T lymphopenia is a common phenomenon in the sepsis patients, closely related with secondary infection and patients death, whereas its mechanism is still largely unelucidated. Hence, it is urgent to study the mechanism underlying sepsis induced T lymphopenia and lower morbidity and mortality of septic infection. We performed Single-cell RNA-seq (scRNA-seq) and created an atlas of peripheral blood mononuclear cells (PBMCs) from sepsis patients and healthy volunteers (n = 3). To further illustrate mechanisms related to fundamental biological in sepsis, we investigated SNHG5 mediated T cell apoptosis. We collected blood samples of 3 sepsis patients and 3 healthy donors, separated PBMCs, and performed scRNA-seq to create a atlas of PBMCs. 7 cell clusters were identified and annotated, followed by differentially expressed genes and pathway analysis. Then, we systematically discussed the cellular heterogeneity, and generated gene expression patterns of 7 different cellular cluster in sepsis and healthy group. Further analysis DEG and further bioinformatics analysis of different cellular cluster indicated that SNHG5/miR-324-5p/CDK16 axis contributed to inflammatory T cell apoptosis in sepsis. And further inhibitory and functional experiments indicated that SNHG5/miR-324-5p/CDK16 axis contributed to inflammatory T cell apoptosis in sepsis. This study unveiled molecular mechanisms related to T lymphopenia in sepsis, such as cell fate decisions and modulation of SNHG5/miR-324-5p/CDK16 axis, making SNHG5 a promising therapeutic measurement for sepsis.

BACKGROUND:Adipose-derived stem cell exosome (ADSC-exo) has been reported to be effective in alleviating organ dysfunction in sepsis, including acute liver injury (ALI). Whether ADSC-exo protects the liver via suppression of vascular endothelial cell (VEC) ferroptosis is unclear. METHODS:We evaluated the viability and migration of VECs and their ferroptosis-related indices. To further elucidate this mechanism, we examined the Nrf2/GPX4 pathway. Cecal ligation and puncture (CLP) was performed to establish a sepsis model to observe the protective effect of ADSC-exo. The death rate and liver tissue injury were observed. We also evaluated inflammation- and ferroptosis-related indices. Next, we examined the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) pathway-related molecules to elucidate the underlying mechanism. RESULTS:ADSC-exo reduced cell injury and ferroptosis in VECs. ADSC-exo increased the expression and nuclear translocation of Nrf2. In the CLP-induced sepsis model, ADSC-exo relieved liver injury and reduced the death rate. Further observations showed that ADSC-exo significantly alleviated oxidative stress injury and ferroptosis in liver tissue, while remarkably increasing the expression of Nrf2 and GPX4. CONCLUSIONS:These findings demonstrate the remarkable ability of ADSC-exo to alleviate sepsis-induced ALI by mitigating endothelial cell ferroptosis, providing evidence for the potential clinical application of ADSC-exo in ALI therapy.

Background:Diabetic Wound (DW) is one of the most prevalent complications in diabetes patients, impairing patient wellbeing and quality of life severely. The pathogenesis of DW remains incompletely understood, hindering the development of targeted therapies. Methods:We analyzed single-cell RNA sequencing data and tissue samples from DW patients and healthy controls to investigate characteristic of DW. A high-glucose (30 mM) stimulation model was used to mimic Vascular endothelial cells （VECs) injury in vitro. We evaluated the effects of BAI1 on high-glucose-induced VECs dysfunction, cellular senescence, mitochondrial DNA (mtDNA) leakage, and cGAS-STING pathway activation. To enable topical wound delivery, BAI1 was loaded into mesoporous silica nanoparticles and encapsulated within a polyvinyl alcohol-alginate-tannic acid-borax composite hydrogel. A diabetic mouse wound model was established to assess the therapeutic efficacy of the BAI1-loaded hydrogel. Results:Single-cell sequencing and histopathological analyses revealed severe VECs injury in diabetic wounds, accompanied by STING activation and cellular senescence. In vitro, high glucose induced mtDNA leakage, cGAS-STING activation, and senescence in VECs. BAI1 treatment attenuated mtDNA leakage, suppressed STING activation, reduced senescence, and restored VECs function. The BAI1-loaded hydrogel significantly accelerated wound closure and improved healing quality in diabetic mice. Tissue analysis further demonstrated that the hydrogel reduced STING activation and senescence markers in wounds. Conclusion:mtDNA leakage in VECs drive cellular senescence and contribute to impaired healing in diabetic wounds. BAI1 alleviates senescence by inhibiting BAX, thereby reducing mtDNA release and subsequent cGAS-STING activation. The BAI1-PSTB-Hydrogel is a promising topical dressing for DW, with broad clinical translation potential.

