International Journal of Medical Sciences最新文献

{"title":"Patients with hidradenitis suppurativa are associated with risk of new-onset glaucoma: a propensity-score-matched cohort study.","authors":"Chen-Pi Li, Chen-Yu Lin, Hsin-Yo Lu, San-Ni Chen, Ru-Yin Tsai, Hui-Chin Chang, Shiu-Jau Chen, Shuo-Yan Gau","doi":"10.7150/ijms.95395","DOIUrl":"10.7150/ijms.95395","url":null,"abstract":"<p><p><b>Background:</b> Ocular comorbidities of hidradenitis suppurativa (HS) has been widely evaluated; however real-world evidence was scarce. Moreover, risk of glaucoma in HS patients remained unclear. This study aimed to evaluate the 5-year glaucoma risk in HS patients. <b>Methods:</b> This retrospective cohort study used the TriNetX database covering 2005-2017. In total, 53,281 HS patients were propensity score matched 1:1 to controls based on demographics, including comorbidities, medications, healthcare utilization, etc. Patients were followed for 5 years post-index date. Glaucoma risks were calculated based on hazard ratios and 95% confidence intervals (95% CI). Stratified analyses by sex and age were performed. <b>Results:</b> After matching, baseline characteristics were similar between groups. HS was associated with a 1.25 times higher 5-year glaucoma risk (95% CI, 1.10-1.42). The risk was significant within 1 year (HR=1.37; 95% CI, 1.03-1.82), 3 years (HR=1.31; 95% CI, 1.12-1.54), and 5 years post-index. In subgroup analysis, women had a 1.28 times higher risk (95% CI, 1.10-1.49). Patients aged 18-64 years (HR=1.33; 95% CI, 1.14-1.55) and ≥65 years (HR=1.33; 95% CI, 1.05-1.67) also presented elevated glaucoma risks. <b>Conclusion:</b> This real-world data analysis demonstrated a significantly increased 5-year glaucoma risk in HS patients versus matched controls. Ocular complications should be concerned while managing HS patients.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140048","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 long noncoding RNA GAS5 gene polymorphism with progression of diabetic kidney disease.","authors":"Po-Jen Yang, Ke-Hsin Ting, Po-Yu Tsai, Shih-Chi Su, Shun-Fa Yang","doi":"10.7150/ijms.99545","DOIUrl":"10.7150/ijms.99545","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, whose complex etiology involves a genetic component. <i>Growth arrest-specific 5</i> (GAS5), a long noncoding RNA (lncRNA) gene, has been recently shown to regulate renal fibrosis. Here, we aimed to explore the potential role of <i>GAS5</i> gene polymorphisms in the predisposition to DKD. One single-nucleotide (rs55829688) and one insertion/deletion polymorphism (rs145204276) of <i>GAS5</i> gene were surveyed in 778 DKD cases and 788 DKD-free diabetic controls. We demonstrated that diabetic subjects who are heterozygous at rs55829688 (TC; AOR, 1.737; 95% CI, 1.028-2.937; p=0.039) are more susceptible to advanced DKD but not early-staged DKD, as compared to diabetic subjects who are homozygous for the major allele of rs55829688 (TT). Carriers of at least one minor allele (C) of rs55829688 (TC and CC; AOR, 1.317; 95% CI, 1.023-1.696; p=0.033) more frequently suffer from advanced DKD than do those homozygotes for the major allele (TT). Furthermore, in comparison to those who do not carry the minor allele of rs55829688 (TT), advanced DKD patients possessing at least one minor allele of rs55829688 (TC and CC) exhibited a lower glomerular filtration rate, revealing an impact of rs55829688 on renal co-morbidities of diabetes. In conclusion, our data indicate an association of <i>GAS5</i> gene polymorphisms with the progression of DKD.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140005","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":"Matrix Metalloproteinase 11 Promotes Migration and Invasion of Colorectal Cancer by Elevating Slug Protein.","authors":"Chaomin Pan, Jingping Dai, Yiyi Wei, Li Yang, Zhuoyu Ding, Xinke Wang, Juan He","doi":"10.7150/ijms.98007","DOIUrl":"10.7150/ijms.98007","url":null,"abstract":"<p><p><b>Purpose:</b> Matrix metalloproteinase-11 (MMP11), which belongs to the stromelysin subgroup, has been reported to play a role in the progression of colorectal cancer (CRC). However, the significance of MMP11 in the tumor microenvironment, immune/stromal cells, and its mechanism in CRC remain unclear. <b>Methods:</b> The impact of MMP11 knockdown using specific short hairpin RNAs (shRNAs) on the metastasis and invasion of colorectal cancer RKO and SW480 cells was investigated using western blot, quantitative real-time polymerase chain reaction (qRT-PCR), transwell assays, and immunohistochemistry. <b>Results:</b> MMP11 mRNA expression was significantly higher in CRC cells than in normal cells, and its expression was stimulated in CCD-18Co fibroblasts. Additionally, MMP11 expression was found to be higher in individuals aged ≤ 65 years, the T4/T3 group, and Stage III/IV patients. Overall survival (OS) and disease-free