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Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system 被引量:3
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作者 Bai-Wei Zhao Ying-Jia Chen +2 位作者 Ruo-Peng Zhang Yong-Ming Chen Bo-Wen Huang 《World Journal of Gastroenterology》 SCIE CAS 2024年第6期607-609,共3页
The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can ... The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system. 展开更多
关键词 angiotensin-converting enzyme 2 Hepatic stellate cells Liver fibrosis Angiotensin II Angiotensin 1-7 Renin-angiotensin system
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Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19 被引量:1
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作者 Angus K Jacobs Steven D Morley +7 位作者 Kay Samuel Katie Morgan Lyndsey Boswell Timothy J Kendall David A Dorward Jonathan A Fallowfield Peter C Hayes John N Plevris 《World Journal of Gastroenterology》 SCIE CAS 2024年第31期3705-3716,共12页
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)i... BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy.Mechanisms of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell invasion.AIM To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19.METHODS ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel classifiers.RESULTS ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes.Strikingly,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis.ACE2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum.Hepatic ACE2 levels are also increased in COVID-19 patients,especially those showing evidence of LI,but are not correlated with the presence of SARS-CoV-2 virus in the liver.However,there is a clear association between the hepatic lipid droplet content and the presence of the virus,suggesting a possible functional link.CONCLUSION Hepatic ACE2 levels were elevated in nonfibrotic MASH and COVID-19 patients with LI,while lipid accumulation may promote intra-hepatic SARS-CoV-2 replication,accelerating MASLD progression and COVID-19-mediated liver damage. 展开更多
关键词 Metabolic dysfunction-associated steatotic liver disease angiotensin-converting enzyme 2 IMMUNOHISTOCHEMISTRY COVID-19 COVID-19-associated cholangiopathy
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Polymorphisms of angiotensin-converting enzyme 2 gene associated with magnitude of left ventricular hypertrophy in male patients with hypertrophic cardiomyopathy 被引量:8
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作者 WANG Shu-xia FU Chun-yan +7 位作者 ZOU Yu-bao WANG Hu SHI Yi XU Xi-qi CHEN Jing-zhou SONG Xiao-dong HUAN Tu-jun HUI Ru-tai 《Chinese Medical Journal》 SCIE CAS CSCD 2008年第1期27-31,共5页
Background Even carrying an identical gene mutation, inter- and intra-family variations have been noticed worldwide in the presence and the severity of left ventricular hypertrophy and sudden death in patients with hy... Background Even carrying an identical gene mutation, inter- and intra-family variations have been noticed worldwide in the presence and the severity of left ventricular hypertrophy and sudden death in patients with hypertrophic cardiomyopathy (HCM). Modifier genes may contribute to the diversity. Angiotensin-converting enzyme 2 (ACE2) gene has been established to be associated with parameters of left ventricular hypertrophy in community based male subjects. The objective of the present study was to investigate the association of ACE2 gene polymorphisms with the phenotype of HCM. Methods A total of 261 consecutive HCM patients and 609 healthy controls were enrolled into this study. The polymorphism of rs2106809 and rs6632677 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Logistic regression model and multivariate analysis were used to determine the odds ratio (OR) and 95% confidence intervals (CO of variations of ACE2 for HCM. Results The T allele of rs2106809 and C allele of rs6632677 conferred increasing risk for HCM (OR 1.34, 95%C/ 1.01-1.77, P=0.04; OR 1.11, 95%C/ 1.03-1.21, P=0.002, respectively), and the 2 single nucleotide polymorphisms (SNPs) were in strong linkage disequilibrium (LD), the TC haplotype was independently associated with a higher OR for HCM (OR=1.59, 95%C/1.21-1.87) after adjusted for conventional risk factors. And the risk alleles were associated with thicker interventricular septal thickness of HCM ((20.0±6.3) mm vs (17.9±5.5) mm, P=0.03 and (21.3±5.9) mm vs (17.9±5.8) mm, P=0.04, respectively). No association was found between the two polymorphisms with female patients with HCM. Conclusion Minor alleles of ACE2 gene might be the genetic modifier for the magnitude of left ventricular hypertrophy in male patients with HCM. 展开更多
关键词 POLYMORPHISM angiotensin-converting enzyme 2 gene hypertrophic cardiomyopathy
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Plasma Levels of Angiotensin-Converting Enzymes 1 and 2 and <i>AGTR</i>2 (T1247G and A5235G) Gene Polymorphisms Are Associated to Breast Cancer Progression
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作者 Maria Del Carmen Garcia Molina Wolgien Ismael Dale Cotrim Guerreiro da Silva +4 位作者 Afonso Celso Pinto Nazário Clovis Riyuchi Nakaie Silvana Aparecida Alves Corrêa de Noronha Samuel Marcos Ribeiro de Noronha Gil Facina 《Journal of Cancer Therapy》 2013年第9期1403-1410,共8页
