Molecular Medicine最新文献

{"title":"Plasma-derived extracellular vesicles prime alveolar macrophages for autophagy and ferroptosis in sepsis-induced acute lung injury.","authors":"Rongzong Ye, Yating Wei, Jingwen Li, Yu Zhong, Xiukai Chen, Chaoqian Li","doi":"10.1186/s10020-025-01111-x","DOIUrl":"10.1186/s10020-025-01111-x","url":null,"abstract":"<p><p>Sepsis-induced acute respiratory distress syndrome (ARDS) is a severe complication of sepsis and the leading cause of mortality. Although the role of alveolar macrophages (AMs) in stabilizing pulmonary homeostasis is well established, the effects of circulating extracellular vesicles (EVs) on AMs remain largely unknown. In this study, an investigation was conducted to map the miRNA and protein expression profiles of EVs derived from septic plasma. Notably, EV-based panels (miR-122-5p, miR-125b-5p, miR-223-3p, OLFM4, and LCN2) have been found to be associated with the severity or prognosis of sepsis, with promising AUC values. Moreover, the levels of LCN2, miR-122-5p, and miR-223-3p were identified as independent predictors of septic ARDS. The in vitro coculture results revealed that the effects of LPS-EVs from the plasma of sepsis-induced acute lung injury (ALI), which carry pro-inflammatory EVs, were partly mediated by miR-223-3p, as evidenced by the promotion of inflammation, autophagy and ferroptosis in AMs. Mechanistically, the upregulation of miR-223-3p in LPS-EVs triggers autophagy and ferroptosis in AMs by activating Hippo signaling via the targeting of MEF2C. In vivo, the inhibition of miR-223-3p effectively mitigated LPS-EV-induced inflammation and AM death in the lungs, as well as histological lesions. Overall, miR-223-3p in LPS-EVs contributes to sepsis-induced ALI by priming AMs for autophagy and ferroptosis through the MEF2C/Hippo signaling pathway. These findings suggest a novel mechanism of plasma-AM interaction in sepsis-induced ALI, offering a plausible strategy for assessing septic progression and treating lung injury.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"40"},"PeriodicalIF":6.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing amino acid pathways to influence myeloid cell function in tumor immunity.","authors":"Jiongli Pan, Yi Lin, Xinyuan Liu, Xiaozhen Zhang, Tingbo Liang, Xueli Bai","doi":"10.1186/s10020-025-01099-4","DOIUrl":"10.1186/s10020-025-01099-4","url":null,"abstract":"<p><p>Amino acids are pivotal regulators of immune cell metabolism, signaling pathways, and gene expression. In myeloid cells, these processes underlie their functional plasticity, enabling shifts between pro-inflammatory, anti-inflammatory, pro-tumor, and anti-tumor activities. Within the tumor microenvironment, amino acid metabolism plays a crucial role in mediating the immunosuppressive functions of myeloid cells, contributing to tumor progression. This review delves into the mechanisms by which specific amino acids-glutamine, serine, arginine, and tryptophan-regulate myeloid cell function and polarization. Furthermore, we explore the therapeutic potential of targeting amino acid metabolism to enhance anti-tumor immunity, offering insights into novel strategies for cancer treatment.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"44"},"PeriodicalIF":6.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insights into 5-aminolevulinic acid photodynamic therapy for acne vulgaris: targeting lipogenesis via the OLR1-Wnt/β-catenin pathway.","authors":"Jia Yan, Linglin Zhang, Qingyu Zeng, Yitao Qian, Ke Li, Xiaojing Liu, Yun Wu, Yu Yan, Haiyan Zhang, Szeman Cheung, Jia Liu, Ronald Sroka, Xiuli Wang, Lei Shi","doi":"10.1186/s10020-025-01104-w","DOIUrl":"10.1186/s10020-025-01104-w","url":null,"abstract":"<p><p>Acne vulgaris, a prevalent chronic inflammatory skin disorder, is often characterized by hyperactive sebaceous glands and excessive sebum production, presenting a significant therapeutic challenge. While 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is clinically effective in treating moderate to severe acne, the molecular mechanisms underlying its therapeutic effects remain largely unexplored. In this study, we investigated the impact of ALA-PDT on lipid metabolism in an acne-like mouse model and in immortalized human sebocytes (XL-i-20), focusing on the role of the OLR1-Wnt/β-catenin pathway. We employed transcriptomic analysis, lipid staining, and gene silencing techniques to dissect the molecular interactions induced by ALA-PDT. Our findings revealed that ALA-PDT significantly reduces lipogenesis by upregulating OLR1, which in turn suppresses the SREBP1-FAS axis, thereby decreasing lipid accumulation in sebocytes. Furthermore, activation of the OLR1-Wnt/β-catenin pathway was essential for these lipogenic effects, as silencing OLR1 or activating Wnt/β-catenin signaling reversed lipogenesis inhibition. This study elucidates a novel mechanistic pathway in ALA-PDT-mediated acne treatment, highlighting OLR1 as a promising target for future therapeutic strategies.