Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology最新文献

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Stimulant Use, HIV, and Plasma Metabolites Among Men. 男性兴奋剂使用、HIV和血浆代谢物
IF 6.2
Emily M Cherenack, Michaela E Larson, Kevin Murray, Zachary J Mayer, Candace Guerrero, Courtney A Broedlow, Nichole R Klatt, Adam W Carrico
{"title":"Stimulant Use, HIV, and Plasma Metabolites Among Men.","authors":"Emily M Cherenack, Michaela E Larson, Kevin Murray, Zachary J Mayer, Candace Guerrero, Courtney A Broedlow, Nichole R Klatt, Adam W Carrico","doi":"10.1007/s11481-025-10223-4","DOIUrl":"https://doi.org/10.1007/s11481-025-10223-4","url":null,"abstract":"<p><p>Metabolomics can be used to identify biological targets to mitigate the negative impacts of HIV and stimulant use on neuroimmune and cardiometabolic functioning. However, studies are needed to characterize the plasma metabolome among sexual minority men (SMM) in the context of independent and co-occurring HIV and stimulant use. From 2020 to 2022, we collected plasma samples and assessed biologically confirmed HIV status and stimulant use among 61 community-recruited SMM in Miami, Florida. Cross-sectional bivariate analyses and multivariable regressions correcting for false discovery rate compared 390 mass spectrometry-based plasma metabolites across four HIV/stimulant use groups: (1) living without HIV and no stimulant use (HIV-STIM-), (2) living with HIV and no stimulant use (HIV + STIM-), (3) living without HIV with stimulant use (HIV-STIM +), and (4) living with HIV with stimulant use (HIV + STIM +). Six metabolites showed differences between HIV/stimulant use groups at p < 0.05 in both Kruskal-Wallis tests and linear regressions: choline, tryptophan, two lysophosphatidylcholines, one triacylglyceride, and one dihexosylceramide. After correcting for false discovery rate, in linear regressions controlling for BMI and age, the HIV + STIM + group had lower aspartic acid than the HIV-STIM- group, higher lysophosphatidylcholine a C18:1 than the HIV-STIM + group, and higher triacylglyceride(20:3_34:0) than the HIV-STIM- and HIV + STIM- groups. In SMM, co-occurring stimulant use and HIV were associated with perturbations in certain metabolites. Metabolites such as aspartic acid and lysophosphatidylcholines are potentially involved in immune dysregulation, addiction, energy use, and cardiovascular disease. Trials of interventions to reduce stimulant use could elucidate its causal relationship to metabolites.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"68"},"PeriodicalIF":6.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328002","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}
引用次数: 0
Puerarin Improves Cancer-Induced Bone Pain by Recovering Mitochondrial Dysfunction in the Spinal Cord. 葛根素通过恢复脊髓线粒体功能障碍改善癌症引起的骨痛。
IF 6.2
Gege Sheng, Yin Wu, Hongyan Liu, Peigen Zhang, Zhipeng Zhang, Liangzhu Yu, Menglin Cheng, Haili Zhu
{"title":"Puerarin Improves Cancer-Induced Bone Pain by Recovering Mitochondrial Dysfunction in the Spinal Cord.","authors":"Gege Sheng, Yin Wu, Hongyan Liu, Peigen Zhang, Zhipeng Zhang, Liangzhu Yu, Menglin Cheng, Haili Zhu","doi":"10.1007/s11481-025-10224-3","DOIUrl":"https://doi.org/10.1007/s11481-025-10224-3","url":null,"abstract":"<p><p>Cancer metastases induce bone pain and central sensitization in the spinal cord. Mitochondrial dysfunction is associated with pian signal transmission and involved in cancer-induced bone pain. Pueratin (Pue) is a natural isoflavone compound that works as a potential natural neuroprotective agent. However, the mechanisms of Pue on cancer pain remain unclear. In this study, a cancer-induced bone pain (CIBP) rat model was established and Pue was administered intrathecally. As a result, CIBP model rats exhibited as