Background: Breast cancer is the most common type of cancer among women. Diagnosed and treated timely, patients may have good prognostics. In Brazil, in 2012, the estimate of new cases was 52,680 and the number of reg... Background: Breast cancer is the most common type of cancer among women. Diagnosed and treated timely, patients may have good prognostics. In Brazil, in 2012, the estimate of new cases was 52,680 and the number of registered deaths in 2012 was 12,852. The Renin-Angiotensin System (RAS) is known for its role in arterial hypertension and in other cardiovascular diseases. Angiotensin-Converting Enzyme 2 (ACE2) is the key to Ang-(1-7) formation, and counterbalances the ACE1/AngII/AGTR1 axis actions. RAS components have complex interactions with different tissues and their actions are not restricted to the cardiovascular system. Recently, the RAS has been associated with different types of cancers and in particular with gynecological cancers. Objectives: Our aim is to investigate possible associations between allelic distribution of two genetic polymorphisms in the AGTR2 receptor with ACEs 1 and 2 plasma levels among women with breast cancer. Patients and Methods: Patients with breast cancer were genotyped for two polymorphisms of the AGTR2 (T1247G and A5235G). Genotyping assays (TaqMan) were performed with genomic DNA extracted from blood cells. ACEs plasma level measurements were conducted in women from the breast-cancer group (N = 53). ACEs were measured in the plasma of these patients using ELISA kits. Results: SNPs genotype distribution is correlated with ACEs plasma levels. ACEs plasma levels are also correlated with clinical variables and ACE2 high levels are associated with better prognostics. Conclusions: Changes in circulating levels of ECA1/AngII ECA2/ Ang-(1-7) determine the magnitude of the inflammatory response that an individual can trigger and the variation in ACE 1 and 2 plasma level measurements in the blood of breast cancer patients suggests an association with the process of mammary carcinogenesis. Thus, the RAS may be associated with the process of mammary carcinogenesis by both genotypic variations of RAS components and by circulating levels of ACEs. 展开更多
关键词 angiotensin-converting enzyme 1 angiotensin-converting enzyme 2 ANGIOTENSIN II Type 2 Receptor Breast Neoplasm ACES Plasma Level genetic Polymorphisms
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Relationship between polymorphism of angiotensin-converting enzyme 2 gene and the risk factor of essential hypertension with complicated stroke
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作者 陈东骊 张曹进 +2 位作者 符永恒 莫与京 陈富荣 《South China Journal of Cardiology》 CAS 2013年第2期89-95,共7页
Background Essential hypertension (EH) is considered to be one of the most important risk factor of ischemic stroke. Studies about risk factors in the patients are meaningful in early forecast and effective preventi... Background Essential hypertension (EH) is considered to be one of the most important risk factor of ischemic stroke. Studies about risk factors in the patients are meaningful in early forecast and effective prevention of the onset of stroke. Renin-angiotensin-aldosterone system plays an important role in the regulation of blood pressure and the development of stroke, while recent studies have found that the angiotensin-converting enzyme 2 (ACE2) may be a reversal agent for the development and progression of ischemic stroke. Methods The ACE2 gene was measured in 139 EH patients with ischemic stroke using polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR-RFLP) tests. Detailed and complete clinical and biochemical data were collected, including pulse pressure, hsCRP, IMT, HDL-C and uric acid levels. Study the correlation between angiotensin-converting enzyme 2 gene and the risk factor for onset of ischemic stroke in EH patients. Results Pulse pressure, hsCRP, IMT and uric acid levels had a positive correlation with on- set of ischemic stroke in EH patients. Among male patients, pulse pressure, hsCRP, IMT and HDL-C were higher in patients carrying A allele than B allele (P 〈 0.05). While these factors were different in female patients carrying different genotypes in which A.A allele were highest. Patients with various genotypes showed different uric acid levels but showed no significant difference. Conclusion Among EH patients with complicated ischemic stroke, those carrying the A/AA allele show high level of risk factors and is likely to have the susceptibility of recurrence of stroke. 展开更多
关键词 angiotensin-converting enzyme 2 essential hypertension STROKE risk factors
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Angiotensin-converting Enzyme Gene Insertion/Deletion Polymorphism in Children with Henoch-Schonlein Purpua Nephritis 被引量:17
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作者 周建华 田雪飞 徐钦儒 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2004年第2期158-161,共4页
