Pub Date : 2024-09-16eCollection Date: 2024-01-01DOI: 10.7150/ijms.101043
Xiaojie Zhao, Xin Yu, Wenge Li, Zhiyuan Chen, Tingting Niu, Xiaodong Weng, Lei Wang, Xiuheng Liu
Background: CDK6 is linked to tumor progression and metastasis, although its molecular mechanism and prognostic value are unclear in bladder cancer. Materials and methods: In our study, raw data were obtained from public databases and Single-center retrospective case series. We conducted a bioinformatics analysis and immunohistochemistry to explore the biological landscape of CDK6 in tumors, with a particular focus on bladder cancer. We examined its expression characteristics and prognostic value and performed functional annotation analysis using gene function enrichment. We also assessed the association between bladder cancer molecular subtypes and mutation spectra and analyzed the landscape of the tumor immune microenvironment to predict treatment response sensitivity. Results: Our study found that CDK6 was a potential prognostic marker for bladder cancer. We discovered that bladder cancer patients with high CDK6 expression do not respond well to immunotherapy and have a poor prognosis. CDK6 regulates tumor immune status, metabolism, and cell cycle-related signaling pathways, thereby influencing tumor biological behavior. Furthermore, CDK6 mediated the suppression of the immune microenvironment to weaken anti-tumor immune responses. Finally, a comprehensive characterization of CDK6 was applied in the prognostic prediction of bladder cancer, suggesting that targeting CDK6 represents a potential therapeutic option. Conclusions: These results indicated that CDK6 is an independent biomarker for predicting prognosis and immunotherapy efficacy of bladder cancer. A deeper understanding of its specific molecular mechanisms may provide new treatment strategies.
{"title":"CDK6 as a Biomarker for Immunotherapy, Drug Sensitivity, and Prognosis in Bladder Cancer: Bioinformatics and Immunohistochemical Analysis.","authors":"Xiaojie Zhao, Xin Yu, Wenge Li, Zhiyuan Chen, Tingting Niu, Xiaodong Weng, Lei Wang, Xiuheng Liu","doi":"10.7150/ijms.101043","DOIUrl":"10.7150/ijms.101043","url":null,"abstract":"<p><p><b>Background:</b> CDK6 is linked to tumor progression and metastasis, although its molecular mechanism and prognostic value are unclear in bladder cancer. <b>Materials and methods:</b> In our study, raw data were obtained from public databases and Single-center retrospective case series. We conducted a bioinformatics analysis and immunohistochemistry to explore the biological landscape of CDK6 in tumors, with a particular focus on bladder cancer. We examined its expression characteristics and prognostic value and performed functional annotation analysis using gene function enrichment. We also assessed the association between bladder cancer molecular subtypes and mutation spectra and analyzed the landscape of the tumor immune microenvironment to predict treatment response sensitivity. <b>Results:</b> Our study found that CDK6 was a potential prognostic marker for bladder cancer. We discovered that bladder cancer patients with high CDK6 expression do not respond well to immunotherapy and have a poor prognosis. CDK6 regulates tumor immune status, metabolism, and cell cycle-related signaling pathways, thereby influencing tumor biological behavior. Furthermore, CDK6 mediated the suppression of the immune microenvironment to weaken anti-tumor immune responses. Finally, a comprehensive characterization of CDK6 was applied in the prognostic prediction of bladder cancer, suggesting that targeting CDK6 represents a potential therapeutic option. <b>Conclusions:</b> These results indicated that CDK6 is an independent biomarker for predicting prognosis and immunotherapy efficacy of bladder cancer. A deeper understanding of its specific molecular mechanisms may provide new treatment strategies.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286419","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}
Lower limb ischemia is characterized by reduced arterial perfusion in the lower limbs, leading to tissue ischemia and cell death. It is primarily caused by thrombosis and the rupture of arterial plaques, resulting in damage to ischemic muscle tissues. Metabolic processes are crucial in its development. Herein we combined single-cell data with metabolomics data to explore the pathways and mechanisms influencing lower limb ischemia. We analyzed single-cell and metabolomics data. In single-cell analysis, we identified different cell subpopulations and key regulatory genes, and biological enrichment analysis was performed to understand their functions and relationships. For metabolomics, mass spectrometry and chromatography techniques were employed to analyze metabolites in clinical samples. We performed differential analysis, correlation analysis, and Mendelian randomization to determine the relationships between key metabolites and genes. Nebl, Dapl1, Igfbp4, Lef1, Klrd1, Ciita, Il17f, Cd8b1, Il17a, Cd180, Il17re, Trim7, and Slc6a19 were identified to play a crucial role in lower limb ischemia. Important metabolites included L-threonine and L-tryptophan. The metabolism of L-threonine and L-tryptophan is linked to lower limb ischemia and thrombosis. B0AT1, encoded by SLC6A19, is closely related to these metabolites and appears to play a key role in lower limb ischemia development. Our analysis revealed the roles of key genes and metabolites in lower limb ischemia. These findings enhance our understanding of the pathogenesis of lower limb ischemia and provide new insights into its prevention and treatment.
