Journal of Advanced Research最新文献

{"title":"FGF21 ameliorates septic liver injury by restraining proinflammatory macrophages activation through the autophagy/HIF-1α axis","authors":"Junjie Zhu ,&nbsp;Zhouxiang Jin ,&nbsp;Jie Wang ,&nbsp;Zhaohang Wu ,&nbsp;Tianpeng Xu ,&nbsp;Gaozan Tong ,&nbsp;Enzhao Shen ,&nbsp;Junfu Fan ,&nbsp;Chunhui Jiang ,&nbsp;Jiaqi Wang ,&nbsp;Xiaokun Li ,&nbsp;Weitao Cong ,&nbsp;Li Lin","doi":"10.1016/j.jare.2024.04.004","DOIUrl":"10.1016/j.jare.2024.04.004","url":null,"abstract":"<div><h3>Introduction</h3><div>Sepsis, a systemic immune syndrome caused by severe trauma or infection, poses a substantial threat to the health of patients worldwide. The progression of sepsis is heavily influenced by septic liver injury, which is triggered by infection and cytokine storms, and has a significant impact on the tolerance and prognosis of septic patients. The objective of our study is to elucidate the biological role and molecular mechanism of fibroblast growth factor 21 (FGF21) in the process of sepsis.</div></div><div><h3>Objectives</h3><div>This study was undertaken in an attempt to elucidate the function and molecular mechanism of FGF21 in therapy of sepsis.</div></div><div><h3>Methods</h3><div>Serum concentrations of FGF21 were measured in sepsis patients and septic mice. Liver injury was compared between mice FGF21 knockout (KO) mice and wildtype (WT) mice. To assess the therapeutic potential, recombinant human FGF21 was administered to septic mice. Furthermore, the molecular mechanism of FGF21 was investigated in mice with myeloid-cell specific HIF-1α overexpression mice (LyzM-Cre^DIO-HIF-1α) and myeloid-cell specific <em>Atg7</em> knockout mice (<em>Atg7</em>^△mye).</div></div><div><h3>Results</h3><div>Serum level of FGF21 was significantly increased in sepsis patients and septic mice. Through the use of recombinant human FGF21 (rhFGF21) and FGF21 KO mice, we found that FGF21 mitigated septic liver injury by inhibiting the initiation and propagation of inflammation. Treatment with rhFGF21 effectively suppressed the activation of proinflammatory macrophages by promoting macroautophagy/autophagy degradation of hypoxia-inducible factor-1α (HIF-1α). Importantly, the therapeutic effect of rhFGF21 against septic liver injury was nullified in LyzM-Cre^DIO-HIF-1α mice and <em>Atg7</em>^△mye mice.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate that FGF21 considerably suppresses inflammation upon septic liver injury through the autophagy/ HIF-1α axis.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 477-494"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140604292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the regulatory mechanisms of nodules development and quality formation in Panax notoginseng using multi-omics and MALDI-MSI","authors":"Muyao Yu ,&nbsp;Chunxia Ma ,&nbsp;Badalahu Tai ,&nbsp;Xueqing Fu ,&nbsp;Qi Liu ,&nbsp;Guanhua Zhang ,&nbsp;Xiuteng Zhou ,&nbsp;Liyuan Du ,&nbsp;Yan Jin ,&nbsp;Yang Han ,&nbsp;Han Zheng ,&nbsp;Luqi Huang","doi":"10.1016/j.jare.2024.04.003","DOIUrl":"10.1016/j.jare.2024.04.003","url":null,"abstract":"<div><h3>Introduction</h3><div>Renowned for its role in traditional Chinese medicine, <em>Panax notoginseng</em> exhibits healing properties including bidirectional regulatory effects on hematological system diseases. However, the presence of nodular structures near the top of the main root, known as nail heads, may impact the quality of the plant's valuable roots.</div></div><div><h3>Objectives</h3><div>In this paper, we aim to systematically analyze nail heads to identify their potential correlation with <em>P. notoginseng</em> quality. Additionally, we will investigate the molecular mechanisms behind nail head development.</div></div><div><h3>Methods</h3><div>Morphological characteristics and anatomical features were analyzed to determine the biological properties of nail heads. Active component analysis and MALDI mass spectrometry imaging (MALDI-MSI) were performed to determine the correlation between nail heads and <em>P. notoginseng</em> quality. Phytohormone quantitation, MALDI-MSI, RNA-seq, and <em>Arabidopsis</em> transformation were conducted to elucidate the mechanisms of nail head formation. Finally, protein-nucleic acid and protein–protein interactions were investigated to construct a transcriptional regulatory network of nodule development and quality formation.