Cytokine最新文献

{"title":"Dioclea violacea lectin exerts pro-angiogenic effects by increasing VEGF and TNF-α levels via carbohydrate recognition domain","authors":"Abel Vieira de Melo Bisneto ,&nbsp;Felipe Eduardo Alves de Paiva ,&nbsp;Amanda Silva Fernandes ,&nbsp;Renato Rodrigues Roma ,&nbsp;Luana Santos Silva ,&nbsp;Giovana Valsani Chiesi ,&nbsp;Leonardo Pereira Franchi ,&nbsp;Clever Gomes Cardoso ,&nbsp;Claudener Souza Teixeira ,&nbsp;Lee Chen-Chen","doi":"10.1016/j.cyto.2025.156966","DOIUrl":"10.1016/j.cyto.2025.156966","url":null,"abstract":"<div><div>Due to their interesting biological activities, a mannose-binding lectin isolated from <em>Dioclea violacea</em> seeds, known as DvL have attracted considerable attention. In this study, we performed macroscopic, histologic, and immunohistochemical analysis on chicken embryo chorioallantoic membranes (CAM) to investigate the effects of DvL on the angiogenic process. Data showed a potential angiogenic effect of DvL at the highest concentrations tested (50 and 100 μg/mL). This effect was confirmed through increased neovascularization, inflammatory cells, and fibroblasts in histological analysis of the CAM. In addition, the immunohistochemistry of CAM showed that DvL induced secretion of TNF-α and VEGF, important cytokines involved in angiogenesis. Therefore, increased neovascularization may result from a pro-inflammatory response through VEGF and TNF-α secretion. In contrast, the DvL effects on the angiogenic process and the TNF-α and VEGF secretion were significantly reduced by co-incubation with mannose. Thus, protein-carbohydrate interactions between DvL and cell membrane glycans are likely the main events involved in this effect. Therefore, our results demonstrated that DvL is a potent angiogenic agent, suggesting its potential application as a prototype molecule for developing new drugs with healing properties<em>.</em></div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"192 ","pages":"Article 156966"},"PeriodicalIF":3.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The correlation between obesity and leptin signaling pathways","authors":"Miriam Jasim Shehab ,&nbsp;Sarah T. AL-Mofarji ,&nbsp;Batool Mutar Mahdi ,&nbsp;Rasha Sadeq Ameen ,&nbsp;Mohammed Mahdi AL-Zubaidi","doi":"10.1016/j.cyto.2025.156970","DOIUrl":"10.1016/j.cyto.2025.156970","url":null,"abstract":"<div><div>Obesity is a global epidemic associated with increased morbidity and mortality. It is a major risk factor for the development of chronic diseases such as type 2 diabetes mellitus, cardiovascular diseases, and certain cancers, primarily due to excessive fat accumulation in the body. Both environmental and genetic factors contribute to the development of obesity. A key pathophysiological feature of obesity is resistance to the metabolic hormones leptin and ghrelin, which play critical roles in neuroendocrine regulation of energy homeostasis. Leptin, a proinflammatory peptide hormone encoded by the obese (<em>ob</em>) gene, is primarily secreted by white adipose tissue. It functions as an anti-obesity hormone by suppressing appetite, reducing food intake, and increasing energy expenditure. Leptin resistance, resulting from altered expression of leptin (<em>LEP</em>) and its receptor (<em>LEP-R</em>), impairs its regulatory effects on energy balance. Additionally, aberrant leptin signaling and genetic mutations in the leptin gene or its receptor are associated with morbid obesity and other related diseases. The treatment of obesity using leptin-based therapeutics may be one of the methods to treat obesity. The present review aimed to explore the molecular mechanisms of leptin signaling, leptin resistance in obesity, and the potential of leptin-based therapies as novel interventions in obesity management.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"192 ","pages":"Article 156970"},"PeriodicalIF":3.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peritoneal membrane transport characteristics in patients undergoing peritoneal Dialysis are associated with systemic IL-8 levels","authors":"Yufei Ye ,&nbsp;Weiyan Huang ,&nbsp;Xuelin Zhang ,&nbsp;Xiaolu Bian ,&nbsp;Haiyan Wang ,&nbsp;Xinrui Liang ,&nbsp;Xiaojuan Sun ,&nbsp;Zhiyong Guo ,&nbsp;Xueli Lai","doi":"10.1016/j.cyto.2025.156965","DOIUrl":"10.1016/j.cyto.2025.156965","url":null,"abstract":"<div><h3>Background</h3><div>Several cytokine levels in dialysate, particularly interleukin-6 (IL-6), have been investigated as potential biomarkers for peritoneal solute transport rate (PSTR). However, studies examining the relationship between systemic cytokine levels and PSTR have yielded contradictory results. In this study, we aimed to assess 12 kinds of cytokines in serum and explore their potential relationship with peritoneal transport function.