the evoked mechanical pain, thermal pain, and spontaneous pain, the elevated neurological damage and mitochondrial dysfunction in the spinal cord. Pue administration improved pain related behaviors, decreased the neuronal activity, reduced NLRP3 inflammasome-mediated inflammation, and elevated mitochondrial dysfunction in the spinal cords of CIBP rats. Proteomical data showed that in the spinal synaptosomes, 59 differentially expressed proteins (DEPs) were significantly up-regulated while 128 DEPs were down-regulated. Among them, 5 genes were found to be overlapped for CIBP and Pue-potential targets and Src was belonged to the hub genes. Database analysis and experimental assay showed that Pue bound with Src at the affinity of 7.9 ± 0.2 µM, and decreased Src level and phosphorylation in the spinal cord of CIBP rats and in primary astrocytic cells. In addition, Pue also recovered levels of mitochondrial membrane potential and reactive oxygen species, and decreased inflammation in primary astrocytic cells. To summarize, Pue inhibits spinal Src activity, restores mitochondrial function, reduces central sensitization in the spinal cord, and relieves cancer-induced bone pain. This study may provide a basis for the application of Pue on the relief of cancer pain.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"67"},"PeriodicalIF":6.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259552","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}
引用次数: 0
The Dopaminergic and Anti-Neuroinflammatory Properties of Functionalized Nanoliposomes Containing Levodopa and Ibuprofen and Conjugated with Anti-Alpha-Synuclein Aptamer. 含有左旋多巴和布洛芬并与抗-突触核蛋白适配体偶联的功能化纳米脂质体的多巴胺能和抗神经炎症特性。
IF 6.2
Sara Mostafa-Tehrani, Mostafa Saffari, Ebrahim Balali, Ramona Khadivi, Ali Jebali
{"title":"The Dopaminergic and Anti-Neuroinflammatory Properties of Functionalized Nanoliposomes Containing Levodopa and Ibuprofen and Conjugated with Anti-Alpha-Synuclein Aptamer.","authors":"Sara Mostafa-Tehrani, Mostafa Saffari, Ebrahim Balali, Ramona Khadivi, Ali Jebali","doi":"10.1007/s11481-025-10227-0","DOIUrl":"https://doi.org/10.1007/s11481-025-10227-0","url":null,"abstract":"<p><p>The purpose of this study was to design, synthesize, characterize, and evaluate the functionalized nanoliposomes containing levodopa and ibuprofen and conjugated with Anti-alpha-synuclein aptamer (FNLLICAASA). In this study, different aptamer sequences were designed and the best aptamer was selected. Then, the FNLLICAASA was synthesized, characterized, and the amount of dopamine level changes in SH-SY5Y cells after exposure to FNLLICAASA was evaluated. Also, the interferon-gamma (INFG) expression was assessed. The binding of FNLLICAASA to SH-SY5Y cells was also investigated using a fluorescent microscope and flow cytometry. The results of molecular docking and molecular dynamics simulation showed that aptamer APT46 with GAGGAG sequence was the best-chosen aptamer. The FNLLICAASA have a size range of 120 to 310 nm with an average positive zeta potential of 30 mV. The dopamine level change was increased in treated SH-SY5Y nerve cells, indicating the dopaminergic property of FNLLICAASA. Also, the expression of INFG was decreased in treated SH-SY5Y nerve cells, indicating the anti-neuroinflammatory property of FNLLICAASA. The binding tests showed the targeted binding of synthesized nanoliposomes to alpha-synuclein molecules on the cell surface of SH-SY5Y cells.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"66"},"PeriodicalIF":6.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251160","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}
引用次数: 0
Extracellular Vesicles from Peripheral Blood Mononuclear Cells of Hyperammonemic Rats Induce Neuroinflammation in Hippocampus, Impairing Memory and Learning in Normal Rats. 高氨血症大鼠外周血单核细胞胞外泡诱导海马神经炎症,损害正常大鼠的记忆和学习能力。