{"title":"A Circular Network of Coregulated L-Threonine and L-Tryptophan Metabolism Dictates Acute Lower Limb Ischemic Injury.","authors":"Liheng Li, Chengjiang Xiao, Hao Liu, Siliang Chen, Yinhong Tang, Hao Zhou, Guihua Jiang, Junzhang Tian","doi":"10.7150/ijms.102177","DOIUrl":"10.7150/ijms.102177","url":null,"abstract":"<p><p>Lower limb ischemia is characterized by reduced arterial perfusion in the lower limbs, leading to tissue ischemia and cell death. It is primarily caused by thrombosis and the rupture of arterial plaques, resulting in damage to ischemic muscle tissues. Metabolic processes are crucial in its development. Herein we combined single-cell data with metabolomics data to explore the pathways and mechanisms influencing lower limb ischemia. We analyzed single-cell and metabolomics data. In single-cell analysis, we identified different cell subpopulations and key regulatory genes, and biological enrichment analysis was performed to understand their functions and relationships. For metabolomics, mass spectrometry and chromatography techniques were employed to analyze metabolites in clinical samples. We performed differential analysis, correlation analysis, and Mendelian randomization to determine the relationships between key metabolites and genes. Nebl, Dapl1, Igfbp4, Lef1, Klrd1, Ciita, Il17f, Cd8b1, Il17a, Cd180, Il17re, Trim7, and Slc6a19 were identified to play a crucial role in lower limb ischemia. Important metabolites included L-threonine and L-tryptophan. The metabolism of L-threonine and L-tryptophan is linked to lower limb ischemia and thrombosis. B0AT1, encoded by <i>SLC6A19</i>, is closely related to these metabolites and appears to play a key role in lower limb ischemia development. Our analysis revealed the roles of key genes and metabolites in lower limb ischemia. These findings enhance our understanding of the pathogenesis of lower limb ischemia and provide new insights into its prevention and treatment.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286406","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}
Objective: This study aims to propose a personalized cancer prediction model based on the metabolic-inflammatory-nutritional score (MINS) for predicting lymph node metastasis (LNM) in endometrial cancer (EC) and validated prediction of survival probability in patients with a family history of Lynch syndrome-associated cancers (LSAC). Methods: A total of 676 patients diagnosed with EC were enrolled in this study. We calculated the optimal cutoff value using restricted cubic splines (RCS) analysis or the mean value. Our feature selection process for constructing the MINS involved using the LASSO regression model. MINS were evaluated for LNM using logistic regression analysis. To assess the prognostic value of the MINS, we generated survival curves using the Kaplan-Meier method with a log-rank test. Furthermore, we constructed a nomogram to validate the prognostic significance of the MINS. The predictive accuracy of nomogram was evaluated using the concordance index (C-index) and calibration plot. Results: LNM risk was associated with family history of LSAC and MINS group (all adjusted p<0.05). Patients in the high-risk MINS group or patients with a family history of LSAC exhibited poorer overall survival (p=0.038, p=0.001, respectively). Additionally, a nomogram was demonstrated effective predictive performance with a C-index of 0.778 (95% CI: 0.725-0.832). Conclusion: Preoperative MINS has been determined to be associated with the risk of LNM in EC patients. Utilizing MINS as a basis, the development of a prognostic nomogram holds promise as an effective tool for risk stratification in clinical settings among EC patients with a family history of LSAC.
研究目的本研究旨在提出一种基于代谢-炎症-营养评分(MINS)的个性化癌症预测模型,用于预测子宫内膜癌(EC)的淋巴结转移(LNM),并对有林奇综合征相关癌症(LSAC)家族史的患者的生存概率进行有效预测。研究方法本研究共纳入了 676 名确诊为子宫内膜癌的患者。我们使用限制性三次样条(RCS)分析或平均值计算出最佳临界值。在构建 MINS 的特征选择过程中,我们使用了 LASSO 回归模型。利用逻辑回归分析对 MINS 进行 LNM 评估。为了评估 MINS 的预后价值,我们使用 Kaplan-Meier 法和对数秩检验生成了生存曲线。此外,我们还构建了一个提名图来验证 MINS 的预后意义。我们使用一致性指数(C-index)和校准图评估了提名图的预测准确性。结果显示LNM风险与LSAC家族史和MINS组相关(所有调整后的P结论:已确定术前 MINS 与 EC 患者发生 LNM 的风险有关。以 MINS 为基础开发的预后提名图有望成为临床上对有 LSAC 家族史的心血管疾病患者进行风险分层的有效工具。
{"title":"A metabolic-inflammatory-nutritional score (MINS) is associated with lymph node metastasis and prognostic stratification for endometrial cancer patients.","authors":"Xite Lin, Tianai Chen, Liang Wang, Yuan Ren, Wenyu Lin, Xiaodan Mao, Pengming Sun","doi":"10.7150/ijms.96179","DOIUrl":"10.7150/ijms.96179","url":null,"abstract":"<p><p><b>Objective:</b> This study aims to propose a personalized cancer prediction model based on the metabolic-inflammatory-nutritional score (MINS) for predicting lymph node metastasis (LNM) in endometrial cancer (EC) and validated prediction of survival probability in patients with a family history of Lynch syndrome-associated cancers (LSAC). <b>Methods:</b> A total of 676 patients diagnosed with EC were enrolled in this study. We calculated the optimal cutoff value using restricted cubic splines (RCS) analysis or the mean value. Our feature selection process for constructing the MINS involved using the LASSO regression model. MINS were evaluated for LNM using logistic regression analysis. To assess the prognostic value of the MINS, we generated survival curves using the Kaplan-Meier method with a log-rank test. Furthermore, we constructed a nomogram to validate the prognostic significance of the MINS. The predictive accuracy of nomogram was evaluated using the concordance index (C-index) and calibration plot. <b>Results:</b> LNM risk was associated with family history of LSAC and MINS group (all adjusted p<0.05). Patients in the high-risk MINS group or patients with a family history of LSAC exhibited poorer overall survival (p=0.038, p=0.001, respectively). Additionally, a nomogram was demonstrated effective predictive performance with a C-index of 0.778 (95% CI: 0.725-0.832). <b>Conclusion:</b> Preoperative MINS has been determined to be associated with the risk of LNM in EC patients. Utilizing MINS as a basis, the development of a prognostic nomogram holds promise as an effective tool for risk stratification in clinical settings among EC patients with a family history of LSAC.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286416","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}