</div></div><div><h3>Methods</h3><div>Patients undergoing peritoneal dialysis (PD) from September 2022 to September 2024 were retrospectively analyzed at our PD center. The patients were categorized into fast and non-fast PSTR groups based on the 4-h dialysate creatinine /plasma creatinine ratio (D/P Cr). The systemic levels of 12 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17 A, TNF-α, IFN-α, and IFN-γ) in both groups were measured using flow cytometry and compared. The relationship between serum cytokine levels and baseline peritoneal transport status was analyzed by univariate and multivariate logistic regression analyses.</div></div><div><h3>Results</h3><div>A total of 284 patients were enrolled in this study. According to the D/P Cr, 171 patients (60.2 %) were classified as non-fast PSTR group, while 113 patients (39.8 %) were classified as fast PSTR group. Among the 12 cytokines analyzed, serum IL-8 exhibited a significant difference between the two groups (<em>P</em> = 0.01). IL-8/IL-10 and IL-12p70/IL-10 ratios were also significantly higher in fast PSTR group. In the subgroup of incident PD patients, multivariate analysis revealed that total cholesterol (OR 0.559, 95 % CI 0.323–0.966, <em>P</em> = 0.037) and serum IL-8 (OR 1.040, 95 % CI 1.006–1.075, <em>P</em> = 0.021) were significantly and independently associated with baseline fast PSTR.</div></div><div><h3>Conclusion</h3><div>The systemic IL-8 level is positively correlated with PSTR in patients undergoing PD, which may serve as an indicator of baseline peritoneal transport function.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"192 ","pages":"Article 156965"},"PeriodicalIF":3.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The clinical characteristics and significance of novel inflammatory biomarkers in patients with polymyalgia rheumatica: A single-center study from China","authors":"Ruohan Yu ,&nbsp;Miao Miao ,&nbsp;Siying Li ,&nbsp;Xue Li ,&nbsp;Haihong Yao ,&nbsp;Yuan Jia","doi":"10.1016/j.cyto.2025.156953","DOIUrl":"10.1016/j.cyto.2025.156953","url":null,"abstract":"<div><h3>Objective</h3><div>Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disorder predominantly affecting older adults, characterized by proximal muscle pain and stiffness. The prevalence of PMR in Chinese population is relatively low comparing to European population, resulting in limited research regarding its clinical manifestations and serological characteristics among Chinese patients. We aimed to analyse the features of Chinese patients with PMR and explore the significance of novel inflammatory biomarkers.</div></div><div><h3>Methods</h3><div>We retrospectively collected the medical data of hospitalized patients diagnosed with PMR at Peking University People's Hospital between 1992 and 2022. Electronic medical records were reviewed. We analyzed the clinical and laboratory characteristics of patients with PMR, and explored new inflammatory markers.</div></div><div><h3>Results</h3><div>A total of 87 patients were included in the study, with a male-to-female ratio of 1:2.6. The most common clinical manifestation was shoulder girdle pain (96.6 %), followed by pelvic girdle pain (89.7 %), cervical spine pain (63.2 %), morning stiffness (48.3 %), and lumbar spine pain (40.2 %). Cervical spine pain was more common in female patients than in male patients. 12 out of 87 (13.8 %) patients with PMR were complicated with giant cell arteritis (GCA). Anorexia was more commonly seen in patients with GCA (<em>P</em> = 0.024). IL-6 was the most frequently elevated cytokine and was significantly associated with fever. The systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) were correlated with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).</div></div><div><h3>Conclusion</h3><div>Shoulder girdle and pelvic girdle pain were the most common manifestations of PMR. 13.8 % of the patients had concurrent GCA. Elevated levels of IL-6 were significantly correlated with fever, indicating that IL-6 may contribute to the systemic inflammation of PMR. SII, NLR and PLR were positively associated with the levels of ESR and CRP, suggesting that these novel markers are promising inflammatory markers in patients with PMR.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"192 ","pages":"Article 156953"},"PeriodicalIF":3.