The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has triggered a widespread outbreak since December 2019.The SARS-CoV-2 infection-related illness has been dubbed the coronavirus disease 2019(COVID-19)by ...The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has triggered a widespread outbreak since December 2019.The SARS-CoV-2 infection-related illness has been dubbed the coronavirus disease 2019(COVID-19)by the World Health Organization.Asymptomatic and subclinical infections,a severe hyperinflammatory state,and mortality are all examples of clinical signs.After attaching to the angiotensin converting enzyme 2(ACE2)receptor,the SARSCoV-2 virus can enter cells through membrane fusion and endocytosis.In addition to enabling viruses to cling to target cells,the connection between the spike protein(S-protein)of SARS-CoV-2 and ACE2 may potentially impair the functionality of ACE2.Blood pressure is controlled by ACE2,which catalyzes the hydrolysis of the active vasoconstrictor octapeptide angiotensin(Ang)II to the heptapeptide Ang-(1-7)and free L-Phe.Additionally,Ang I can be broken down by ACE2 into Ang-(1-9)and metabolized into Ang-(1-7).Numerous studies have demonstrated that circulating ACE2(cACE2)and Ang-(1-7)have the ability to restore myocardial damage in a variety of cardiovascular diseases and have antiinflammatory,antioxidant,anti-apoptotic,and anti-cardiomyocyte fibrosis actions.There have been some suggestions for raising ACE2 expression in COVID-19 patients,which might be used as a target for the creation of novel treatment therapies.With regard to this,SARS-CoV-2 is neutralized by soluble recombinant human ACE2(hrsACE2),which binds the viral S-protein and reduces damage to a variety of organs,including the heart,kidneys,and lungs,by lowering Ang II concentrations and enhancing conversion to Ang-(1-7).This review aims to investigate how the presence of SARS-CoV-2 and cACE2 are related.Additionally,there will be discussion of a number of potential therapeutic approaches to tip the ACE/ACE-2 balance in favor of the ACE-2/Ang-(1-7)axis.展开更多
Extracellular vesicles(EVs)are membranous vesicular structures released from almost all eukaryotic cell types under different physiological or pathological conditions.Growing evidence demonstrates that EVs can serve a...Extracellular vesicles(EVs)are membranous vesicular structures released from almost all eukaryotic cell types under different physiological or pathological conditions.Growing evidence demonstrates that EVs can serve as mediators of intercellular communication between donor and recipient cells or microorganism-infected and noninfected cells.Coronavirus disease 2019(COVID-19)disease is caused by infection of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)of host cells in the respiratory system and various extra-pulmonary tissue/organs,resulting in complications of multiple organ systems.As the cell surface receptor,angiotensin-converting enzyme 2(ACE2)mediates cellular entry of SARS-CoV-2 into the host cells in patients with COVID-19.Recent studies have found that ACE2 can be released with EVs,which have been shown to interfere with the entry of the virus into host cells and thus may be involved in COVID-19 pathophysiology.In addition,ACE2,neprilysin(NEP),and thimet oligopeptidase(TOP)are the key enzymes that regulate angiotensin metabolism by converting angiotensin II or angiotensin I to angiotensin 1-7,the latter of which has protective effects in counterbalancing the harmful effects of angiotensin II in COVID-19 disease.This review summarizes the recent research progress regarding EV-associated ACE2,NEP,and TOP and the perspectives of their potential involvement in the pathophysiology of COVID-19 disease.展开更多
The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the virus responsible for coronavirus disease 2019(COVID-19),enters affected cells through the angiotensin-converting enzyme 2(ACE2)receptor,which is hig...The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the virus responsible for coronavirus disease 2019(COVID-19),enters affected cells through the angiotensin-converting enzyme 2(ACE2)receptor,which is highly expressed in type II alveolar cells,enterocytes,and cholangiocytes.SARS-CoV-2 infection causes fever,dry cough,and breathing difficulty,which can progress to respiratory distress due to interstitial pneumonia,and hepatobiliary injury due to COVID-19 is increasingly recognized.The hepatobiliary injury may be evident at presentation of the disease or develop during the disease progression.The development of more severe clinical outcomes in patients with chronic liver diseases(CLD)with or without cirrhosis infected with SARS-CoV-2 has not been elucidated.Moreover,there is limited data related to common medications that affect the disease severity of COVID-19 patients.Additionally,ACE2 receptor expression of hepatobiliary tissue related to the disease severity also have not been clarified.This review summarized the current situation regarding the clinical outcomes of COVID-19 patients with chronic liver diseases who were treated with common medications.Furthermore,the association between ACE2 receptor expression and disease severity in these patients is discussed.展开更多