Recent advancements have elucidated the multifaceted roles of the Schlafen (SLFN) family, including SLFN5, SLFN11, SLFN12, SLFN13, and SLFN14, which are implicated in immunological responses. However, little is known about the roles of this gene family in relation to malignancy development. The current study aimed to explore the diagnostic and prognostic potential of Schlafen family genes in colorectal adenocarcinoma (COAD) through bioinformatics analysis. Leveraging advanced bioinformatics tools of bulk RNA-sequencing and single-cell sequencing, we conducted in-depth analyses of gene expressions, functional enrichment, and survival patterns of patients with colorectal cancer compared to normal tissue. Among Schlafen family genes, the transcription levels of SLFN5 in COAD tissues were significantly elevated and correlated with poor survival outcomes. Furthermore, SLFN5 regulated the immune response via Janus kinase (JAK)/signal transduction and activator of transcription (STAT)/interferon (IFN)-alpha/beta signaling. These chemokines in inflammation are associated with diabetes and metabolism, suggesting their involvement in altered cellular energetics for COAD progress. In addition, an immune cell deconvolution analysis indicated a correlation between SLFN5 expression and immune-related cell populations, such as regulatory T cells (Tregs). These findings highlighted the potential clinical significance of SLFN5 in COAD and provided insights into its involvement in the tumor microenvironment and immune regulation. Meanwhile, the drug discovery data of SFLN5 with potential targeted small molecules suggested its therapeutic potential for COAD. Collectively, the current research demonstrated that SFLN5 play crucial roles in tumor development and serve as a prospective biomarker for COAD.
{"title":"Comprehensive analysis of bulk and single-cell RNA sequencing data reveals Schlafen-5 (SLFN5) as a novel prognosis and immunity.","authors":"Yueh-Jung Wu, Chung-Chieh Chiao, Po-Kai Chuang, Chung-Bao Hsieh, Chou-Yuan Ko, Ching-Chung Ko, Chuan-Fa Chang, Tung-Yuan Chen, Ngoc Uyen Nhi Nguyen, Ching-Cheng Hsu, Tian-Huei Chu, Cheng-Chieh Fang, Hsuan-Yen Tsai, Hsien-Chun Tsai, Gangga Anuraga, Hoang Dang Khoa Ta, Do Thi Minh Xuan, Sachin Kumar, Sanskriti Dey, Fitria Sari Wulandari, Rosario Trijuliamos Manalu, Ngoc Phung Ly, Chih-Yang Wang, Yung-Kuo Lee","doi":"10.7150/ijms.97975","DOIUrl":"10.7150/ijms.97975","url":null,"abstract":"<p><p>Recent advancements have elucidated the multifaceted roles of the Schlafen (SLFN) family, including SLFN5, SLFN11, SLFN12, SLFN13, and SLFN14, which are implicated in immunological responses. However, little is known about the roles of this gene family in relation to malignancy development. The current study aimed to explore the diagnostic and prognostic potential of Schlafen family genes in colorectal adenocarcinoma (COAD) through bioinformatics analysis. Leveraging advanced bioinformatics tools of bulk RNA-sequencing and single-cell sequencing, we conducted in-depth analyses of gene expressions, functional enrichment, and survival patterns of patients with colorectal cancer compared to normal tissue. Among Schlafen family genes, the transcription levels of SLFN5 in COAD tissues were significantly elevated and correlated with poor survival outcomes. Furthermore, SLFN5 regulated the immune response via Janus kinase (JAK)/signal transduction and activator of transcription (STAT)/interferon (IFN)-alpha/beta signaling. These chemokines in inflammation are associated with diabetes and metabolism, suggesting their involvement in altered cellular energetics for COAD progress. In addition, an immune cell deconvolution analysis indicated a correlation between SLFN5 expression and immune-related cell populations, such as regulatory T cells (Tregs). These findings highlighted the potential clinical significance of SLFN5 in COAD and provided insights into its involvement in the tumor microenvironment and immune regulation. Meanwhile, the drug discovery data of SFLN5 with potential targeted small molecules suggested its therapeutic potential for COAD. Collectively, the current research demonstrated that SFLN5 play crucial roles in tumor development and serve as a prospective biomarker for COAD.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286420","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}
