Brain Behavior and Immunity Integrative最新文献

{"title":"Therapeutic evaluation of herbal drug Paeonia officinalis in the management of generalized anxiety disorder – A single blind randomized placebo controlled trial","authors":"Swaleha Akhtar ,&nbsp;Tanzeel Ahmad ,&nbsp;Jamal Azmat ,&nbsp;S Javed Ali","doi":"10.1016/j.bbii.2025.100145","DOIUrl":"10.1016/j.bbii.2025.100145","url":null,"abstract":"<div><h3>Background</h3><div>Generalized Anxiety Disorder (GAD) is a prevalent psychiatric condition characterized by persistent and excessive worry, often accompanied by physical symptoms such as restlessness, fatigue, and difficulty concentrating. Conventional treatments, including benzodiazepines and selective serotonin reuptake inhibitors (SSRIs), have limitations such as side effects and dependence potential. Unani medicine offers herbal alternatives with promising therapeutic potential. <em>Ood saleeb (Paeonia officinalis)</em> has been historically used for neurological and psychological disorders, but its efficacy in GAD remains underexplored.</div></div><div><h3>Methods</h3><div>A single blind randomized placebo-controlled trial was conducted involving participants diagnosed with GAD based on DSM-5 criteria. Patients were divided into two groups: one receiving <em>Ood saleeb</em> and the other receiving a placebo treatment. Grading of anxiety was done using the Hamilton Anxiety Rating Scale (HAM-A) at baseline, 15th, 30th,45th, and 60th day. Secondary outcomes included Restlessness, Insomnia, Palpitations, Fatigue and Irritability. Data were analyzed using appropriate statistical methods to determine efficacy.</div></div><div><h3>Results</h3><div><em>Ood saleeb</em> significantly reduced HAM-A scores compared to placebo, demonstrating notable anxiolytic effects. Improvements in subjective parameters were observed in the treatment group. No severe adverse effects were reported, suggesting a good safety profile. The findings indicate that Ood saleeb may offer a natural alternative for managing GAD with minimal side effects.</div></div><div><h3>Conclusion</h3><div><em>Ood saleeb (Paeonia officinalis)</em> exhibited significant anxiolytic properties in patients with GAD, supporting its potential as a complementary or alternative treatment in Unani medicine. Further large-scale studies are recommended to validate these findings.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"13 ","pages":"Article 100145"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Same signals, different conductors: A gut–brain perspective on bone regulation—parallels and particularities","authors":"Lu Qiao ,&nbsp;Wei-Ting Zeng ,&nbsp;Yu-Xin Zhu ,&nbsp;Man-Sau Wong ,&nbsp;Hui-Hui Xiao","doi":"10.1016/j.bbii.2026.100151","DOIUrl":"10.1016/j.bbii.2026.100151","url":null,"abstract":"<div><div>Osteoporosis, a systemic metabolic bone disorder characterized by reduced bone mineral density (BMD) and compromised bone microarchitecture, poses a significant public health challenge globally. Emerging evidence underscores the pivotal role of the gut-brain-bone axis in modulating skeletal homeostasis through a complex interplay of neurotransmitters, immune responses, and endocrine signals. This review elucidates the molecular mechanisms by which gut-derived and brain-derived signals converge, diverge, or synergize to regulate bone metabolism. We explore the contrasting effects of sympathetic and parasympathetic nervous systems on bone remodeling, highlighting the role of neurotransmitters such as serotonin, dopamine, and GABA. Furthermore, we discuss the contribution of gut microbiota to bone health via the synthesis of neurotransmitters and modulation of immune responses. The endocrine interactions between the brain and gut, involving hormones like cortisol, leptin, and GLP-1, are also examined. By identifying potential drug targets, this review aims to pave the way for novel, mechanism-based interventions for osteoporosis, emphasizing the importance of a holistic approach that integrates gut, brain, and bone health.