International Journal of Medical Sciences最新文献

{"title":"Gene Signature-Based Prognostic Model for Acute Myeloid Leukemia: The Role of <i>BATF</i>, <i>EGR1</i>, <i>PD-1</i>, <i>PD-L1</i>, and <i>TIM-3</i>.","authors":"Yupei Zhang, Zhixi Chen, Jiamian Zheng, Shaohua Chen, Liye Zhong, Jie Chen, Cunte Chen, Songnan Sui, Yangqiu Li","doi":"10.7150/ijms.108527","DOIUrl":"https://doi.org/10.7150/ijms.108527","url":null,"abstract":"<p><p><b>Background:</b> Acute myeloid leukemia (AML) is a malignancy of hematopoietic stem and progenitor cells, with T cell exhaustion linked to poor outcomes. Our previous research has shown that basic leucine zipper ATF-like transcription factor (<i>BATF</i>) and early growth response 1 (<i>EGR1</i>) play a role in chimeric antigen receptor T (CAR-T) cell exhaustion during AML tumor elimination. However, the roles of <i>BATF</i> and <i>EGR1</i> and their association with immune checkpoint genes in AML prognosis remain underexplored. <b>Methods:</b> Bone marrow (BM) samples from 92 newly diagnosed AML patients at our clinical center (JUN-dataset) were analyzed to detect the expression levels of <i>BATF</i>, <i>EGR1</i>, programmed cell death 1 (<i>PD-1</i>), programmed death-ligand 1 (<i>PD-L1</i>), T cell immunoglobulin and mucin domain-containing protein 3 (<i>TIM3</i>) together with conducting a prognostic assessment. Our findings were validated using RNA sequencing data from 155 AML patients from the TCGA database and 199 AML patients from the Beat-AML database. <b>Results:</b> High <i>BATF</i> expression correlated with poor overall survival (OS) (<i>P</i> = 0.030), whereas high <i>EGR1</i> expression indicated a favorable prognosis (<i>P</i> = 0.040). Patients with high <i>BATF</i> and low <i>EGR1</i> expression had worst outcomes (<i>P</i> < 0.001). Among those receiving allogenic hematopoietic stem cell transplantation (allo-HSCT), high <i>BATF</i> expression was linked to shorter OS (<i>P</i> = 0.004). Moreover, a prognostic model incorporating <i>BATF</i>, <i>EGR1</i>, <i>PD-1</i>, <i>PD-L1</i>, and <i>TIM-3</i> calculated a risk score, with high-risk patients demonstrating significantly shorter OS than low-risk patients in both total AML patients and allo-HSCT recipients (<i>P</i> < 0.001). Similar results were found in both the TCGA and Beat-AML datasets. <b>Conclusions:</b> We establish a prognostic model based on <i>BATF</i>, <i>EGR1</i>, <i>PD-1</i>, <i>PD-L1</i>, and <i>TIM-3</i> expression that effectively predicts survival outcomes for AML patients and allo-HSCT recipients. This model may provide valuable insights for prognosis assessment and treatment strategies.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1875-1884"},"PeriodicalIF":3.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioprospection of <i>Hura crepitans</i> metabolites against oxidative stress and inflammation: An <i>in vitro</i> and <i>in silico</i> exploration.","authors":"Yu-Cheng Kuo, Bashir Lawal, Halimat Yusuf Lukman, Lung-Ching Chen, Sheng-Liang Huang, Yi-Fong Chen, Adewale O Fadaka, Femi Olawale, Ayo Olasupo, Olabode T Ajenifujah, Dalia Fouad, Marios Papadakis, Gaber El-Saber Batiha, Saheed Sabiu, Alexander T H Wu, Hsu-Shan Huang","doi":"10.7150/ijms.109116","DOIUrl":"https://doi.org/10.7150/ijms.109116","url":null,"abstract":"<p><p><b>Background</b>: Despite the recognized therapeutic potential of <i>Hura crepitans</i>, its mechanistic antioxidant and anti-inflammatory actions remain underexplored. <b>Methods</b>: This study investigates the inhibitory effects, binding stability, and interactions of metabolites from <i>H. crepitans</i> on oxidative and inflammatory biomarkers/targets using <i>in vitro</i> analyses and molecular dynamics (MD) simulations. <b>Results</b>: <i>In vitro</i> experiments revealed significant dose-dependent antioxidant and anti-inflammatory activities. The crude methanolic extract (CMEHC) showed notable half-maximal inhibitory concentration (IC₅₀) values for antioxidant assays, such as diphenyl picrylhydrazine (45.51 µg/mL) and ferric-reducing power (10.86 µg/mL), with comparable performance to standard ascorbic acid. Anti-inflammatory activities, including protein denaturation, proteinase inhibition, and membrane stabilization, demonstrated IC₅₀ values between 77.29-171.30 µg/mL. Liquid chromatography-mass spectrophotometry identified five primary compounds, predominantly phenolics, with rutin as the most abundant. Computational analyses confirmed these compounds' safety profiles, robust binding interactions, and stability against oxidative and inflammatory targets, with rutin forming the most stable interactions. <b>Conclusion</b>: These findings highlight the potential of <i>H. crepitans</i> phenolics as alternative therapies for oxidative stress and inflammation, warranting further drug development studies.