</div></div><div><h3>Results</h3><div>Our analyses have revealed that nail heads originate from an undeveloped lateral root. The content of ginsenosides was found to be positively associated with the amount of nail heads. Ginsenoside Rb₁ specifically accumulated in the cortex of nail heads, while IAA, tZR and JAs also showed highest accumulation in the nodule. RNA-seq analysis identified <em>PnIAA14</em> and <em>PnCYP735A1</em> as inhibitors of lateral root development. PnMYB31 and PnMYB78 were found to form binary complexes with PnbHLH31 to synergistically regulate the expression of <em>PnIAA14</em>, <em>PnCYP735A1</em>, <em>PnSS</em>, and <em>PnFPS</em>.</div></div><div><h3>Conclusion</h3><div>Our study details the major biological properties of nodular structures in <em>P. notoginseng</em> and outlines their impact on the quality of the herb. It was also determined that PnMYB31- and PnMYB78-PnbHLH31 regulate phytohormones and ginsenosides accumulation, further affecting plant development and quality. This research provides insights for quality evaluation and clinical applications of <em>P. notoginseng</em>.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 463-475"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140760560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive insights into potential roles of purinergic P2 receptors on diseases: Signaling pathways involved and potential therapeutics","authors":"Yanshuo Guo ,&nbsp;Tianqi Mao ,&nbsp;Yafei Fang ,&nbsp;Hui Wang ,&nbsp;Jiayue Yu ,&nbsp;Yifan Zhu ,&nbsp;Shige Shen ,&nbsp;Mengze Zhou ,&nbsp;Huanqiu Li ,&nbsp;Qinghua Hu","doi":"10.1016/j.jare.2024.03.027","DOIUrl":"10.1016/j.jare.2024.03.027","url":null,"abstract":"<div><h3>Background</h3><div>Purinergic P2 receptors, which can be divided into ionotropic P2X receptors and metabotropic P2Y receptors, mediate cellular signal transduction of purine or pyrimidine nucleoside triphosphates and diphosphate. Based on the wide expression of purinergic P2 receptors in tissues and organs, their significance in homeostatic maintenance, metabolism, nociceptive transmission, and other physiological processes is becoming increasingly evident, suggesting that targeting purinergic P2 receptors to regulate biological functions and signal transmission holds significant promise for disease treatment.</div></div><div><h3>Aim of review</h3><div>This review highlights the detailed mechanisms by which purinergic P2 receptors engage in physiological and pathological progress, as well as providing prospective strategies for discovering clinical drug candidates.</div></div><div><h3>Key scientific concepts of review</h3><div>The purinergic P2 receptors regulate complex signaling and molecular mechanisms in nervous system, digestive system, immune system and as a result, controlling physical health states and disease progression. There has been a significant rise in research and development focused on purinergic P2 receptors, contributing to an increased number of drug candidates in clinical trials. A few influential pioneers have laid the foundation for advancements in the evaluation, development, and of novel purinergic P2 receptors modulators, including agonists, antagonists, pharmaceutical compositions and combination strategies, despite the different scaffolds of these drug candidates. These advancements hold great potential for improving therapeutic outcomes by specifically targeting purinergic P2 receptors.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 427-448"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140343638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The CsTM alters multicellular trichome morphology and enhances resistance against aphid by interacting with CsTIP1;1 in cucumber","authors":"Songlin Yang ,&nbsp;Shudan Xue ,&nbsp;Li Shan ,&nbsp;Shanshan Fan ,&nbsp;Lei Sun ,&nbsp;Yuming Dong ,&nbsp;Sen Li ,&nbsp;Yiming Gao ,&nbsp;Yu Qi ,&nbsp;Lin Yang ,&nbsp;Menghang An ,&nbsp;Fang Wang ,&nbsp;Jin'an Pang ,&nbsp;Wenzhu Zhang ,&nbsp;Yiqun Weng ,&nbsp;Xingwang Liu ,&nbsp;Huazhong Ren","doi":"10.1016/j.jare.2024.04.008","DOIUrl":"10.1016/j.jare.2024.04.008","url":null,"abstract":"<div><div>The multicellular trichomes of cucumber (<em>Cucumis sativus</em> L.) serve as the primary defense barrier against external factors, whose impact extends beyond plant growth and development to include commercial characteristics of fruits. The aphid (<em>Aphis gossypii</em> Glover) is one of prominent pests in cucumber cultivation. However, the relationship between physical properties of trichomes and the aphid resistance at molecular level remains largely unexplored. Here, a spontaneous mutant <em>trichome morphology</em> (<em>tm</em>) was characterized by increased susceptibility towards aphid. Further observations showed the <em>tm</em> exhibited a higher and narrower trichome base, which was significantly distinguishable from that in wild-type (WT). We conducted map-based cloning and identified the