Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences最新文献

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[Research progress of iron metabolism and ferroptosis in myeloid neoplasms]. 髓系肿瘤铁代谢与铁下垂的研究进展。
Yudi Wang, Weiying Feng, Fudi Wang, Junxia Min
{"title":"[Research progress of iron metabolism and ferroptosis in myeloid neoplasms].","authors":"Yudi Wang, Weiying Feng, Fudi Wang, Junxia Min","doi":"10.3724/zdxbyxb-2024-0211","DOIUrl":"10.3724/zdxbyxb-2024-0211","url":null,"abstract":"<p><p>It is reported that iron metabolism and ferroptosis can influence the occurrence and development of myeloid tumors, which can serve as therapeutic targets. Dysregulation of iron metabolism is present in a variety of myeloid neoplasms. The prognosis of acute myeloid leukemia is related to differential expression of molecules related to iron metabolism. The prognosis of myelodysplastic syndrome patients with iron overload is poor. Myeloproliferative neoplasms are often characterized by the coexistence of iron deficiency and erythrocytosis, which can be treated by targeting hepcidin. Myeloid tumor cells are susceptible to oxidative damage caused by the accumulation of reactive oxygen species and are sensitive to ferroptosis. Ferroptosis has anti-tumor effect in acute myeloid leukemia and myelodysplastic syndrome. Targeting ferroptosis can reverse imatinib resistance in chronic myeloid leukemia. This article reviews the characteristics of iron metabolism in the development and progression of myeloid neoplasms, as well as the mechanism of ferroptosis, to provide a basis for the development of new therapeutic strategies.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"735-746"},"PeriodicalIF":0.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Knockdown of nuclear protein 1 delays pathological pro-gression of osteoarthritis through inhibiting chondrocyte ferroptosis]. 敲除核蛋白1可通过抑制软骨细胞的铁突变,延缓骨关节炎的病理发展。
Taiyang Liao, Zhenyuan Ma, Deren Liu, Lei Shi, Jun Mao, Peimin Wang, Liang Ding
{"title":"[Knockdown of nuclear protein 1 delays pathological pro-gression of osteoarthritis through inhibiting chondrocyte ferroptosis].","authors":"Taiyang Liao, Zhenyuan Ma, Deren Liu, Lei Shi, Jun Mao, Peimin Wang, Liang Ding","doi":"10.3724/zdxbyxb-2024-0091","DOIUrl":"10.3724/zdxbyxb-2024-0091","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To investigate the effect of nuclear protein (Nupr) 1 on the pathological progression of osteoarthritis and its relationship with ferroptosis of chondrocytes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Chondrocytes from mouse knees were divided into small interfering RNA (siRNA) control group, small interfering RNA targeting Nupr1 (siNupr1) group, siRNA control+IL-1β group (siRNA control interference for 24 h followed by 10 ng/mL IL-1β) and siNupr1+IL-1β group (siNupr1 interference for 24 h followed by 10 ng/mL IL-1β). The protein and mRNA expressions of Nupr1 were detected by Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell proliferation viabilities were measured using the cell counting kit-8 method. The levels of ferrous ions were detected by FerroOrange staining. Lipid peroxidation levels were detected by C11-BODIPY-591 fluorescence imaging. The contents of malondialdehyde (MDA) and glutathione (GSH) were detected by enzyme-linked immunosorbent assay. The protein expressions of acyl-CoA synthetase long-chain family (ACSL) 4, P53, glutathione peroxidase (GPX) 4 and solute carrier family 7 member 11 gene (SLC7A11) were detected by Western blotting. The osteoarthritis model was constructed by destabilization of the medial meniscus (DMM) surgery in 7-week-old male C57BL/6J mice. The mice were randomly divided into four groups with 10 animals in each group: sham surgery (Sham)+adeno-associated virus serotype 5 (AAV5)-short hairpin RNA (shRNA) control group, Sham+AAV5-shRNA control targeting &lt;i&gt;Nupr1&lt;/i&gt; (shNupr1) group, DMM+AAV5-shRNA control group, and DMM+AAV5-shNupr1 group. Hematoxylin and eosin staining and Safranin O-Fast Green staining were used to observe the morphological changes in cartilage tissue. The Osteoarthritis Research Society International (OARSI) osteoarthritis cartilage histopathology assessment system was used to evaluate the degree of cartilage degeneration in mice. The mRNA expressions of matrix metallopeptidase (MMP) 13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 5, cyclooxy-genase (COX) 2, and GPX4 were detected by qRT-PCR.