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1837-1851"},"PeriodicalIF":3.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indoxyl sulfate is associated with cognitive impairment in ESRD patients by activating the extrinsic apoptosis in the neuronal cells during differentiating process.","authors":"Chih-Chuan Hsieh, Kuo-Cheng Lu, Chuen-Lin Huang, Jiun-Jie Wang, Ting-Yin Yeh, Shyh-Min Lin, Ya-Ling Chung, Yi-Chou Hou, Yuahn-Sieh Huang","doi":"10.7150/ijms.109245","DOIUrl":"https://doi.org/10.7150/ijms.109245","url":null,"abstract":"<p><p><b>Aim:</b> This study investigates the correlation between indoxyl sulfate (IS) levels and cognitive impairment in end-stage renal disease (ESRD) patients from human study, <i>in vivo</i> and <i>in vitro</i> study. <b>Materials and Methods:</b> Comparison of demographic and biochemical data, including IS concentrations, was conducted between a control group(n=16) and the ESRD with cognitive impairment group (n=14) and without cognitive impairment (n=17). A CKD animal model induced renal impairment in adenine-fed C57BL/6 mice, assessing memory loss and behavioral changes. Immunohistochemistry evaluated choline acetyltransferase activity and GFAP expression. Differentiating SH-SY5Y cells were treated with IS, assessing cell viability and apoptosis via annexin V and propidium iodide staining and western blotting. Reactive oxidized species generation was measured using DCFCA fluorescence and NAC pretreatment. <b>Results:</b> In ESRD patients with cognitive impairment, IS levels were significantly higher compared to healthy controls, along with older age. CKD mice exhibited renal impairment and memory loss, accompanied by altered choline acetyltransferase activity and GFAP expression. IS treatment induced early apoptosis in SH-SY5Y cells, associated with increased cleaved caspase 3 levels and Fas/Fas-ligand activity, altered Bax/Bcl2 ratio, and reactive oxidized species generation. <b>Conclusion:</b> Elevated IS levels are associated with cognitive impairment and neuronal apoptosis, potentially mediated by oxidative stress. IS could be a therapeutic target for cognitive dysfunction in CKD, necessitating further research into its mechanisms and therapeutic interventions.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1736-1749"},"PeriodicalIF":3.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of Huhuang decoction in treating diabetic wounds: a network pharmacological and experimental study.","authors":"Jie Zhang, Yan Shi, Jiaqiang Wang, Min Gao, Shan Zhong, Yunsheng Chen, Jiaqi Hao, Peilang Yang, Shun Xu, Yan Liu","doi":"10.7150/ijms.108187","DOIUrl":"https://doi.org/10.7150/ijms.108187","url":null,"abstract":"<p><p><b>Background:</b> Huhuang (HH) decoction, a composition of seven traditional Chinese medicines, has demonstrated clinical efficacy in wound healing. However, its pharmacological foundation and potential mechanisms remain unclear. This study aimed to elucidate the mechanisms of action of HH decoction in the treatment of diabetic wounds. <b>Methods:</b> The chemical composition of HH decoction was analysed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. The targets of the HH decoction in treating diabetic wounds were predicted using network pharmacology. The gene ontology and pathway enrichment analyses were performed using the DAVID functional annotation tool. The compound targets and PPI networks were established using Cytoscape. Molecular docking was implemented using the AutoDock Vina software. Experimental verification was performed on the target prediction of the HH decoction in treating diabetic wounds, both <i>in vivo</i> and <i>in vitro</i>. <b>Results:</b> The study identified 53 chemical components in HH decoction, with tetrahydropalmatine, emodin, rosmarinic acid, citric acid, berberine, and cryptotanshinone as key components for treating diabetic wounds. Twenty-one target genes were identified as core genes. Gene ontology analysis indicated that the therapeutic effects of HH on diabetic foot ulcers may occur through the regulation of cell proliferation, migration, and inflammation. Pathway enrichment was found to be mainly related to the HIF-1 and TNF signalling pathways. HH promoted proliferation, migration, and tube formation in vascular endothelial cells <i>in vitro</i>. Compared with the control group, the expression levels of HIF-1α, VEGF-α, cyclinD1 in the HH group were higher while the phosphorylation level of p65 in the HH group was significantly lower. The concentrations of IL-6, TNF-α, and IL-1β in wound tissue in the HH group were significantly lower than those in the control group. The expression levels of CD31, VEGF-α, Ki67 and HIF-1α in the wounds of diabetic rats in the HH group were higher than those in the control group. <b>Conclusions:</b> The HH decoction promotes diabetic wound healing via multiple components, targets, and pathways. It may enhance vascular endothelial cell proliferation via cyclinD1, promote vascularization through the HIF-1α/VEGF-α signalling pathway, and inhibit inflammation through NF-κB signalling pathways.