Objective:This study aims to summarize current perspectives on the underlying mechanisms, conceptual frameworks, and potential clinical implications of pain catastrophizing (PC). Methods:A narrative review approach was employed. Results:Existing studies suggest that PC may be associated with functional activity in several brain regions, including the anterior cingulate cortex, amygdala, and prefrontal cortex, which are involved in pain perception and emotional regulation. From a psychosocial perspective, catastrophizing has been linked to psychological distress, social support, and behavioral responses to pain. Various interventions, including psychological therapies, pain neuroscience education, exercise-based approaches, and complementary therapies have been explored as potential strategies for addressing PC. However, findings across studies remain heterogeneous. Discussion:This study integrates current evidence on neurobiological mechanisms and psychosocial models related to PC and discusses their potential clinical implications. By summarizing existing findings and highlighting areas of uncertainty, this work aims to provide a more comprehensive understanding of the multidimensional nature of PC and may inform future research and clinical approaches in chronic pain management.

Oral lichen planus (OLP) is a recalcitrant inflammatory disease with potential for malignant transformation, involving a cytotoxic CD8+ T cell-mediated basal keratinocyte apoptosis. However, it lacks an appropriate mouse model for study. Here we developed an OLP-like mouse model using topical oxazolone to induce a delayed-type hypersensitivity-mediated oral lichenoid reaction. Histological and ultrastructural analysis confirmed hallmark pathological features of OLP, including band-like CD8+ T cell infiltration and basal cell damage as well as the presence of Civatte bodies. Comparative transcriptomic analysis revealed significant similarity between RNA-Seq profiles of the mouse model and human OLP lesions, highlighting shared upregulated genes and enriched pathways, particularly those related to IFN-γ signaling and cytotoxic T cell activity. Functional studies demonstrated that the OLP phenotype depended on IFN-γ, with local priming by IFN-γ intensifying the disease through upregulation of major histocompatibility complex class I. Additionally, the absence of Langerhans cells exacerbated disease severity in vivo. Therapeutic evaluation showed that the JAK inhibitors baricitinib and ruxolitinib effectively reduced disease burden and provided mechanistic insights. In conclusion, this OLP-like mouse model recapitulates key immunopathological and transcriptomic features of human OLP, offering a robust platform for dissecting disease mechanisms and evaluating novel therapeutic strategies.

Sepsis, a systemic inflammatory response syndrome induced by infection, has seen a rising incidence in recent years, partly attributed to environmental factors. Several studies have suggested that TCDD, a toxic environmental pollutant, may contribute to an elevated risk of sepsis. As a Class I human carcinogen, TCDD disrupts normal vascular and immune system functions—critical risk factors for sepsis onset. However, the key targets and underlying mechanisms by which TCDD influences sepsis remain unclear. Through network toxicology, transcriptomics, machine learning, and Mendelian randomization, the biomarkers PPARG and CASPASE-3 were identified, both of which are significantly associated with oxidative phosphorylation and other signaling pathways. These biomarkers also correlate with γδT cell infiltration in the immune response. Molecular docking studies confirm the stable interaction between TCDD, PPARG, and CASPASE-3, supporting their involvement in sepsis progression. A single-cell dataset was used to analyze the dynamic changes of key immune cells in sepsis pathogenesis, highlighting their connection to PPARG and CASPASE-3. The study conducted rigorous validation and in-depth analysis of the identified biomarkers by incorporating an external validation set and single-cell data, significantly strengthening the reliability of the results. This comprehensive approach offers valuable clues for identifying potential therapeutic targets for sepsis.