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;&lt;i&gt;In vitro&lt;/i&gt; experiments showed that knocking down &lt;i&gt;Nupr1&lt;/i&gt; alleviated the decrease of chondrocyte proliferation activity induced by IL-1β, reduced iron accumulation in mouse chondrocytes, lowered lipid peroxidation, downregulated ACSL4 and P53 protein expression and upregulated GPX4 and SLC7A11 protein expression (all &lt;i&gt;P&lt;/i&gt;&lt;0.01), thereby inhibiting ferroptosis in mouse chondrocytes. Meanwhile, &lt;i&gt;in vivo&lt;/i&gt; animal experiments demonstrated that knocking down &lt;i&gt;Nupr1&lt;/i&gt; delayed the degeneration of articular cartilage in osteoarthritis mice, improved the OARSI score, slowed down the degradation of the extracellular matrix in osteoarthritis cartilage, and reduced the expression of the key ferroptosis regulator GPX4 (all &lt;i&gt;P&lt;/i&gt;&lt;0.01).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"669-679"},"PeriodicalIF":0.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Research progress on the role of ferroptosis in aortic dissection]. 主动脉夹层中铁下垂作用的研究进展。
Xiang Hong, Yuchong Zhang, Weiguo Fu, Lixin Wang
{"title":"[Research progress on the role of ferroptosis in aortic dissection].","authors":"Xiang Hong, Yuchong Zhang, Weiguo Fu, Lixin Wang","doi":"10.3724/zdxbyxb-2024-0186","DOIUrl":"10.3724/zdxbyxb-2024-0186","url":null,"abstract":"<p><p>Recent studies have shown that iron metabolism dysregulation and lipid peroxidation-induced ferroptosis, triggered by oxidative stress, play a key role in the development of aortic dissection. Dysregulated iron metabolism leads to excessive production of hydroxyl radicals due to abnormal iron levels and heme metabolism, while lipid peroxidation is linked to system Xc<sup>-</sup> dysfunction and accumulation of phospholipid hydroperoxides. These factors synergistically disrupt aortic homeostasis and drive ferroptosis in vascular cells, including endothelial and smooth muscle cells. Furthermore, disruptions in ferroptosis-related genes, along with risk factors such as smoking, epigenetic modifications such as protein methylation, and abnormalities in immune cells, particularly T cells, are closely linked to aortic dissection. Several small molecules and nanomaterials have shown potential in inhibiting ferroptosis in this context. This review elucidates the roles of ferroptosis in aortic dissection and proposes strategies for its targeted prevention and treatment.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"726-734"},"PeriodicalIF":0.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Research progress on metal pollutants inducing neurotoxicity through ferroptosis]. 金属污染物通过铁下垂诱导神经毒性的研究进展。
Ziyu Qin, Yuqing Chen, Xinyuan Zhao, Shali Yu
{"title":"[Research progress on metal pollutants inducing neurotoxicity through ferroptosis].","authors":"Ziyu Qin, Yuqing Chen, Xinyuan Zhao, Shali Yu","doi":"10.3724/zdxbyxb-2024-0127","DOIUrl":"10.3724/zdxbyxb-2024-0127","url":null,"abstract":"<p><p>It has been confirmed that exposure to various metal pollutants can induce neurotoxicity, which is closely associated with the occurrence and development of neurological disorders. Ferroptosis is a form of cell death in response to metal pollutant exposure and it is closely related to oxidative stress, iron metabolism and lipid peroxidation. Recent studies have revealed that ferroptosis plays a significant role in the neurotoxicity induced by metals such as lead, cadmium, manganese, nickel, and antimony. Lead exposure triggers ferroptosis through oxidative stress, iron metabolism disorder and inflammation. Cadmium can induce ferroptosis through iron metabolism, oxidative stress and ferroptosis related signaling pathways. Manganese can promote ferroptosis through mitochondrial dysfunction, iron metabolism disorder and oxidative stress. Nickel can promote ferroptosis by influencing mitochondrial function, disrupting iron homeostasis and facilitating lipid peroxidation in the central nervous system. Antimony exposure can induce glutathione depletion by activating iron autophagy, resulting in excessive intracellular iron deposition and ultimately causing ferroptosis. This article reviews the effects of metal pollutants on ferroptosis-related indicators and discusses the specific mechanisms by which each metal triggers ferroptosis. It provides a reference for identifying targets for preventing neurotoxicity and for developing treatment strategies for neurological disorders.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"699-707"},"PeriodicalIF":0.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Research progress on ferroptosis regulation in tumor immunity of hepatocellular carcinoma]. 铁下垂对肝癌肿瘤免疫调节的研究进展。
