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

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[Advances in the development of transient receptor potential melastatin 2 channel inhibitors].
Shiyao Chen, Yanping Luo, Peilin Yu, Xiaomin Yue, Wei Yang
{"title":"[Advances in the development of transient receptor potential melastatin 2 channel inhibitors].","authors":"Shiyao Chen, Yanping Luo, Peilin Yu, Xiaomin Yue, Wei Yang","doi":"10.3724/zdxbyxb-2024-0586","DOIUrl":"10.3724/zdxbyxb-2024-0586","url":null,"abstract":"<p><p>Studies on specific transient receptor potential melastatin 2 (TRPM2) channel inhibitors can deepen our understanding of the pathological mechanism of related diseases, and allow discovery of novel, effective targets and drugs for therapy. The development of TRPM2 channel inhibitors can be broadly classified into four categories with distinct characteristics: reutilization and structural modification of homologous ion channel modulators to produce a diverse array of TRPM2 channel inhibitors with strong inhibitory effects; TRPM2 channel inhibitors based on channel gating mechanism with high specificity; inhibitors identified through high-throughput screening with novel chemical structures; inhibitors developed from natural antioxidants with higher safety. In recent years, the application of computer-aided drug design has significantly accelerated the development of TRPM2 channel inhibitors. Several promising compounds such as ZA18, A1 and D9 have been discovered, and it is expected that more potent and selective TRPM2 channel inhibitor scaffolds will be discovered in the future. This article reviews the advances on the studies of TRPM2 channel inhibitors, aiming to provide insights for further research and clinical application of TRPM2 channel inhibitors.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"120-130"},"PeriodicalIF":0.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Medium- and long-term efficacy of percutaneous mechanical thrombectomy with stent implantation in patients with iliac vein stenosis and thrombosis].
Chunlun Chen, Chenyang Qiu, Lan Shen, Renda Zhu, Huaji Zhou, Hongkun Zhang
{"title":"[Medium- and long-term efficacy of percutaneous mechanical thrombectomy with stent implantation in patients with iliac vein stenosis and thrombosis].","authors":"Chunlun Chen, Chenyang Qiu, Lan Shen, Renda Zhu, Huaji Zhou, Hongkun Zhang","doi":"10.3724/zdxbyxb-2024-0537","DOIUrl":"10.3724/zdxbyxb-2024-0537","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the medium- and long-term efficacy of percutaneous mechanical thrombectomy (PMT) combined with stent implantation for treatment of iliac vein stenosis with lower extremity deep venous thrombosis (LEDVT).</p><p><strong>Methods: </strong>Clinical and follow-up data of 125 patients with iliac vein stenosis and LEDVT who underwent PMT and stent implantation at five hospitals in northern Zhejiang province from January 2017 to June 2021 were collected. The thrombus clearance rate, thrombus recurrence rate, patency rate of iliac vein stents and post-thrombotic syndrome (PTS) occurrence rate were documented, and safety indicators such as bleeding, death, pulmonary embolism, stent fracture and displacement were assessed.</p><p><strong>Results: </strong>Among 125 patients, for clearance of limb thrombosis, there were 8 cases of grade I (6.4%), 10 cases of grade II (8.0%), and 107 cases of grade III (85.6%). Patients were followed up for a median period of 74 months. According to the Villalta score, the recurrence rates of limb thrombosis at 12, 24 and 36 months were 8.48%, 8.93% and 10.91%; the iliac vein patency rates were 91.52%, 91.07%, and 89.09%; and the incidences of PTS were 5.08%, 5.36% and 6.36%, respectively. There were no major adverse events such as death, massive pulmonary embolism or severe hepatic and renal insufficiency, and no readmission intervention events due to stent fracture or other incidence were found.</p><p><strong>Conclusions: </strong>PMT combined with iliac vein stent implantation is effective for patients with iliac vein stenosis complicated by LEDVT with good medium- and long-term efficacy and safety, which is worthy of clinical application.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"108-114"},"PeriodicalIF":0.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Disease burden and trend of melanoma among middle-aged and elderly population in China from 1990 to 2020, and prediction for 2022 to 2035]. 1990 - 2020年中国中老年人群黑色素瘤疾病负担、趋势及2022 - 2035年预测