IF 6.2
Paula Izquierdo-Altarejos, Adrià López-Gramaje, Maria A Pedrosa, Valentina E Sebestyén, Lola Vazquez, Mar Martinez-Garcia, Marta Llansola, Vicente Felipo
{"title":"Extracellular Vesicles from Peripheral Blood Mononuclear Cells of Hyperammonemic Rats Induce Neuroinflammation in Hippocampus, Impairing Memory and Learning in Normal Rats.","authors":"Paula Izquierdo-Altarejos, Adrià López-Gramaje, Maria A Pedrosa, Valentina E Sebestyén, Lola Vazquez, Mar Martinez-Garcia, Marta Llansola, Vicente Felipo","doi":"10.1007/s11481-025-10225-2","DOIUrl":"https://doi.org/10.1007/s11481-025-10225-2","url":null,"abstract":"","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"65"},"PeriodicalIF":6.2,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251159","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}
引用次数: 0
Efficacy of 6-nitrobenzo[d]thiazol-2 Amine Derivative (N3) in Mitigating PTZ-Induced Epileptic Conditions Via Modulation of Inflammatory and Neuroprotective Pathways in-vivo Zebrafish. 6-硝基苯并[d]噻唑-2胺衍生物(N3)通过调节炎症和神经保护通路减轻ptz诱导的斑马鱼癫痫的疗效。
IF 6.2
Karthikeyan Ramamurthy, S P Ramya Ranjan Nayak, S Madesh, Siva Prasad Panda, K Manikandan, Rajakrishnan Rajagopal, Ahmed Alfarhan, Senthilkumar Palaniappan, Ajay Guru, M K Kathiravan, Jesu Arockiaraj
{"title":"Efficacy of 6-nitrobenzo[d]thiazol-2 Amine Derivative (N3) in Mitigating PTZ-Induced Epileptic Conditions Via Modulation of Inflammatory and Neuroprotective Pathways in-vivo Zebrafish.","authors":"Karthikeyan Ramamurthy, S P Ramya Ranjan Nayak, S Madesh, Siva Prasad Panda, K Manikandan, Rajakrishnan Rajagopal, Ahmed Alfarhan, Senthilkumar Palaniappan, Ajay Guru, M K Kathiravan, Jesu Arockiaraj","doi":"10.1007/s11481-025-10221-6","DOIUrl":"https://doi.org/10.1007/s11481-025-10221-6","url":null,"abstract":"<p><p>Epilepsy, a chronic neurological illness affecting 50 million people worldwide, causes recurring seizures due to abnormal brain activity. Current anti-epileptic medications have serious side effects and low efficacy, requiring alternative treatments. The current study investigated the anti-inflammatory, antioxidant, and neuroprotective effects of 6-nitrobenzo[d]thiazol-2-amine (N3) derivatives in a zebrafish larvae model of epilepsy caused by 6 mM pentylenetetrazole (PTZ). Furthermore, N3 was tested for its safety, potential to reduce oxidative stress, inflammation, and neurodegeneration, and effects on motor coordination and neurotransmitter levels. The study utilized in vitro hemolysis assays to evaluate the membrane-stabilizing properties of N3. Zebrafish larvae were pre-treated with N3 at varying concentrations and subsequently exposed to PTZ to induce epilepsy-like conditions. Antioxidant enzyme activities superoxide dismutase (SOD), catalase CAT), glutathione (GSH) levels, lactate dehydrogenase (LDH) activity, and reactive oxygen species (ROS) levels were analyzed. Gene expression for pro-inflammatory and neuroprotective markers was quantified using qPCR, while histological assessments were performed to evaluate amyloid plaque formation, collagen accumulation, and calcium deposition. Behavioral tests measured motor coordination, and gamma-aminobutyric acid (GABA) levels were quantified using high-performance liquid chromatography. N3 demonstrated dose-dependent hemolysis inhibition, confirming its membrane-stabilizing and anti-inflammatory properties up to 43.47 ± 1.36%. It enhanced antioxidant enzyme activities, increased GSH levels 0.76 ± 0.03 nmol/mg, reduced LDH and ROS levels 7.47 ± 0.07 U/mg protein, and suppressed pro-inflammatory gene expression. Histological analysis revealed reduced neurodegenerative markers, including amyloid plaques and calcium deposition. Behavioral improvements were observed, including enhanced motor coordination and increased GABA levels. The findings suggest that N3 derivatives have significant therapeutic potential in epilepsy by reducing oxidative stress, inflammation, and neurodegeneration. Further studies are needed to optimize dosing and confirm safety for clinical applications.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"64"},"PeriodicalIF":6.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236113","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}
