Clinical science最新文献_第4页

Retraction: Balancing mitochondrial dynamics via increasing mitochondrial fusion attenuates infarct size and left ventricular dysfunction in rats with cardiac ischemia/reperfusion injury. 收缩：通过增加线粒体融合来平衡线粒体动力学可以减轻心肌缺血/再灌注损伤大鼠的梗死面积和左心室功能障碍。

IF 6.7 2区医学

Clinical science Pub Date : 2025-06-23 DOI: 10.1042/CS20190014_RET

引用次数: 0

Dysregulation of NK cell subsets and phenotypes in COVID-19 patients with comorbid type 2 diabetes. 新冠肺炎合并2型糖尿病患者NK细胞亚群和表型失调

IF 6.7 2区医学

Clinical science Pub Date : 2025-06-23 DOI: 10.1042/CS20243133

Kang Lei, Wenqi Fan, Ting Zhong, Xinyu Li, Rong Tang, Bin Zhao, Xia Li

{"title":"Dysregulation of NK cell subsets and phenotypes in COVID-19 patients with comorbid type 2 diabetes.","authors":"Kang Lei, Wenqi Fan, Ting Zhong, Xinyu Li, Rong Tang, Bin Zhao, Xia Li","doi":"10.1042/CS20243133","DOIUrl":"10.1042/CS20243133","url":null,"abstract":"Recent studies have linked natural killer (NK) cells to COVID-19. However, the role of NK cells in COVID-19 patients complicated with type 2 diabetes (T2D) remains unexplored. Our findings indicate no significant differences in the frequency or immunophenotype of total NK cells and the CD56bright CD16- subset among COVID-19 patients, T2D patients, and healthy individuals. Patients with severe COVID-19 had a greater prevalence of CD56dim CD16- cells subset and a lower prevalence of CD56dim CD16+ cells subset, with these trends being even more pronounced in those with comorbid T2D. The proportion of CD56dim CD16+ cell subset exhibited a significant negative correlation with both interleukin-6 levels and the duration of hospital stay. Furthermore, when COVID-19 patients were compared with patients with T2D or control subjects, a trend was noted toward increased expression of CD69, KIR, and CD52 and decreased expression of CD226, NKG2D, and CD62L. These immunophenotypic changes were particularly accentuated in COVID-19 patients with comorbid T2D. Importantly, the CD56dim CD16+ cells subset emerges as a substantial predictor of COVID-19 severity. Together, COVID-19 patients exhibit alterations in NK cell subsets, with aggravated dysregulation in individuals with T2D, and the CD56dim CD16+ cells subset may serve as an indicator of COVID-19 severity.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retraction: Differential temporal inhibition of mitochondrial fission by Mdivi-1 exerts effective cardioprotection in cardiac ischemia/reperfusion injury. 收缩：Mdivi-1对线粒体分裂的不同时间抑制对心脏缺血/再灌注损伤具有有效的心脏保护作用。

IF 6.7 2区医学

Clinical science Pub Date : 2025-06-23 DOI: 10.1042/CS20180510_RET

引用次数: 0

Expression of Concern: Mitochondrial dynamic modulation exerts cardiometabolic protection in obese insulin-resistant rats. 关注表达：线粒体动态调节在肥胖胰岛素抵抗大鼠中发挥心脏代谢保护作用。

IF 6.7 2区医学

Clinical science Pub Date : 2025-06-19 DOI: 10.1042/CS20190960_EOC

引用次数: 0

DAPK1 acts as a positive regulator of hypertension via induction of vasoconstriction. DAPK1通过诱导血管收缩作为高血压的积极调节因子。

IF 6.7 2区医学

Clinical science Pub Date : 2025-06-18 DOI: 10.1042/CS20255840

Xiuli Zhang, Ying Cheng, Yao Lu, Nanhui Xu, Zhi Guo, Meizhu Wu, Guosheng Lin, Mengying Yao, Yanyan Yang, Yao Lin, Jun Peng, Aling Shen