Exosomes have emerged as central mediators in sepsis pathogenesis and therapy. Exosomes play an important role in cell communication by transferring functional proteins, metabolites, and nucleic acids to recipient cells. Recently, Low-immunogenic exosomes serve as novel biomarkers in sepsis, and they confer a 46% enhancement in survival benefit in animal models. However, exosomes drive the early inflammatory storm and late immune paralysis in sepsis. There are also limitations related to heterogeneity and translational barriers. Therefore, this review discusses the basic signaling pathways underlying the bidirectional effects of exosomes in the pathogenesis and treatment of sepsis, the interaction between organ dysfunction and exosomes in sepsis, the current progress in exosome therapy for sepsis, as well as the challenges and limitations faced in this field. In summary, exosomes have bright prospects in diagnosis and clinical translation, as well as the potential for standardized production.

Background:The timely administration of platelet transfusions is critical for patient survival, and the clinical demand for platelet transfusions has been steadily increasing. However, platelet storage lesions (PSLs) that develop during in vitro preservation exacerbate these shortages. The PSL is significantly influenced by various factors, including temperature, gas composition, and buffering systems. Strategies to mitigate PSLs and improve platelet storage have been actively explored in recent years. Objectives:This study aimed to investigate whether elevated carbon dioxide (CO2) levels improve platelet quality and functionality during storage. Methods:Platelet concentrates from 28 donors were stored under control or 3% CO2 conditions at 22 ± 2 °C for up to 7 days. Platelet quality was evaluated through scanning electron microscopy, adhesion, aggregation, clot contraction, activation, apoptosis assays, blood gas, adenosine triphosphate, metabolomics analyses, and in vivo thrombosis and survival tests. Results:Our findings indicate that increasing the CO2 concentration in the storage environment mitigates PSLs and improves platelet quality. Conclusion:Our study highlights the potential benefits of utilizing a high CO2 storage environment to improve platelet preservation, offering a promising method to address clinical platelet shortages.

Our study seeks to provide a theoretical foundation for the clinical use of cold-stored platelets (CSPs) by interpreting ultrastructural images and quantitatively analyzing structural changes. CSPs, room temperature -stored platelets (RTPs), and delayed CSPs (delayed-CSPs) were continuously observed using scanning electron microscopy and transmission electron microscopy at eight time points. Super-resolution fluorescence microscopy was employed to observe changes in platelet microtubules and mitochondrial structure and function, whereas platelet counts, metabolism, and relevant functional indicators were measured concurrently. Quantitative statistical analysis of platelet size, morphology, canalicular systems, and five organelles was performed under electron microscopy. In CSPs stored for 1 day, the platelet shape changed from circular or elliptical to spherical, with size decreasing from 2.8 pound 2.2 mm to 2.0 pound 2.0 mm. CSPs exhibited wrinkling and reorganization of platelet microtubule proteins, with organelles aggregating toward the central region. CSPs stored for 14 days and delayed-CSPs for stored for 10 days exhibited numerous structurally intact and active cells. The percentage of structure-intact active cells was 92% in both groups, respectively. RTPs stored for 5 and 7 days showed minimal changes in size, a normal microtubule skeleton, and were primarily in a resting state. However, RTPs stored for 10 and 14 days displayed swelling, irregular disintegration of the microtubule skeleton, and the presence of membranous structures and vacuolated cells. The percentage of structure-intact active cells was only 45% and 7%, respectively. Our findings confirmed that the maximum storage time of platelets was 5-7 days for RTPs, within 10 days for delayed-CSPs, and 14 days for CSPs. (c) 2024 International Society for Experimental Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Transfusions of platelets are often used as prophylaxis in patients with hematologic malignancies and as treatment for active bleeding. However, platelets are in short supply due to the fact that they could only be kept for 5-7 days in vitro and they lose some of their functionality as a result of platelet storage lesions. To address this issue, refrigeration, cryopreservation and platelet additive solutions have been researched to determine their abilities to extend platelet storage duration. However, refrigerated platelets are quickly cleared after transfusion, while platelets in platelet additive solutions still present issues such as platelets quality and the risk of allergic reactions. Recent studies showed that changes in lipid metabolites during platelet storage and inadequate of fatty acid metabolism may also limit platelet shelf life and function. In this review, we address the principles of lipid metabolism during platelet storage and discuss the strategies for effective platelet storage systems. The findings of this review highlight the role of lipid metabolism during platelet storage, providing insights into future research focused on extending the preservation period and function of platelet.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common drug-resistant bacteria that cause community and hospital infections. As one of the most common "superbugs" and the pathogen with the highest global incidence of hospital-acquired infections, MRSA has developed resistance to multiple antibiotics, posing a serious threat to public health. The rapid emergence and spread of multidrug resistance have increased the urgent need for new antimicrobial strategies and agents to combat MRSA-associated infections. In recent years, platelets have been widely recognized to play an important role in human immune defense. We have previously reported that platelets inhibit MRSA by inducing hydroxyl radical (OH●)-mediated apoptosis-like cell death. To further explore the platelet antibacterial mechanism, supernatants from co-culture of platelets and MRSA in vitro were used for proteomic analysis. Based on our observations using confocal and immunoelectron microscopy, we found a previously unrecognized platelet antimicrobial peptide, dermcidin (DCD), in the alpha (α-) granules. Furthermore, after co-culturing with MRSA in vitro, activated platelets secreted large amounts of DCD. Additionally, we confirmed that DCD displayed anti-MRSA activity in a concentration-dependent manner and contributed to the inhibition of MRSA growth by platelets in vitro. Our findings provide important insights into the immune defense functions of platelets.IMPORTANCEThe emerging multidrug resistance in many pathogenic bacterial species poses a serious problem worldwide. Methicillin-resistant Staphylococcus aureus (MRSA), one of the most common gram-positive pathogenic bacteria, has also evolved strains with multidrug resistance. This calls for the urgent development of novel and effective treatments or bactericidal agents to mitigate this issue in clinical settings. In this study, we identified for the first time a previously unrecognized platelet antimicrobial peptide, DCD, which impedes the proliferation of MRSA and promotes the antibacterial effect of platelets on MRSA. Our findings enrich our understanding of platelet physiological function and antibacterial mechanisms and provide new insights into the development of novel natural antimicrobial agents for controlling infections.