引用次数: 0
Motor-Related Neural Dynamics are Modulated by Regular Cannabis Use Among People with HIV. 艾滋病毒感染者经常使用大麻可调节运动相关神经动力学。
IF 6.2
Lauren K Webert, Mikki Schantell, Lucy K Horne, Jason A John, Ryan Glesinger, Jennifer O'Neill, Maureen Kubat, Anna T Coutant, Grace C Ende, Sara H Bares, Pamela E May-Weeks, Tony W Wilson
{"title":"Motor-Related Neural Dynamics are Modulated by Regular Cannabis Use Among People with HIV.","authors":"Lauren K Webert, Mikki Schantell, Lucy K Horne, Jason A John, Ryan Glesinger, Jennifer O'Neill, Maureen Kubat, Anna T Coutant, Grace C Ende, Sara H Bares, Pamela E May-Weeks, Tony W Wilson","doi":"10.1007/s11481-025-10219-0","DOIUrl":"10.1007/s11481-025-10219-0","url":null,"abstract":"<p><p>Recent work has shown that people with HIV (PWH) exhibit deficits in cognitive control and altered brain responses in the underlying cortical networks, and that regular cannabis use has a normalizing effect on these neural responses. However, the impact of regular cannabis use on the neural oscillatory dynamics underlying motor control deficits in PWH remains less understood. Herein, 102 control cannabis users, control nonusers, PWH who regularly use cannabis, and PWH who do not use cannabis performed a motor control task with and without interference during high-density magnetoencephalography. The resulting neural dynamics were examined using whole-brain, voxel-wise statistical analyses that examined the impact of HIV status, cannabis use, and their interaction on the neural oscillations serving motor control, spontaneous activity during the baseline period, and neurobehavioral relationships. Our key findings revealed cannabis-by-HIV group interactions in oscillatory gamma within the prefrontal cortices, higher-order motor areas, and other regions, with the non-using PWH typically exhibiting the strongest gamma interference responses. Cannabis-by-HIV interactions were also found for oscillatory beta in the dorsal premotor cortex. Spontaneous gamma during the baseline was elevated in PWH and suppressed in cannabis users in all regions exhibiting interaction effects and the left primary motor cortex, with spontaneous levels being correlated with behavioral performance. These findings suggest that regular cannabis use has a normalizing effect on the neural oscillations serving motor control and the abnormally elevated spontaneous gamma activity that has been widely replicated in PWH, which may suggest that cannabis has at least some therapeutic utility in PWH.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"63"},"PeriodicalIF":6.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Melatonin Promotes B-Cell Maturation and Attenuates Post-Ischemic Immunodeficiency in a Murine Model of Transient Focal Cerebral Ischemia. 褪黑素在小鼠短暂局灶性脑缺血模型中促进b细胞成熟和减轻缺血后免疫缺陷。
IF 6.2
Shih-Huang Tai, Hao-Hsiang Hsu, Sheng-Yang Huang, Yu-Ning Chen, Liang-Yi Chen, Ai-Hua Lee, Ai-Chiang Lee, E-Jian Lee
