","url":null,"abstract":"<div><div>Generalized Anxiety Disorder (GAD) is a prevalent psychiatric condition marked by persistent worry that disrupts daily life. Conventional treatments, such as SSRIs and benzodiazepines, are often limited by side effects, including sedation and dependence. Sphaeranthus indicus Linn., a well-known Ayurvedic herb, has shown promising anxiolytic potential. This randomized, single-blind, placebo-controlled trial evaluated the efficacy and safety of Sphaeranthus indicus Ghana Vati (SIGV) in patients with GAD. Fifty patients diagnosed according to DSM-IV criteria were randomly assigned to receive either SIGV (500 mg, twice daily) or placebo for eight weeks. Anxiety reduction, the primary outcome, was measured using the Hamilton Anxiety Rating Scale (HAM-A), while secondary outcomes included psychological assessments with the NIMHANS Screening Tool and Manas Bhava Parikshana. The SIGV group exhibited significantly greater improvement in anxiety symptoms than the placebo group. Reductions in anxious mood (63.2 % vs. 41.7 %, p < 0.05), tension (64.0 % vs. 40.4 %, p < 0.01), and insomnia (72.9 % vs. 43.9 %, p < 0.001) were notable. The most significant difference was observed in fear reduction (80.0 % vs. 44.7 %, p < 0.001). Additionally, improvements in depressed mood (62.2 % vs. 41.5 %, p < 0.05) and somatic complaints were significant. However, autonomic symptom improvement (17.8 % vs. 38.1 %) did not reach statistical significance (p = 0.08). These findings suggest that SIGV is a safe and effective intervention for GAD, producing substantial improvements in core anxiety symptoms and emotional well-being compared to placebo. The results highlight SIGV’s potential as a natural and well-tolerated treatment option. Further research is warranted to assess its long-term efficacy and explore its integration into standard psychiatric care.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"10 ","pages":"Article 100110"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transcriptome profiling after Sudarshan Kriya Yoga and its practice – A pilot study","authors":"Vinod Mony, Saumya Subramanian, Divya Kanchibhotla","doi":"10.1016/j.bbii.2025.100109","DOIUrl":"10.1016/j.bbii.2025.100109","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Mind body interventions (MBIs) originated in ancient India like yoga, pranayama and meditation have been found to provide positive health benefits. How these interventions bring about changes affecting improved holistic health at the molecular level is still being investigated. Earlier indications are that the mind body interventions reprogram the body towards improved immunity and reduced inflammation that contrasts with the transcriptome response to chronic stress. Beyond this, if there are other gene expression signatures that are common to MBIs, or any other functions affected are yet to be looked into.</div></div><div><h3>Methods</h3><div>Sudarshan Kriya Yoga (SKY) is an integrated yoga-pranayama-meditation technique that has shown to provide multiple health benefits including better immunity and stress reduction. Previous work looking at the transcriptome changes after SKY has found that the genes involved in immune functions are upregulated. Nevertheless, how novices respond to SKY at the level of their gene expression is still largely unknown. In this study, we looked at the global transcriptome after SKY program as well as its practice in novices in a longitudinal study.</div></div><div><h3>Results</h3><div>Immediately after the SKY program, we found 175 genes changed in expression that mainly relates to functions such as neuronal regeneration, resisting cancer progression and lowering inflammation. Interestingly, after 30 days of SKY practice a separate set of 44 genes are differentially expressed, cytoskeletal reorganization being one of the major functions.</div></div><div><h3>Conclusions</h3><div>Contrary to the transcriptional responses to chronic stress, molecular reprogramming after MBIs such as SKY reduced inflammatory responses along with improved regenerative functions.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"10 ","pages":"Article 100109"},"PeriodicalIF":0.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu Liu, Daniel H. Lee, Ella Kosowicz, Justin Lin, Linting Ma, Sean Yao, Kyra Bi, Jennifer Huang, Julia Chang, Yuanyuan Li , Keming Yan , Albert S. Yeung, Jian Kong