survival rates were significantly different between the high and low MMP11 groups. Furthermore, the receiver operating characteristic (ROC) curves for MMP11 at 1-, 3-, and 5-years were 0.450, 0.552, and 0.560, respectively. Moreover, MMP11 promoted the migration and invasion of CRC cells by elevating the expression of Slug protein. Most importantly, MMP11 was positively associated with M0-macrophages and negatively associated with M1-macrophages, NK cells activated, NK cells resting, T cells CD4 memory activated, and T cells follicular helper, indicating the remarkable interactions of MMP11 with tumor immunology. <b>Conclusions:</b> MMP11 plays an important role in colorectal cancer development, and its mechanism in CRC needs to be further explored in the future.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140025","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":"Multiple Comprehensive Analyses Identify Lysine Demethylase KDM as a Potential Therapeutic Target for Pancreatic Cancer.","authors":"Wan-Jou Shen, Hsuan-Min Kao, Chih-Yang Wang, Rubina Kousar, Jing-Shan Lin, Ching-Chung Ko, Hung-Yun Lin, Hoang Dang Khoa Ta, Gangga Anuraga, Do Thi Minh Xuan, Sachin Kumar, Sanskriti Dey, Ngoc Phung Ly, Wei-Jan Wang","doi":"10.7150/ijms.96134","DOIUrl":"10.7150/ijms.96134","url":null,"abstract":"<p><p>Pancreatic cancer (PC) is a challenging and heterogeneous disease with a high mortality rate. Despite advancements in treatment, the prognosis for PC patients remains poor, with a high chance of disease recurrence. Biomarkers are crucial for diagnosing cancer, predicting patient prognosis and selecting treatments. However, the current lack of effective biomarkers for PC could contribute to the insufficiency of existing treatments. These findings underscore the urgent need to develop novel strategies to fight this disease. This study utilized multiple comprehensive bioinformatic analyses to identify potential therapeutic target genes in PC, focusing on histone lysine demethylases (KDMs). We found that high expression levels of KDM family genes, particularly KDM1A, KDM5A and KDM5B, were associated with improved overall survival in the cohort. Furthermore, the infiltration of various immune cells, including B cells, neutrophils, CD8⁺ T cells, dendritic cells, and macrophages, was positively correlated with KDM1A, KDM5A, and KDM5B expression. Moreover, MetaCore pathway analysis revealed interesting connections between KDM1A and the cell cycle and proliferation, between KDM5A and DNA damage and double-strand break repair through homologous recombination, and between KDM5B and WNT/β-catenin signaling. These findings suggest that KDM1A, KDM5A and KDM5B may serve as promising biomarkers and therapeutic targets for PC, a disease of high importance due to its aggressive nature and urgent need for novel biomarkers to improve diagnosis and treatment.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140046","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":"Estrogen Status Influences Whole-Body Vibration Training-Induced Improvements on Muscle Mass and Strength in Female Ovariectomized Mice.","authors":"Xiangyang Tian, Cong Li, Tao Li, Fangfang Yu, Rengfei Shi","doi":"10.7150/ijms.97770","DOIUrl":"10.7150/ijms.97770","url":null,"abstract":"<p><p>Estradiol (E2) deficiency arising from menopause is closely related to changes in body composition and declines of muscle mass and strength in elderly women. Whole-body vibration training (WBV) is an emerging approach expected to improve muscle mass and strength of older person, but the underlying mechanisms remain unclear. The balance between protein synthesis and degradation is a determining factor for muscle mass and strength, which is regulated by Akt-mTOR and FoxO1 signal pathway, respectively. In the present study, we firstly determined whether the effects of WBV on muscle mass and strength in ovariectomized female mice was affected by estrogen level, then investigated whether this was associated with Akt-mTOR and FoxO1 signal pathways. We found that (1) WBV, E2 supplementation (E) and WBV combined with E2 supplementation (WBV+E) significantly increased serum estradiol content, quadriceps muscle mass and grip strength in ovariectomized mice, accompanied with alterations of body composition (reducing fat content, increasing lean body mass and lean percent), furthermore, the altered degrees of these indicators by WBV+E were greater than WBV alone; (2) WBV, E and WBV+E remarkably increased the activities of Akt and mTOR and decreased FoxO1 activity, and the changed degrees by WBV+E were greater than WBV alone; (3) Pearson correlation coefficient revealed that serum estradiol content was positively correlated with Akt and mTOR activities, while inversely associated with FoxO1 activity. We concluded that WBV could significantly increase muscle mass and strength in ovariectomized mice, which might achieve through activating Akt-mTOR and suppressing FoxO1 signal pathways, and the improving effect of WBV on muscle mass and strength was better when in the presence of estrogen.