Pub Date : 2025-11-20DOI: 10.1016/j.bbii.2025.100141
Ubiratan Cardinalli Adler, Lia Lira Olivier Sanders
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 Sulphur 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.
{"title":"Clinical and proteomic evidence supporting the significance of individualized homeopathic treatment in depression","authors":"Ubiratan Cardinalli Adler, 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":"2025-11-20","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}
Pub Date : 2025-09-12DOI: 10.1016/j.bbii.2025.100140
Lin Zhu , En Thong Low , Hong Zhang , Zhenbo Xu , Peijin Tong , Jianchun Wan , Boyan Gao , Liangli (Lucy) Yu , Yaqiong Zhang
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 Lachnoclostridium, Dubosiella, and Muribaculum, 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 Akkermansia, Parabacteroides, and Blautia 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.
{"title":"Sn-2 palmitate attenuates neuroinflammation in aged mice via sex-specific modulation of the microbiota-gut-brain axis","authors":"Lin Zhu , En Thong Low , Hong Zhang , Zhenbo Xu , Peijin Tong , Jianchun Wan , Boyan Gao , Liangli (Lucy) Yu , 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":"2025-09-12","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}
Pub Date : 2025-08-30DOI: 10.1016/j.bbii.2025.100138
Francesco Bottaccioli , Anna Giulia Bottaccioli
The integrated care needs of a philosophical paradigm. Psychoneuroendocrineimmunology can be it, provided that a consensus is created on its profound meaning. What is Psychoneuroendocrineimmunology (PNEI)? It is not Neuroendocrinoimmunology. PNEI (also called PNI, Psychoneuroimmunology) describes the relationships of mutual influence between the psyche and biological systems and between the whole organism and the physical and social environment, showing the scientific inconsistency of the reductionist dogma that makes the psyche a mere epiphenomenon of brain activity. We are in a phase of research that allows the definitive overcoming of the dualistic conception of the human being without falling into the trap of the mind-brain identity, in the reduction of the psychic dimension to the biological one, from which it undoubtedly originates but on which it influences. To this end, it is essential to critique the philosophical foundations of contemporary reductionism, while, at the same time, highlighting the theoretical-conceptual paradigm that underlies PNEI research and the practice of treatments that integrate medicine and psychology, which descend from this paradigm.
{"title":"A systemic and dialectical paradigm for Psychoneuroendocrineimmunology and integrated care science","authors":"Francesco Bottaccioli , Anna Giulia Bottaccioli","doi":"10.1016/j.bbii.2025.100138","DOIUrl":"10.1016/j.bbii.2025.100138","url":null,"abstract":"<div><div>The integrated care needs of a philosophical paradigm. Psychoneuroendocrineimmunology can be it, provided that a consensus is created on its profound meaning. What is Psychoneuroendocrineimmunology (PNEI)? It is not Neuroendocrinoimmunology. PNEI (also called PNI, Psychoneuroimmunology) describes the relationships of mutual influence between the psyche and biological systems and between the whole organism and the physical and social environment, showing the scientific inconsistency of the reductionist dogma that makes the psyche a mere epiphenomenon of brain activity. We are in a phase of research that allows the definitive overcoming of the dualistic conception of the human being without falling into the trap of the mind-brain identity, in the reduction of the psychic dimension to the biological one, from which it undoubtedly originates but on which it influences. To this end, it is essential to critique the philosophical foundations of contemporary reductionism, while, at the same time, highlighting the theoretical-conceptual paradigm that underlies PNEI research and the practice of treatments that integrate medicine and psychology, which descend from this paradigm.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"12 ","pages":"Article 100138"},"PeriodicalIF":0.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926626","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}
Pub Date : 2025-08-29DOI: 10.1016/j.bbii.2025.100137
Ariadni Mesquita Peres , Ricardo Maia Dantas , Aline Candida Ferreira , Ana Caroline Silva Silveira , Letícia Cunha Pereira de Souza , Giovana Barbosa Raphaelli , Diorlon Nunes Machado , Lucas dos Santos da Silva , Jéssica Hauschild Taday , Danusa Mar Arcego , João Paulo Maires Hoppe , Randriely Merscher Sobreira de Lima , Patricia P. Silveira , Carlos Alexandre Netto , José Cláudio Fonseca Moreira , Marina Concli Leite , Daniel Pens Gelain , Carla Dalmaz , Rachel Krolow S.S. Bast
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.