This study investigated the relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism and the occurrence, severity, prognosis of HSPN. The polymorphism of ACE gene in 103 HSPN case... This study investigated the relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism and the occurrence, severity, prognosis of HSPN. The polymorphism of ACE gene in 103 HSPN cases and 100 healthy children was studied by using the polymerase chain reactions (PCR). Its relation to the clinical manifestation, pathological classification and prognosis of HSPN was analyzed accordingly. The results showed that: (1) there was a significantly higher frequency for DD genotype in HSPN children (P<0.01); (2) DD genotype was more frequently seen in HSPN children with gross hematuria and massive proteinuria (P<0.05), while DI genotype was more common in HSPN children group with renal insufficiency (P<0.05); (3) although mesangial proliferative lesion was most frequently observed in 21 biopsied HSPN children, and DD genotype frequency was still higher in children with severe pathology (Class Ⅲ Ⅳ); (4)II genotype was significantly frequent in HSPN children with complete remission in the follow-up of 32 HSPN children. It was concluded that the deletion allele of ACE gene might play a role, at least to some extent, in the occurrence, deterioration and progression in juvenile HSPN. 展开更多
关键词 angiotensin-converting enzyme gene insertion/deletion polymorphism Henoch-Schonlein purura nephritis children
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Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells 被引量:3
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作者 Ying Wu Ai-Hong Yin +2 位作者 Jun-Tao Sun Wei-Hua Xu Chun-Qing Zhang 《World Journal of Gastroenterology》 SCIE CAS 2023年第33期4975-4990,共16页
BACKGROUND Liver fibrosis is the common pathological process associated with the occurrence and development of various chronic liver diseases.At present,there is still a lack of effective prevention and treatment meth... BACKGROUND Liver fibrosis is the common pathological process associated with the occurrence and development of various chronic liver diseases.At present,there is still a lack of effective prevention and treatment methods in clinical practice.Hepatic stellate cell(HSC)plays a key role in liver fibrogenesis.In recent years,the study of liver fibrosis targeting HSC autophagy has become a hot spot in this research field.Angiotensin-converting enzyme 2(ACE2)is a key negative regulator of reninangiotensin system,and its specific molecular mechanism on autophagy and liver fibrosis needs to be further explored.AIM To investigate the effect of ACE2 on hepatic fibrosis in mice by regulating HSC autophagy through the Adenosine monophosphate activates protein kinases(AMPK)/mammalian target of rapamycin(mTOR)pathway.METHODS Overexpression of ACE2 in a mouse liver fibrosis model was induced by injection of liver-specific recombinant adeno-associated virus ACE2 vector(rAAV2/8-ACE2).The degree of liver fibrosis was assessed by histopathological staining and the biomarkers in mouse serum were measured by Luminex multifactor analysis.The number of apoptotic HSCs was assessed by terminal deoxynucleoitidyl transferase-mediated dUTP nick-end labeling(TUNEL)and immunofluorescence staining.Transmission electron microscopy was used to identify the changes in the number of HSC autophagosomes.The effect of ACE2 overexpression on Wu Y et al.ACE2 improves liver fibrosis through autophagy WJG https://www.wjgnet.com 4976 September 7,2023 Volume 29 Issue 33 autophagy-related proteins was evaluated by multicolor immunofluorescence staining.The expression of autophagy-related indicators and AMPK pathway-related proteins was measured by western blotting.RESULTS A mouse model of liver fibrosis was successfully established after 8 wk of intraperitoneal injection of carbon tetrachloride(CCl4).rAAV2/8-ACE2 administration reduced collagen deposition and alleviated the degree of liver fibrosis in mice.The serum levels of platelet-derived growth factor,angiopoietin-2,vascular endothelial growth factor and angiotensin II were decreased,while the levels of interleukin(IL)-10 and angiotensin-(1-7)were increased in the rAAV2/8-ACE2 group.In addition,the expression of alpha-smooth muscle actin,fibronectin,and CD31 was down-regulated in the rAAV2/8-ACE2 group.TUNEL and immunofluorescence staining showed that rAAV2/8-ACE2 injection increased HSC apoptosis.Moreover,rAAV2/8-ACE2 injection notably decreased the number of autophagosomes and the expression of autophagy-related proteins(LC3I,LC3II,Beclin-1),and affected the expression of AMPK pathway-related proteins(AMPK,p-AMPK,p-mTOR).CONCLUSION ACE2 overexpression can inhibit HSC activation and promote cell apoptosis by regulating HSC autophagy through the AMPK/mTOR pathway,thereby alleviating liver fibrosis and hepatic sinusoidal remodeling. 展开更多
关键词 angiotensin-converting enzyme 2 Hepatic stellate cells AUTOPHAGY Liver fibrosis Portal hypertension MICE
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Angiotensin-converting enzyme gene polymorphism and middle cerebral artery stenosis in a Chinese Han population