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes from renal cells and macrophages: Bidirectional communication in the pathogenesis of kidney disease","authors":"Jing Gao ,&nbsp;Pan Chen ,&nbsp;Wen-jing Zhao ,&nbsp;Hong-wei Su ,&nbsp;Li Wang ,&nbsp;Rui-zhi Tan ,&nbsp;Jian Liu","doi":"10.1016/j.cyto.2025.156961","DOIUrl":"10.1016/j.cyto.2025.156961","url":null,"abstract":"<div><div>Macrophages are key cells in the immune response, and their abnormal infiltration into the kidney is a common pathological feature in kidney diseases. Exosomes, acting as carriers for transporting essential proteins and genetic materials, can be derived from various cell types and are involved in a wide range of physiological and pathological processes in the kidney. As primary inflammatory immune cells, macrophages have garnered significant attention from scholars regarding the effects of their secreted exosomes on renal intrinsic cells in kidney diseases, as well as the interactive effects of exosomes derived from other cells on macrophages. This review delves into the detailed characteristics of macrophage-derived exosomes in kidney diseases, the mechanisms by which they promote damage to specific cells, and the signaling pathways involved. Additionally, it examines the reverse direction, elucidating the circulatory mechanisms of substances carried by exosomes from renal intrinsic cells that induce phenotypic transformation and inflammatory responses in macrophages, ultimately leading to further damage of renal intrinsic cells. The pathological role of exosome-macrophage interconnections in various renal diseases has received increasing attention, and understanding this mechanism can help unravel the microscopic immunoregulatory processes underlying kidney diseases. Moreover, the identification of therapeutic targets related to macrophage-related exosomes offers new strategies for the treatment of these conditions.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"192 ","pages":"Article 156961"},"PeriodicalIF":3.7,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144072087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the correlation between intestinal flora and cytokines in children with Henoch-Schönlein purpura","authors":"Mingxin Liang ,&nbsp;Zhaoxu Deng ,&nbsp;Weiyi Wu ,&nbsp;Qinqin Dong ,&nbsp;Juan Fan","doi":"10.1016/j.cyto.2025.156959","DOIUrl":"10.1016/j.cyto.2025.156959","url":null,"abstract":"<div><h3>Background</h3><div>The pathogenesis of Henoch-Schönlein purpura (HSP) is complex. It is currently believed that the development of HSP involves abnormalities in humoral immunity and cellular immunity. The intestinal microbiota has a powerful regulatory effect on the human immune system and has been shown to serve a significant role in the pathogenesis of various immune-mediated disorders. This study examines changes in intestinal flora and cytokines(IFN-γ, IL-4, IL-10, and IL-17) in children with HSP and explores their correlation, offering fresh insights for the prevention and treatment of HSP. METHODS: Blood and stool specimens were collected from 25 healthy children (control group) and 27 children with HSP (observation group). Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of cytokines IFN-γ, IL-4, IL-17, and IL-10 in the serum of all the study participants, and the 16S rRNA gene sequencing combined with high-throughput sequencing technology was used to analyze the intestinal flora of the study subjects. Finally, the correlation between serum cytokines and gut microbiota was analyzed in the children with HSP. RESULT:1)The serum levels of IL-4 and IL-17 in the observation group were higher than those in the control group, while the levels of IFN-γ and IL-10 were lower than those in the control group. 2) At the level of phylum, the abundance of <em>Fusobacteria</em> and <em>Verrucomicrobia</em> was higher than that in the control group, while the abundance of <em>Firmicutes</em> was lower than that of the control group, and the differences were statistically significant (<em>P</em> &lt; 0.05); At the level of genus, the abundance of <em>Prevotella</em> and <em>Akkermansia</em> were higher than the control group, while the abundance of <em>Bifidobacterium</em>, <em>Blautia</em>, and <em>Clostridium</em> XlVa was lower than that in the control group, and the differences were all statistically significant (<em>P</em> &lt; 0.05); At the species level, the abundance of <em>Akkermansia muciniphila</em>, <em>Prevotella copri</em>, and <em>Subdoligranulum variabile</em> was higher than that of the control group, while the abundance of <em>Bifidobacterium pseudolongum</em>, <em>Brautella Weiss</em>, and <em>Bacteroides fragilis</em> was lower than that in the control group, and the differences were statistically significant (<em>P</em> &lt; 0.05). 3) The abundance of <em>Blautia</em> and <em>Blautia wexlerae</em> in the observation group was positively associated with the IL-10 level (<em>r</em> = 0.522, <em>r</em> = 0.578, <em>P</em> &lt; 0.01). CONCLUSION: Disturbances in intestinal flora and changes in serum cytokines IFN-γ, IL-4, IL-10, and IL-17 were present in children with HSP. The abundance of <em>Blautia</em> and <em>Blautia wexlerae</em> in the gut microbiota of children with HSP was positively correlated with serum IL-10 levels.