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"13 ","pages":"Article 100151"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysbiosis and the modern lifestyle: Mechanisms, health impacts, and microbiome based interventions","authors":"Swapnanil Mahanta,&nbsp;Keya Nath,&nbsp;Kristipriya Boruah,&nbsp;Tapash Chakraborty","doi":"10.1016/j.bbii.2025.100146","DOIUrl":"10.1016/j.bbii.2025.100146","url":null,"abstract":"<div><div>The human gut microbiota, comprising more than 100 trillion microorganisms, is at the heart of digestive, metabolic, immune, and neuroendocrine health. But with advancing lifestyle, factors such as diets rich in processed food, physical inactivity, chronic stress, circadian disturbance, overuse of medications, and exposure to environmental toxins are progressively linked to microbial dysbiosis, a perturbation that underlies a wide range of diseases. This review critically discusses the pathways by which novel exposures interfere with gut microbial balance, emphasizing roles of hormonal changes, deranged motility, nutrient malabsorption, and biofilm disruption. We discuss how dysbiosis induces gastrointestinal diseases like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), metabolic and endocrine illness like obesity and polycystic ovary syndrome (PCOS), neuropsychiatric disorders, autoimmune disease, and even respiratory and skin disease through gut-organ axes. In addition, the review offers evidence-based approaches to restore microbial homeostasis through high-fiber and polyphenol-dense diets, physical activity, stress reduction, wise use of medications, and innovative microbiome-directed therapies such as probiotics, synbiotics, postbiotics, and fecal microbiota transplantation. Directions for the future including microbiome profiling, designer probiotics, and AI-directed personalized interventions are addressed. This review highlights the importance of bringing microbiota-focused strategies into public health policy and lifestyle medicine to reduce the global burden of disorders related to dysbiosis.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"13 ","pages":"Article 100146"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145739338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Itrīfal Mulayyin, a promising drug to manage Shaqīqa Muzmin (chronic migraine): A comprehensive review","authors":"Iram Jahan,&nbsp;Abdul Rafeh Wani,&nbsp;Mohd Asif Hussain Usmani,&nbsp;Usamah Ahmad","doi":"10.1016/j.bbii.2026.100150","DOIUrl":"10.1016/j.bbii.2026.100150","url":null,"abstract":"<div><h3>Background</h3><div>Migraine is a highly disabling neurological disorder and the second leading cause of disability-adjusted life years (DALYs) among neurological conditions worldwide. Chronic migraine (<em>Shaqīqa Muzmin</em>) is associated with inadequate management of acute episodes, medication overuse, psychological stress, obesity, and systemic inflammation. Increasing evidence implicates the gut–brain axis—a bidirectional communication network involving neural, immune, and endocrine pathways—in migraine pathophysiology. Alterations in gut microbiota, pro-inflammatory cytokines, hypothalamic–pituitary–adrenal (HPA) axis dysregulation, and neurotransmitters such as serotonin, dopamine, and calcitonin gene-related peptide (CGRP) are considered central to this mechanism.</div></div><div><h3>Objective</h3><div>This review explores the therapeutic potential of <em>Itrīfal Mulayyin</em>, a classical Unani polyherbal formulation, in chronic migraine through its effects on the gut–brain axis, humoral balance, and neuroinflammatory pathways.</div></div><div><h3>Methods</h3><div>Data were synthesized from classical Unani texts, the Unani Formulary of India, and modern biomedical literature. Pharmacological activities of the formulation’s constituents were examined in relation to migraine and gut–brain regulation.</div></div><div><h3>Results</h3><div><em>Itrīfal Mulayyin</em> is a semisolid formulation comprising <em>Terminalia chebula</em>, <em>Terminalia bellirica</em>, <em>Phyllanthus emblica</em>, <em>Rheum emodi</em>, <em>Convolvulus scammonia</em>, <em>Operculina turpethum</em>, <em>Foeniculum vulgare</em>, <em>Lavandula stoechas</em>, <em>Pistacia lentiscus</em>, and sugar base (<em>Qiwām</em>). Classical literature attributes to it three core actions: (i) <em>Munaqqi Dimāgh</em> (brain cleanser) – detoxifying humoral imbalance; (ii) <em>Mulayyin-i-Am‘a</em> (laxative) – enhancing gastrointestinal motility and waste elimination; and (iii) <em>Musakkin-i-Alam</em> (analgesic) – alleviating pain. Modern pharmacology supports these actions, demonstrating antioxidant, anti-inflammatory, neuroprotective, and gut-modulating properties of its ingredients. Together, these mechanisms suggest a regulatory role on the gut–brain axis and a potential in reducing migraine frequency and severity.</div></div><div><h3>Conclusion</h3><div>By bridging Unani theory and biomedical evidence, <em>Itrīfal Mulayyin</em> emerges as a promising complementary therapy for chronic migraine. Its multimodal actions warrant systematic pharmacological validation and clinical trials to establish its efficacy and safety in migraine management.