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作者 Chunshu Rong Yingqi Xing +4 位作者 Xinmei Jiang Juan Wang Baoshan Gao Jianjun Zhao Kangding Liu 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第15期1410-1417,共8页
The angiotensin-converting enzyme gene is a candidate gene of stroke. The present study involved 62 healthy volunteers and 148 patients with middle cerebral artery stenosis as confirmed by brain color ultrasound from ... The angiotensin-converting enzyme gene is a candidate gene of stroke. The present study involved 62 healthy volunteers and 148 patients with middle cerebral artery stenosis as confirmed by brain color ultrasound from a Han population in North China, and determined the peripheral blood angiotensin-converting enzyme genotype using PCR-restriction fragment length polymorphism analysis. The results showed that the frequencies of the DD genotype and D allele were increased in patients with middle cerebral artery stenosis, but the difference was not statistically significant compared with healthy controls. The findings of this study on the relationship between stroke genes and middle cerebral artery stenosis indicate no significant correlation between the frequencies of the DO genotype and D allele of angiotensin-converting enzyme and middle cerebral artery stenosis in this Han population from North China. In the future, studies will be carried out to investigate correlations between multiple stroke candidate gene synergy and middle cerebral artery stenosis to provide a foundation for the development of gene therapy. 展开更多
关键词 neural regeneration brain injury STROKE angiotensin-converting enzyme gene POLYMORPHISM middle cerebral artery angiostenosis North China Han population NEUROREgeneRATION
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Angiotensin-converting enzyme 2 connects COVID-19 with cancer and cancer immunotherapy
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作者 Xiao-Sheng Wang 《World Journal of Gastrointestinal Oncology》 SCIE 2021年第3期157-160,共4页
The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than two million deaths.Underlying diseases,including cancer,are high-risk facto... The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than two million deaths.Underlying diseases,including cancer,are high-risk factors for severe COVID-19 outcomes.Angiotensin-converting enzyme 2(ACE2),as a SARS-CoV-2 host cell receptor,plays a crucial role in SARS-CoV-2 invading human cells.ACE2 also has significant associations with cancer.Recent studies showed that ACE2 was inversely correlated with the activities of multiple oncogenic pathways and tumor progression phenotypes,and was positively correlated with antitumor immune response and survival prognosis in diverse cancers,suggesting a potential protective role of ACE2 in cancer progression.Positive expression of ACE2 is also correlated with programmed death-ligand 1(PD-L1)in cancer.The positive associations of ACE2 expression with antitumor immune signatures and PD-L1 expression indicate that ACE2 expression is a positive predictor for the response to immune checkpoint inhibitors(ICIs).This was evidenced in multiple cancer cohorts treated with ICIs.Thus,ACE2 may build potential connections between COVID-19 and cancer and cancer immunotherapy.The potential connections suggest that ACE2 inhibitors may not be a good option for treating COVID-19 patients with cancer,particularly in cancer patients who are receiving immunotherapy.Furthermore,the relationships between ACE2,COVID-19,and cancer are worth confirming by more experimental and clinical data,considering that many cancer patients are at high risk for COVID-19. 展开更多
关键词 angiotensin-converting enzyme 2 COVID-19 Cancer progression Antitumor immune responses Cancer immunotherapy
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New perspectives on angiotensin-converting enzyme 2 and its related diseases
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作者 Li-Ping Liu Xiao-Li Zhang Jian Li 《World Journal of Diabetes》 SCIE 2021年第6期839-854,共16页
Since the worldwide outbreak of coronavirus disease 2019,angiotensin-converting enzyme 2(ACE2)has received widespread attention as the cell receptor of the severe acute respiratory syndrome coronavirus 2 virus.At the ... Since the worldwide outbreak of coronavirus disease 2019,angiotensin-converting enzyme 2(ACE2)has received widespread attention as the cell receptor of the severe acute respiratory syndrome coronavirus 2 virus.At the same time,as a key enzyme in the renin-angiotensin-system,ACE2 is considered to be an endogenous negative regulator of vasoconstriction,proliferation,fibrosis,and proinflammation caused by the ACE-angiotensin II-angiotensin type 1 receptor axis.ACE2 is now implicated as being closely connected to diabetes,cardiovascular,kidney,and lung diseases,and so on.This review covers the available information on the host factors regulating ACE2 and discusses its role in a variety of pathophysiological conditions in animal models and humans. 展开更多
关键词 angiotensin-converting enzyme 2 COVID-19 SALT Renin-angiotensinsystem inhibitors Diabetes and cardiovascular disease Renal and lung disease