TBI and shock are common conditions in emergency departments, with the combination of both accounting for approximately 15%-30% of severe trauma cases. This study, based on the MIMIC-IV database, included 1144 TBI and 3102 shock patients, analyzing the clinical significance of SIRI, LMR, and PIV in these patients. The findings revealed a strong association between these biomarkers and baseline clinical characteristics as well as long-term survival outcomes, with a notable nonlinear relationship. Among these, LMR, an easily accessible immuno-inflammatory marker, demonstrated the highest prognostic predictive value for both patient groups and serves as a practical tool for assessing immune imbalance and prognostic risk in TBI and shock patients. These results lay a critical foundation for monitoring and stratifying inflammatory status in critically ill patients. However, the clinical translational value of these biomarkers warrants further validation through prospective studies and mechanistic investigations.

Traumatic brain injury has a high neurological morbidity, it is characterized by structural and physiological damage to brain function caused by external forces. Extensive and sustained damage mediated by neuroimmune and neuroinflammation may be closely associated with the prolonged course of TBI and the worsening of its prognosis. Tumor necrosis factor-alpha, one of the pro-inflammatory mediators, has been identified as a key regulator of the inflammatory response. It has attracted attention for binding to two different receptors, thereby initiating distinct signal transduction pathways. It has been found that there is a lack of relevant summaries of the different factors that make the pro-inflammatory or anti-inflammatory effects of TNF-α in TBI vary significantly. Therefore, this review examines the fundamental signaling pathways that regulate TNF-α in TBI in both the neuroimmune and inflammatory responses. It also reviews the progress of research on the pharmacological and physical technologies that target TNF-α for the treatment of TBI. The review emphasizes the biological effects of TNF-α as a receptor and ligand, as well as current difficulties and challenges.

Background Because no clinically approved NLRP3 inhibitors are currently available, the identification of novel small-molecule candidates with optimal pharmacological and safety profiles is urgently needed. In this study, we rationally selected and systematically evaluated clinically relevant small-molecule NLRP3 inhibitors for the potential treatment of sepsis using an integrated computational and experimental strategy. Methods A semi-empirical (PM6)–optimized structure-based virtual screening of 34 clinically relevant NLRP3 inhibitors was conducted via molecular docking, followed by 50 docking runs with 20 generated poses for each ligand to ensure conformational reliability. The top-ranked compounds were subjected to the prediction of ADME/T properties, assessment of cytotoxicity, qPCR, and mechanistic correlation through density functional theory (DFT), potential energy surface (PES) analysis, and molecular dynamics (MD) simulations. Results: Among the tested inhibitors, ZYIL1 exhibited the strongest binding affinity (–7.23 kcal/mol) and superior pharmacokinetic stability, with moderate plasma protein binding and low predicted hepatotoxicity. ZYIL1 demonstrated potent suppression of inflammatory cytokines (IL-1β, IL-6, TNF-α, and NLRP3) comparable to MCC950 in vitro. DFT and MD analyses revealed that ZYIL1 has greater polarizability, lower HOMO–LUMO energy gap, and higher binding free energy (–49.46 kcal/mol) than MCC950, indicating superior electronic stability and binding dynamics. Conclusion This integrated multilevel approach identified ZYIL1 as a highly promising NLRP3 inhibitor with balanced pharmacological properties and strong molecular stability. The integrated multilevel screening strategy provides a robust framework for accelerating the development of targeted therapy for sepsis, requiring further biological and clinical validation.