{"title":"Extra virgin olive oil supplementation attenuates hippocampal inflammation in high-fat diet-induced obesity animals with a depressive phenotype","authors":"Ariadni Mesquita Peres , Ricardo Maia Dantas , Aline Candida Ferreira , Ana Caroline Silva Silveira , Letícia Cunha Pereira de Souza , Giovana Barbosa Raphaelli , Diorlon Nunes Machado , Lucas dos Santos da Silva , Jéssica Hauschild Taday , Danusa Mar Arcego , João Paulo Maires Hoppe , Randriely Merscher Sobreira de Lima , Patricia P. Silveira , Carlos Alexandre Netto , José Cláudio Fonseca Moreira , Marina Concli Leite , Daniel Pens Gelain , Carla Dalmaz , 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":"2025-08-29","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}
Pub Date : 2025-07-01DOI: 10.1016/j.bbii.2025.100136
Yuxuan Zhang , Gang Chen
{"title":"Personalized homeopathic treatment for Major Depressive Disorder: Insights from an N-of-1 trial and translational analysis","authors":"Yuxuan Zhang , Gang Chen","doi":"10.1016/j.bbii.2025.100136","DOIUrl":"10.1016/j.bbii.2025.100136","url":null,"abstract":"","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"11 ","pages":"Article 100136"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851930","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}
Aging is associated with chronic cerebral hypoperfusion (CCH). These blood flow age-related alterations might be attenuated by progesterone (P4), a neurosteroid which has been proven to exert pleiotropic neuroprotective effects in brain injury models. The aim of this study was to evaluate the effects of P4 on the blood-brain barrier (BBB) and on spatial learning and memory in rats subjected to CCH.
Methods
Male Sprague-Dawley rats (12–14 month-old) were distributed in groups: CCH+vehicle; CCH+P4 and SHAM. At 7 and 14 days, the function of the BBB, the tight junction proteins and inflammatory factor levels were evaluated. At 180 days spatial learning and memory were evaluated.
Results
CCH induced BBB dysfunction, alters tight junction protein, inflammation factors and spatial learning and memory. Treatment with P4 ameliorated these alterations.
Discussion
Our results suggest that P4 plays an important role in protecting the brain from hypoperfusion in old male rats.
{"title":"Progesterone restores blood-brain barrier and memory after chronic cerebral hypoperfusion in male rats","authors":"Maydelín Espadín , Miguel Cervantes , Angélica Coyoy-Salgado , Claudia Espinosa-Garcia , Beatriz Gómez-González , Gabriela Moralí","doi":"10.1016/j.bbii.2025.100132","DOIUrl":"10.1016/j.bbii.2025.100132","url":null,"abstract":"<div><h3>Introduction</h3><div>Aging is associated with chronic cerebral hypoperfusion (CCH). These blood flow age-related alterations might be attenuated by progesterone (P4), a neurosteroid which has been proven to exert pleiotropic neuroprotective effects in brain injury models. The aim of this study was to evaluate the effects of P4 on the blood-brain barrier (BBB) and on spatial learning and memory in rats subjected to CCH.</div></div><div><h3>Methods</h3><div>Male Sprague-Dawley rats (12–14 month-old) were distributed in groups: CCH+vehicle; CCH+P4 and SHAM. At 7 and 14 days, the function of the BBB, the tight junction proteins and inflammatory factor levels were evaluated. At 180 days spatial learning and memory were evaluated.</div></div><div><h3>Results</h3><div>CCH induced BBB dysfunction, alters tight junction protein, inflammation factors and spatial learning and memory. Treatment with P4 ameliorated these alterations.</div></div><div><h3>Discussion</h3><div>Our results suggest that P4 plays an important role in protecting the brain from hypoperfusion in old male rats.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"11 ","pages":"Article 100132"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144595516","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}
Pub Date : 2025-07-01DOI: 10.1016/j.bbii.2025.100133
Ubiratan Cardinalli Adler , Maristela Schiabel Adler , Renan dos Santos Nogueira , Márcio Normando Borges Coelho Filho , Eugênio de Moura Campos , Patrícia Andréa da Fonseca Magalhães , Antonio Brazil Viana Júnior , Suellen Monike do Vale Sabino , Annyta Fernandes Frota , Michelle Verde Ramo Soares , Anderson Carneiro Costa , Raelle Ferreira Gomes , Regina Celia Monteiro de Paula , Rosemayre Souza Freire , Eduardo Mello Barroso Filho , Carla Soraya Costa Maia , Felipe Domingos de Sousa , Allysson Allan de Farias , Francisco Luan Fonsêca da Silva , Caren Nádia Soares de Sousa , Lia Lira Olivier Sanders
Background
Major Depressive Disorder (MDD) treatment remains challenging. This N-of-1 study evaluated a personalized integrative homeopathic protocol for MDD. Methods: A 28-week, double-blind, randomized, placebo-controlled crossover trial assessed Sulphur fifty-millesimal potencies (LM4–7) effectiveness and safety in a 45-year-old female with MDD. The primary outcomes were Beck Depression Inventory-II (BDI-II) scores, and secondary outcomes included SF-12 and Clinical Global Impression Scale scores. We conducted Plasma proteomics and physicochemical analyses (SEM, DLS, ICP-MS) of Sulphur LM2–7.