Yuqian Mo, Zhilin Zou, Erbao Chen
{"title":"[Research progress on ferroptosis regulation in tumor immunity of hepatocellular carcinoma].","authors":"Yuqian Mo, Zhilin Zou, Erbao Chen","doi":"10.3724/zdxbyxb-2024-0117","DOIUrl":"10.3724/zdxbyxb-2024-0117","url":null,"abstract":"<p><p>Ferroptosis is a form of regulated cell death, which is dependent on iron metabolism imbalance and characterized by lipid peroxidation. Ferroptosis plays a crucial role in various pathological processes. Studies have shown that the occurrence of ferroptosis is closely associated with the progression of hepatocellular carcinoma (HCC). Ferroptosis is involved in regulating the lipid metabolism, iron homeostasis, mitochondrial metabolism, and redox processes in HCC. Additionally, ferroptosis plays a key role in HCC tumor immunity by modulating the phenotype and function of various immune cells in the tumor microenvironment, affecting tumor immune escape and progression. Ferroptosis-induced lipid peroxidation and oxidative stress can promote the polarization of M1 macrophages and enhance the pro-inflammatory response in tumors, inhibiting immune suppressive cells such as myeloid-derived suppressor cells and regulatory T cells to disrupt their immune suppression function. The regulation of expression of ferroptosis-related molecules such as GPX4 and SLC7A11 not only affects the sensitivity of tumor cells to immunotherapy but also directly influences the activity and survival of effector cells such as T cells and dendritic cells, further enhancing or weakening host antitumor immune response. Targeting ferroptosis has demonstrated significant clinical potential in HCC treatment. Induction of ferroptosis by nanomedicines and molecular targeting strategies can directly kill tumor cells or enhance antitumor immune responses. The integration of multimodal therapies with immunotherapy further expands the application of ferroptosis targeting as a cancer therapy. This article reviews the relationship between ferroptosis and antitumor immune responses and the role of ferroptosis in HCC progression from the perspective of tumor immune microenvironment, to provide insights for the development of antitumor immune therapies targeting ferroptosis.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"715-725"},"PeriodicalIF":0.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Preparation of decellularized bone graft material with supercritical carbon dioxide extraction technique]. 利用超临界二氧化碳萃取技术制备脱细胞骨移植材料。
Feng Hao, Kaifeng Pan, Liuyun Huang, Xuhong Chen, Haikun Wei, Xianhua Chen, Jianfeng Zhang
{"title":"[Preparation of decellularized bone graft material with supercritical carbon dioxide extraction technique].","authors":"Feng Hao, Kaifeng Pan, Liuyun Huang, Xuhong Chen, Haikun Wei, Xianhua Chen, Jianfeng Zhang","doi":"10.3724/zdxbyxb-2024-0108","DOIUrl":"10.3724/zdxbyxb-2024-0108","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the immunogenicity and osteogenic ability of animal-derived bone graft material decellularized with supercritical carbon dioxide.</p><p><strong>Methods: </strong>Porcine femurs were randomly divided into two groups after preliminary treatment, and decellularized with conventional method (control group) or supercritical carbon dioxide (experimental group). Allogenic demineralized bone matrix was used as positive control. Clearance rate of galactose-α-1, 3-galactose (α-Gal) antigen was determined by enzyme-linked immunosorbent assay and residual DNA was detected by a fluorescence method. Nine SPF-grade male athymic nude mice of 6 weeks old were randomly divided into experimental, control and positive control groups. Samples were implanted over biceps femoris muscle of athymic nude mice. The explants were collected 4 weeks post implantation. Hematoxylin and eosin (HE) staining and immunohistochemistry were applied to determine the osteogenic ability and bone tissue-associated protein expressions of the implants.