{"title":"Melatonin Promotes B-Cell Maturation and Attenuates Post-Ischemic Immunodeficiency in a Murine Model of Transient Focal Cerebral Ischemia.","authors":"Shih-Huang Tai, Hao-Hsiang Hsu, Sheng-Yang Huang, Yu-Ning Chen, Liang-Yi Chen, Ai-Hua Lee, Ai-Chiang Lee, E-Jian Lee","doi":"10.1007/s11481-025-10222-5","DOIUrl":"https://doi.org/10.1007/s11481-025-10222-5","url":null,"abstract":"<p><p>In this study, we investigated the immunomodulatory effects of melatonin on B-cell maturation and its potential to mitigate immunodeficiency following transient focal cerebral ischemia in mice. Transient middle cerebral artery occlusion (MCAO) was induced in adult C57BL/6 mice, followed by melatonin administration. We evaluated the effects of melatonin on neutrophil infiltration, macrophage and microglial activation in the ischemic brain, and B-cell maturation in both the central nervous system and peripheral blood. Melatonin treatment significantly reduced pro-inflammatory cell infiltration in the ischemic hemisphere and promoted B-cell maturation, reflecting robust immunomodulatory activity. These immune changes coincided with improved neurological outcomes and reduced cerebral edema. Collectively, our findings suggest that melatonin may serve as a promising therapeutic candidate in ischemic stroke, addressing both immunodeficiency and neuronal injury.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"62"},"PeriodicalIF":6.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201010","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}
引用次数: 0
The Sympathetic Nervous Influence on Hematopoiesis Up To Date. 交感神经对造血的影响。
IF 6.2
Georges Maestroni
{"title":"The Sympathetic Nervous Influence on Hematopoiesis Up To Date.","authors":"Georges Maestroni","doi":"10.1007/s11481-025-10220-7","DOIUrl":"https://doi.org/10.1007/s11481-025-10220-7","url":null,"abstract":"<p><p>Hematopoiesis is a tightly regulated process taking place in specialized bone marrow structures called hematopoietic niches. In these structures, hematopoietic stem cells produce all hematopoietic lineages by their self-renewal and differentiation abilities. Sympathetic nerve fibers, entering the bone marrow in association with blood vessels, regulate on a circadian basis the hematopoietic stem cells and leukocytes migration in and out the bone marrow. This cellular traffic, that is mainly regulated by beta-adrenergic receptors expressed on mesenchymal stem cells, is needed to maintain an efficient hematopoietic niche and for immunosurveillance against infections. Both alpha- and beta-adrenergic receptors seem involved in the regeneration of hematopoiesis after myeloablative treatments. Likewise, the effects of psychogenic stress and of ageing on the hematopoietic system are also mediated by adrenergic signals. Yet, the exact mechanisms regulating hematopoietic regeneration and the differentiation ratio between lymphoid and myeloid cells are still obscure. A comprehensive understanding of the adrenergic influence on hematopoiesis holds the potential for novel therapeutic approaches in a variety of hematological diseases.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"61"},"PeriodicalIF":6.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188643","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}
引用次数: 0
TNF-Stimulated Gene-6, Part of Extracellular Vesicles in Adipose Tissue-Derived Mesenchymal Stem Cell Concentrated Conditioned Medium, Affects Microglial Activity. 脂肪组织源性间充质干细胞浓缩条件培养基中部分细胞外囊泡tnf刺激基因-6影响小胶质细胞活性
IF 6.2
Mohammad Shahadat Hossain, Pratheepa Kumari Rasiah, Amritha T M Seetharaman, Dulce Alvarado, Megan Luo, James A Wohlschlegel, Mickey Pentecost, Rajashekhar Gangaraju