Results
BDI-II scores increased significantly in the placebo group (P = 0.017), whereas no significant change was observed in the Sulphur-treated group (P = 0.243). Overall symptom improvement with homeopathy compared to placebo, controlling for baseline, was 78 % (p < 0.05). MCS-12 significantly decreased during placebo (P = 0.008) but remained stable during homeopathic treatment (P = 0.542). No significant PCS-12 changes were observed (P > 0.2). CGI-I scores improved during the run-in treatment but showed no further change during the N-of-1 trial. Sulfur-loaded LM formulations presented nanoparticles, as confirmed by SEM analysis, demonstrated distinct particle size characteristics via DLS, and exhibited quantifiable sulfur concentrations detected through ICP-MS. Proteomic analysis suggested that Sulphur treatment modulates immune response pathways, highlighting a potential mechanism underlying its antidepressant-like effects.
Conclusions
This personalized integrative homeopathic protocol demonstrated superior effectiveness to placebo in the studied individual. The physicochemical characteristics and proteomic findings indicate potential immunomodulatory effects mediated by nanomedicine mechanisms. However, further research involving larger cohorts is warranted to confirm these preliminary observations.
{"title":"A personalized, integrative approach in treating major depressive disorder: N-of-1 study with plasma proteome and physicochemical analysis of homeopathic preparations","authors":"Ubiratan Cardinalli Adler , Maristela Schiabel Adler , Renan dos Santos Nogueira , Márcio Normando Borges Coelho Filho , Eugênio de Moura Campos , Patrícia Andréa da Fonseca Magalhães , Antonio Brazil Viana Júnior , Suellen Monike do Vale Sabino , Annyta Fernandes Frota , Michelle Verde Ramo Soares , Anderson Carneiro Costa , Raelle Ferreira Gomes , Regina Celia Monteiro de Paula , Rosemayre Souza Freire , Eduardo Mello Barroso Filho , Carla Soraya Costa Maia , Felipe Domingos de Sousa , Allysson Allan de Farias , Francisco Luan Fonsêca da Silva , Caren Nádia Soares de Sousa , Lia Lira Olivier Sanders","doi":"10.1016/j.bbii.2025.100133","DOIUrl":"10.1016/j.bbii.2025.100133","url":null,"abstract":"<div><h3>Background</h3><div>Major Depressive Disorder (MDD) treatment remains challenging. This N-of-1 study evaluated a personalized integrative homeopathic protocol for MDD. Methods: A 28-week, double-blind, randomized, placebo-controlled crossover trial assessed <em>Sulphur</em> fifty-millesimal potencies (LM4–7) effectiveness and safety in a 45-year-old female with MDD. The primary outcomes were Beck Depression Inventory-II (BDI-II) scores, and secondary outcomes included SF-12 and Clinical Global Impression Scale scores. We conducted Plasma proteomics and physicochemical analyses (SEM, DLS, ICP-MS) of <em>Sulphur</em> LM2–7.</div></div><div><h3>Results</h3><div>BDI-II scores increased significantly in the placebo group (P = 0.017), whereas no significant change was observed in the <em>Sulphur</em>-treated group (P = 0.243). Overall symptom improvement with homeopathy compared to placebo, controlling for baseline, was 78 % (p < 0.05). MCS-12 significantly decreased during placebo (P = 0.008) but remained stable during homeopathic treatment (P = 0.542). No significant PCS-12 changes were observed (P > 0.2). CGI-I scores improved during the run-in treatment but showed no further change during the N-of-1 trial. Sulfur-loaded LM formulations presented nanoparticles, as confirmed by SEM analysis, demonstrated distinct particle size characteristics via DLS, and exhibited quantifiable sulfur concentrations detected through ICP-MS. Proteomic analysis suggested that <em>Sulphur</em> treatment modulates immune response pathways, highlighting a potential mechanism underlying its antidepressant-like effects.