</p><p><strong>Results: </strong>The clearance rates of α-Gal antigen in the experimental group and the control group were (99.09±0.26)% and (30.18±2.02)%, respectively (<i>t</i>=58.67, <i>P<</i>0.01). The residual DNA of the experimental, control and positive control groups were (13.49±0.07), (15.20±0.21) and (14.70±0.17) ng/mg. The residual DNA in the experimental group was significantly lower than that in the control group (<i>t</i>=-13.41, <i>P</i><0.01) and positive control group (<i>t</i>=-11.30, <i>P</i><0.01). HE staining results showed that multiple bone formation centers with active osteogenesis and rich bone marrow were observed in experimental group 4 weeks after implantation, but only a small number of bone formation centers were observed in the control and positive control groups, with no obvious osteoblasts present. Immunohistochemistry results indicated that the expressions of alkaline phosphatase, Runt-related transcription factor 2, collagen typeⅠand osteocalcin in the experimental group showed an increasing trend compared with those in the control and positive control groups.</p><p><strong>Conclusions: </strong>Compared with clinically used allogenic demineralized bone matrix and bone graft material decellularized with conventional method, bone graft material decellularized with supercritical carbon dioxide exhibits lower immunogenicity and better osteogenic ability.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"772-778"},"PeriodicalIF":0.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Inhibition of miR-30d-5p promotes mitochondrial autophagy and alleviates high glucose-induced injury in podocytes]. 抑制miR-30d-5p可促进线粒体自噬,减轻高糖诱导的足细胞损伤。
Ying Cai, Sheng Chen, Xiaoli Jiang, Qiyuan Wu, Bei Guo, Fang Wang
{"title":"[Inhibition of miR-30d-5p promotes mitochondrial autophagy and alleviates high glucose-induced injury in podocytes].","authors":"Ying Cai, Sheng Chen, Xiaoli Jiang, Qiyuan Wu, Bei Guo, Fang Wang","doi":"10.3724/zdxbyxb-2024-0504","DOIUrl":"10.3724/zdxbyxb-2024-0504","url":null,"abstract":"<p><strong>Objectives: </strong>To study the role of microRNA (miR)-30d-5p in high glucose-induced podocyte injury.</p><p><strong>Methods: </strong>Podocytes were hyperglycated with 30 mmol/L glucose, transfected with miR-30d-5p inhibitor and mimic, and then treated with 1 mg/mL 3-methyladenine (3-MA). The transfection efficiency of miR-30d-5p was quantified by reverse transcription PCR. Apoptosis was detected by flow cytometry. The expressions of nephrin, microtubule-associated protein light chain (LC) 3Ⅱ/LC3Ⅰ, P62, autophagy-related gene (ATG) 5, PTEN induced putative kinase (PINK) 1 and Parkin gene (PARK2) were detected by Western blotting. The mito-chondrial membrane potential was detected by JC-1 fluorescent probe, and adenosine triphosphate (ATP) content in cells was detected by relevant kits.</p><p><strong>Results: </strong>Under high glucose induction, podocyte apoptosis increased, miR-30d-5p and P62 expressions were upregulated, while nephrin, ATG5, PINK1, PARK2 and LC3Ⅱ/LC3Ⅰ expressions decreased (all <i>P</i><0.01). MiR-30d-5p inhibitor reversed the effect of high glucose on apoptosis, and the expression of ATG5, PINK1, PARK2, nephrin, LC3Ⅱ/LC3Ⅰ and P62 (all <i>P</i><0.01). High glucose induced loss of mitochondrial membrane potential and ATP content in podocytes, while inhibition of miR-30d-5p increased them. Autophagy inhibitors 3-MA and miR-30d-5p mimics reversed the effects of miR-30d-5p inhibition on apoptosis, autophagy and mitochondrial function of podocytes induced by high glucose (all <i>P</i><0.05).</p><p><strong>Conclusions: </strong>Inhibition of miR-30d-5p may promote mitochondrial autophagy (mitophagy) by promoting the expression of ATG5, PINK1, PARK2 and alleviating high glucose-induced podocyte damage.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"756-764"},"PeriodicalIF":0.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Protective environment strategies for hematopoietic stem cell transplantation: progress and prospects]. 造血干细胞移植的保护环境策略:进展与展望。
Xiaoyu Zhou, Jianli Zhang, Liwei Xu, Aiyun Jin
{"title":"[Protective environment strategies for hematopoietic stem cell transplantation: progress and prospects].","authors":"Xiaoyu Zhou, Jianli Zhang, Liwei Xu, Aiyun Jin","doi":"10.3724/zdxbyxb-2024-0082","DOIUrl":"10.3724/zdxbyxb-2024-0082","url":null,"abstract":"<p><p>With the progress of hematopoietic stem cell transplantation technology, the reduction of pretreatment intensity, the shortening of bone marrow suppression time and the reduction of infection risk, especially the physical and psychological stress for doctors and patients caused by rigorous protection procedures, the protective environment strategies need improvement. It has been found that, regardless of whether total