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AT1a Receptor Has Interacted with Angiotensin-converting Enzymes 2 mRNA Expression in Mouse Brainstem
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作者 林展翼 林曙光 《South China Journal of Cardiology》 CAS 2008年第2期71-75,共5页
Objectives To examine in vivo interactions between angiotensin Ⅱ (Ang Ⅱ ) AT1 a receptor (AT1 aR), angiotensin-converting enzymes (ACE) and ACE2 using small hairpin RNA (shRNA) gene-silencing methods in mice... Objectives To examine in vivo interactions between angiotensin Ⅱ (Ang Ⅱ ) AT1 a receptor (AT1 aR), angiotensin-converting enzymes (ACE) and ACE2 using small hairpin RNA (shRNA) gene-silencing methods in mice brainstem nucleus tractus solitarius (NTS). Methods C57BL mice (n = 8 ) were used as animal model. Method of micro-injection in the nucleus of NTS was adopted. After ten days, mice were killed and their brain tissue were fixed and sectioned. The expression levels of AT1 aR, ACE and ACE2 mRNA at both sides of NTS were examined by in situ hybridization. Based on compared t-test, the changing for mRNA expression was examined. Results After the expression of ATlaR mRNA was significantly inhibited (61.6% ± 6.8% ) by ATlaR-shRNA, it was associated with decreases in ACE2 mRNA expression from ( 1.05 ± 0. 12) μCi/mg to (0. 74 ± 0.09 ) μCi/mg ( 29.0% ± 14. 5% , P 〈 0. 01 ) on the same side of the brainstem. ACE mRNA expression was consistent at both sides ( 0. 50 μCi/mg ± 0. 09μCi/mg and 0. 53 μCi/mg ± 0. 08 μCi/mg), with insignificant difference ( P 〉 0. 05 ). Conclusions The gene silencing result showed that there were interactions between brainstem AT1 aR and ACE2. ACE mRNA expression was not altered by RNA interference treatment at AT1 aR. 展开更多
关键词 small hairpin RNA angiotensin-converting enzymes 2 BRAINSTEM MOUSE
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Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus 被引量:1
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作者 Ashwin Kumar Shukla Komal Awasthi +1 位作者 Kauser Usman Monisha Banerjee 《World Journal of Diabetes》 SCIE 2024年第4期606-622,共17页
Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus.It has affected over 768 million people worldwide,result... Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus.It has affected over 768 million people worldwide,resulting in approx-imately 6900000 deaths.High-risk groups,identified by the Centers for Disease Control and Prevention,include individuals with conditions like type 2 diabetes mellitus(T2DM),obesity,chronic lung disease,serious heart conditions,and chronic kidney disease.Research indicates that those with T2DM face a hei-ghtened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals.Examining the renin-angiotensin system(RAS),a vital regulator of blood pressure and pulmonary stability,reveals the significance of the angiotensin-converting enzyme(ACE)and ACE2 enzymes.ACE converts angiotensin-I to the vasoconstrictor angiotensin-II,while ACE2 counters this by converting angiotensin-II to angiotensin 1-7,a vasodilator.Reduced ACE2 exp-ression,common in diabetes,intensifies RAS activity,contributing to conditions like inflammation and fibrosis.Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels,concerns arise regarding the potential elevation of ACE2 receptors on cell membranes,potentially facilitating COVID-19 entry.This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome cor-onavirus 2 infection and associated complications in T2DM.Potential treatment strategies,including recombinant human ACE2 therapy,broad-spectrum antiviral drugs,and epigenetic signature detection,are discussed as promising avenues in the battle against this pandemic. 展开更多
关键词 angiotensin-converting enzyme 2 angiotensin-converting enzyme inhibitors Angiotensin-II receptor blockers Complex diseases COVID-19 Type 2 diabetes
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Serum angiotensin-converting enzyme level for evaluating significant fibrosis in chronic hepatitis B 被引量:7
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作者 Ryuichi Noguchi Kosuke Kaji +9 位作者 Tadashi Namisaki Kei Moriya Mitsuteru Kitade Kosuke Takeda Hideto Kawaratani Yasushi Okura Yosuke Aihara Masanori Furukawa Akira Mitoro Hitoshi Yoshiji 《World Journal of Gastroenterology》 SCIE CAS 2017年第36期6705-6714,共10页
AIM To evaluate the diagnostic performance of angiotensinconverting enzyme(ACE)on significant liver fibrosis in patients with chronic hepatitis B(CHB). METHODS In total,100 patients with CHB who underwent liver biopsy... AIM To evaluate the diagnostic performance of angiotensinconverting enzyme(ACE)on significant liver fibrosis in patients with chronic hepatitis B(CHB). METHODS In total,100 patients with CHB who underwent liver biopsy in our hospital were enrolled,and 70 patients except for 30 patients with hypertension,fatty liver or habitual alcoholic consumption were analyzed.We compared histological liver fibrosis and serum ACE levels and evaluated the predictive potential to diagnose significant liver fibrosis by comparison with several biochemical marker-based indexes such