{"title":"Targeting mental health: A scoping review of acupoints selection in acupressure for depression, anxiety, and stress","authors":"Yu Liu, Daniel H. Lee, Ella Kosowicz, Justin Lin, Linting Ma, Sean Yao, Kyra Bi, Jennifer Huang, Julia Chang, Yuanyuan Li , Keming Yan , Albert S. Yeung, Jian Kong","doi":"10.1016/j.bbii.2025.100111","DOIUrl":"10.1016/j.bbii.2025.100111","url":null,"abstract":"<div><h3>Background</h3><div>Depression, anxiety, and stress are prevalent mental health conditions that significantly affect global well-being. Conventional treatments, including pharmacological and psychotherapeutic approaches, often have limitations. Acupressure, a Traditional Chinese Medicine (TCM) technique, has gained attention as a complementary, non-invasive therapy. Acupressure stimulates specific acupoints to balance the body’s energy (<em>Qi</em>) and promote relaxation. This scoping review explores the effectiveness of acupressure for managing depression, anxiety, and stress by analyzing the frequency and selection of key acupoints in randomized controlled trials.</div></div><div><h3>Methods</h3><div>A comprehensive search was conducted in the PubMed database, focusing on RCTs that evaluated acupressure's effects on depression, anxiety, and stress. Studies were screened based on predefined inclusion criteria, including formal diagnoses, well-documented acupressure points, and standardized outcome measures. Data on acupoint usage, meridian applications, and treatment outcomes were also extracted and analyzed.</div></div><div><h3>Results</h3><div>Nineteen studies met the inclusion criteria, with a median sample size of 58 participants. The analysis highlighted the frequent use of auricular Shenmen (TF4) in treating depression, stress, and combined conditions, while Yintang (EX-HN3) and body acupoint Shenmen (HT7) were prominent for managing anxiety. Auricular points played a central role in stress management, comprising 62.50 % of applications, while body acupoints like Taichong (LV3) and Zusanli (ST36) supported overall emotional balance and physical well-being. Although no significant adverse events were reported, studies often lacked standardized safety reporting and follow-up data.</div></div><div><h3>Conclusion</h3><div>This review highlights the frequent use of acupoints such as the auricular Shenmen (TF4), as well as body acupoints Yintang (EX-HN3)and Shenmen (HT7) in promoting emotional regulation and stress relief. The integration of auricular and body acupoints, combined with targeted meridians, provides a foundational framework for utilizing acupressure as a complementary therapy for depression, anxiety, and stress.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"10 ","pages":"Article 100111"},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeevitha Gowda R , Anish Mehta , Krishnamurthy Jayanna
{"title":"The impact of chronic diseases on cognitive impairment in rural population of India: A focus on diabetes, hypertension, cardiovascular disease, and stroke","authors":"Jeevitha Gowda R , Anish Mehta , Krishnamurthy Jayanna","doi":"10.1016/j.bbii.2025.100107","DOIUrl":"10.1016/j.bbii.2025.100107","url":null,"abstract":"<div><h3>Background</h3><div>Chronic diseases such as diabetes, hypertension, cardiovascular disease, and stroke have long been associated with a range of metabolic and cardiovascular complications. Increasing evidence also suggests that these conditions contribute significantly to cognitive impairment, including dementia. This is particularly concerning for rural populations, where access to healthcare is limited, and the prevalence of chronic diseases is high. This review explores the relationship between multiple chronic diseases and cognitive decline, highlighting the mechanisms involved, the specific challenges rural populations face, and potential strategies to mitigate the effects of chronic diseases on brain health.</div></div><div><h3>Methods</h3><div>A rapid evidence-based review was conducted, focusing on existing literature about the impact of chronic diseases on cognitive health, particularly in rural settings. The studies gathered were assessed to understand how these chronic diseases contribute to cognitive impairment, the socio-economic factors influencing rural healthcare, and strategies for improving management and prevention in these communities.</div></div><div><h3>Results</h3><div>Chronic diseases such as diabetes, hypertension, cardiovascular disease, and stroke affect the brain through various mechanisms including insulin resistance, vascular damage, neuroinflammation, and cerebrovascular events. For rural populations, limited access to healthcare, lack of awareness, and insufficient infrastructure further exacerbate the risk of cognitive impairment. Inadequate healthcare resources in rural areas hinder effective management of these chronic conditions, thereby increasing the risk of cognitive decline.</div></div><div><h3>Conclusion</h3><div>The rising prevalence of chronic diseases globally and their association with cognitive impairment is a major concern, particularly for underserved rural populations. Addressing this issue requires integrated healthcare approaches, public health education, and significant improvements in rural healthcare infrastructure.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"9 ","pages":"Article 100107"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiyi Xu , Yi Zhang , Lei Li , Xiaodong Zhao , Feilong Huang , Jing Du