</div></div><div><h3>Conclusions</h3><div>This personalized integrative homeopathic protocol demonstrated superior effectiveness to placebo in the studied individual. The physicochemical characteristics and proteomic findings indicate potential immunomodulatory effects mediated by nanomedicine mechanisms. However, further research involving larger cohorts is warranted to confirm these preliminary observations.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"11 ","pages":"Article 100133"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767095","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}
Pub Date : 2025-07-01DOI: 10.1016/j.bbii.2025.100131
Jagrati Sharma , Saumya Subramanian , Puja Mali , Dipika Das Mahapatra , Divya Kanchibhotla
Background and purpose
Congenital hearing impairment possesses a significant challenge to children's quality of life (QoL). This quasi-experimental study investigates the potential benefits of a two-day yogic practice, Prajñā Yoga in enhancing the auditory skills and improving QoL among hearing impaired children.
Methods
The total sample size is 304 with 178 children in the intervention arm who received the daily yogic practice and 126 children in the waitlist control arm. Audiological assessments were done by Pure Tone Audiometry, Immittance Audiometry and reflexometry. To capture any hearing enhancement, QoL and behavioral improvement various psychometric scales were used. The assessments were done at Day 0, 3, 15 and 30 days of practice. Quantitative data were presented using Mean (SD) while the categorical values were done in the form of numbers and percentages. Paired t test was used to compare the data across different time points.
Results
The results revealed a significant improvement in hearing ability among the intervention group practitioners evidenced by a 10–15 dB decrease in hearing thresholds compared to the control group (p value <0.001). 91.5 % and 55 % of the participants in the intervention arm demonstrated an improvement in at least one ear and have turned responsive from non-responsive respectively. Additionally, the intervention group also demonstrated significant improvement in QoL, compared to the control group (p value <0.001).
Conclusion
With the growing rate of hearing impairment among children, the present study underscores the importance of Prajñā Yoga as a non-pharmacological solution to improve the QoL and enhance auditory abilities.
背景与目的继发性听力障碍是影响儿童生活质量的重要因素。这项准实验研究探讨了为期两天的瑜伽练习,Prajñā瑜伽在提高听力障碍儿童听觉技能和改善生活质量方面的潜在益处。方法总样本量为304例,干预组178例为每日瑜伽练习组,等候组126例为对照组。听力学评估采用纯音测听、阻抗测听和反射测听。为了捕捉任何听力增强、生活质量和行为改善,使用了各种心理测量量表。分别于训练第0、3、15、30天进行评估。定量数据采用均数(SD)表示,分类值采用数字和百分比表示。采用配对t检验比较不同时间点的数据。结果干预组从业人员的听力能力显著改善,听力阈值比对照组降低10-15 dB (p值<;0.001)。干预组中91.5 %和55 %的参与者分别在至少一只耳朵上表现出改善,并从无反应转变为反应。此外,与对照组相比,干预组的生活质量也有显著改善(p值<;0.001)。结论随着儿童听力障碍的增加,本研究强调Prajñā瑜伽作为一种非药物解决方案在改善生活质量和增强听觉能力方面的重要性。
{"title":"Enhancement of hearing capability among children with congenital sensorineural hearing impairment following the Prajñā Yoga: An Indian knowledge system based intervention","authors":"Jagrati Sharma , Saumya Subramanian , Puja Mali , Dipika Das Mahapatra , Divya Kanchibhotla","doi":"10.1016/j.bbii.2025.100131","DOIUrl":"10.1016/j.bbii.2025.100131","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Congenital hearing impairment possesses a significant challenge to children's quality of life (QoL). This quasi-experimental study investigates the potential benefits of a two-day yogic practice, Prajñā Yoga in enhancing the auditory skills and improving QoL among hearing impaired children.