{"title":"DAPK1 acts as a positive regulator of hypertension via induction of vasoconstriction.","authors":"Xiuli Zhang, Ying Cheng, Yao Lu, Nanhui Xu, Zhi Guo, Meizhu Wu, Guosheng Lin, Mengying Yao, Yanyan Yang, Yao Lin, Jun Peng, Aling Shen","doi":"10.1042/CS20255840","DOIUrl":"10.1042/CS20255840","url":null,"abstract":"Death-associated protein kinase 1 (DAPK1) is a tumor suppressor gene involved in apoptosis, autophagy, and tumor progression. However, its role in hypertension (HTN) remains largely unexplored and lacks systematic evaluation. We administered adeno-associated virus (AAV) harboring short hairpin RNA targeting DAPK1 or control short hairpin RNA to male spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats. Additionally, wildtype and DAPK1 knockout mice were infused with angiotensin II (Ang II) or saline for four weeks. Male C57BL/6 mice underwent a four-week Ang II infusion and were treated with TC-DAPK6, a selective DAPK1 inhibitor. We examined the abdominal aortas (AAs) of mice and rats for pathological changes, measured blood pressure (BP) and pulse wave velocity using noninvasive BP methods, ultrasound, and hematoxylin and eosin staining. The role of DAPK1 in early HTN was further assessed through immunofluorescence, ex vivo isometric constriction of the AA, RNA sequencing, Western blot, and immunohistochemistry. Our study demonstrated that the targeted inhibition of DAPK1 with AAV significantly ameliorated HTN in SHRs and reduced damage to the AAs and target organs, including the heart and kidneys. Meanwhile, DAPK1 knockout or inhibition in mice significantly ameliorates Ang II-induced HTN in mice, as well as reducing damage to the AAs and target organs, including the heart and kidneys. Mechanistically, DAPK1 inhibition prevents myosin light chain (MLC) phosphorylation at serine 19, reducing vasoconstriction and protecting against HTN. In conclusion, DAPK1 is involved in HTN pathogenesis by regulating the MLC pathway to mediate vascular constriction, highlighting potential as a therapeutic target for HTN.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epac1 mediates thermogenesis and lipolysis in white adipose tissue via the p38γ-NFAT5 axis in a PKA-independent manner. Epac1通过p38γ-NFAT5轴以不依赖pka的方式介导白色脂肪组织的产热和脂肪分解。

IF 6.7 2区医学

Clinical science Pub Date : 2025-06-17 DOI: 10.1042/CS20256710

Baile Wang, Christina Yingxian Chen, Jie Liu, Qin Wang, Wenxia Zhang, Jingwen Liu, Andrew C P Tai, Alan Kai, Ben C B Ko, Aimin Xu, Sookja Kim Chung

{"title":"Epac1 mediates thermogenesis and lipolysis in white adipose tissue via the p38γ-NFAT5 axis in a PKA-independent manner.","authors":"Baile Wang, Christina Yingxian Chen, Jie Liu, Qin Wang, Wenxia Zhang, Jingwen Liu, Andrew C P Tai, Alan Kai, Ben C B Ko, Aimin Xu, Sookja Kim Chung","doi":"10.1042/CS20256710","DOIUrl":"10.1042/CS20256710","url":null,"abstract":"Beige adipocytes in white adipose tissue (WAT) share similar functions as brown adipocytes by converting lipids into heat through thermogenesis, while lipolysis is considered as a prerequisite for the activation of non-shivering thermogenesis. β3-adrenergic receptor (β3-AR) agonist CL316,243 (CL) and cold exposure are known to enhance lipolysis and beiging of WAT in a protein kinase A (PKA)-dependent manner, while the role of PKA-independent pathways involved is still poorly understood. Here, we show that the exchange protein directly activated by cAMP 1 (Epac1), a downstream target of cAMP, mediates β3-AR activation to modulate thermogenesis and lipolysis in a PKA-independent manner. Upon CL treatment or cold exposure, both thermogenic and lipolytic responses were compromised in Epac1-deficient mice, as evidenced by reduced oxygen consumption, less beige adipocytes, lower body temperature, and decreased circulating glycerol. Additionally, in vitro beige adipogenesis with or without cAMP analog treatment was significantly impaired in Epac1-deficient mice. Mechanistically, reduced total and phosphorylated p38γ and decreased induction of nuclear factor activated in T cells 5 (NFAT5) were observed in Epac1-deficient mice, which may contribute to the defective beiging of WAT. However, WAT of wildtype and Epac1-deficient mice showed no significant induction difference in phosphorylation of hormone-sensitive lipase at PKA and AMP-activated protein kinase sites with PKA activator, and in vitro beige adipogenesis was not altered in Epac1-deficient mice in response to PKA activation, indicating that Epac1 mediates lipolysis and beige adipogenesis in a PKA-independent manner. Taken together, Epac1 mediates β3-AR-induced beiging and lipolysis of WAT via the p38γ-NFAT5 axis in a PKA-independent manner.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glycogen synthase kinase 3β: a key player in progressive chronic kidney disease. 糖原合成酶激酶3β：进展性慢性肾脏疾病的关键参与者。