candidate, <em>CsTM</em>, encoding a C-lectin receptor-like kinase. The knockout mutant demonstrated the role of <em>CsTM</em> in trichome morphogenesis. The presence of SNP does not regulate the relative expression of <em>CsTM,</em> but diminishes the CsTM abundance of membrane proteins in <em>tm</em>. Interestingly, CsTM was found to interact with CsTIP1;1, which encodes an aquaporin with extensive reports in plant resistance and growth development. The subsequent aphid resistance experiments revealed that both <em>CsTM</em> and <em>CsTIP1;1</em> regulated the development of trichomes and conferred resistance against aphid by affecting cytoplasmic H₂O₂ contents. Transcriptome analysis revealed a significant enrichment of genes associated with pathogenesis, calcium binding and cellulose synthase. Overall, our study elucidates an unidentified mechanism that <em>CsTM-CsTIP1;1</em> alters multicellular trichome morphology and enhances resistance against aphid, thus providing a wholly new perspective for trichome morphogenesis in cucumber.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 17-30"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140640583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in molecular mechanisms and therapeutic strategies for central nervous system diseases based on gut microbiota imbalance","authors":"Wei Tao ,&nbsp;Yanren Zhang ,&nbsp;Bingbin Wang ,&nbsp;Saiqun Nie ,&nbsp;Li Fang ,&nbsp;Jian Xiao ,&nbsp;Yanqing Wu","doi":"10.1016/j.jare.2024.03.023","DOIUrl":"10.1016/j.jare.2024.03.023","url":null,"abstract":"<div><h3>Backgroud</h3><div>Central nervous system (CNS) diseases pose a serious threat to human health, but the regulatory mechanisms and therapeutic strategies of CNS diseases need to be further explored. It has been demonstrated that the gut microbiota (GM) is closely related to CNS disease. GM structure disorders, abnormal microbial metabolites, intestinal barrier destruction and elevated inflammation exist in patients with CNS diseases and promote the development of CNS diseases. More importantly, GM remodeling alleviates CNS pathology to some extent.</div></div><div><h3>Aim of review</h3><div>Here, we have summarized the regulatory mechanism of the GM in CNS diseases and the potential treatment strategies for CNS repair based on GM regulation, aiming to provide safer and more effective strategies for CNS repair from the perspective of GM regulation.</div></div><div><h3>Key scientific concepts of review</h3><div>The abundance and composition of GM is closely associated with the CNS diseases. On the basis of in-depth analysis of GM changes in mice with CNS disease, as well as the changes in its metabolites, therapeutic strategies, such as probiotics, prebiotics, and FMT, may be used to regulate GM balance and affect its microbial metabolites, thereby promoting the recovery of CNS diseases.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 261-278"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140542195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tanshinone IIA destabilizes SLC7A11 by regulating PIAS4-mediated SUMOylation of SLC7A11 through KDM1A, and promotes ferroptosis in breast cancer","authors":"Na Luo,&nbsp;KeJing Zhang,&nbsp;Xin Li,&nbsp;Yu Hu,&nbsp;Lei Guo","doi":"10.1016/j.jare.2024.04.009","DOIUrl":"10.1016/j.jare.2024.04.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Breast cancer (BC) is the most common malignancy in women with unfavorite prognosis.</div></div><div><h3>Objectives</h3><div>Tanshinone IIA (Tan IIA) inhibits BC progression, however, the underlying mechanism remains largely undefined.</div></div><div><h3>Methods</h3><div>The cytotoxicity of Tan IIA was assessed by CCK-8 and LDH assays. Ferroptosis was monitored by the level of MDA, Fe²⁺, lipid ROS and GSH. IHC and western blot were employed to detect the localization and expression of SLC7A11, PIAS4, KDM1A and other key molecules. The SUMOylation of SLC7A11 was detected by Ni-beads pull-down assay and Co-IP. Luciferase and ChIP assays were employed to detect the direct association between KDM1A and PIAS4 promoter. The proliferative and metastatic properties of BC cells were assessed by colony formation, CCK-8 and Transwell assays, respectively. The <em>in vitro</em> findings were verified in xenograft and lung metastasis models.</div></div><div><h3>Results</h3><div>Tan IIA promoted ferroptosis by suppressing SLC7A11 in BC cells. Silencing of PIAS4 or KDM1A inhibited cell growth and metastasis in BC. Mechanistically, PIAS4 facilitated the SUMOylation of SLC7A11 via direct binding to SLC7A11, and KDM1A acted as a transcriptional activator of PIAS4. Functional studies further revealed that Tan IIA decreased KDM1A expression, thus suppressing PIAS4 expression transcriptionally. The inhibition of PIAS4-dependent SUMOylation of SLC7A11 further induced ferroptosis, thereby inhibiting proliferation and metastasis in BC.