</div></div><div><h3>Methods</h3><div>The total sample size is 304 with 178 children in the intervention arm who received the daily yogic practice and 126 children in the waitlist control arm. Audiological assessments were done by Pure Tone Audiometry, Immittance Audiometry and reflexometry. To capture any hearing enhancement, QoL and behavioral improvement various psychometric scales were used. The assessments were done at Day 0, 3, 15 and 30 days of practice. Quantitative data were presented using Mean (SD) while the categorical values were done in the form of numbers and percentages. Paired t test was used to compare the data across different time points.</div></div><div><h3>Results</h3><div>The results revealed a significant improvement in hearing ability among the intervention group practitioners evidenced by a 10–15 dB decrease in hearing thresholds compared to the control group (p value <0.001). 91.5 % and 55 % of the participants in the intervention arm demonstrated an improvement in at least one ear and have turned responsive from non-responsive respectively. Additionally, the intervention group also demonstrated significant improvement in QoL, compared to the control group (p value <0.001).</div></div><div><h3>Conclusion</h3><div>With the growing rate of hearing impairment among children, the present study underscores the importance of Prajñā Yoga as a non-pharmacological solution to improve the QoL and enhance auditory abilities.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"11 ","pages":"Article 100131"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879894","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}
Pub Date : 2025-07-01DOI: 10.1016/j.bbii.2025.100135
Nalini Saini, Shalini Rai, Rupashri Nath, Anand More
Introduction
Iron deficiency anemia (IDA) affects nearly a quarter of the global population, disproportionately burdening women and children in resource-scarce settings like India, which reports the highest global incidence. Driven by inadequate iron intake, increased demand, poor absorption, or chronic blood loss, IDA impairs oxygen transport, physical capacity, cognition, and quality of life, delaying individual and societal progress. While global strategies like iron supplementation have curbed its prevalence, India lags behind. This study explored Ayurveda’s holistic framework, focusing on Pandu Roga, a condition mirroring IDA, and its unique emphasis on psychological triggers of excessive desire, anger, stress, fear, or sorrow as a contributing factor to this complex disorder. We investigated whether combining relaxation techniques (Pranayama and meditation) to mitigate the effects of the above mentioned psychological triggers, along with standard Ayurvedic treatments [Punarnavadi Mandoor (PM) and Dadimadi Ghrita (DG)], outperforms standalone therapy in managing IDA’s subjective and objective markers as a proof-of-concept study.
Materials and methods
In a parallel-arm clinical trial, 76 IDA patients were randomized into two groups of 38 each, following informed consent and strict eligibility criteria. Conducted from October 2023 to May 2024, the 30-day intervention assigned the experimental group PM and DG plus daily guided relaxation (via online/offline sessions), while the control group received only PM and DG. Efficacy was assessed through symptomatic and laboratory outcomes.
Observations and result
Both groups showed significant improvements in anemia symptoms, Pandu Roga features, hemoglobin, complete blood count (CBC), and serum ferritin. However, the relaxation-augmented group demonstrated greater gains in hemoglobin, CBC parameters, and ferritin, and superior reductions in psychological distress (Manasa Bhava) with statistically significant differences.
Conclusion
This study highlights the value of integrating psychological care with Ayurvedic treatment for IDA. Patients receiving relaxation alongside PM and DG exhibited enhanced symptom relief and biomarker improvements, suggesting a synergistic effect. Larger, longer-term multicentric trials are needed to confirm these findings.