Enhancement of Connexin43 (Cx43) and ferroptosis are respectively associated with the exacerbation of myocardial ischemia-reperfusion injury (MIRI) in diabetes. Myocardial vulnerability to ischemic insult has been shown to vary during early and later phases of diabetes in experimental settings. Whether or not Connexin43 (Cx43) and ferroptosis interplay during MIRI in diabetes is unknown. We, thus, aimed to investigate whether or not the content of myocardial Cx43 may be attributable to myocardial vulnerability to MIRI at different stages of diabetes and also to explore the potential interplay between Cx43 and ferroptosis in this pathology. Age-matched control and subgroups of Streptozotocin-induced diabetic mice were subjected to MIRI induced by 30 minutes coronary artery occlusion and 2 hours reperfusion respectively at 1, 2 and 5 weeks of diabetes. Rat cardiac H9C2 cells were exposed to high glucose (HG) for 48h in the absence or presence of Cx43 gene knockdown followed by hypoxia/reoxygenation (HR) respectively for 6 and 12 hours. Post-ischemic myocardial infarct size was reduced in 1 and 2 weeks DM mice concomitant with enhanced GPX4 and reduced cardiac Cx43 and ferroptosis as compared to control. By contrast, cardiac GPX4 was significantly reduced while Cx43 increased at DM 5 weeks (D5w) which was correspondent to significant increases in ferroptosis and myocardial infarction. Post-ischemic cardiac function was improved in 1 and 2 weeks but worsened in 5w DM mice as compared with non-diabetic control. GAP19 (Cx43 inhibitor) significantly attenuated ferroptosis and reduced myocardial infarction in D5w mice. Erastin (ferroptosis activator) reversed the cardioprotective effect of GAP19. In vitro, HR significantly reduced cell viability accompanied with reduced GPX4 but elevated Cx43 expression, MDA production and ferroptosis. Cx43 gene knockdown in H9C2 resulted in a significant increase in GPX4, reduction in MDA and ferroptosis, and subsequently reduced post-hypoxic cell viability. The beneficial effects of Cx43 gene knock-down was minified or eliminated by Erastin. It is concluded that Cx43 overexpression exacerbates MIRI under diabetic conditions via promoting ferroptosis, while its down-regulation at early state of diabetes is attributable to enhanced myocardial tolerance to MIRI.
{"title":"Connexin43 overexpression promoted ferroptosis and increased myocardial vulnerability to ischemia-reperfusion injury in type 1 diabetic mice.","authors":"Yuhui Yang, Jiajia Chen, Jiaqi Zhou, Dongcheng Zhou, Anyuan Zhang, Yuxin Jiang, Jiefu Lin, Weiyi Xia, Yin Cai, Ronghui Han, Yan Lu, Danyong Liu, Zhengyuan Xia","doi":"10.7150/ijms.95170","DOIUrl":"10.7150/ijms.95170","url":null,"abstract":"<p><p>Enhancement of Connexin43 (Cx43) and ferroptosis are respectively associated with the exacerbation of myocardial ischemia-reperfusion injury (MIRI) in diabetes. Myocardial vulnerability to ischemic insult has been shown to vary during early and later phases of diabetes in experimental settings. Whether or not Connexin43 (Cx43) and ferroptosis interplay during MIRI in diabetes is unknown. We, thus, aimed to investigate whether or not the content of myocardial Cx43 may be attributable to myocardial vulnerability to MIRI at different stages of diabetes and also to explore the potential interplay between Cx43 and ferroptosis in this pathology. Age-matched control and subgroups of Streptozotocin-induced diabetic mice were subjected to MIRI induced by 30 minutes coronary artery occlusion and 2 hours reperfusion respectively at 1, 2 and 5 weeks of diabetes. Rat cardiac H9C2 cells were exposed to high glucose (HG) for 48h in the absence or presence of Cx43 gene knockdown followed by hypoxia/reoxygenation (HR) respectively for 6 and 12 hours. Post-ischemic myocardial infarct size was reduced in 1 and 2 weeks DM mice concomitant with enhanced GPX4 and reduced cardiac Cx43 and ferroptosis as compared to control. By contrast, cardiac GPX4 was significantly reduced while Cx43 increased at DM 5 weeks (D5w) which was correspondent to significant increases in ferroptosis and myocardial infarction. Post-ischemic cardiac function was improved in 1 and 2 weeks but worsened in 5w DM mice as compared with non-diabetic control. GAP19 (Cx43 inhibitor) significantly attenuated ferroptosis and reduced myocardial infarction in D5w mice. Erastin (ferroptosis activator) reversed the cardioprotective effect of GAP19. In vitro, HR significantly reduced cell viability accompanied with reduced GPX4 but elevated Cx43 expression, MDA production and ferroptosis. Cx43 gene knockdown in H9C2 resulted in a significant increase in GPX4, reduction in MDA and ferroptosis, and subsequently reduced post-hypoxic cell viability. The beneficial effects of Cx43 gene knock-down was minified or eliminated by Erastin. It is concluded that Cx43 overexpression exacerbates MIRI under diabetic conditions via promoting ferroptosis, while its down-regulation at early state of diabetes is attributable to enhanced myocardial tolerance to MIRI.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286421","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}
Pub Date : 2024-09-09eCollection Date: 2024-01-01DOI: 10.7150/ijms.101094
Shuo Wang, Shan Gao, Fei Wang
Research on G protein-coupled receptor 75 (GPR75) in metabolic dysfunction-related steatosis liver disease (MASLD) reveals its potential role in regulating body weight and energy balance. Loss-of-function mutations in the GPR75 gene are significantly associated with lower body mass index and reduced body weight. Studies demonstrate that GPR75 knockout mice exhibit lower fasting blood glucose levels, improved glucose homeostasis, and significant prevention of high-fat diet-induced MASLD. The absence of GPR75 reduces fat accumulation by beneficially altering energy balance rather than restricting adipose tissue expansion. Moreover, female GPR75 knockout mice show greater protection against lipid accumulation on a high-fat diet compared to males, potentially attributed to higher physical activity and energy expenditure. However, current research primarily relies on mouse models, and its applicability to humans requires further validation. Future studies should explore the role of GPR75 across diverse populations, its clinical potential, and delve into its specific mechanisms and interactions with other metabolic pathways. Ultimately, targeted therapies based on GPR75 could offer novel strategies for the prevention and treatment of MASLD and other metabolic disorders.