as the aspartate aminotransferase(AST)-to-platelet ratio index(APRI),the fibrosis index based on four factors(FIB-4),the Mac-2 binding protein glycosylation isomer(M2BPGi)level and the number of platelets(Plt). RESULTS Serum ACE levels showed moderately positive correlation with liver fibrotic stages(R2=0.181).Patients with significant,advanced fibrosis and cirrhosis(F2-4)had significantly higher serum ACE levels than those with early-stage fibrosis and cirrhosis(F0-1).For significant fibrosis(≥F2),the 12.8 U/L cut-off value of ACE showed 91.7%sensitivity and 75.0%specificity.The receiver-operating characteristic(ROC)curves analysis revealed that the area under the curve(AUC)value of ACE was 0.871,which was higher than that of APRI,FIB-4,M2BPGi and Plt. CONCLUSION The serum ACE level could be a novel noninvasive,easy,accurate,and inexpensive marker of significant fibrosis stage in patients with CHB. 展开更多
关键词 angiotensin-converting enzyme Hepatitis B virus Liver FIBROSIS Noninvasive FIBROSIS marker ASPARTATE aminotransferase-to-platelet ratio INDEX FIBROSIS INDEX based on four factors Mac-2 binding protein GLYCOSYLATION ISOMER
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Association of Angiotensin Converting Enzyme Gene I/D Polymorphism With Type 2 Diabetes Mellitus 被引量:1
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作者 MIN YANG CHANG-CHUN QIU +1 位作者 QUN XU HONG-DING XIANG 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2006年第4期323-327,共5页
Objective To investigate the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with type 2 diabetes mellitus (T2DM). Methods Two hundred and nine patients with T2DM di... Objective To investigate the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with type 2 diabetes mellitus (T2DM). Methods Two hundred and nine patients with T2DM diagnosed based on the criteria for diabetes mellitus in 1999 by WHO and 221 controls were recruited from general population of Dongcheng District in Beijing. All subjects were genotyped for the I/D polymorphism of ACE gene by PCR-fragment length polymorphism (FLP) assay. Blood pressure, levels of plasma glucose, lipids and serum insulin were determined. Body mass index (BMI), waist-trip ratio (WHR) and homeostasis model assessment-insulin resistance index (HOMA-IR) were calculated. Results The genotype frequencies for ACE genes DD, ID, and II were 19.1%, 42.1%, and 38.8% in patients, respectively, and 9.6%, 49.4%, and 41.0% in controls, respectively. The ACE DD genotype frequency was significantly higher in patients than in controls (χ^2=7.61, P=0.022). Multivariate logistic regression analysis showed that the ACE DD genotype was a risk factor for T2DM, with the OR of 2.35 (95% CI 1.17-4.71) adjusted for age, sex, BMI, WHR, blood pressure, and serum cholesterol levels. Conclusion The ACE DD genotype is associated with the increased susceptibility to type 2 diabetes mellitus. 展开更多
关键词 angiotensin-converting enzyme gene POLYMORPHISM Diabetes meUitus Risk factor geneTICS
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Angiotensin converting enzymes inhibitors or angiotensin receptor blockers should be continued in COVID-19 patients with hypertension 被引量:1
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作者 Ci Tian Nan Li +5 位作者 Yi Bai Han Xiao Shu Li Qing-Gang Ge Ning Shen Qing-Bian Ma 《World Journal of Clinical Cases》 SCIE 2021年第1期47-60,共14页
BACKGROUND Recent studies have revealed that sustained ingestion of angiotensin converting enzymes inhibitors or angiotensin receptor blockers(ACEIs/ARBs)had no harmful effects on coronavirus disease 2019(COVID-19)pat... BACKGROUND Recent studies have revealed that sustained ingestion of angiotensin converting enzymes inhibitors or angiotensin receptor blockers(ACEIs/ARBs)had no harmful effects on coronavirus disease 2019(COVID-19)patients complicated with hypertension.AIM To investigate the impact on COVID-19 patients complicated with hypertension who discontinued using ACEIs/ARBs.METHODS All COVID-19 patients complicated with hypertension admitted to our isolated unit were consecutively recruited in this study.Some patients switched from ACEIs/ARBs to calcium channel blocker(CCBs)after admission,while others continued using non-ACEIs/ARBs.We compared characteristics and clinical outcomes between these two groups of patients.RESULTS A total of 53 patients were enrolled,27 patients switched from ACEIs/ARBs to CCBs while 26 patients continued with non-ACEIs/ARBs.After controlling potential confounding factors using the Cox proportional hazards model,hospital stay was longer in patients who discontinued ACEIs/ARBs,with a hazard ratio of 0.424(95%confidence interval:0.187-0.962;P=0.040),upon discharge than patients using other anti-hypertensive drugs.A sub-group analysis showed that the effect of discontinuing use of ACEIs/ARBs was stronger in moderate cases[hazard ratio=0.224(95%confidence interval:0.005-0.998;P=0.0497)].CONCLUSION Patients in the discontinued ACEIs/ARBs group had longer hospital stays.Our findings suggest that COVID-19 patients complicated with hypertension should continue to use ACEIs/ARBs. 展开更多