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1811-1824"},"PeriodicalIF":3.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the Role of Polyamine Metabolites in Blood and the DNA Methylation of <i>Mycobacterium Tuberculosis</i> in Patients with Multidrug-Resistant Tuberculosis.","authors":"Li Yan, Xinxin Niu, Kuidi Liang, Feifeng Guan, Xiaolin Yu, Ziyu Ye, Mingyuan Huang, Hancheng Liang, Xinguang Zhong, Jincheng Zeng","doi":"10.7150/ijms.102568","DOIUrl":"https://doi.org/10.7150/ijms.102568","url":null,"abstract":"<p><p><b>Background:</b> Tuberculosis (TB) is the second largest infectious disease killer in China, and the increasing prevalence of drug-resistant TB patients complicates treatment efforts and raises associated costs. Research on the mechanisms and characteristics of drug-resistant TB contributes to the discovery of new drug targets and the development of new anti-tuberculosis drugs. <b>Methods:</b> In this study, high-performance liquid chromatography (HPLC) was used to detect the content of polyamine metabolites, while western blotting, qPCR and ELISA were used to detect the expression of polyamine metabolism-related enzymes. The Oxford Nanopore Technologies (ONT) sequencing was applied to profile DNA methylation in multidrug-resistant <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>). Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the screened differentially hypermethylated genes. Furthermore, STRING and Cytoscape software were used to construct a protein-protein interaction (PPI) network to identify the key genes. <b>Results:</b> The findings indicated the spermidine (SPD) and polyamine metabolism-related enzymes were elevated in the peripheral blood of TB patients. In addition, the production of polyamines and polyamine metabolism-related enzymes was increased in the peripheral blood of multidrug-resistant tuberculosis (MDR-TB) patients. GO and KEGG analyses showed that the differentially hypermethylated genes were mainly enriched in arginine metabolism. The PPI network analysis identified the top five key genes with the highest degrees: <i>moaX</i>, <i>vapC49</i>, <i>vapB49</i>, <i>highA3</i> and <i>nuoC</i>. <b>Conclusions:</b> Polyamine metabolites were increased in the peripheral blood of MDR-TB patients. The differentially hypermethylated genes in multidrug-resistant <i>Mtb</i> are involved in the arginine biosynthetic process, the differentially methylated genes may play an important biological role in the multidrug resistance of <i>Mtb</i>.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1762-1772"},"PeriodicalIF":3.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Relationship Between Gut Microbiota and Aortic Stenosis: Role of Inflammatory Proteins, Blood Metabolites, and Immune Cells.","authors":"Fanhui Jing, Jiapeng Zhou, Fengwen Zhang, Guangzhi Zhao, Fang Fang, Xiangbin Pan","doi":"10.7150/ijms.110392","DOIUrl":"https://doi.org/10.7150/ijms.110392","url":null,"abstract":"<p><p><b>Background:</b> Aortic stenosis is the most prevalent valvular heart disease in high-income population, and there are currently no medical therapies to slow the disease progression. Given that gut microbiota influences the immune system, lipid metabolism, and inflammation, there may be a potential link between gut microbiota and AS. <b>Aims:</b> We aimed to examine the causal effects of gut microbiota on AS and to investigate the mediating roles of inflammatory proteins, blood metabolites, and immune cells. <b>Methods:</b> Bidirectional Mendelian randomization analysis was performed to assess the causal relationships between gut microbiota, inflammatory proteins, blood metabolites, immune cells, and AS. Two-step Mendelian randomization was utilized to explore direct and indirect effects. The data were derived from genome-wide association study summary statistics available in public databases. <b>Results:</b> The study identified nine gut microbial features (six microbial taxa and three pathways), four inflammatory proteins, 91 blood metabolites, and four immune cell traits associated with AS. However, no significant mediating roles were found for inflammatory proteins, blood metabolites, and immune cells in the causal pathway between gut microbiota and AS. <b>Conclusion:</b> This study revealed novel causal associations between gut microbial features, inflammatory proteins, blood metabolites, and immune cell traits with AS. These findings offer new insights into the pathophysiology of AS and provide potential targets for therapeutic approaches.