{"title":"Effect and mechanism of GPR75 in metabolic dysfunction-related steatosis liver disease.","authors":"Shuo Wang, Shan Gao, Fei Wang","doi":"10.7150/ijms.101094","DOIUrl":"10.7150/ijms.101094","url":null,"abstract":"<p><p>Research on G protein-coupled receptor 75 (GPR75) in metabolic dysfunction-related steatosis liver disease (MASLD) reveals its potential role in regulating body weight and energy balance. Loss-of-function mutations in the GPR75 gene are significantly associated with lower body mass index and reduced body weight. Studies demonstrate that GPR75 knockout mice exhibit lower fasting blood glucose levels, improved glucose homeostasis, and significant prevention of high-fat diet-induced MASLD. The absence of GPR75 reduces fat accumulation by beneficially altering energy balance rather than restricting adipose tissue expansion. Moreover, female GPR75 knockout mice show greater protection against lipid accumulation on a high-fat diet compared to males, potentially attributed to higher physical activity and energy expenditure. However, current research primarily relies on mouse models, and its applicability to humans requires further validation. Future studies should explore the role of GPR75 across diverse populations, its clinical potential, and delve into its specific mechanisms and interactions with other metabolic pathways. Ultimately, targeted therapies based on GPR75 could offer novel strategies for the prevention and treatment of MASLD and other metabolic disorders.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286422","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}
Background: Persistent inflammation over time can cause gradual harm to the body. Molecular hydrogen has the potential to specifically counteract reactive oxygen species (ROS), reduce disease severity, and enhance overall health. Investigations of the anti-inflammatory and antioxidant properties of oral solid hydrogen capsules (OSHCs) are currently limited, prompting our examination of the beneficial effects of OSHCs. Subsequently, we conducted a clinical study to assess the impact of OSHCs supplementation on individuals with chronic inflammation. Materials and methods: Initially, we evaluated the oxidative reduction potential (ORP) properties of the OSHCs solution by comparing it to hydrogen-rich water (HRW) and calcium hydride (CaH2) treated water. In our outpatient department, stable patients with chronic illnesses who were treated with varying doses of OSHCs were randomized into low-, medium-, and high-dose groups for 4 weeks. Primary outcomes included changes in the serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) concentrations after four weeks of OSHCs consumption. Secondary outcomes included changes in the Brief Fatigue Inventory-Taiwan (BFI-T) fatigue scale, Control Status Scale for Diabetes (CSSD70) scores, and Disease Activity Score 28 (DAS28). Results: Compared to HRW and CaH2, OSHCs demonstrated a prolonged reduction in ORP for 60 minutes in vitro and enabled a regulated release of hydrogen over 24 hours. A total of 30 participants, with 10 in each dosage (low/medium/high) group, completed the study. The average ESR120 significantly decreased from the first week to the fourth week, with a noticeable dose effect (low-dose group, p = 0.494; high-dose group, p = 0.016). Overall, the average CRP concentration showed a distinct decreasing trend after four weeks of OSHCs administration (w0 vs. w4, p = 0.077). The average DAS28 score demonstrated a significant decrease following OSHCs treatment. Furthermore, there were improvements in the BFI-T and CSSD70 scores. Conclusion: OSHCs supplementation may exert anti-inflammatory and antioxidant effects on individuals with chronic inflammation. However, further clinical studies could be investigated to explore the potential therapeutic effects of OSHCs.