{"title":"TNF-Stimulated Gene-6, Part of Extracellular Vesicles in Adipose Tissue-Derived Mesenchymal Stem Cell Concentrated Conditioned Medium, Affects Microglial Activity.","authors":"Mohammad Shahadat Hossain, Pratheepa Kumari Rasiah, Amritha T M Seetharaman, Dulce Alvarado, Megan Luo, James A Wohlschlegel, Mickey Pentecost, Rajashekhar Gangaraju","doi":"10.1007/s11481-025-10216-3","DOIUrl":"10.1007/s11481-025-10216-3","url":null,"abstract":"<p><p>Identifying the specific bioactive molecules produced by mesenchymal stem cells (MSCs) and the signaling pathways and cell types upon which they act is critical to developing MSC-based therapeutics for inflammatory diseases with high unmet needs. Our study aimed to investigate the impact of extracellular vesicle (EV)-derived TNF-Stimulated Gene-6 (TSG-6, from adipose tissue-derived mesenchymal stem cell concentrated conditioned medium, ASC-CCM or TSG-6 overexpression in ASC using ORF expression-ready clone) on microglia and its potential anti-inflammatory effects. EV but not non-vesicular secretome prepared by ultracentrifugation confirmed the expression of TSG-6 exclusively in the small EV (sEV) fraction. sEV ranged from 50-150 nm as determined by Zetasizer, demonstrated bilipid membrane evidenced by transmission electron microscopy, expressed positive exosomal (e.g. CD63) markers, and were endocytosed by BV2 cells confirmed by DiI fluorescently labeled exosomes. BV2 microglia cultured under serum-free conditions stimulated with TLR4 agonists (LPS and IFNγ) for 12 h in the presence of p-ASC-EV (sEV derived from ASC after cytokine stimulation) and TSG-6-ORF-EV significantly reduced nitrite release (p < 0.001), phagocytic activity (p < 0.001) and reduced CD44 expression (p < 0.05). CD44 knockdown in BV2 cells ablated TSG-6-ORF-EV mediated nitrite release, IL1β downregulation, and phagocytosis with TLR4 agonists. Our results revealed that under cytokine stimulation, the EV portion of ASC-CCM becomes enriched with TSG-6. Overexpressing TSG-6 in ASC leads to an increased concentration of TSG-6 in sEVs. This enriched EV fraction, containing TSG-6, regulates microglial dynamics through a feedback loop with CD44. EV-associated TSG-6 can influence immune cell behavior and signaling, mitigating excessive inflammation or immune dysfunction.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"60"},"PeriodicalIF":6.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RIPK1: A Promising Target for Intervention Neuroinflammation. RIPK1:干预神经炎症的一个有希望的靶点。
IF 6.2
Feixing Yan, Yujun Qiao, Shunli Pan, Anjuan Kang, Haile Chen, Yinliang Bai
{"title":"RIPK1: A Promising Target for Intervention Neuroinflammation.","authors":"Feixing Yan, Yujun Qiao, Shunli Pan, Anjuan Kang, Haile Chen, Yinliang Bai","doi":"10.1007/s11481-025-10208-3","DOIUrl":"https://doi.org/10.1007/s11481-025-10208-3","url":null,"abstract":"<p><p>Necroptosis is a novel mode of cell death that differs from traditional apoptosis, characterized by distinct molecular mechanisms and physiopathological features. Recent research has increasingly underscored the pivotal role of necroptosis in various neurological diseases, including stroke, Alzheimer's disease and multiple sclerosis. A defining hallmark of these conditions is neuroinflammation, a complex inflammatory response that critically influences neuronal survival. This review provides a comprehensive analysis of the mechanistic underpinnings of necroptosis and its intricate interplay with neuroinflammation, exploring the interrelationship between the two processes and their impact on neurological disorders. In addition, we discuss potential therapeutic strategies that target the intervention of necroptosis and neuroinflammation, offering novel avenues for intervention. By deepening our understanding of these interconnected processes, the development of more effective treatments approaches holds significant promise for improving patient outcomes in neurological disorders.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"59"},"PeriodicalIF":6.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144703","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}
引用次数: 0
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