{"title":"An insightful comparison of the current neuroimmune mechanism(s) with the thoughts of differential syndromes from traditional Chinese medicine for the treatment of MDD","authors":"Jiyi Xu , Yi Zhang , Lei Li , Xiaodong Zhao , Feilong Huang , Jing Du","doi":"10.1016/j.bbii.2024.100100","DOIUrl":"10.1016/j.bbii.2024.100100","url":null,"abstract":"<div><div>Major depressive disorder (MDD) is a common disease affecting 300 million people worldwide. Current drugs are ineffective for at least 30 % of the patients. Novel and personalized medication is needed urgently. Cumulative studies suggest that the neuroinflammation of the glial cells, particularly NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation and subsequent regulation of synaptic functions may be the key for the pathophysiology and treatment of MDD. In this review, we delve to compare the modern mechanism of MDD treatment with the theories of differential symptoms for personalized treatment of the ancient decoctions from traditional Chinese Medicine (TCM). Interestingly, the mechanisms of MDD treatment from Western and TCM theories overlap to a nexus on regulating neuro-immune signaling pathways, including NLRP 3 inflammasome, cytokine expressions and synaptic functions. In this review, we have summarized 8 differential syndromes and 10 decoctions for the TCM treatment of MDD in modulation of immune system and synaptic functions. The neuroimmune modulation of the 10 decoctions for the treatment MDD from TCM are amazingly similar towards the anti-inflammatory effects and enhancing synaptic functions. The comparison of theories and therapies from Western medicine and TCM may contribute to the development of more effective and safer medication for MDD.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"9 ","pages":"Article 100100"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143097035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"School-based yoga intervention for internet resilience and holistic well-being of adolescents","authors":"Reshu , Surendra Kumar , Ashutosh Rathi","doi":"10.1016/j.bbii.2024.100102","DOIUrl":"10.1016/j.bbii.2024.100102","url":null,"abstract":"<div><h3>Background</h3><div>In today’s educational milieu, rising mental and physical health issues among adolescents pose an imperative concern for schools. While yoga has shown growing therapeutic benefits, research addressing emerging concerns—such as internet addiction, and associated cognitive and sleep disorders—remains underexplored, especially in the post-COVID-19 era and within school curricula.</div></div><div><h3>Objective</h3><div>This pilot, randomized-controlled trial with high school students aimed to validate a concise, 25-minute yogic intervention tailored for adolescent well-being in academic settings.</div></div><div><h3>Measures</h3><div>Quantitative assessment tools included the Academic Anxiety Scale for Children, Concentration Questionnaire, Internet Addiction Test, Insomnia Severity Index, and General Health Questionnaire.</div></div><div><h3>Results</h3><div>Over a three-month period, students who practiced yoga reported marked improvements in internet resilience, academic anxiety, concentration, and insomnia symptoms (all p < 0.0001). Additionally, they showed significant reductions in general health complaints (e.g., headaches, stomach aches), with p-values ranging from p < 0.05 to p < 0.001. Conversely, the control group showed no significant changes, except for a worsening of internet addiction.</div></div><div><h3>Conclusion</h3><div>These findings suggest that even brief, consistent yoga practice can yield substantial benefits, advocating for its integration into school curricula to promote a healthier, more resilient generation of learners.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"9 ","pages":"Article 100102"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143097043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kaixuan Xu , Dongli Song , Hui Li , Yushan Lu , Zhongliang Zhu
{"title":"Advance in the mechanisms underlying prenatal stress-induced depressive-like behavior in offspring","authors":"Kaixuan Xu , Dongli Song , Hui Li , Yushan Lu , Zhongliang Zhu","doi":"10.1016/j.bbii.2025.100108","DOIUrl":"10.1016/j.bbii.2025.100108","url":null,"abstract":"<div><div>Prenatal stress (PS) represents a critical environmental factor that causes developmental disruptions in offspring, characterized by multisystemic vulnerabilities across neuropsychiatric, cardiovascular, metabolic, and immunological domains. Through intricate embryonic reprogramming mechanisms, PS alters brain developmental trajectories and physiological regulatory networks, resulting in increased long-term risks for neurodevelopmental disorders, particularly depressive-like behavior. PS causes dysregulation in multiple physiological processes, including hypothalamic-pituitary-adrenal (HPA) axis activation, epigenetic modifications, neurotransmitter systems, brain-derived neurotrophic factor (BDNF), gut microbiota, and neuroimmune responses. Additionally, genetic factors, sex specificity, and critical developmental windows further complicate the PS-mediated onset of depressive-like behavior. Here, we review clinical and animal studies and analyze how the multiple mechanisms form complex regulatory networks during intrauterine development, leading to long-lasting psychopathological effects in offspring.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"9 ","pages":"Article 100108"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}