IF 6.7 2区医学

Clinical science Pub Date : 2025-06-17 DOI: 10.1042/CS20245219

Mingzhuo Zhang, Marc Tatar, Rujun Gong

{"title":"Glycogen synthase kinase 3β: a key player in progressive chronic kidney disease.","authors":"Mingzhuo Zhang, Marc Tatar, Rujun Gong","doi":"10.1042/CS20245219","DOIUrl":"10.1042/CS20245219","url":null,"abstract":"Chronic kidney disease (CKD) is a serious medical condition that poses substantial burdens on patients, families, healthcare systems, and society as a whole. It is characterized by progressive kidney damage and loss of function in the kidney, often compounded by underlying conditions such as diabetes, hypertension, and autoimmune diseases. Glycogen synthase kinase 3 beta (GSK3β), a highly conserved serine/threonine kinase originally implicated in insulin signaling, has emerged as a convergent point of multiple pathways implicated in the pathogenesis and progression of CKD. In the kidney, GSK3β regulates cell fate across diverse cells, including podocytes, mesangial cells, and renal tubular cells, through its interactions with key signaling pathways such as Wnt/β-catenin, NF-κB, Nrf2, PI3K/Akt, and cytoskeleton remodeling pathways. Evidence suggests that dysregulation of GSK3β is closely associated with pathological changes in the kidney, including podocyte injury, mesangial expansion, interstitial fibrosis, and tubular atrophy, which collectively drive chronic kidney destruction. In CKD, GSK3β is overexpressed and thus hyperactive in kidney cells. This sustained hyperactivity perpetuates oxidative stress and profibrotic signaling, particularly in renal tubular cells, thus accelerating the transition from acute kidney injury to CKD. Pharmacological targeting of GSK3β with selective inhibitors has shown promise in preclinical models, by reducing kidney injury, attenuating renal fibrosis, and promoting renal recovery, positioning GSK3β as a potential therapeutic target for CKD. This review highlights recent advances in understanding the molecular and cellular mechanisms through which GSK3β contributes to CKD and underscores its potential as a therapeutic target for various chronic renal diseases.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"139 12","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex differences in the chronic autoimmune response to myocardial infarction. 慢性自身免疫反应对心肌梗死的性别差异

IF 6.7 2区医学

Clinical science Pub Date : 2025-06-17 DOI: 10.1042/CS20243091

Erin B Taylor, Luciano D Mendoza, Jayla D Sandifer, Jemylle G Morato, Nikaela M Aitken, Katherine R O'Quinn, Indu Raman, Chengsong Zhu, Robert W Spitz, John E Hall, Alan J Mouton

{"title":"Sex differences in the chronic autoimmune response to myocardial infarction.","authors":"Erin B Taylor, Luciano D Mendoza, Jayla D Sandifer, Jemylle G Morato, Nikaela M Aitken, Katherine R O'Quinn, Indu Raman, Chengsong Zhu, Robert W Spitz, John E Hall, Alan J Mouton","doi":"10.1042/CS20243091","DOIUrl":"10.1042/CS20243091","url":null,"abstract":"Myocardial infarction (MI) causes a robust inflammatory response, which is necessary for remodeling and scar formation of the infarcted left ventricle (LV). However, this can lead to chronic systemic inflammation and persistent autoimmune responses. In this study, we analyzed sex differences in the inflammatory autoimmune response to chronic MI. MI was induced by permanent left coronary artery ligation in adult male and female C57BL/6J mice for one, four, and eight weeks. Both sexes exhibited similar declines in LV function. Females had higher levels of total immune cells and T cells in the infarct and remote area at D7 post-MI, and B cells at D56. MI increased levels of pro-inflammatory cytokines (Il1b, Il6, Tnf, Ccl2, Ifng, Il18) in the LV infarct that peaked at one week, which was exaggerated in females for Il6, Ifng, and Il10. In the remote LV, females had higher levels of Il6, Tnf, Ccl2, and Il18. MI increased spleen mass in females only, and splenic cytokines were higher in females at several time points, including Il1b, Il12a, Il10, Ifng, Il18, Ccl2, and Il4. IgG and IgM deposition in the LV infarct increased over time in both sexes, but more so in females. In the remote area, both sexes had increased IgG and IgM at eight weeks. Plasma IgM was higher in females at one, four, and eight weeks post-MI compared with males. Plasma IgG and IgM autoantibodies were detected in males and females after MI, but the number of autoantibodies displaying reactivity to autoantigens was much higher in females, particularly at week 8. In summary, MI leads to the development of systemic and myocardial autoimmune activation, which is more pronounced in females.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"139 12","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aging and sinus node dysfunction: mechanisms and future directions. 衰老与窦结功能障碍：机制和未来方向。