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"41"},"PeriodicalIF":6.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Celastrol promotes DNA damage and apoptosis in uterine corpus endometrial carcinoma via promotion of KAT2B-mediated RBPJ acetylation and repression of MCM4 transcription.","authors":"Lipeng Pei, Yan Zhu, Wenpeng Li, Bin Xu, Jingli Sun","doi":"10.1186/s10020-025-01082-z","DOIUrl":"10.1186/s10020-025-01082-z","url":null,"abstract":"<p><strong>Background: </strong>Uterine corpus endometrial carcinoma (UCEC) is one of the most frequent female genital malignant tumors. Targeting DNA damage and cell apoptosis are regarded as effective ways for UCEC therapy. Celastrol is a natural anti-cancer product from the Celastraceae plant family, while its role in UCEC has not been investigated.</p><p><strong>Methods: </strong>UCEC cell lines Ishikawa and HEC-1-A were applied and treated with different concentrations of Celastrol. The appropriate and nontoxic concentrations were used for the subsequent experiments. Functional experiments analyzed the cell viability, cell cycle distribution, DNA damage, apoptosis and the expression of related proteins. We determined tumor growth in xenograft nude mice. Bioinformatic analysis, protein coimmunoprecipitation (Co-IP), luciferase assay, cell experiments were performed to reveal the relationship of Celastrol/KAT2B/RBPJ/MCM4 in UCEC.</p><p><strong>Results: </strong>Treatment of Celastrol inhibited cell viability in a dose-dependent manner, and caused cell cycle arrest, accompanied by the downregulation of CDK2 and cyclin E expression and the upregulation of p21. Celastrol treatment resulted DNA damage and apoptosis in cultured cells, as demonstrated by increased number of TUNEL-positive cells, activity of caspase-3 and expression of cleaved-caspase-9, cleaved PARP1 and γ-H2AX. In xenograft nude mice, Celastrol also repressed tumor growth. Furthermore, lysine acetyltransferase KAT2B was a putative target of Celastrol, and its expression was upregulated by Celastrol in vitro and in vivo. Overexpression of KAT2B in UCEC inhibited cell proliferation and increased DNA damage and apoptosis. KAT2B knockdown overcame the anti-proliferative and pro-apoptotic roles of Celastrol. Moreover, Co-IP demonstrated that KAT2B bound to RBPJ, a transcriptional repressor, and increased the acetylation of RBPJ. RBPJ could bind to the MCM4 promoter to suppress the luciferase activity. Further functional analysis revealed that the functions of KAT2B in UCEC cell proliferation, DNA damage and apoptosis were mediated by MCM4, and Celastrol enhanced RBPJ acetylation and reduced MCM4 expression.</p><p><strong>Conclusions: </strong>These results underscore that Celastrol is a promising anti-cancer agent in UCEC with preferential anti-proliferative, pro-apoptotic and DNA damage effects through the KAT2B/RBPJ/MCM4 axis, and KAT2B is a promising therapeutic target for UCEC.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"39"},"PeriodicalIF":6.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NUAK1 acts as a novel regulator of PD-L1 via activating GSK-3β/β-catenin pathway in hepatocellular carcinoma.","authors":"Chao-Yan Yao, Hang-Tian Tao, Jin-Jin He, Feng-Yi Zhu, Cui-Qing Xie, Yu-Na Cheng, Ji-Qin Li, Zhuang-Zhuang Liu, Chun-Yu Hou, Xue-Li Liu, Yong-Li Fan, Dong Fang, Xin-Rui Lv","doi":"10.1186/s10020-025-01088-7","DOIUrl":"10.1186/s10020-025-01088-7","url":null,"abstract":"<p><strong>Background: </strong>NUAK1 is associated with metastasis and drug resistance in hepatocellular carcinoma (HCC). However, little is known about the immune functions of NUAK1 in HCC. Therefore, the aim of this study was to elucidate the novel role of NUAK1 in facilitating immune evasion in HCC and to investigate the mechanisms underpinning this process.