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156959"},"PeriodicalIF":3.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular insights into diabetic wound healing: Focus on Wnt/β-catenin and MAPK/ERK signaling pathways","authors":"Shricharan Pandey ,&nbsp;Tushar Anshu ,&nbsp;Krushna Ch. Maharana ,&nbsp;Suhani Sinha","doi":"10.1016/j.cyto.2025.156957","DOIUrl":"10.1016/j.cyto.2025.156957","url":null,"abstract":"<div><div>Diabetic wounds manifest significant clinical challenge with approximately 50–70 % reporting non-traumatic lower limb amputations annually. This review examines the intricate relationship between impaired wound healing in diabetes mellitus and two crucial signaling pathways: Wnt/β-catenin and MAPK/ERK. Chronic hyperglycemia in diabetes mellitus leads to peripheral neuropathy, vascular dysfunction, and compromised immune responses, resulting in delayed wound healing. The Wnt/β-catenin pathway, which is essential for cellular proliferation, differentiation, and tissue homeostasis, shows altered activity in diabetic wounds, particularly through decreased R-spondin 3 protein expression. Similarly, the MAPK/ERK pathway, which regulates cellular proliferation and differentiation through hierarchical kinase cascades, exhibits dysregulation under diabetic conditions. This review describes the current understanding of normal wound healing processes, diabetic wound pathophysiology, and the molecular mechanisms of both signaling pathways. Evidence suggests that targeting these pathways, either individually or synergistically offer promising therapeutic approaches for diabetic wound management. Future directions include, developing targeted delivery systems, exploring pathway cross-talk, and investigating dual-pathway modulators to enhance wound healing outcomes in diabetic patients. This comprehensive analysis provides insights into potential therapeutic strategies and emphasizes the necessity of research in this crucial area of diabetes treatment. (Graphical Abstract)</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156957"},"PeriodicalIF":3.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FokI polymorphism of the vitamin D receptor gene: Linking COVID-19 risk to genetic susceptibility in children","authors":"Amal Ahmed Mohamed ,&nbsp;Abdullah Taher Alanazi ,&nbsp;Hoda H. Ahmed ,&nbsp;Samar Elfiky ,&nbsp;Muhammad T Abdel Ghafar ,&nbsp;Ingy Maher ,&nbsp;Sherin A. Taha ,&nbsp;Mohammed Zakaria Ali AbuRahma ,&nbsp;Waleed Elagawy ,&nbsp;Dina A. Mohareb ,&nbsp;Abeer M. Rawy ,&nbsp;Heba M. Abostate ,&nbsp;Amira AlSayed Youssef ,&nbsp;Dalia Saeed Elsayed ,&nbsp;Rasha M. Abdel-Hamid","doi":"10.1016/j.cyto.2025.156958","DOIUrl":"10.1016/j.cyto.2025.156958","url":null,"abstract":"<div><h3>Background</h3><div>Vitamin D receptor (VDR), influenced by gene polymorphisms like <em>FokI</em>, may affect susceptibility to infections, including coronavirus disease 2019 (COVID-19). Since studies in children are limited, we aimed to analyze the correlation between the VDR <em>FokI</em> variant and both the incidence and severity of COVID-19 in Egyptian children.</div></div><div><h3>Methods</h3><div>Seventy-seven COVID-19-positive and 107 COVID-19-negative pediatric patients were included. Participants' serum 25(OH)D levels, inflammatory biomarkers, and demographics were evaluated. Real-time polymerase chain reaction (PCR) was used for genotyping the VDR <em>FokI</em> (rs2228570) polymorphism.</div></div><div><h3>Results</h3><div>Absolute lymphocyte count (ALC) was significantly lower in COVID-19 patients than in controls, while interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin, and D-dimer were significantly higher (all <em>p</em> &lt; 0.001). Vitamin D insufficiency was significantly more common in COVID-19 cases (18.2 % versus 3.7 %, <em>p</em> = 0.002). Male sex, increased tumor necrosis factor-alpha (TNF-α), and CRP were significantly associated with severe COVID-19 (<em>p</em> = 0.032, 0.029, &lt; 0.001, respectively). The <em>FokI</em> TT genotype in codominant and recessive models and the T allele in the multiplicative model were significantly correlated with 2.4, 3.0, and 1.8 folds increased COVID-19 risk (<em>p</em> = 0.043, &lt; 0.001, and 0.004, respectively). However, VDR <em>FokI</em> variants did not significantly associate with severe COVID-19.</div></div><div><h3>Conclusion</h3><div>The T allele and TT genotype of the <em>FokI</em> variant in the <em>VDR</em> gene increase susceptibility to COVID-19 but not its severity in Egyptian children. Additional research is required to validate the potential role of vitamin D and its receptor polymorphism in COVID-19.