{"title":"Using oral molecular hydrogen supplements to combat microinflammation in humans: a pilot observational study.","authors":"Kuo-Cheng Lu, Min-Chung Shen, Reui-Lin Wang, Wen-Wen Chen, Szu-Han Chiu, Yung-His Kao, Feng-Cheng Liu, Po-Jen Hsiao","doi":"10.7150/ijms.101114","DOIUrl":"10.7150/ijms.101114","url":null,"abstract":"<p><p><b>Background:</b> Persistent inflammation over time can cause gradual harm to the body. Molecular hydrogen has the potential to specifically counteract reactive oxygen species (ROS), reduce disease severity, and enhance overall health. Investigations of the anti-inflammatory and antioxidant properties of oral solid hydrogen capsules (OSHCs) are currently limited, prompting our examination of the beneficial effects of OSHCs. Subsequently, we conducted a clinical study to assess the impact of OSHCs supplementation on individuals with chronic inflammation. <b>Materials and methods:</b> Initially, we evaluated the oxidative reduction potential (ORP) properties of the OSHCs solution by comparing it to hydrogen-rich water (HRW) and calcium hydride (CaH<sub>2</sub>) treated water. In our outpatient department, stable patients with chronic illnesses who were treated with varying doses of OSHCs were randomized into low-, medium-, and high-dose groups for 4 weeks. Primary outcomes included changes in the serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) concentrations after four weeks of OSHCs consumption. Secondary outcomes included changes in the Brief Fatigue Inventory-Taiwan (BFI-T) fatigue scale, Control Status Scale for Diabetes (CSSD70) scores, and Disease Activity Score 28 (DAS28). <b>Results:</b> Compared to HRW and CaH<sub>2</sub>, OSHCs demonstrated a prolonged reduction in ORP for 60 minutes in vitro and enabled a regulated release of hydrogen over 24 hours. A total of 30 participants, with 10 in each dosage (low/medium/high) group, completed the study. The average ESR120 significantly decreased from the first week to the fourth week, with a noticeable dose effect (low-dose group, p = 0.494; high-dose group, p = 0.016). Overall, the average CRP concentration showed a distinct decreasing trend after four weeks of OSHCs administration (w0 vs. w4, p = 0.077). The average DAS28 score demonstrated a significant decrease following OSHCs treatment. Furthermore, there were improvements in the BFI-T and CSSD70 scores. <b>Conclusion:</b> OSHCs supplementation may exert anti-inflammatory and antioxidant effects on individuals with chronic inflammation. However, further clinical studies could be investigated to explore the potential therapeutic effects of OSHCs.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286441","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}
Pub Date : 2024-09-03eCollection Date: 2024-01-01DOI: 10.7150/ijms.97240
Bin Zeng, Yuming Jin, Xingyang Su, Mi Yang, Xinyi Huang, Shi Qiu
Background: Older adults in low- and middle-income countries (LMICs) often suffer from both sarcopenia and stress urinary incontinence (SUI), two conditions that can significantly impact their health. However, the relationship between these conditions has not been thoroughly explored. Methods: We conducted a cross-sectional study using data from older adults aged 50 years or older from the first wave of the Longitudinal Ageing Study in India (LASI). Participants with complete data on sarcopenia and SUI were included, excluding female participants who were still menstruating. Sarcopenia was defined as decreased grip strength and slow movement. SUI was assessed based on questionnaire responses about whether the participant had ever passed urine when sneezing, coughing, laughing, or lifting heavy objects. We analyzed the data using multiple logistic regression analysis, interaction tests, and stratified analysis. Results: Our results showed that sarcopenia was positively correlated with SUI in male participants after adjusting for adequate confounding factors (odds ratio [OR] = 1.37, 95% confidence interval [CI] [1.20, 1.56], p < 0.001). This correlation remained stable after adjusting for additional confounding factors (OR = 1.27, 95% CI [1.11, 1.45], p < 0.001). In female participants, a stable correlation between sarcopenia and SUI was also observed after adjusting for appropriate confounding factors (OR = 1.11, 95% CI [1.01, 1.23], p = 0.037). According to the results of interaction tests and stratified analysis, the positive correlation between sarcopenia and SUI is notably stronger among men who abstain from alcohol and women who haven't undergone hysterectomy. Conclusions: Sarcopenia and SUI were positively correlated in older Indian adults, regardless of gender. Drinking and a history of hysterectomy may be important influencing factors for both male and female older adults. Further large-scale clinical trials are necessary to confirm this association.