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1750-1761"},"PeriodicalIF":3.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The roles of the ubiquitin-proteasome system in renal disease.","authors":"Danqin Lu, Yingying Zhang, Ping Zhu, Jiao Wu, Cheng Yuan, Lihua Ni","doi":"10.7150/ijms.107284","DOIUrl":"https://doi.org/10.7150/ijms.107284","url":null,"abstract":"<p><p>The ubiquitin-proteasome system (UPS) is a major pathway of specific intracellular protein degradation through proteasome degradation of ubiquitin-labeled substrates. Numerous biological processes, including the cell cycle, transcription, translation, apoptosis, receptor activity, and intracellular signaling, are regulated by UPS. Alterations of the UPS, which render them more or less susceptible to degradation, are responsible for disorders of renal diseases. This review aims to summarize the mechanism of UPS in renal diseases. Besides, this review explores the relationship among UPS, autophagy, and deubiquitination in the development of renal disease. The specific molecular linkages among these systems and pathogenesis, on the other hand, are unknown and controversial. In addition, we briefly describe some anti-renal disease agents targeting UPS components. This review emphasizes UPS as a promising therapeutic modality for the treatment of kidney disease. Our work, though still basic and limited, could provide options to future potential therapeutic targets for renal diseases with a UPS underlying basis.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1791-1810"},"PeriodicalIF":3.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncogenic and Immunological Roles of FRS2 and its Potential Value in Retroperitoneal Liposarcoma: from Bioinformatics Analysis to Clinicopathological Evidence.","authors":"Hao Yu, Shuquan Li, Yifan Wu, Zhen Wang, Xiaopeng Wang, Sha Zhang, Xiaoya Guan, Bin Dong, Chunyi Hao, Xiuyun Tian, Ang Lv","doi":"10.7150/ijms.103802","DOIUrl":"https://doi.org/10.7150/ijms.103802","url":null,"abstract":"<p><p><b>Background:</b> Retroperitoneal liposarcoma (RLPS) is a rare malignancy with no effective treatment beyond surgical intervention. Identifying novel therapeutic targets and prognostic markers is critical to improving outcomes. Fibroblast growth factor receptor substrate 2 (FRS2), located near MDM2 on chromosome 12q13-15, has a biological role and prognostic value in liposarcoma, which remain to be fully explored. <b>Methods:</b> Bioinformatics tools were used to analyze the differential expression of FRS2 across various malignancies using public databases, such as GTEx, TCGA, and cBioPortal. In sarcomas (SARC), clinicopathological features, prognostic outcomes, co-expressed genes, levels of tumor-infiltrating immune cells, immunostimulators, major histocompatibility complex (MHC) molecules, and immunochemokines were extracted from multiple public databases. Tumor specimens from 82 RLPS patients at our sarcoma center were collected, and FRS2 expression was assessed through immunohistochemistry. <b>Results:</b> FRS2 was found to be upregulated and amplified in most cancers. GEPIA 2 analysis showed significant variation in FRS2 mRNA expression across cancer types, especially in sarcomas (SARC). Lower FRS2 expression in SARC was correlated with improved overall survival (OS) and disease-free survival (DFS). FRS2 may affect the tumor immune microenvironment, inhibiting immune cell infiltration and promoting immune evasion. In our RLPS cohort, FRS2 overexpression was observed in 58.53% (48/82) of cases and was correlated with age (P = 0.009). High FRS2 expression was associated with poorer OS and DFS (P = 0.049 and P < 0.001, respectively), and multivariate analysis confirmed FRS2 as an independent prognostic factor. <b>Conclusion:</b> FRS2 may serve as a potential prognostic biomarker and therapeutic oncogene target. Additionally, FRS2 could play a role in immune cell infiltration in SARC and represents a promising immunotherapeutic target for cancer treatment.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1825-1836"},"PeriodicalIF":3.