INTRODUCTION:Eczematous cheilitis is a common manifestation in patients with atopic dermatitis, and restoration of lip barrier function is essential for effective management. Wet wrap dressing is a widely used adjuvant therapy for atopic dermatitis lesions; a similar approach may be beneficial for treating atopic cheilitis. This study aimed to evaluate the short-term effects of saline gauze wet dressing on lip barrier function and to compare the clinical efficacy of this method, as an adjunct to standard therapy, in patients with eczematous cheilitis. METHODS:Patients with eczematous cheilitis and age-matched healthy volunteers were enrolled. Lip barrier function was assessed via transepidermal water loss, stratum corneum hydration (SCH), pH, and erythema values. Short-term changes were measured at 15, 30, and 60 min after application of saline gauze wet dressing. In addition, a case-control design was used to compare the 7-day efficacy of gauze wet dressing as adjuvant therapy combined with topical glucocorticoid and petroleum jelly versus standard therapy alone. RESULTS:Compared with healthy controls, patients with eczematous cheilitis demonstrated impaired lip barrier function. Application of saline gauze wet dressing significantly improved SCH and normalized pH within 30 min, with sustained barrier restoration over the 7-day treatment period. The adjuvant therapy group showed significantly greater clinical improvement than controls, including marked resolution of fissures and erythema and enhanced barrier function. CONCLUSION:Saline gauze wet dressing, as an adjunct to standard topical therapy, provides a simple, convenient, and cost-effective option for improving lip barrier function and accelerating clinical recovery in eczematous cheilitis, thereby enhancing therapeutic outcomes and patient satisfaction.

BackgroundBlunt chest trauma, commonly caused by traffic accidents, falls, and violent incidents, results in both direct mechanical injury to the thoracic cavity—leading to increased intrathoracic pressure and vascular rupture—and indirect effects on the central nervous system (CNS), causing extensive damage that severely impacts patient health and quality of life. Akkermansia muciniphila (AKK), a probiotic bacterium inhabiting the gut mucus layer, modulates gut microbiota and metabolites, with potential therapeutic effects on various neurological disorders through the gut-brain axis.MethodsMice were divided into four groups: control, trauma, trauma+PBS, and trauma+AKK. AKK bacterial suspension was administered via gavage for three weeks. Behavioral tests including the OFT, EPM, NORT, and Y-maze were conducted to assess anxiety-like behaviors and cognitive function. Neuroinflammatory markers in the hippocampus were measured using qPCR, immunofluorescence, and Western blot. Gut microbiota and metabolites were analyzed through 16S rRNA sequencing and metabolomics.ResultsMice subjected to blunt chest trauma displayed emotional abnormalities and cognitive deficits. AKK treatment significantly alleviated anxiety-like behaviors and improved cognitive function, reduced pro-inflammatory cytokine levels in the hippocampus, and reshaped gut microbiota composition. AKK also modulated the expression of metabolites linked to neuroinflammation and cognitive function, upregulated BDNF and TrkB, and decreased IBA1, suggesting it enhances cognitive function by modulating neuroinflammation and the BDNF/TrkB signaling pathway.ConclusionsAKK mitigates cognitive impairment and neuroinflammation after blunt chest trauma by modulating gut microbiota and metabolites. Targeting the gut-brain axis may offer new strategies for preventing and treating trauma-induced neurological disorders.