Lyuxin Guan, Ziqin Gan, Guangtao Huang, Suchun Hou, Yansi Lyu
{"title":"[Disease burden and trend of melanoma among middle-aged and elderly population in China from 1990 to 2020, and prediction for 2022 to 2035].","authors":"Lyuxin Guan, Ziqin Gan, Guangtao Huang, Suchun Hou, Yansi Lyu","doi":"10.3724/zdxbyxb-2024-0385","DOIUrl":"10.3724/zdxbyxb-2024-0385","url":null,"abstract":"<p><strong>Objectives: </strong>To analyze the disease burden of melanoma among middle-aged and elderly populations in China, and to predict the future trend.</p><p><strong>Methods: </strong>Data from the Global Burden of Disease (GBD) 2021 were utilized to collect incidence and mortality rates of melanoma, disability-adjusted life years (DALYs), and corresponding age crude rates among the middle-aged and elderly population in China during 1990 and 2021. Additionally, the estimated annual percentage change (EAPC) was employed to assess the temporal trends. Age-period-cohort (APC) and Bayesian age-period-cohort (BAPC) models were utilized to compute age, period, and cohort effects on incidence and mortality rates of melanoma, as well as to predict future trends up to 2035.</p><p><strong>Results: </strong>During 1990-2021, the incidence rate of melanoma for males was higher than that for females among the middle-aged and elderly population in China, and the overall incidence rate increased annually with an EAPC of 2.13 (1.90-2.36), while the overall mortality rate and DALY rate showed a declining trend with an EAPC of -0.28 (-0.41--0.15) and -0.54 (-0.68--0.41), respectively. The results of the APC model analysis revealed that age effects on both incidence and mortality rates of melanoma in China's middle-aged and elderly population were significant, with both increasing with age. Period and cohort effects showed an upward trend for incidence rates but a downward trend for mortality rates. Moreover, the period and cohort effects for mortality rates were not significant among females. In the BAPC prediction model, the number of incidences of melanoma in middle-aged and elderly people in China would increase dramatically. By 2035, the number of incidence cases is expected to reach approximately 9600 (males) and 10 300 (females), corresponding to an incidence rate of 2.66/10<sup>5</sup> and 2.67/10<sup>5</sup>, respectively. The number of deaths is projected to be about 2600 (males) and 3500 (females) by 2035, corresponding to a mortality rate of 0.72/10<sup>5</sup> and 0.91/10<sup>5</sup>, respectively.</p><p><strong>Conclusions: </strong>The disease burden of melanoma among the middle-aged and elderly population in China remains substantial and is expected to increase over the next decade.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Analysis of burden and equality of lower extremity peripheral artery disease in people aged 40 and above in the Belt and Road partner countries from 1990 to 2021]. 1990 - 2021年“一带一路”伙伴国40岁及以上人群下肢外周动脉疾病负担与公平性分析
Guangdian Shen, Longzhu Zhu, Jiayao Ying, Shiyi Shan, Zeyu Luo, Denan Jiang, Jing Wu, Yuefeng Zhu
{"title":"[Analysis of burden and equality of lower extremity peripheral artery disease in people aged 40 and above in the Belt and Road partner countries from 1990 to 2021].","authors":"Guangdian Shen, Longzhu Zhu, Jiayao Ying, Shiyi Shan, Zeyu Luo, Denan Jiang, Jing Wu, Yuefeng Zhu","doi":"10.3724/zdxbyxb-2024-0540","DOIUrl":"10.3724/zdxbyxb-2024-0540","url":null,"abstract":"<p><strong>Objectives: </strong>To analyze the disease burden and inequalities of lower extremity peripheral artery disease (LEPAD) among people aged 40 and above in the Belt and Road partner countries from 1990 to 2021.</p><p><strong>Methods: </strong>Data were retrieved from the Global Burden of Disease 2021 database. The age-standardized prevalence rates, mortality rates, and the annual rate of years lived with disability (YLDs) of LEPAD were analyzed. Trends were measured using the estimated annual percentage change (EAPC), and the slope index of inequality (SII) and concentration index were used to quantify the absolute and relative inequalities.