关键词 COVID-19 HYPERTENSION Angiotensin converting enzymes inhibitors Angiotensin receptor blockers angiotensin-converting enzyme-2 PROGNOSIS
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Histopathological impact of SARS-CoV-2 on the liver:Cellular damage and long-term complications 被引量:1
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作者 Alfonso Rodriguez-Espada Moises Salgado-de la Mora +4 位作者 Briana Mariette Rodriguez-Paniagua Nathaly Limonde la Rosa Monica Itzel Martinez-Gutierrez Santiago Pastrana-Brandes Nalu Navarro-Alvarez 《World Journal of Gastroenterology》 SCIE CAS 2024年第22期2866-2880,共15页
Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute resp... Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome,multiple organ failure,and death.Despite extensive studies on the pathogenicity of SARS-CoV-2,its impact on the hepatobiliary system remains unclear.While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels,the exact source of this damage is not fully understood.Proposed mechanisms for injury include direct cytotoxicity,collateral damage from inflammation,drug-induced liver injury,and ischemia/hypoxia.However,evidence often relies on blood tests with liver enzyme abnormalities.In this comprehensive review,we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients,drawing from liver biopsies,complete autopsies,and in vitro liver analyses.We present evidence of the direct impact of SARS-CoV-2 on the liver,substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes,including mitochondrial swelling,endoplasmic reticulum dilatation,and hepatocyte apoptosis.Additional ly,we describe the diverse liver pathology observed during COVID-19 infection,encompassing necrosis,steatosis,cholestasis,and lobular inflammation.We also discuss the emergence of long-term complications,notably COVID-19-related secondary sclerosing cholangitis.Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making. 展开更多
关键词 LIVER SARS-CoV-2 COVID-19 angiotensin-converting enzyme 2 HISTOPATHOLOGY Liver biopsies Liver autopsy In vitro
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野酿2号毛葡萄果实发育进程中苹果酸代谢规律及相关基因表达分析
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作者 覃红梅 杨国顺 +2 位作者 梁晓文 罗飞雄 何建军 《南方农业学报》 CAS CSCD 北大核心 2024年第8期2332-2341,共10页
【目的】分析野酿2号毛葡萄果实发育进程中苹果酸代谢规律及相关基因表达情况,为提高野酿2号毛葡萄的酿造品质及优质葡萄酒生产提供参考依据。【方法】以5年生野酿2号毛葡萄为试验材料,于盛花后5~17周采集不同生长发育阶段果实,测定果... 【目的】分析野酿2号毛葡萄果实发育进程中苹果酸代谢规律及相关基因表达情况,为提高野酿2号毛葡萄的酿造品质及优质葡萄酒生产提供参考依据。【方法】以5年生野酿2号毛葡萄为试验材料,于盛花后5~17周采集不同生长发育阶段果实,测定果实单粒重、pH、可溶性固形物和可滴定酸含量,采用高效液相色谱法测定果实中苹果酸、柠檬酸和酒石酸含量;使用酶标仪测定苹果酸代谢关键酶[苹果酸脱氢酶(NAD-MDH)、NADP-苹果酸酶(NADP-ME)和磷酸烯醇式丙酮酸羧化酶(PEPC)]活性;采用实时荧光定量PCR检测苹果酸代谢相关基因PEPC、MDH和ME的相对表达量,并分析3个基因与苹果酸含量的相关性。【结果】野酿2号毛葡萄果实单粒重在转色期前增长较快,转色期的果实pH、可溶性固形物、苹果酸含量分别是盛花后5周的1.03、1.36和2.38倍,盛花后11周可滴定酸含量达峰值,为35.68 mg/g。盛花后5~17周,野酿2号毛葡萄果实中酒石酸和柠檬酸含量变化不明显,而苹果酸含量变化幅度较大。盛花后8周,NAD-MDH和NADP-ME活性最高,分别为736.06和453.50 nmol/(g·min),幼果期PEPC活性较高。转色期果实中MDH基因的相对表达量是盛花后5周的1.62倍,而PEPC和ME基因的相对表达量均低于盛花后5周。相关分析结果表明,苹果酸含量与MDH基因呈极显著正相关(P<0.01),与PEPC基因呈显著正相关(P<0.05,下同),与ME基因呈显著负相关。【结论】野酿2号毛葡萄苹果酸含量变化是影响总酸变化趋势的主要因素,转色期是苹果酸含量由积累到降低的转折期,苹果酸含量受相关基因MDH、PEPC和ME表达调控。 展开更多
关键词 野酿2号毛葡萄 果实不同发育阶段 苹果酸 酶活性 基因表达
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Angiotensin-converting enzyme 2 activation protects against pulmonary arterial hypertension through improving early endothelial function and mediating cytokines levels 被引量:24
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作者 LI Gang XU Yu-lin +4 位作者 LING Feng LIU Ai-jun WANG Dong WANG Qiang LIU Ying-long 《Chinese Medical Journal》 SCIE CAS CSCD 2012年第8期1381-1388,共8页
Background Increasing evidences indicate that an activated renin-angiotensin system (RAS) causes an imbalance between the vasoconstrictive and vasodilator mechanisms involving the pulmonary circulation leading to th... Background Increasing evidences indicate that an activated renin-angiotensin system (RAS) causes an imbalance between the vasoconstrictive and vasodilator mechanisms involving the pulmonary circulation leading to the development of pulmonary arterial hypertension (PAH). Angiotensin-converting enzyme 2 (ACE2), a primary component of the vasoprotective axis in RAS, is recently identified that it has regulatory actions in lung pathophysiology, but the mechanism in these processes is uncertain yet. Methods Severe PAH was induced by monocrotaline injection one week following pneumonectomy in rats. The activation of ACE2 by continuous injection of resorcinolnaphthalein was studied by real time-polymerase chain reaction (RT-PCR), Western blotting and fluorogenic peptide assay. Endothelial functions were evaluated by the response to acetylcholine and cytokines were measured by RT-PCR seven days after monocrotaline injection. The PAH-related hemodynamics and pathological changes were examined at day 21 when severe PAH was completely established. Results Resorcinolnaphthalein caused significant activation of ACE2 in both normal and diseased rats in 7 days after treatment. The pulmonary arterial pressure (PAP) started to increase at least 7 days after monocrotaline injection, and the rats developed severe PAH in 21 days with high PAP, right ventricular hypertrophy and neointimal formation. Treatment with resorcinolnaphthalein prevented these features. Resorcinolnaphthalein caused an improved endothelia-dependent vasorelaxation and decrease in proinflammatory cytokines (tumor necrosis factor (TNF)-a, monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6) and increase in anti-inflammatory cytokine IL-10 in the early stage of the pathogenesis. Conclusions These results demonstrated that activation of ACE2 by continuous injection of resorcinolnaphthalein prevented the development of PAH through improving early endothelial dysfunction and mediating the level of proinflammatory and anti-inflammatory cytokines. 展开更多