</div></div><div><h3>Conclusion</h3><div>Tan IIA promoted ferroptosis and inhibited tumor growth and metastasis via suppressing KDM1A/PIAS4/SLC7A11 axis.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 313-327"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140640635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay between lipid dysregulation and ferroptosis in chondrocytes and the targeted therapy effect of metformin on osteoarthritis","authors":"Zhi Zou ,&nbsp;Wenhui Hu ,&nbsp;Fei Kang ,&nbsp;Zhonghua Xu ,&nbsp;Yuheng Li ,&nbsp;Jing Zhang ,&nbsp;Jianmei Li ,&nbsp;Yuan Zhang ,&nbsp;Shiwu Dong","doi":"10.1016/j.jare.2024.04.012","DOIUrl":"10.1016/j.jare.2024.04.012","url":null,"abstract":"<div><h3>Introduction</h3><div>Osteoarthritis (OA) is a devastating whole-joint disease affecting a large population worldwide; the role of lipid dysregulation in OA and mechanisms underlying targeted therapy effect of lipid-lowering metformin on OA remains poorly defined.</div></div><div><h3>Objectives</h3><div>To investigate the effects of lipid dysregulation on OA progression and to explore lipid dysregulation-targeting OA treatment of metformin.</div></div><div><h3>Methods</h3><div>RNA-Seq data, biochemical, and histochemical assays in human and murine OA cartilage as well as primary chondrocytes were utilized to determine lipid dysregulation. Effects of metformin, a potent lipid-lowering medication, on ACSL4 expression and chondrocyte metabolism were determined. Further molecular experiments, including RT-qPCR, western blotting, flow cytometry, and immunofluorescence staining, were performed to investigate underlying mechanisms. Mice with intra-articular injection of metformin were utilized to determine the effects on ACLT-induced OA progression.</div></div><div><h3>Results</h3><div>ACSL4 and 4-HNE expressions were elevated in human and ACLT-induced mouse OA cartilage and IL-1β-treated chondrocytes (<em>P</em> &lt; 0.05). Ferrostatin-1 largely rescued IL-1β-induced MDA, lipid peroxidation, and ferroptotic mitochondrial morphology (<em>P</em> &lt; 0.05). Metformin decreased the levels of OA-related genes (<em>P</em> &lt; 0.05) and increased the levels of p-AMPK and p-ACC in IL-1β-treated chondrocytes. Intra-articular injection of metformin alleviated ACLT-induced OA lesions in mice, and reverted the percentage of chondrocytes positive for MMP13, Col2a1, ACSL4 and 4-HNE in ACLT mice (<em>P</em> &lt; 0.05). Ferroptotic chondrocytes promoted the recruitment and chemotaxis of RAW264.7 cells via CCL2, which was blocked by metformin <em>in vitro</em> (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>We establish a critical role of polyunsaturated fatty acids metabolic process in OA cartilage degradation and define metformin as a potential OA treatment. Metformin reshapes lipid availability and ameliorates chondrocyte ferroptosis sensitivity via the AMPK/ACC pathway. In the future, gene-edited animals and extensive omics technologies will be utilized to reveal detailed lipids’ involvement in cartilage lesions.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 515-529"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140640673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Irisin alleviates obesity-induced bone loss by inhibiting interleukin 6 expression via TLR4/MyD88/NF-κB axis in adipocytes","authors":"Yuanshu Zhang ,&nbsp;Xu He ,&nbsp;Kai Wang ,&nbsp;Yuan Xue ,&nbsp;Sihan Hu ,&nbsp;Yesheng Jin ,&nbsp;Guoqing Zhu ,&nbsp;Qin Shi ,&nbsp;Yongjun Rui","doi":"10.1016/j.jare.2024.04.013","DOIUrl":"10.1016/j.jare.2024.04.013","url":null,"abstract":"<div><h3>Introduction</h3><div>Obesity-induced bone loss affects the life quality of patients all over the world. Irisin, one of the myokines, plays an essential role in bone and fat metabolism.</div></div><div><h3>Objective</h3><div>Investigate the effects of irisin on bone metabolism <em>via</em> adipocytes in the bone marrow microenvironment.</div></div><div><h3>Methods</h3><div>In this study, we fed fibronectin type III domain-containing protein 5 (FNDC5, the precursor protein of irisin) knockout mice (FNDC5^-/-) with a high-fat diet (HFD) for 10 weeks. The quality of bone mass was assessed by micro-CT analysis, histological staining, and dynamic bone formation. <em>In vitro,</em> the lipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was assayed by Oil Red O staining, and the osteogenic differentiation was assayed by alkaline phosphatase staining. Meanwhile, the gene expression in the BMSC-differentiated adipocytes by RNA sequence and the involved pathway of irisin were determined by western blot and qRT-PCR were performed.