</p><p><strong>Method: </strong>The levels of NUAK1 expression and the infiltration of CD8⁺ T cells were assessed in tumor tissues from HCC patients and mice xenograft model. HCC cell lines were used to validate the role of NUAK1 in regulating the transcription of PD-L1, the diethylnitrosamine-induced HCC model was established and the expression levels of NUAK1 and PD-L1 proteins in the rat livers were detected. Western blotting, immunofluorescence, real time PCR, and immunohistochemical staining were used to investigate the underlying mechanisms by which NUAK1 regulates PD-L1 expression in hepatocellular carcinoma.</p><p><strong>Results: </strong>NUAK1 expression was negatively correlated with CD8⁺ T cell infiltration in tumor tissues from HCC patients and mice xenograft model. Both gain and loss of functions have identified NUAK1 promoted PD-L1 expression at transcriptional level in HCC cells. The increased expression of NUAK1 and PD-L1 proteins were observed in the rat livers of diethylnitrosamine-induced HCC model. Moreover, overexpression of NUAK1 promotes GSK3β Ser⁹ phosphorylation, β-catenin expression and nuclear accumulation in HCC cells. By contrast, knockdown of NUAK1 has opposite effects. Inhibition of GSK3β activity significantly promoted β-catenin expression and PD-L1 expression in HCC cells. IHC analyses of tumor tissues from HCC patients suggested that the levels of p-GSK3β and β-catenin were positively correlated with NUAK1 expression. Knockdown of β-catenin also reversed NUAK1-mediated PD-L1 expression in HCC cells.</p><p><strong>Conclusions: </strong>This study revealed a novel role for NUAK1, which promotes the transcriptional expression of PD-L1 by activating GSK3β/β-catenin signaling pathway, leading to immune escape of hepatocellular carcinoma. Registry and the registration no. of the study/trial: Not applicable.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"38"},"PeriodicalIF":6.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring proteomic immunoprofiles: common neurological and immunological pathways in multiple sclerosis and type 1 diabetes mellitus.","authors":"Fátima Cano-Cano, Almudena Lara-Barea, Álvaro Javier Cruz-Gómez, Francisco Martín-Loro, Laura Gómez-Jaramillo, María Carmen González-Montelongo, María Mar Roca-Rodríguez, Lucía Beltrán-Camacho, Lucía Forero, Javier J González-Rosa, Mª Carmen Durán-Ruiz, Ana I Arroba, Manuel Aguilar-Diosdado","doi":"10.1186/s10020-025-01084-x","DOIUrl":"10.1186/s10020-025-01084-x","url":null,"abstract":"<p><strong>Background: </strong>Interest in the study of type 1 diabetes mellitus (T1DM) and multiple sclerosis (MS) has increased because of their significant negative impact on the patient quality of life and the profound implications for the health care system. Although the clinical symptoms of T1DM differ from those of MS, such as pancreatic β-cell failure in T1DM and demyelination in the central nervous system (CNS) in MS, both pathologies are considered as autoimmune-related diseases with shared pathogenic pathways, which include autophagy, inflammation and degeneration, among others. Considering the challenges in obtaining pancreatic β-cells and CNS tissue from patients with T1DM and MS, respectively, it is fundamental to explore alternative methods for evaluating disease status. Proteomic analysis of peripheral blood mononuclear cells (PBMCs) is an ideal approach for identifying novel and potential biomarkers for both autoimmune diseases.</p><p><strong>Methods: </strong>We conducted a proteomic analysis of PBMCs from patients with T1DM and relapsing remitting Multiple Sclerosis (herein forth MS) patients (n = 9 per condition), using a label-free quantitative proteomics approach. The patients were diagnosed following the American Diabetes Association (ADA) criteria for T1DM and McDonald criteria for MS respectively, and were aged over 18 years and more than 2 years from the onset respectively.</p><p><strong>Results: </strong>A total of 2476 proteins were differentially expressed in PBMCs from patients with T1DM and MS patients compared with those form healthy controls (H). Predictive analysis highlighted 15 common proteins, up- or downregulated in PBMCs from patients with T1DM and MS patients vs. healthy controls, involved in the immune system activity (BTF3, TTR, CD59, CSTB), diseases of the neuronal system (TTR), signal transduction (STMN1, LAMTOR5), metabolism of nucleotides (RPS21), proteins (TTR, ENAM, CD59, RPS21, SRP9) and RNA (SRSF10, RPS21). In addition, this study revealed both shared and distinct molecular patterns between the two conditions.