背景:中低收入国家(LMICs)的老年人往往同时患有肌肉疏松症和压力性尿失禁(SUI),这两种疾病会严重影响他们的健康。然而,这两种疾病之间的关系尚未得到深入探讨。研究方法我们利用第一波印度老龄化纵向研究(LASI)中 50 岁或以上老年人的数据进行了一项横断面研究。研究纳入了具有肌肉疏松症和 SUI 完整数据的参与者,但不包括仍在月经期的女性参与者。肌肉疏松症被定义为握力下降和行动迟缓。尿崩症是根据参与者是否曾在打喷嚏、咳嗽、大笑或举起重物时排尿的问卷回答进行评估的。我们采用多元逻辑回归分析、交互检验和分层分析对数据进行了分析。结果显示我们的结果表明,在调整了足够的混杂因素后,男性参与者的肌肉疏松症与 SUI 呈正相关(几率比 [OR] = 1.37,95% 置信区间 [CI] [1.20, 1.56],P < 0.001)。在对其他混杂因素进行调整后,这一相关性保持稳定(OR = 1.27,95% CI [1.11,1.45],p < 0.001)。在女性参与者中,在调整了适当的混杂因素后,也观察到肌肉疏松症与 SUI 之间存在稳定的相关性(OR = 1.11,95% CI [1.01,1.23],p = 0.037)。根据交互检验和分层分析的结果,在戒酒的男性和未切除子宫的女性中,肌肉疏松症与 SUI 之间的正相关性明显更强。结论在印度老年人中,肌肉疏松症与 SUI 呈正相关,与性别无关。饮酒和子宫切除史可能是男性和女性老年人的重要影响因素。有必要进行更大规模的临床试验来证实这种关联。
{"title":"The Association Between Sarcopenia and Stress Urinary Incontinence Among Older Adults in India: A Cross-Sectional Study.","authors":"Bin Zeng, Yuming Jin, Xingyang Su, Mi Yang, Xinyi Huang, Shi Qiu","doi":"10.7150/ijms.97240","DOIUrl":"10.7150/ijms.97240","url":null,"abstract":"<p><p><b>Background:</b> Older adults in low- and middle-income countries (LMICs) often suffer from both sarcopenia and stress urinary incontinence (SUI), two conditions that can significantly impact their health. However, the relationship between these conditions has not been thoroughly explored. <b>Methods:</b> We conducted a cross-sectional study using data from older adults aged 50 years or older from the first wave of the Longitudinal Ageing Study in India (LASI). Participants with complete data on sarcopenia and SUI were included, excluding female participants who were still menstruating. Sarcopenia was defined as decreased grip strength and slow movement. SUI was assessed based on questionnaire responses about whether the participant had ever passed urine when sneezing, coughing, laughing, or lifting heavy objects. We analyzed the data using multiple logistic regression analysis, interaction tests, and stratified analysis. <b>Results:</b> Our results showed that sarcopenia was positively correlated with SUI in male participants after adjusting for adequate confounding factors (odds ratio [OR] = 1.37, 95% confidence interval [CI] [1.20, 1.56], p < 0.001). This correlation remained stable after adjusting for additional confounding factors (OR = 1.27, 95% CI [1.11, 1.45], p < 0.001). In female participants, a stable correlation between sarcopenia and SUI was also observed after adjusting for appropriate confounding factors (OR = 1.11, 95% CI [1.01, 1.23], p = 0.037). According to the results of interaction tests and stratified analysis, the positive correlation between sarcopenia and SUI is notably stronger among men who abstain from alcohol and women who haven't undergone hysterectomy. <b>Conclusions:</b> Sarcopenia and SUI were positively correlated in older Indian adults, regardless of gender. Drinking and a history of hysterectomy may be important influencing factors for both male and female older adults. Further large-scale clinical trials are necessary to confirm this association.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286440","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}
Pub Date : 2024-09-03eCollection Date: 2024-01-01DOI: 10.7150/ijms.98065
Fumin Zhi, Xiangyi Pu, Wei Wei, Li Liu, Chunyan Liu, Ye Chen, Xing Chang, Hongtao Xu
Diabetic cardiomyopathy (DCM) triggers a detrimental shift in mitochondrial dynamics, characterized by increased fission and decreased fusion, contributing to cardiomyocyte apoptosis and cardiac dysfunction. This study investigated the impact of modulating mitochondrial dynamics on DCM outcomes and underlying mechanisms in a mouse model. DCM induction led to upregulation of fission genes (Drp1, Mff, Fis1) and downregulation of fusion genes (Mfn1, Mfn2, Opa1). Inhibiting fission with Mdivi-1 or promoting fusion with Ginsenoside Rg1 preserved cardiac function, as evidenced by improved left ventricular ejection fraction (LVEF), fractional shortening (FS), and E/A ratio. Both treatments also reduced infarct size and attenuated cardiomyocyte apoptosis, indicated by decreased caspase-3 activity. Mechanistically, Mdivi-1 enhanced mitochondrial function by improving mitochondrial membrane potential, reducing reactive oxygen species (ROS) production, and increasing ATP generation. Ginsenoside Rg1 also preserved mitochondrial integrity and function under hypoxic conditions in HL-1 cardiomyocytes. These findings suggest that restoring the balance of mitochondrial dynamics through pharmacological interventions targeting either fission or fusion may offer a promising therapeutic strategy for mitigating MI-induced cardiac injury and improving patient outcomes.