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Phenotypic and Transcriptomic Analyses of Osteoporosis in Type 2 Diabetic Mice.","authors":"Shu-Juan Xing, Ying-Feng Gao, Lu Liu, Bing-Dong Sui, Ning-Ning Da, Jin-Yu Liu, Hao Wang, Yuan Yuan, Yuan Qin, Pei-Sheng Liu, Si-Qi Ying, Kai Zhang, Jie-Xi Liu, Ji Chen, Yi-Han Liu, Xin Xie, Yan Jin, Sha Zhang, Chen-Xi Zheng","doi":"10.7150/ijms.109537","DOIUrl":"https://doi.org/10.7150/ijms.109537","url":null,"abstract":"<p><p><b>Background:</b> Type 2 diabetes (T2D) is a global metabolic condition associated with complications of multiple organs, including the bone. However, the exact impact of T2D on bone along the disease progression, particularly in the early phase, remains largely unknown. <b>Methods:</b> Four-week and sixteen-week high-fat diet (HFD) feeding-induced T2D mouse models were established, and the glucose metabolic status was examined. Bone mass was evaluated by micro-computed tomography (micro-CT), and immunofluorescent (IF) staining was performed for bone histomorphometry with enzyme-linked immunosorbent assay (ELISA) determining serum markers. RNA sequencing analysis was performed to examine the transcriptome of bone, and single-cell RNA-sequencing (scRNA-seq) analysis was further applied. Bone marrow mesenchymal stem cells (BMMSCs) were isolated and analyzed for functional behaviors. <b>Results:</b> The occurrence of glucose metabolic disorders was confirmed at both four weeks and sixteen weeks of HFD feeding, showing increased blood glucose levels with impaired glucose tolerance and insulin sensitivity. Notably, early T2D osteoporosis symptoms were detected at four weeks, especially in the trabecular bone, demonstrating reduced bone mass and mineral density. Histological analysis confirmed that bone remodeling and immune-related inflammation were also altered in T2D mice, remarkably at the early phase, mainly reflected by suppressed bone formation, stimulated bone resorption, increased macrophages, and elevated tumor necrosis factor-alpha (TNF-α) levels. Transcriptomic sequencing further demonstrated significant yet distinct changes in the gene expression profile of bone during T2D progression, which confirmed the histological findings. Notably, overlapping genes with altered expression at four weeks and sixteen weeks of T2D compared to the respective control were identified, and bone marrow scRNA-seq analysis indicated many of them were expressed in BMMSCs, suggesting BMMSCs critically involved in T2D osteoporosis. Dysregulated molecular profiles and functional abnormalities of BMMSCs in T2D mice were validated by <i>ex vivo</i> assays, showing early and persistent occurrence of impaired colony-forming and proliferative capacities with biased differentiation potential. <b>Conclusions:</b> These findings elucidate the bone lesion phenotype in T2D, particularly at the early phase, uncover changes in gene expression profiles of bone during T2D progression, and clarify the functional alterations in bone stem cells, providing a basis for subsequent research and the development of treatment strategies.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1773-1790"},"PeriodicalIF":3.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of lung immune prognostic index with overall survival in pancreatic ductal adenocarcinoma patients treated using chemotherapy.","authors":"Nan Zhang, Guochao Deng, Ru Jia, Quanli Han, Guanghai Dai","doi":"10.7150/ijms.102404","DOIUrl":"10.7150/ijms.102404","url":null,"abstract":"<p><p><b>Background:</b> The lung immune prognostic index (LIPI) has attracted considerable interest for its prognostic value in several malignancies. However, its prognostic value in pancreatic ductal adenocarcinoma (PDAC) has not yet been clarified. <b>Objective:</b> This study aimed to assess the role of LIPI with regard to overall survival (OS) in locally advanced or metastatic PDAC patients undergoing chemotherapy. <b>Methods:</b> Data from 256 patients with PDAC treated via chemotherapy at the Chinese PLA General Hospital between January 1, 2011 and July 1, 2018 were retrospectively reviewed. Their neutrophil-to-lymphocyte ratio (dNLR) with lactate dehydrogenase (LDH) values were used to calculate each one's LIPI. The Cox proportional hazard model was used to identify the association between LIPI and OS. <b>Results:</b> Of the included patients, 154 were in the good LIPI group and 102 were in the intermediate/poor LIPI group. The OS in the two groups were 9.0 months (95% CI: 7.351-10.649) and 6.0 months (95% CI: 4.812-7.188), respectively. Patients in the good LIPI group had better OS compared to those in the intermediate/poor LIPI group (HR, 0.720; 95% CI: 0.554-0.935; <i>P</i> = 0.014). <b>Conclusion:</b> This study revealed LIPI is significantly associated with OS in PDAC and could play a significant role in helping clinicians make appropriate decisions for PDAC patients undergoing chemotherapy.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 7","pages":"1672-1679"},"PeriodicalIF":3.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}