</div></div><div><h3>Results</h3><div>The FNDC5^-/- mice fed with a HFD showed an increased body weight, fat content of the bone marrow and bone, and a decreased bone formation compared with those with a standard diet (SD). <em>In vitro</em>, irisin inhibited the differentiation of BMSCs into adipocytes and alleviated the inhibition of osteogenesis derived from BMSCs by the adipocyte supernatant. RNA sequence and blocking experiment showed that irisin reduced the production of interleukin 6 (IL-6) in adipocytes through downregulating the TLR4/MyD88/NF-κB pathway. Immunofluorescence staining of bone marrow further confirmed an increased IL-6 expression in the FNDC5^-/- mice fed with HFD compared with those fed with SD, which suffered serious bone loss.</div></div><div><h3>Conclusion</h3><div>Irisin downregulates activation of the TLR4/MyD88/NF-κB pathway, thereby reducing IL-6 production in adipocytes to enhance the osteogenesis of BMSCs. Thus, the rescue of osteogenesis of BMSCs, initially inhibited by IL-6, is a potential therapeutic target to mitigate obesity-induced osteoporosis.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 343-359"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140786121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative analysis of senescence-related genes identifies robust prognostic clusters with distinct features in hepatocellular carcinoma","authors":"Sicheng Liu ,&nbsp;Yang Meng ,&nbsp;Yaguang Zhang ,&nbsp;Lei Qiu ,&nbsp;Xiaowen Wan ,&nbsp;Xuyang Yang ,&nbsp;Yang Zhang ,&nbsp;Xueqin Liu ,&nbsp;Linda Wen ,&nbsp;Xue Lei ,&nbsp;Bo Zhang ,&nbsp;Junhong Han","doi":"10.1016/j.jare.2024.04.007","DOIUrl":"10.1016/j.jare.2024.04.007","url":null,"abstract":"<div><h3>Introduction</h3><div>Senescence refers to a state of permanent cell growth arrest and is regarded as a tumor suppressive mechanism, whereas accumulative evidence demonstrate that senescent cells play an adverse role during cancer progression. The scarcity of specific and reliable markers reflecting senescence level in cancer impede our understanding of this biological basis.</div></div><div><h3>Objectives</h3><div>Senescence-related genes (SRGs) were collected for integrative analysis to reveal the role of senescence in hepatocellular carcinoma (HCC).</div></div><div><h3>Methods</h3><div>Consensus clustering was used to subtype HCC based on SRGs. Several computational methods, including single sample gene set enrichment analysis (ssGSEA), fuzzy c-means algorithm, were performed. Data of drug sensitivities were utilized to screen potential therapeutic agents for different senescence patients. Additionally, we developed a method called signature-related gene analysis (SRGA) for identification of markers relevant to phenotype of interest. Experimental strategies consisting quantitative real-time PCR (qRT-PCR), β-galactosidase assay, western blot, and tumor-T cell co-culture system were used to validate the findings <em>in vitro</em>.</div></div><div><h3>Results</h3><div>We identified three robust prognostic clusters of HCC patients with distinct survival outcome, mutational landscape, and immune features. We further extracted signature genes of senescence clusters to construct the senescence scoring system and profile senescence level in HCC at bulk and single-cell resolution. Senescence-induced stemness reprogramming was confirmed both <em>in silico</em> and <em>in vitro</em>. HCC patients with high senescence were immune suppressed and sensitive to Tozasertib and other drugs. We suggested that MAFG, PLIN3, and 4 other genes were pertinent to HCC senescence, and MAFG potentially mediated immune suppression, senescence, and stemness.</div></div><div><h3>Conclusion</h3><div>Our findings provide insights into the role of SRGs in patients stratification and precision medicine.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 107-123"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140779835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual function of MrgprB2 receptor-dependent neural immune axis in chronic pain","authors":"","doi":"10.1016/j.jare.2025.02.037","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.037","url":null,"abstract":"Neuro-immune interactions have been recognized to be involved in the development of neuropathic pain induced by chemotherapeutic drugs (CINP). However…","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"66 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143518037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}