{"title":"Modulating mitochondrial dynamics ameliorates left ventricular dysfunction by suppressing diverse cell death pathways after diabetic cardiomyopathy.","authors":"Fumin Zhi, Xiangyi Pu, Wei Wei, Li Liu, Chunyan Liu, Ye Chen, Xing Chang, Hongtao Xu","doi":"10.7150/ijms.98065","DOIUrl":"10.7150/ijms.98065","url":null,"abstract":"<p><p>Diabetic cardiomyopathy (DCM) triggers a detrimental shift in mitochondrial dynamics, characterized by increased fission and decreased fusion, contributing to cardiomyocyte apoptosis and cardiac dysfunction. This study investigated the impact of modulating mitochondrial dynamics on DCM outcomes and underlying mechanisms in a mouse model. DCM induction led to upregulation of fission genes (Drp1, Mff, Fis1) and downregulation of fusion genes (Mfn1, Mfn2, Opa1). Inhibiting fission with Mdivi-1 or promoting fusion with Ginsenoside Rg1 preserved cardiac function, as evidenced by improved left ventricular ejection fraction (LVEF), fractional shortening (FS), and E/A ratio. Both treatments also reduced infarct size and attenuated cardiomyocyte apoptosis, indicated by decreased caspase-3 activity. Mechanistically, Mdivi-1 enhanced mitochondrial function by improving mitochondrial membrane potential, reducing reactive oxygen species (ROS) production, and increasing ATP generation. Ginsenoside Rg1 also preserved mitochondrial integrity and function under hypoxic conditions in HL-1 cardiomyocytes. These findings suggest that restoring the balance of mitochondrial dynamics through pharmacological interventions targeting either fission or fusion may offer a promising therapeutic strategy for mitigating MI-induced cardiac injury and improving patient outcomes.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286437","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}
Background: Acute gastrointestinal injury (AGI) has been documented in critically ill patients, yet there remains a dearth of knowledge regarding its occurrence, predisposing factors, and outcomes in elderly polytrauma patients, a significant but overlooked population. This study aims to examine the frequency, risk factors, and clinical implications of AGI in elderly polytrauma patients. Methods: A retrospective, observational, multicenter study was carried out in two Level I trauma centers, encompassing a cohort of 1054 polytrauma patients from July 2020 to April 2022. Results: A total of 965 consecutive polytrauma patients were recruited who were divided into youth group (n=746) and elderly group (n=219). 73.5% of elderly patients after polytrauma were accompanied by AGI. An increasing ISS (OR=2.957, 95%CI: 1.285-7.714), SI (OR=2.861, 95%CI: 1.372-5.823), serum lactate (OR=2.547, 95%CI: 1.254-5.028), IL-6 (OR=1.771, 95%CI: 1.145-8.768), APTT (OR=1.462, 95%CI: 1.364-4.254) and a decreasing GCS (OR=0.325, 95%CI: 0.116-0.906) were each associated with an increasing risk of AGI in elderly polytrauma patients. Elderly polytrauma patients with AGI were presented relatively high 28-day mortality (40.4%) and super high 60-day mortality (61.2%) compared with elderly group without AGI and youth group with AGI. The area under the curve for predicting 28-day mortality in elderly polytrauma patients with AGI was 0.93 for AGI-III,IV with 96% sensitivity and 87% specificity. Conclusion: Elderly patients have a higher incidence and a worse prognosis of AGI after polytrauma. ISS, GCS, SI, serum lactate, IL-6, and APTT are identified as reliable prognostic markers to distinguish the AGI and N-AGI in elderly polytrauma patients. AGI-III,IV was the independent predictor of mortality in elderly polytrauma patients with AGI.
{"title":"Acute Gastrointestinal Injury in Polytrauma: Special Attention to Elderly Patients.","authors":"Cong Zhang, Teding Chang, Deng Chen, Jialiu Luo, Shunyao Chen, Peidong Zhang, Zhiqiang Lin, Jian Luo, Quan Zhou, Wenguo Wang, Huaqiang Xu, Liming Dong, Zhaohui Tang","doi":"10.7150/ijms.98997","DOIUrl":"10.7150/ijms.98997","url":null,"abstract":"<p><p><b>Background:</b> Acute gastrointestinal injury (AGI) has been documented in critically ill patients, yet there remains a dearth of knowledge regarding its occurrence, predisposing factors, and outcomes in elderly polytrauma patients, a significant but overlooked population. This study aims to examine the frequency, risk factors, and clinical implications of AGI in elderly polytrauma patients. <b>Methods:</b> A retrospective, observational, multicenter study was carried out in two Level I trauma centers, encompassing a cohort of 1054 polytrauma patients from July 2020 to April 2022. <b>Results:</b> A total of 965 consecutive polytrauma patients were recruited who were divided into youth group (n=746) and elderly group (n=219). 73.5% of elderly patients after polytrauma were accompanied by AGI. An increasing ISS (OR=2.957, 95%CI: 1.285-7.714), SI (OR=2.861, 95%CI: 1.372-5.823), serum lactate (OR=2.547, 95%CI: 1.254-5.028), IL-6 (OR=1.771, 95%CI: 1.145-8.768), APTT (OR=1.462, 95%CI: 1.364-4.254) and a decreasing GCS (OR=0.325, 95%CI: 0.116-0.906) were each associated with an increasing risk of AGI in elderly polytrauma patients. Elderly polytrauma patients with AGI were presented relatively high 28-day mortality (40.4%) and super high 60-day mortality (61.2%) compared with elderly group without AGI and youth group with AGI. The area under the curve for predicting 28-day mortality in elderly polytrauma patients with AGI was 0.93 for AGI-III,IV with 96% sensitivity and 87% specificity. <b>Conclusion:</b> Elderly patients have a higher incidence and a worse prognosis of AGI after polytrauma. ISS, GCS, SI, serum lactate, IL-6, and APTT are identified as reliable prognostic markers to distinguish the AGI and N-AGI in elderly polytrauma patients. AGI-III,IV was the independent predictor of mortality in elderly polytrauma patients with AGI.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286417","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}