</p><p><strong>Results: </strong>In 2021, the age-standardized prevalence and mortality rates of LEPAD were 3168.26/10<sup>5</sup> and 3.09/10<sup>5</sup>, increasing by 4.30% and 19.31% compared to 1990, while YLDs rates decreased by 4.00%. Females had higher age-standardized prevalence and YLDs rates, while males had higher mortality rates. The EAPC for prevalence rates was slightly higher in males (0.22%) than in females (0.17%); while the EAPC of age-standardized mortality rate was 2.02% for females, compared to 1.45% for males. From 1990 to 2021, the age-standardized YLDs rates decreased from 16.23/10<sup>5</sup> to 15.58/10<sup>5</sup>, with a faster decline in females (-0.12%) than in males (-0.06%). LEPAD prevalence varied across countries, with higher burden in Europe and faster growth in Gulf states. Higher socio-demographic index countries had higher prevalence. Inequity improved, with the SII at 52.90/10<sup>5</sup> and concentration index at 0.038 in 2021. Gender disparities persisted, with concentration index increased to 0.058 in females and reduced to -0.026 in males.</p><p><strong>Conclusions: </strong>LEPAD prevalence and mortality among people aged 40 and above in the Belt and Road partner countries increased, while YLDs rates decreased from 1990 to 2021. Significant differences among people exist depending on gender and country, highlighting the need for enhanced screening, health education, and shared public health strategies across the Belt and Road partner countries.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"10-20"},"PeriodicalIF":0.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Global disease burden of cervical cancer and the association of screening coverage with quality of disease management. 全球宫颈癌疾病负担及筛查覆盖率与疾病管理质量的关系
Chang Sun, Abdalle Abdi Mustafe, Bingqing Liu, Yuanying Ma
{"title":"Global disease burden of cervical cancer and the association of screening coverage with quality of disease management.","authors":"Chang Sun, Abdalle Abdi Mustafe, Bingqing Liu, Yuanying Ma","doi":"10.3724/zdxbyxb-2024-0585","DOIUrl":"https://doi.org/10.3724/zdxbyxb-2024-0585","url":null,"abstract":"<p><strong>Objectives: </strong>To analyze the global disease burden of cervical cancer and the association between screening coverage and the quality of disease management.</p><p><strong>Methods: </strong>The data of global burden of cervical cancer 2021 and the data of cervical cancer screening 2019 were obtained from IHME Global Burden of Disease (GBD) and the WHO Global Health Observatory (GHO), respectively. The age-standardized disease burden index was calculated, the Quality of Disease Management Index (QCI) was determined with principal component analysis, the correlation between QCI and cervical cancer screening coverage was examined with linear regression analysis by regions and populations.</p><p><strong>Results: </strong>The burden of cervical cancer and the quality of its management exhibited significant variability across countries with differing levels of social development. The indicators of cervical cancer burden in China were close to the average level of countries with higher socia-demographic index (SDI). The global QCI was 22.22 (10.50, 35.43), and that of China was 26.30. The global screening coverage rate for cervical cancer was 42% (12%, 86%) and that in China was 31%. After adjusting for the social development level of countries, the coverage level of cervical cancer screening was associated with QCI (<i>β</i>=0.27, <i>P</i><0.01), no matter in countries with low or high SDI (<i>P</i>>0.05). The association was significantly stronger among younger women (<i>β</i>=1.48, <i>P</i><0.05).</p><p><strong>Conclusions: </strong>There are discrepancies in both the disease burden of cervical cancer and the quality of disease management among countries with different socioeconomic levels, and there is still considerable room for improvement in China. Expanding coverage of cervical cancer screening may be an effective strategy to enhance the management quality of cervical cancer, particularly among younger women where the screening benefits are most pronounced.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pachymic acid promotes brown/beige adipocyte differentiation and lipid metabolism in preadipocytes 3T3-L1 MBX. 厚青酸促进褐色/米色脂肪细胞分化和前脂肪细胞3T3-L1 MBX的脂质代谢。
Kunling Chen, Xiaobing Dou, Yiyou Lin, Danyao Bai, Yangzhou Luo, Liping Zhou