environment protection is implemented, there is no significant difference in the outcomes of chemotherapy patients with neutropenia. Therefore, the traditional protective environment strategies are being improved. The protective environment strategies for hematopoietic stem cell transplantation patients have developed rapidly in the past two decades, from the replacement of laminar flow equipment by high-efficiency filtration devices to the development of home care after transplantation. In this article, the progress in protective environment strategies for hematopoietic stem cell transplantation patients is reviewed and further reflect, providing reference for future improvement.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"796-803"},"PeriodicalIF":0.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Causal relationship between ferroptosis-related gene HSPA5 and hepatocellular carcinoma: a study based on mendelian randomization and mediation analysis]. 铁突变相关基因 HSPA5 与肝细胞癌之间的因果关系:基于门德尔随机化和中介分析的研究
Bing Cui, Chengcheng Xu, Yuan Xu, Aqin Chen, Chaoming Mao, Yuehua Chen
{"title":"[Causal relationship between ferroptosis-related gene HSPA5 and hepatocellular carcinoma: a study based on mendelian randomization and mediation analysis].","authors":"Bing Cui, Chengcheng Xu, Yuan Xu, Aqin Chen, Chaoming Mao, Yuehua Chen","doi":"10.3724/zdxbyxb-2024-0095","DOIUrl":"10.3724/zdxbyxb-2024-0095","url":null,"abstract":"<p><strong>Objectives: </strong>To explore a causal relationship between ferroptosis-related gene heat shock protein A5 (HSPA5) and hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>A two-sample Mendelian randomization (MR) design was employed to evaluate the causal relationships among HSPA5, regulatory T cells (Tregs), and HCC. Single nucleotide polymorphisms (SNPs) associated with HSPA5, Tregs and HCC were selected as instrumental variables through publicly available genome-wide association studies (GWAS) databases. MR analysis was used to assess the direct effect of HSPA5 on HCC, followed by two-step MR to analyze the potential mediating role of Tregs. Reverse MR analysis was conducted with HCC as the exposure and HSPA5 as the outcome. Inverse variance weighting was the primary method for testing causal associations in all MR analyses. Robustness of the results was confirmed through MR-Egger, weighted median, weighted mode, and simple mode methods. Heterogeneity of instrumental variables was evaluated using Cochrane's <i>Q</i> statistic, while pleiotropy was tested by MR-Egger intercept and MR-PRESSO, with leave-one-out sensitivity analysis performed for robustness. Data from The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) were utilized to verify the expression levels of HSPA5 in HCC tissues and its correlation with Tregs to reveal the interaction mechanisms between HSPA5 and Tregs in HCC progression and their relationship with patient prognosis.</p><p><strong>Results: </strong>MR analysis showed a positive correlation between elevated HSPA5 expression and HCC risk (all <i>P</i><0.01), while reverse MR analysis found no statistically significant association between HCC and HSPA5 (<i>P</i>>0.05). HSPA5 expression was significantly correlated with Tregs function (all <i>P</i><0.05), and the enrichment of Tregs in HCC microenvironment was positively associated with HCC progression (all <i>P</i><0.05). Mediation analysis indicated that Tregs accounted for 5.00% and 7.45% of the mediation effect between HSPA5 and HCC. TCGA and HPA database analysis revealed that both HSPA5 mRNA and protein expression levels were higher in HCC tissues compared to normal tissues, and high HSPA5 expression was significantly associated with poor prognosis. Immune infiltration analysis confirmed a significant positive correlation between HSPA5 and Tregs, with high Tregs infiltration closely related to HCC progression.</p><p><strong>Conclusions: </strong>Elevated HSPA5 expression is significantly associated with HCC development and poor prognosis. HSPA5 may promote HCC progression by regulating the function of Tregs in the tumor microenvironment.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"691-698"},"PeriodicalIF":0.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Ferroptosis-related genes in osteoporosis: a bioinformatics analysis and in vitro study]. 骨质疏松症中嗜铁相关基因:生物信息学分析和体外研究。
Yushuang Xia, Bo Wang, Pengfei Pan, Xiangshun Ren, Lixi Gao, Jian Xiong, Yan Ma
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