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"13 ","pages":"Article 100150"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced immune fitness is associated with poorer physical and mental health of Turkish community pharmacy visitors","authors":"Lucia Mosquera Macia ,&nbsp;Emina Išerić ,&nbsp;Nurgül Nefçi ,&nbsp;Gökçe Çölkesenoğlu ,&nbsp;Serel Ulusoy ,&nbsp;Nilay Aksoy ,&nbsp;Joris C. Verster","doi":"10.1016/j.bbii.2025.100144","DOIUrl":"10.1016/j.bbii.2025.100144","url":null,"abstract":"<div><div>Adequate immune fitness, i.e. the body’s capacity to respond to health challenges (such as infections) by activating an appropriate immune response is vital to maintain health and prevent or resolve disease. Aim of the current survey among n = 450 Turkish pharmacy visitors was to investigate the sociodemographic, health, and lifestyle factors that are related to experiencing reduced immune fitness. The analyses revealed that individuals with reduced immune fitness reported significantly poorer general health and immune fitness, significantly poorer sleep, and significantly poorer mood, and a significantly lower quality of life. The analyses revealed significantly poorer immune fitness among individuals with a chronic disease, and those with a lower education level. A regression analysis evaluated possible predictors of reduced immune fitness. The strongest predictor of reduced immune fitness was having a chronic disease. Other significant contributing factors were older age, lower BMI, poorer sleep quality, greater anxiety, greater fatigue, lower hostility, and attaining a less healthy daily diet. In conclusion, reduced immune fitness is associated with having chronic diseases, and poorer physical and mental health.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"13 ","pages":"Article 100144"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145739337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yoga-based intervention to alleviate inflammation, pain, and reduce medication burden in sickle cell disease – A review and framework","authors":"Syed Zaeem Haider Zaidi,&nbsp;Mithila Manchenahalli Vasudev,&nbsp;Ramesh Nanjundaiah Mavathur","doi":"10.1016/j.bbii.2026.100152","DOIUrl":"10.1016/j.bbii.2026.100152","url":null,"abstract":"<div><div>Sickle cell disease (SCD) is a chronic hereditary hemoglobinopathy characterized by vaso-occlusive crises, inflammation, and progressive organ damage, leading to severe pain and disability. Current pharmacotherapies, such as hydroxyurea, <span>L</span>-glutamine, and crizanlizumab, can mitigate disease severity but are limited by their high costs, side effects, and accessibility challenges. Emerging evidence suggests that yoga, an integrative mind–body practice, may be a safe, feasible, and cost-effective adjunctive therapy for SCD. Biologically, yoga may mitigate inflammation (e.g., reducing IL-6, CRP, and TNF-α levels), improve autonomic balance and vascular function, and enhance sleep quality, thereby potentially decreasing vaso-occlusive crises and pain sensitization. Psychologically, yoga reduces stress, anxiety, depression, and pain catastrophizing while improving coping, resilience, and perceived control. Socially, yoga fosters peer support, empowerment, and cultural adaptability, which may alleviate stigma, improve adherence, and lessen healthcare burden. Preliminary trials in SCD populations have demonstrated the feasibility and acceptability of yoga, with trends toward pain reduction and enhanced quality of life, although the evidence remains limited by small sample sizes and methodological heterogeneity. Integrating yoga into SCD care may help reduce inflammation, pain, and medication dependence, particularly in low-resource settings. Larger randomized controlled trials combining clinical, psychological, and biomarker endpoints are warranted to establish the efficacy and optimize intervention protocols for sustainable and holistic SCD management. Given these limitations, this narrative review synthesizes broader evidence to construct a biopsychosocial framework that can provide theoretical foundation and guiding principles for future SCD-specific yoga research.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"13 ","pages":"Article 100152"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network pharmacology and experimental verification to explore the anti-depression mechanism of Ganmaidazao-Shanzha Decoction","authors":"Xinlang Yu ,&nbsp;Jiazhen Cai ,&nbsp;Zhangjie Wu ,&nbsp;Jianqing Li ,&nbsp;Ying Yin ,&nbsp;Yifan Chen ,&nbsp;Yan Lu ,&nbsp;Rui Ge ,&nbsp;Xin Zhou ,&nbsp;Hongli Dong ,&nbsp;Wenda Xue ,&nbsp;Wei Wang","doi":"10.1016/j.bbii.2026.100155","DOIUrl":"10.1016/j.bbii.2026.100155","url":null,"abstract":"<div><h3>Background</h3><div>To explore the pharmacological mechanism of the antidepressant-like effects of Ganmaidazao-Shanzha Decoction (GMS) through network pharmacological analysis and experimental verification.