</p><p><strong>Conclusions: </strong>Compared with H, patients with T1DM and MS presented a specific expression pattern of common proteins has been identified. This pattern underscores the shared mechanisms involved in their immune responses and neurological complications, alongside dysregulation of the autophagy pathway. Notably, CSTB has emerged as a differential biomarker, distinguishing between these two autoimmune diseases.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"36"},"PeriodicalIF":6.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conventional type 1 dendritic cells in the lymph nodes aggravate neuroinflammation after spinal cord injury by promoting CD8⁺ T cell expansion.","authors":"Li-Qing Wang, Xiao-Yi Wang, Yue-Hui Ma, Heng-Jun Zhou","doi":"10.1186/s10020-024-01059-4","DOIUrl":"10.1186/s10020-024-01059-4","url":null,"abstract":"<p><strong>Background: </strong>Adaptive immune response is at the core of the mechanism of secondary spinal cord injury (SCI). This study aims to explore the molecular mechanism by which classical dendritic cells (cDC1s) influence CD8⁺ T cell expansion in SCI.</p><p><strong>Methods: </strong>Peripheral blood samples from patients with SCI and spinal cord tissues from SCI mice were collected, and the population of cDC1 subset was analyzed by flow cytometry. In vivo, the fms-like tyrosine kinase 3 (Flt3) inhibitor quizartinib was administered to deplete cDC1s, while intraperitoneal injection of recombinant Flt3L and immunosuppressive drug FTY-720 was used to expand cDC1s and prevent T cell egress from lymph nodes (LNs), respectively. In vitro, the conditioned medium (CM) of isolated LN fibroblastic stromal cells (FSCs) and pre-DCs were co-cultured. Subsequently, FSC CM-induced DCs were stimulated and co-cultured with CD8⁺ T cells for proliferation assay.</p><p><strong>Results: </strong>The cDC1 subset was increased in the peripheral blood of SCI patients and in the injured spinal cord of SCI mice. Depletion of cDC1s decreased the proportion of infiltrating CD8⁺ T cells in the injured spinal cord of SCI mice and reduced the inflammatory response. The Basso Mouse Scale score of SCI mice was increased and the proportion of CD8⁺ T cells in blood and spinal cord tissue was decreased after FTY-720 injection. Both migratory cDC1s (CD103⁺) and resident cDC1s (CD8α⁺) were present in the LNs surrounding the injured spinal cord of SCI mice. Among them, CD103⁺ cells were derived from the migration of cDC1s in spinal cord tissues, and CD8α⁺ cDC1s were directionally differentiated from pre-DCs after co-culture with LN-FSCs. Interferon-γ promoted the secretion of Flt3L by LN-FSCs through the activation of JAK/STAT signaling pathway and enhanced the differentiation of pre-DCs into CD8α⁺ cells.</p><p><strong>Conclusion: </strong>Migratory cDC1s and resident cDC1s promote the expansion of CD8⁺ T cells in LNs around the injured spinal cord and mediate the adaptive immune response to aggravate neuroinflammation in SCI.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"37"},"PeriodicalIF":6.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LRP11 facilitates lipid metabolism and malignancy in hepatocellular carcinoma by stabilizing RACK1 through USP5 regulation.","authors":"Litao Liang, Wenbo Jia, Jinyi Wang, Yanzhi Feng, Deming Zhu, Wenhu Zhao, Chao Xu, Xiangyu Ling, Qingpeng Lv, Xiaoming Ai, Lianbao Kong, Wenzhou Ding","doi":"10.1186/s10020-025-01097-6","DOIUrl":"10.1186/s10020-025-01097-6","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and a major public health challenge. Lipid metabolism plays a crucial role in the metabolic reprogramming observed in HCC, although the underlying mechanisms are still being elucidated. Nile red staining and lipid assays showed that LRP11 knockdown significantly reduces lipid accumulation in HCC cells, with a concurrent decrease in key lipid metabolism markers such as FSAN, ACLY and ACSL4, as demonstrated by Western blotting. Mass spectrometry (MS) and co-immunoprecipitation (Co-IP) revealed that LRP11 recruits USP5, enhancing USP5-mediated deubiquitination of RACK1. Truncation analysis identified LRP11 residues 309-500 as critical for interaction with the RACK1 residues 91-231. These findings suggest that LRP11 may influence lipid metabolism and progression in HCC through USP5-mediated stabilization of RACK1. Based on these results, LRP11 emerges as a potential target for further exploration in HCC therapy. Targeting LRP11 or disrupting its interactions with USP5 or RACK1 could offer new avenues for treatment, though additional research is required to validate these therapeutic possibilities.