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156958"},"PeriodicalIF":3.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eliminating myeloid-derived suppressor cells alleviates immunosuppression and reduces susceptibility to secondary infections in a two-hit sepsis model","authors":"Dongjie Liu ,&nbsp;Wei Fu ,&nbsp;Teng Zhang ,&nbsp;Jianyao Wang ,&nbsp;Yuxin He ,&nbsp;Xiao Wang ,&nbsp;Tongxiang Xu ,&nbsp;Cheng Wang ,&nbsp;Tao Ma","doi":"10.1016/j.cyto.2025.156955","DOIUrl":"10.1016/j.cyto.2025.156955","url":null,"abstract":"<div><div>Myeloid-derived suppressor cells (MDSCs) are known for their immunosuppressive effects on both innate and adaptive immunity, particularly targeting T cells, and they undergo continuous expansion during sepsis. However, the pathophysiological significance of MDSCs in sepsis-induced immunosuppression remains to be fully elucidated. In this study, we investigated the dynamic changes in MDSCs during sepsis and their contribution to sepsis-induced immunosuppression using a clinically relevant “two-hit” sepsis model. Our findings revealed that mice surviving cecal ligation and puncture (CLP) exhibited a significant accumulation and enhanced activity of MDSCs, which correlated with sepsis-related immune paralysis, impaired bacterial clearance, and heightened susceptibility to secondary infections. Importantly, administration of the liver X receptor (LXR) agonist GW3965 at the late stage of sepsis significantly restored immune function, decreased susceptibility to secondary infections, enhanced bacterial clearance, and improved prognosis by eliminating MDSCs. These results highlight the pivotal role of MDSCs in the development of sepsis-associated immunosuppression and indicate that targeting MDSCs could be a promising therapeutic approach to mitigate immunosuppression in sepsis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156955"},"PeriodicalIF":3.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stem cell transplantation ameliorates inflammation in spinal cord injury by inhibiting lactylation-related genes","authors":"Weiwei Zou ,&nbsp;Zelin Zhang ,&nbsp;Tingting Cao ,&nbsp;Mangmang Li","doi":"10.1016/j.cyto.2025.156960","DOIUrl":"10.1016/j.cyto.2025.156960","url":null,"abstract":"<div><h3>Background</h3><div>The immune microenvironment significantly influences neural regeneration in spinal cord injury (SCI). Lactate activates central nervous system (CNS) glial cells, prompting the secretion of proinflammatory cytokines and triggering an inflammatory response. Mesenchymal stem cells (MSCs) make a promising future for SCI therapy due to their immune regulation and anti-inflammatory properties. However, it is unclear whether MSCs inhibit inflammatory responses in the SCI microenvironment through lactylation regulation. This study aimed to identify lactylation-related genes (LRGs) in SCI and investigate their role in immune cell infiltration and MSC-mediated inflammation reduction.</div></div><div><h3>Methods</h3><div>Transcription datasets of SCI patients were acquired from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) underwent functional enrichment analysis, and CIBERSORT assessed immune cell infiltration in SCI. Crucial lactylation-related differentially expressed genes (LRDEGs) associated with SCI were identified via machine learning. The association between LRDEGs and inflammatory response in SCI mediated by immune cell infiltration was confirmed using Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). Rats with subacute thoracic SCI were transplanted with hUC-MSCs, and transcriptome analyses were conducted on their spinal cords and retrieved hUC-MSCs, respectively.</div></div><div><h3>Results</h3><div>The study identified 808 DEGs and 13 differentially infiltrated immune cell types in SCI patients compared to healthy controls. Multiple inflammatory response-related signaling pathways were activated in SCI. Seven LRDEGs, including LSP1, XRCC4, HSDL2, HNRNPH1, RPL14, IKZF1, and TP53, were recognized as key regulators. These genes are linked to immune cell infiltration and inflammatory responses in SCI. In SCI rats, the increased expression of LRDEGs and inflammatory cytokines were observed, which were significantly reduced after hUC-MSC transplantation. Differences in LRDEG expression patterns, enriched functions, and pathways between two SCI subtypes were statistically significant.</div></div><div><h3>Conclusions</h3><div>LRDEGs are involved in immune cell-mediated inflammatory response in SCI, and hUC-MSC transplantation reduces LRDEGs expression and inflammation response in the SCI microenvironment.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156960"},"PeriodicalIF":3.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}