</div></div><div><h3>Methods</h3><div>The active ingredient and the target of action related to depression were clarified by searching the herb group identification, GeneCards and Drugbank, Pharmgkb, CTD, Disgenet databases, and the protein interaction relationship was obtained by using the String database, and the protein interaction network map was constructed by using Cytoscape software. We also performed gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of key targets of the antidepressant-like effects of GMS and predicted the core targets and pathways. Furthermore, BDNF pathway which involved in antidepressant-like effect of GMS was validated by mice model to validate the results of partial network pharmacology analysis.</div></div><div><h3>Results</h3><div>A total of 276 active ingredients and 1142 related targets of action were retrieved from GMS, and a total of 2164 common targets were obtained by mapping the obtained depression disease targets and drug targets. Protein interaction network analysis indicated that targets including AKT1, SRC, HSP90AA1, PRKACA, PIK3R1, PIK3CA and other targets may be the core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that the treatment of depression by GMS might include phosphorylation, synaptic plasticity and growth factor stimulus processes, and the signaling pathways might include AGE-RAGE signaling pathway in diabetic complications, Neurotrophin signaling pathway, and PI3K-Akt signaling pathway. The results of the in vivo tests showed that GMS could reverse the depressive behaviors induced by corticosterone in mice. The activity of GMS against depression was found to be mediated through neurotrophin signaling pathway by targeting the Brain-derived neurotropic factor (BDNF) signaling proteins and downstream synaptic proteins, promoting the c-fos positive cell restoration and finally leading to hippocampal neurogenesis in age difference.</div></div><div><h3>Conclusions</h3><div>Through the application of network pharmacology and in vivo validation experiments, this study revealed the active components and the potential targets of GMS for the treatment of depression, providing a theoretical basis for the research and clinical application of GMS.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"13 ","pages":"Article 100155"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extra virgin olive oil supplementation attenuates hippocampal inflammation in high-fat diet-induced obesity animals with a depressive phenotype","authors":"Ariadni Mesquita Peres ,&nbsp;Ricardo Maia Dantas ,&nbsp;Aline Candida Ferreira ,&nbsp;Ana Caroline Silva Silveira ,&nbsp;Letícia Cunha Pereira de Souza ,&nbsp;Giovana Barbosa Raphaelli ,&nbsp;Diorlon Nunes Machado ,&nbsp;Lucas dos Santos da Silva ,&nbsp;Jéssica Hauschild Taday ,&nbsp;Danusa Mar Arcego ,&nbsp;João Paulo Maires Hoppe ,&nbsp;Randriely Merscher Sobreira de Lima ,&nbsp;Patricia P. Silveira ,&nbsp;Carlos Alexandre Netto ,&nbsp;José Cláudio Fonseca Moreira ,&nbsp;Marina Concli Leite ,&nbsp;Daniel Pens Gelain ,&nbsp;Carla Dalmaz ,&nbsp;Rachel Krolow S.S. Bast","doi":"10.1016/j.bbii.2025.100137","DOIUrl":"10.1016/j.bbii.2025.100137","url":null,"abstract":"<div><div>Obesity and depression are major public health concerns that often co-occur. High-fat diets (HFD) in rodents are commonly used to model both conditions, triggering hippocampal inflammation. In this context, extra virgin olive oil (EVOO) supplementation, with its anti-obesogenic, anti-inflammatory, antioxidant and neuroprotective properties, shows potential as a therapeutic intervention. This study investigates the effects of EVOO supplementation in adult male and female rats receiving HFD. Depressive-like behavior was assessed through the Porsolt forced swim and splash tests, while neuroinflammation, activation of glial cells, and neuroplasticity-related proteins, were evaluated in the hippocampus. Our results showed that HFD induced depressive-like-behavior, which EVOO supplementation significantly alleviated by reducing immobility time and anhedonia. EVOO supplementation also reduced IL-1β, IL-6 and TNF-α levels and increased the immunocontent of neuroplasticity-related proteins in the hippocampus of female rats. In males with obesity, EVOO supplementation decreased glial fibrillary acidic protein (GFAP) and IL-6 levels in the hippocampus. Additionally, EVOO decreased the immunoreactivity of Toll-like receptor-4 (TLR-4) and ionized calcium-binding adaptor molecule-1 (IBA-1) in the hippocampus of both sexes. The clustering analysis made using the behavioral and neurochemical parameters measured in these animals further highlight the effectiveness of EVOO in attenuating HFD effects on these markers, with females displaying greater heterogeneity forming four distinct clusters and males exhibiting a clearer separation between groups. These findings suggest EVOO supplementation as a promising non-pharmacological strategy to counteract factors associated with obesity and depression, particularly by modulation of hippocampal neuroinflammation, astrocytic reactivity, and neuroplasticity.