IF 6.7 2区医学

Clinical science Pub Date : 2025-06-11 DOI: 10.1042/CS20231025

Thassio Mesquita, Rodrigo Miguel-Dos-Santos, Eugenio Cingolani

{"title":"Aging and sinus node dysfunction: mechanisms and future directions.","authors":"Thassio Mesquita, Rodrigo Miguel-Dos-Santos, Eugenio Cingolani","doi":"10.1042/CS20231025","DOIUrl":"10.1042/CS20231025","url":null,"abstract":"Aging is a natural biological process influenced by endogenous and exogenous factors such as genetics, environment, and individual lifestyle. The aging-dependent decline in resting and maximum heart rate is a conserved feature across multiple species, including humans. Such changes in heart rhythm control underscore fundamental alterations in the primary cardiac pacemaker, the sinoatrial node (SAN). Older individuals often present symptoms of SAN dysfunction (SND), including sinus bradycardia, sinus arrest, and bradycardia-tachycardia syndrome. These can lead to a broad range of symptoms from palpitations, dizziness to recurrent syncope. The sharp rise in the incidence of SND among individuals over 65 years old, coupled with projected longevity over the next decades, highlights the urgent need for a deeper mechanistic understanding of aging-related SND to develop novel and effective therapeutic alternatives. In this review, we will revisit current knowledge on the ionic and structural remodeling underlying age-related decline in SAN function, and a particular emphasis will be made on new directions for future research.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"139 11","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elevated phenylacetylglutamine caused by gut dysbiosis associated with type 2 diabetes increases neutrophil extracellular traps formation and exacerbates brain infarction. 与2型糖尿病相关的肠道生态失调引起的苯乙酰谷氨酰胺升高会增加中性粒细胞胞外陷阱的形成并加剧脑梗死。

IF 7.7 2区医学

Clinical science Pub Date : 2025-06-05 DOI: 10.1042/CS20242943

Minping Wei, Qin Huang, Fang Yu, Yun-Fang Luo, Xianjing Feng, Di Liao, Jiaxin Li, Boxin Zhang, Ze-Yu Liu, Jian Xia

{"title":"Elevated phenylacetylglutamine caused by gut dysbiosis associated with type 2 diabetes increases neutrophil extracellular traps formation and exacerbates brain infarction.","authors":"Minping Wei, Qin Huang, Fang Yu, Yun-Fang Luo, Xianjing Feng, Di Liao, Jiaxin Li, Boxin Zhang, Ze-Yu Liu, Jian Xia","doi":"10.1042/CS20242943","DOIUrl":"10.1042/CS20242943","url":null,"abstract":"Type 2 diabetes (T2D) aggravates ischemic stroke. The association between gut microbiota-derived metabolite phenylacetylglutamine (PAGln) and ischemic stroke patients with T2D remains unclear. Therefore, we aimed to explore the change of gut microbiota and its metabolite, PAGln in ischemic stroke patients with T2D, as well as investigate the role of PAGln in this disease. We performed two clinical cohort studies to investigate the changes of gut microbiota and PAGln in ischemic stroke patients with T2D. Then, we transplanted fecal microbiota from patients into rats and established a middle cerebral artery occlusion model. Finally, an intraperitoneal injection of PAGln was administered to rats to test whether it exacerbates brain infarction. Plasma PAGln levels were significantly higher in stroke patients with T2D compared to those without T2D. There was a positive correlation of Plasma PAGln with NETs. Enterobacteriaceae, Verrucomicrobiota, and Klebsiella were enriched in stroke patients with T2D and showed a significant positive correlation with PAGln levels. The rats transplanted with fecal microbes from stroke patients with T2D developed a more severe brain injury and had higher levels of plasma PAGln and NETs compared to the rats transplanted with fecal microbes from stroke patients without T2D. Additionally, rats treated with PAGln exhibited more severe brain injury accompanied by increased systemic inflammation, oxidative stress and NET formation. Our results suggest elevated circulating PAGln levels, resulting from gut dysbiosis in stroke patients with T2D, may exacerbate brain infarction through NETs formation, systemic inflammation, and oxidative stress.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0