{"title":"Enhancing iron deficiency anemia outcomes: Integrating psychological relaxation with ayurvedic treatment","authors":"Nalini Saini, Shalini Rai, Rupashri Nath, Anand More","doi":"10.1016/j.bbii.2025.100135","DOIUrl":"10.1016/j.bbii.2025.100135","url":null,"abstract":"<div><h3>Introduction</h3><div>Iron deficiency anemia (IDA) affects nearly a quarter of the global population, disproportionately burdening women and children in resource-scarce settings like India, which reports the highest global incidence. Driven by inadequate iron intake, increased demand, poor absorption, or chronic blood loss, IDA impairs oxygen transport, physical capacity, cognition, and quality of life, delaying individual and societal progress. While global strategies like iron supplementation have curbed its prevalence, India lags behind. This study explored Ayurveda’s holistic framework, focusing on <em>Pandu Roga</em>, a condition mirroring IDA, and its unique emphasis on psychological triggers of excessive desire, anger, stress, fear, or sorrow as a contributing factor to this complex disorder. We investigated whether combining relaxation techniques (<em>Pranayama</em> and meditation) to mitigate the effects of the above mentioned psychological triggers, along with standard Ayurvedic treatments [<em>Punarnavadi Mandoor</em> (PM) and <em>Dadimadi Ghrita</em> (DG)], outperforms standalone therapy in managing IDA’s subjective and objective markers as a proof-of-concept study.</div></div><div><h3>Materials and methods</h3><div>In a parallel-arm clinical trial, 76 IDA patients were randomized into two groups of 38 each, following informed consent and strict eligibility criteria. Conducted from October 2023 to May 2024, the 30-day intervention assigned the experimental group PM and DG plus daily guided relaxation (via online/offline sessions), while the control group received only PM and DG. Efficacy was assessed through symptomatic and laboratory outcomes.</div></div><div><h3>Observations and result</h3><div>Both groups showed significant improvements in anemia symptoms, Pandu Roga features, hemoglobin, complete blood count (CBC), and serum ferritin. However, the relaxation-augmented group demonstrated greater gains in hemoglobin, CBC parameters, and ferritin, and superior reductions in psychological distress (Manasa Bhava) with statistically significant differences.</div></div><div><h3>Conclusion</h3><div>This study highlights the value of integrating psychological care with Ayurvedic treatment for IDA. Patients receiving relaxation alongside PM and DG exhibited enhanced symptom relief and biomarker improvements, suggesting a synergistic effect. Larger, longer-term multicentric trials are needed to confirm these findings.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"11 ","pages":"Article 100135"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886092","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}
Pub Date : 2025-06-04DOI: 10.1016/j.bbii.2025.100128
Monalisa Das , G. Muralitharan , Sarashti Saini , Sanjib Patra
Sleep is an intricate physiological process that is essential to both mental and physical well-being. The microbiota-gut-brain axis may be a key factor in the etiology and pathophysiology of sleep disorders, according to mounting evidence that it, directly and indirectly, influences sleep behavior. Sleep problems are linked to altered gut microbial composition, and sleep deprivation causes malfunction of the gut microbiota. Because the gut microbiota produces many of the neurotransmitters involved in sleep, altered microbial diversity is also linked to disrupted sleep. By inhibiting the HPA axis, mindbody therapies such as yoga, tai chi, mindfulness-based cognitive therapy (MBCT), and mindful meditation primarily enhance sleep quality. The microbial community is also greatly impacted by mind-body treatment. Our hypothesis in this study is that mind-body medicine enhances the microbial population, which in turn improves the quality of sleep.
{"title":"Sleep, gut microbiota, and mind-body medicine","authors":"Monalisa Das , G. Muralitharan , Sarashti Saini , Sanjib Patra","doi":"10.1016/j.bbii.2025.100128","DOIUrl":"10.1016/j.bbii.2025.100128","url":null,"abstract":"<div><div>Sleep is an intricate physiological process that is essential to both mental and physical well-being. The microbiota-gut-brain axis may be a key factor in the etiology and pathophysiology of sleep disorders, according to mounting evidence that it, directly and indirectly, influences sleep behavior. Sleep problems are linked to altered gut microbial composition, and sleep deprivation causes malfunction of the gut microbiota. Because the gut microbiota produces many of the neurotransmitters involved in sleep, altered microbial diversity is also linked to disrupted sleep. By inhibiting the HPA axis, mindbody therapies such as yoga, tai chi, mindfulness-based cognitive therapy (MBCT), and mindful meditation primarily enhance sleep quality. The microbial community is also greatly impacted by mind-body treatment. Our hypothesis in this study is that mind-body medicine enhances the microbial population, which in turn improves the quality of sleep.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"11 ","pages":"Article 100128"},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231337","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}