Background and objective Exertional heatstroke (EHS) mainly occurs in healthy young people with rapid onset and high mortality. EHS immune disorders can cause systemic inflammatory responses and multiple organ failure; however, the underlying mechanisms remain unclear. As high mobility group box 1 (HMGB1) is a prototypical alarmin that activates inflammatory and immune responses, this study aimed to investigate the effect and mechanism of HMGB1 in the pathogenesis of EHS.Methods Peripheral blood mononuclear cell (PBMC) transcriptome sequencing of healthy volunteers, classical heatstroke patients, and EHS patients was performed. A mouse model of EHS was established and murine tissue damage was evaluated by H&E staining. HMGB1 localization and release were visualized using immunofluorescence staining. Human umbilical vein endothelial cells (HUVECs) and THP-1 cells were co-cultured to study the effects of HMGB1 on macrophages. A neutralizing anti-HMGB1 antibody was used to evaluate the efficacy of EHS treatment in mice.Results Plasma and serum HMGB1 levels were significantly increased in EHS patients or mice. EHS-induced endothelial cell pyroptosis promoted HMGB1 release in mice. HMGB1 derived from endothelial cell pyroptosis enhanced macrophage pyroptosis, resulting in immune disorders under EHS conditions. Administration of anti-HMGB1 markedly alleviated tissue injury and systemic inflammatory responses after EHS.Conclusions The release of HMGB1 from pyroptotic endothelial cells after EHS promotes pyroptosis of macrophages and systemic inflammatory response, and HMGB1-neutralizing antibody therapy has good application prospects for EHS.

Platelet-rich plasma (PRP) has significant potential for various applications and holds clinical value in regenerative medicine. Cryopreservation is used to extend the preservation period of PRP, facilitating its clinical application. However, the potential negative effects of long-term cryopreservation on platelet storage lesion are still uncertain. In this study, PRP was stored at − 30 °C or − 80 °C. Platelet count, apoptosis, reactive oxygen species (ROS) content, and CD62P expression were assessed on the 14th and 28th days. The study also evaluated platelet mitochondria morphology and function, serotonin (5-HT) secretion by platelets, and the inflammatory activating effect of cryopreserved platelets in PRP. The results showed that there were no significant differences in platelet count, the content of 5-HT, and inflammatory effects between fresh PRP and PRP cryopreserved at both − 30 °C and − 80 °C. However, there was an increase in ROS level, apoptosis, and CD62P level after cryopreservation at both temperatures. Additionally, the levels of ROS, apoptosis, and CD62P in platelets were similar after storage at − 30 °C and − 80 °C. The main difference observed was that the morphology and function of mitochondria were severely damaged after storage at − 30 °C, while they were less affected at − 80 °C. Based on these findings, it can be concluded that storing PRP at − 80 °C is more suitable for achieving a better therapeutic effect in clinical applications, but cryopreservation could not replace the current standard.

Background The incidence of exertional heat stroke (EHS) escalates during periods of elevated temperatures, potentially leading to persistent cognitive impairment postrecovery. Currently, effective prophylactic or therapeutic measures against EHS are nonexistent.Methods The selection of days 14 and 23 postinduction for detailed examination was guided by TEM of neuronal cells and HE staining of intestinal villi and the hippocampal regions. Fecal specimens from the ileum and cecum at these designated times were analyzed for changes in gut microbiota and metabolic products. Bioinformatic analyses facilitated the identification of pivotal microbial species and metabolites. The influence of supplementing these identified microorganisms on behavioral outcomes and the expression of functional proteins within the hippocampus was subsequently assessed.Results TEM analyses of neurons, coupled with HE staining of intestinal villi and the hippocampal region, indicated substantial recovery in intestinal morphology and neuronal injury on Day 14, indicating this time point for subsequent microbial and metabolomic analyses. Notably, a reduction in the Lactobacillaceae family, particularly Lactobacillus murinus, was observed. Functional annotation of 16S rDNA sequences suggested diminished lipid metabolism and glycan biosynthesis and metabolism in EHS models. Mice receiving this intervention (EHS + probiotics group) exhibited markedly reduced cognitive impairment and increased expression of BDNF/TrKB pathway molecules in the hippocampus during behavioral assessment on Day 28.Conclusion Probiotic supplementation, specifically with Lactobacillus spp., appears to mitigate EHS-induced cognitive impairment, potentially through the modulation of the BDNF/TrKB signaling pathway within the hippocampus, illustrating the therapeutic potential of targeting the gut-brain axis.