{"title":"Pachymic acid promotes brown/beige adipocyte differentiation and lipid metabolism in preadipocytes 3T3-L1 MBX.","authors":"Kunling Chen, Xiaobing Dou, Yiyou Lin, Danyao Bai, Yangzhou Luo, Liping Zhou","doi":"10.3724/zdxbyxb-2024-0355","DOIUrl":"https://doi.org/10.3724/zdxbyxb-2024-0355","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effect of pachymic acid on brown/beige adipocyte differentiation and lipid metabolism in preadipocytes 3T3-L1 MBX.</p><p><strong>Methods: </strong>The brown cocktail method was employed to induce 3T3-L1 MBX cells to differentiate into beige adipocytes. The impact of pachymic acid on the viability of 3T3-L1 MBX preadipocytes was evaluated using the CCK-8 assay. The formation of lipid droplets following treatment with pachymic acid was observed through oil red O staining, and the content of lipids in differentiated cells was determined. The expression levels of key browning genes, including uncoupling protein (Ucp) 1, the peroxisome proliferation-activating receptor gamma coactivator (Pgc)-1α, and the transcription factor containing PR domain 16 (Prdm16) were detected by quantitative reverse transcription polymerase chain reaction. The expression of sterol regulatory element binding protein (Srebp) 1c, acetyl-CoA carboxylase (Acc), fatty acid synthetase (Fas), and steroid-sensitive lipase (Hsl), fatty triglyceride hydrolase (Atgl), and carnitine palmitoyl transferase (Cpt) 1 of lipolysis-related genes were also examined.</p><p><strong>Results: </strong>The 3T3-L1 MBX was induced <i>in vitro</i> to form beige adipocytes with high expression of key browning genes, including <i>Ucp1</i>, <i>Pgc-1α</i>, <i>Prdm16</i>, and beige adipose-marker genes, including <i>Cd137</i>, <i>Tbx1</i>, and <i>Tmem26</i>. The concentration range of 0-80 μM pachymic acid was non-cytotoxic to 3T3-L1 MBX. Pachymic acid treatment significantly inhibited the differentiation of 3T3-L1 MBX, resulting in a notable decrease in lipid accumulation content (<i>P</i><0.01). Additionally, there was a marked increase in the expression of key browning genes and their proteins, such as Ucp1, Pgc-1α, and Prdm16, while the expressions of fat synthesis-related genes <i>Srebp1c</i>, <i>Acc</i> and <i>Fas</i> were significantly decreased (all <i>P<</i>0.05). The expressions of lipolysis-related genes, including <i>Hsl</i>, <i>Atgl</i>, and <i>Cpt1</i>, were significantly increased (all <i>P</i><0.05). Besides, treating with 20 μmol/L pachymic acid showed the most pronounced effect.</p><p><strong>Conclusions: </strong>Pachymic acid can inhibit fat synthesis and promote lipid decomposition by regulating the brown formation and lipid differentiation of 3T3-L1 MBX preadipocytes.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Ferroptosis and liver diseases]. [铁下垂和肝脏疾病]。
Xin Li, Liang Tao, Meijuan Zhong, Qian Wu, Junjia Min, Fudi Wang
{"title":"[Ferroptosis and liver diseases].","authors":"Xin Li, Liang Tao, Meijuan Zhong, Qian Wu, Junjia Min, Fudi Wang","doi":"10.3724/zdxbyxb-2024-0566","DOIUrl":"10.3724/zdxbyxb-2024-0566","url":null,"abstract":"<p><p>As the central organ of metabolism, the liver plays a pivotal role in the regulation of the synthesis and metabolism of various nutrients within the body. Ferroptosis, as a newly discovered type of programmed cell death caused by the accumulation of iron-dependent lipid peroxides, is involved in the physiological and pathological processes of a variety of acute and chronic liver diseases. Ferroptosis can accelerate the pathogenetic process of acute liver injury, metabolic associated fatty liver disease, alcoholic liver disease, viral hepatitis, and autoimmune hepatitis; while it can slower disease progression in advanced liver fibrosis and hepatocellular carcinoma. This suggests that targeted regulation of ferroptosis may impact the occurrence and development of various liver diseases. This article reviews the latest research progress of ferroptosis in various liver diseases, including acute liver injury, metabolic associated fatty liver disease, alcoholic liver disease, viral hepatitis, autoimmune hepatitis, liver fibrosis and hepatocellular carcinoma. It aims to provide insights for the prevention and treatment of acute and chronic liver diseases through targeting ferroptosis.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":"53 6","pages":"747-755"},"PeriodicalIF":0.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932927","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 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
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