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140020","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":"Nicotinamide Riboside-Driven Modulation of SIRT3/mtROS/JNK Signaling Pathways Alleviates Myocardial Ischemia-Reperfusion Injury.","authors":"Lingqing Wang, Changgong Chen, Hao Zhou, Luyuan Tao, Enguo Xu","doi":"10.7150/ijms.97530","DOIUrl":"10.7150/ijms.97530","url":null,"abstract":"<p><p>Myocardial ischemia-reperfusion (I/R) injury exacerbates cellular damage upon restoring blood flow to ischemic cardiac tissue, causing oxidative stress, inflammation, and apoptosis. This study investigates Nicotinamide Riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD⁺), for its cardioprotective effects. Administering NR to mice before I/R injury and evaluating heart function via echocardiography showed that NR significantly improved heart function, increased left ventricular ejection fraction (LVEF) and fractional shortening (FS), and reduced left ventricular end-diastolic (LVDd) and end-systolic diameters (LVSd). NR also restored E/A and E/e' ratios. It reduced cardiomyocyte apoptosis both <i>in vivo</i> and <i>in vitro</i>, inhibiting elevated caspase-3 activity and returning Bax protein levels to normal. <i>In vitro</i>, NR reduced the apoptotic rate in hydrogen peroxide (H2O2)-treated HL-1 cells from 30% to 10%. Mechanistically, NR modulated the SIRT3/mtROS/JNK pathway, reversing H2O2-induced SIRT3 downregulation, reducing mitochondrial reactive oxygen species (mtROS), and inhibiting JNK activation. Using SIRT3-knockout (SIRT3-KO) mice, we confirmed that NR's cardioprotective effects depend on SIRT3. Echocardiography showed that NR's benefits were abrogated in SIRT3-KO mice. In conclusion, NR provides significant cardioprotection against myocardial I/R injury by enhancing NAD+ levels and modulating the SIRT3/mtROS/JNK pathway, suggesting its potential as a novel therapeutic agent for ischemic heart diseases, meriting further clinical research.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140047","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 Association between Percentage of Mean Arterial Pressure and Long-Term Mortality in Acute Myocardial Infarction Patients: An Observational Cohort Study.","authors":"Yi-Hsueh Liu, Wei-Chung Tsai, Nai-Yu Chi, Ching-Tang Chang, Wen-Hsien Lee, Chun-Yuan Chu, Tsung-Hsien Lin, Sheng-Hsiung Sheu, Ho-Ming Su, Po-Chao Hsu","doi":"10.7150/ijms.95430","DOIUrl":"10.7150/ijms.95430","url":null,"abstract":"<p><p><b>Background:</b> Acute myocardial infarction (AMI) is a critical cardiovascular disease with high morbidity and mortality. Identifying practical parameters for predicting long-term mortality is crucial in this patient group. The percentage of mean arterial pressure (%MAP) is a useful parameter used to assess peripheral artery disease. It can be easily calculated from ankle pulse volume recording. Previous studies have shown that %MAP is a useful predictor of all-cause mortality in specific populations, but its relationship with mortality in AMI patients is unclear. <b>Methods:</b> In this observational cohort study, 191 AMI patients were enrolled between November 2003 and September 2004. Ankle-brachial index (ABI) and %MAP were measured using an ABI-form device. All-cause and cardiovascular mortality data were collected from a national registry until December 2018. Cox proportional hazards model and Kaplan-Meier survival plot were used to analyze the association between %MAP and long-term mortality in AMI patients. <b>Results:</b> The median follow-up to mortality was 65 months. There were 130 overall and 36 cardiovascular deaths. High %MAP was associated with increased overall mortality after multivariable analysis (HR = 1.062; 95% CI: 1.017-1.109; <i>p</i> =0.006). However, high % MAP was only associated with cardiovascular mortality in the univariable analysis but became insignificant after the multivariable analysis. <b>Conclusions:</b> In conclusion, this study is the first to evaluate the usefulness of %MAP in predicting long-term mortality in AMI patients. Our study shows that %MAP might be an independent predictor of long-term overall mortality in AMI patients and has better predictive power than ABI.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140050","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":"Investigation of cardiorenal outcomes and incidence of genitourinary tract infection after combined SGLT2 inhibitor and ACEI/ARB use in patients with chronic kidney disease stages 3-5: A real-world retrospective cohort study in Taiwan.","authors":"Yu-Hsuan Joni Shao, Wan-Ting Chen, Samuel Mon-Wei Yu, Liam Li-An Tsou, Yung-Ho Hsu, Mai-Szu Wu, Yung-Hsi Kao, Chu-Lin Chou, Po-Jen Hsiao","doi":"10.7150/ijms.96969","DOIUrl":"10.7150/ijms.96969","url":null,"abstract":"<p><p><b>Background:</b> Sodium‒glucose cotransporter-2 (SGLT2) inhibitors offer glycaemic and cardiorenal benefits in the early stage of chronic kidney disease (CKD). However, the use of SGLT2 inhibitors may increase the risk of genitourinary tract infection (GUTI). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may also cause deterioration of kidney function. The long-term follow-up of cardiorenal outcomes and GUTI incidence in patients with advanced CKD receiving SGLT2 inhibitors combined with ACEIs/ARBs should be further investigated. <b>Methods:</b> We analysed data from 5,503 patients in Taiwan's Taipei Medical University Research Database (2016-2020) who were part of a pre-end-stage renal disease (ESRD) program (CKD stages 3-5) and received ACEIs/ARBs. SGLT2 inhibitor users were matched 1:4 with nonusers on the basis of sex, CKD, and program entry duration. <b>Results:</b> The final cohort included 205 SGLT2 inhibitor users and 820 nonusers. SGLT2 inhibitor users experienced a significant reduction in ESRD/dialysis risk (aHR = 0.35, 95% CI = 0.190.67), and SGLT2 inhibitor use was not significantly associated with acute kidney injury or acute kidney disease risk. Among SGLT2 inhibitor users, those with a history of cardiovascular disease (CVD) had greater CVD rates. Conversely, those without a CVD history had lower rates of congestive heart failure, arrhythmia, acute pulmonary oedema, and acute myocardial infarction, although the differences were not statistically significant. Notably, SGLT2 inhibitor usage was associated with a greater GUTI incidence (aHR = 1.78, 95% CI = 1.122.84) shortly after initiation, irrespective of prior GUTI history status. <b>Conclusion:</b> Among patients with CKD stages 3-5, SGLT2 inhibitor use was linked to increased GUTI incidence, but it also significantly reduced the ESRD/dialysis risk without an episodic AKI or AKD risk. Clinical physicians should consider a personalized medicine approach by balancing GUTI episodes and cardiorenal outcomes for advanced CKD patients receiving SGLT2 inhibitors.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140023","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":"Bibliometric analysis of renal cell carcinoma with venous tumor thrombus.","authors":"Jinbin Xu, Weijen Lee, Shoudong Yang, Shuntian Gao, Yuedian Ye, Gengguo Deng, Weixing Zhang, Jinming Di","doi":"10.7150/ijms.98359","DOIUrl":"10.7150/ijms.98359","url":null,"abstract":"<p><p><b>Objectives:</b> To identify the cooperation of authors, countries, institutions and explore the hot spots regarding research of renal cell carcinoma with venous tumor thrombus. <b>Methods:</b> Relevant articles were obtained from the Web of Science Core database (WoSC) from 1999 to 2024. CiteSpace was used to perform the analysis and visualization of scientific productivity and emerging trends. Network maps were generated to evaluate the collaborations between different authors, countries, institutions, and keywords. <b>Results:</b> A total of 2180 related articles were identified. We observed an increased enthusiasm in related fields during the past two decades. The USA dominated the field in all countries, and the University of Miami was the core institution. Ciancio G might have a significant influence with more publications and co-citations. Current research hotspots in this field mainly included thrombectomy, tyrosine kinase inhibitors, immune checkpoint inhibitors, vena cava inferior, and microvascular invasion. Thrombectomy complications, thrombectomy survival outcome, and preoperative neoadjuvant immunotherapy represented the frontiers of research in this field, undergoing an explosive phase. <b>Conclusion:</b> This is the first bibliometric study that comprehensively visualize the research trends and status of RCC with VTT. We hope that this work will provide new ideas for advancing the scientific research and clinical application.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140006","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":"Causal Association of Golgi Protein 73 With Coronary Artery Disease: Evidence from Proteomics and Mendelian Randomization.","authors":"Yi-Fen Lin, Li-Zhen Liao, Shu-Yi Wang, Shao-Zhao Zhang, Xiang-Bin Zhong, Hui-Min Zhou, Xing-Feng Xu, Zhen-Yu Xiong, Yi-Quan Huang, Meng-Hui Liu, Yue Guo, Xin-Xue Liao, Xiao-Dong Zhuang","doi":"10.7150/ijms.94179","DOIUrl":"10.7150/ijms.94179","url":null,"abstract":"<p><p><b>Background:</b> Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. <b>Methods:</b> Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein <i>in situ</i> was also detected. <b>Results:</b> Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). <b>Conclusions:</b> Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140007","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}