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"12 ","pages":"Article 100137"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sn-2 palmitate attenuates neuroinflammation in aged mice via sex-specific modulation of the microbiota-gut-brain axis","authors":"Lin Zhu ,&nbsp;En Thong Low ,&nbsp;Hong Zhang ,&nbsp;Zhenbo Xu ,&nbsp;Peijin Tong ,&nbsp;Jianchun Wan ,&nbsp;Boyan Gao ,&nbsp;Liangli (Lucy) Yu ,&nbsp;Yaqiong Zhang","doi":"10.1016/j.bbii.2025.100140","DOIUrl":"10.1016/j.bbii.2025.100140","url":null,"abstract":"<div><div>Previous studies have demonstrated that sn-2 palmitate promotes neurodevelopment in early-life hosts (e.g., infants and newly weaned mice). However, its neuroprotective effects in aged mice and the underlying mechanisms remain unclear. In this study, we employed 18-month-old C57BL/6 mice as an aging model. After six months of dietary supplementation with sn-2 palmitate at varying concentrations (47.62 %, 59.15 % or 75.79 %), both male and female aged mice exhibited attenuated neuroinflammation accompanied by the reduced expression of glial activation markers (IBA-1 and GFAP). Notably, this neuroprotective effect was mediated by regulating the microbiota-gut-brain axis in a sex-dependent manner and was most pronounced in aged mice supplemented with 75.79 % sn-2 palmitate. In females, it enriched gut microbiota belonging to the genera <em>Lachnoclostridium, Dubosiella,</em> and <em>Muribaculum,</em> up-regulated phenylalanine, tyrosine and tryptophan biosynthesis, and phenylalanine metabolism pathways in serum and enhanced fecal sphingolipid excretion, collectively reducing systemic inflammation. Meanwhile, the up-regulation of arginine and proline metabolism in the hippocampus enhanced its energy buffering capacity and stress resilience. In males, sn-2 palmitate increased the abundances of <em>Akkermansia, Parabacteroides,</em> and <em>Blautia</em> genera, which enhanced tryptophan metabolism and elevated its serum derivatives, while reducing circulating glycerolipid levels and promoting their fecal excretion. The tryptophan-glycerolipid metabolic regulation exerted a dual anti-inflammatory effect, suppressing systemic inflammation and directly attenuating neuroinflammation. Together, our findings provide novel insights into the neuroprotective potential of dietary sn-2 palmitate in aged models and establish a foundation for developing precision dietary interventions tailored to sex differences, with potential implications for improving brain health in aging populations.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"12 ","pages":"Article 100140"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and proteomic evidence supporting the significance of individualized homeopathic treatment in depression","authors":"Ubiratan Cardinalli Adler,&nbsp;Lia Lira Olivier Sanders","doi":"10.1016/j.bbii.2025.100141","DOIUrl":"10.1016/j.bbii.2025.100141","url":null,"abstract":"<div><div>This Letter to the Editor addresses concerns raised about our recently published N-of-1 trial on an individualized integrative approach for major depressive disorder. N-of-1 designs inherently control for baseline variability, as each participant serves as their own control across randomized treatment periods. The psychiatric diagnosis was confirmed by experienced clinicians using DSM-5 criteria, consistent with pragmatic practice. Although the participant entered the double-blind phase in remission, within-subject analyses showed a clinically meaningful 78 % improvement on the Beck Depression Inventory-II with homeopathic <em>Sulphur</em> compared with placebo, corroborated by parallel SF-12 Mental Component findings. Proteomic analyses further revealed immune-inflammatory modulation, offering biological convergence. These clinical and molecular findings support the validity of this individualized integrative approach and call for replication in more N-of-1 trials.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"12 ","pages":"Article 100141"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}