关键词 pulmonary hypertension angiotensin-converting enzyme 2 ENDOTHELIUM INFLAMMATION
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Angiotensin-converting enzyme 2(ACE2):SARS-CoV-2 receptor and RAS modulator 被引量:11
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作者 Jingwei Bian Zijian Li 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2021年第1期1-12,共12页
The coronavirus disease 2019(COVID-19)outbreak is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Angiotensin-converting enzyme 2(ACE2)was rapidly identified as the critical functional receptor f... The coronavirus disease 2019(COVID-19)outbreak is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Angiotensin-converting enzyme 2(ACE2)was rapidly identified as the critical functional receptor for SARS-CoV-2.ACE2 is well-known as a counter-regulator of the renin-angiotensin system(RAS)and plays a key role in the cardiovascular system.Given that ACE2 functions as both a SARS-CoV-2 receptor and a RAS modulator,the treatment for COVID-19 presents a dilemma of how to limit virus entry but protect ACE2 physiological functions.Thus,an in-depth summary of the recent progress of ACE2 research and its relationship to the virus is urgently needed to provide possible solution to the dilemma.Here,we summarize the complexity and interplay between the coronavirus,ACE2 and RAS(including anti-RAS drugs).We propose five novel working modes for functional receptor for SARS-CoV-2 infection and the routes of ACE2-mediated virus entering host cells,as well as its regulatory mechanism.For the controversy of anti-RAS drugs application,we also give theoretical analysis and discussed for drug application.These will contribute to a deeper understanding of the complex mechanisms of underlying the relationship between the virus and ACE2,and provide guidance for virus intervention strategies. 展开更多
关键词 SARS-CoV-2 angiotensin-converting enzyme 2 Renin-angiotensin system RECEPTOR MODULATOR COVID-19 Anti-RAS drug Drug target
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Single-cell analysis of angiotensin-converting enzyme II expression in human kidneys and bladders reveals a potential route of 2019 novel coronavirus infection 被引量:2
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作者 Wei Lin Jue Fan +14 位作者 Long-Fei Hu Yan Zhang Joshua DOoi Ting Meng Peng Jin Xiang Ding Long-Kai Peng Lei Song Rong Tang Zhou Xiao Xiang Ao Xiang-Cheng Xiao Qiao-Ling Zhou Ping Xiao Yong Zhong 《Chinese Medical Journal》 SCIE CAS CSCD 2021年第8期935-943,共9页
Background::Since 2019,a novel coronavirus named 2019 novel coronavirus(2019-nCoV)has emerged worldwide.Apart from fever and respiratory complications,acute kidney injury has been observed in a few patients with coron... Background::Since 2019,a novel coronavirus named 2019 novel coronavirus(2019-nCoV)has emerged worldwide.Apart from fever and respiratory complications,acute kidney injury has been observed in a few patients with coronavirus disease 2019.Furthermore,according to recent findings,the virus has been detected in urine.Angiotensin-converting enzyme II(ACE2)has been proposed to serve as the receptor for the entry of 2019-nCoV,which is the same as that for the severe acute respiratory syndrome.This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system.Methods::We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders.The Pearson correlation coefficients between ACE2 and all other genes were first generated.Then,genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2.Results::Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule(PT)cells of the kidney.ACE2 expression was found in 5.12%,5.80%,and 14.38%of the proximal convoluted tubule cells,PT cells,and proximal straight tubule cells,respectively,in three published kidney cell atlas datasets.In addition,ACE2 expression was also confirmed in 12.05%,6.80%,and 10.20%of cells of the proximal convoluted tubule,PT,and proximal straight tubule,respectively,in our own two healthy kidney samples.For the analysis of public data from three bladder samples,ACE2 expression was low but detectable in bladder epithelial cells.Only 0.25%and 1.28%of intermediate cells and umbrella cells,respectively,had ACE2 expression.Conclusion::This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system. 展开更多
关键词 2019-nCoV Acute kidney injury angiotensin-converting enzyme 2 BLADDER COVID-19 KIDNEY RNA sequence analysis Single-cell analysis
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