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"35"},"PeriodicalIF":6.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-6 related signaling pathways as the intersection between chronic diseases and sepsis.","authors":"Jie Yang, Lin Yang, Yanjiao Wang, Lu Huai, Bohan Shi, Di Zhang, Wei Xu, Di Cui","doi":"10.1186/s10020-025-01089-6","DOIUrl":"10.1186/s10020-025-01089-6","url":null,"abstract":"<p><p>Sepsis is associated with immune dysregulated and organ dysfunction due to severe infection. Clinicians aim to restore organ function, rather than prevent diseases that are prone to sepsis, resulting in high mortality and a heavy public health burden. Some chronic diseases can induce sepsis through inflammation cascade reaction and Cytokine Storm (CS). Interleukin (IL)-6, the core of CS, and its related signaling pathways have been considered as contributors to sepsis. Therefore, it is important to study the relationship between IL-6 and its related pathways in sepsis-related chronic diseases. This review generalized the mechanism of sepsis-related chronic diseases via IL-6 related pathways with the purpose to take rational management for these diseases. IL-6 related signaling pathways were sought in Kyoto Encyclopedia of Genes and Genomes (KEGG), and retrieved protein-protein interaction in the Search for Interaction Genes tool (STRING). In PubMed and Google Scholar, the studies were searched out, which correlating to IL-6 related pathways and associating with the pathological process of sepsis. Focused on the interactions of sepsis and IL-6 related pathways, some chronic diseases have been studied for association with sepsis, containing insulin resistance, Alcoholic liver disease (ALD), Alzheimer disease (AD), and atherosclerosis. This article summarized the inflammatory mechanisms of IL-6 cross-talked with other mediators of some chronic diseases in vitro, animal models, and human experiments, leading to the activation of pathways and accelerating the progression of sepsis. The clinicians should be highlight to this kind of diseases and more clinical trials are needed to provide more reliable theoretical basis for health policy formulation.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"34"},"PeriodicalIF":6.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single cell RNA sequencing improves the next generation of approaches to AML treatment: challenges and perspectives.","authors":"Zahra Khosroabadi, Samaneh Azaryar, Hassan Dianat-Moghadam, Zohreh Amoozgar, Mohammadreza Sharifi","doi":"10.1186/s10020-025-01085-w","DOIUrl":"10.1186/s10020-025-01085-w","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is caused by altered maturation and differentiation of myeloid blasts, as well as transcriptional/epigenetic alterations, all leading to excessive proliferation of malignant blood cells in the bone marrow. Tumor heterogeneity due to the acquisition of new somatic alterations leads to a high rate of resistance to current therapies or reduces the efficacy of hematopoietic stem cell transplantation (HSCT), thus increasing the risk of relapse and mortality. Single-cell RNA sequencing (scRNA-seq) will enable the classification of AML and guide treatment approaches by profiling patients with different facets of the same disease, stratifying risk, and identifying new potential therapeutic targets at the time of diagnosis or after treatment. ScRNA-seq allows the identification of quiescent stem-like cells, and leukemia stem cells responsible for resistance to therapeutic approaches and relapse after treatment. This method also introduces the factors and mechanisms that enhance the efficacy of the HSCT process. Generated data of the transcriptional profile of the AML could even allow the development of cancer vaccines and CAR T-cell therapies while saving valuable time and alleviating dangerous side effects of chemotherapy and HSCT in vivo. However, scRNA-seq applications face various challenges such as a large amount of data for high-dimensional analysis, technical noise, batch effects, and finding small biological patterns, which could be improved in combination with artificial intelligence models.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"33"},"PeriodicalIF":6.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}