The emergence of coronavirus disease-2019 induced by a newly identified bcoronavirus, namely severe acute respiratory syndrome coronavirus 2(SARSCoV-2) has constituted a public health emergency. Even though it was con...The emergence of coronavirus disease-2019 induced by a newly identified bcoronavirus, namely severe acute respiratory syndrome coronavirus 2(SARSCoV-2) has constituted a public health emergency. Even though it was considered a zoonotic disease, the virus has also spread among humans via respiratory secretions. The expression and distribution of angiotensin converting enzyme type 2(ACE2) in various human organs might also show other possible infection routes. High ACE2 ribonucleic acid expression has been identified in the gastrointestinal tract(GI) indicating its importance as a possible infection pathway of SARS-CoV-2. ACE2 induces viral entry into the host and most importantly has been found to be associated with the function of the gut. Its deficiency has been implicated in several pathologies such as colorectal inflammation. The renin-angiotensin system(RAS) is an essential regulatory cascade operating both at a local tissue level and at the systemic or circulatory level. The RAS may be important in the pathogenesis of chronic liver disease and is associated with the up-regulation of ACE2. Thus, the aim of this review is firstly, the analysis of some important general and genome characteristics of SARS-CoV-2 and secondly, and most importantly, to focus on the utility of ACE2 receptors in both SARS-CoV-2 replication and pathogenesis, especially in the GI tract.展开更多
Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)seems to employ two routes of entrance to the host cell;via membrane fusion(with the cells expressing both angiotensin converting enzyme 2(ACE2)and transmembr...Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)seems to employ two routes of entrance to the host cell;via membrane fusion(with the cells expressing both angiotensin converting enzyme 2(ACE2)and transmembrane peptidase/serine subfamily member 2/4(TMPRSS2/4))or via receptor-mediated endocytosis(to the target cells expressing only ACE2).The second mode is associated with cysteine cathepsins(probably cathepsin L)involvement in the virus spike protein(S protein)proteolytic activation.Also furin might activate the virus S protein enabling it to enter cells.Gastrointestinal tract(GIT)involvement in SARS-CoV-2 infection is evident in a subset of coronavirus disease 2019(COVID-19)patients exhibiting GIT symptoms,such as diarrhea,and presenting viral-shedding in feces.Considering the abundance and co-localization of ACE2 and TMPRSS2 in the lower GIT(especially brush-border enterocytes),these two receptors seem to be mainly involved in SARS-CoV-2 invasion of the digestive tract.Additionally,in vitro studies have demonstrated the virions capability of infection and replication in the human epithelial cells lining GIT.However,also furin and cysteine cathepsins(cathepsin L)might participate in the activation of SARS-CoV-2 spike protein contributing to the virus invasiveness within GIT.Moreover,cathepsin L(due to its involvement in extracellular matrix components degradation and remodeling,the processes enhanced during SARS-CoV-2-induced inflammation)might be responsible for the dysregulation of absorption/digestion functions of GIT,thus adding to the observed in some COVID-19 patients symptoms such as diarrhea.展开更多
The renin-angiotensin system(RAS) regulates blood pressure(BP) homeostasis, systemic fluid volume and electrolyte balance. The RAS cascade includes over twenty peptidases, close to twenty angiotensin peptides and at l...The renin-angiotensin system(RAS) regulates blood pressure(BP) homeostasis, systemic fluid volume and electrolyte balance. The RAS cascade includes over twenty peptidases, close to twenty angiotensin peptides and at least six receptors. Out of these, angiotensin Ⅱ, angiotensin converting enzyme 1 and angiotensin Ⅱ type 1 receptor(AngⅡ-ACE1-AT1R) together with angiotensin(1-7), angiotensin converting enzyme 2 and Mas receptor(Ang(1-7)-ACE2-Mas R) are regarded as the main components of RAS. In addition to circulating RAS, local RA-system exists in various organs. Local RA-systems are regarded as tissue-specific regulatory system accounting for local effects and long term changes in different organs. Many of the central components such as the two main axes of RAS: AngⅡ-ACE1-AT1 R and Ang(1-7)-ACE2-Mas R, have been identified in the human eye. Furthermore, it has been shown that systemic antihypertensive RAS- inhibiting medications lower intraocular pressure(IOP). These findings suggest the crucial role of RAS not only in the regulation of BP but also in the regulation of IOP, and RAS potentially plays a role in the development of glaucoma and antiglaucomatous drugs.展开更多
People across the world are affected by the"coronavirus disease 2019(COVID-19)",brought on by the"SARS-CoV type-2 coronavirus".Due to its high incidence in individuals with diabetes,metabolic syndr...People across the world are affected by the"coronavirus disease 2019(COVID-19)",brought on by the"SARS-CoV type-2 coronavirus".Due to its high incidence in individuals with diabetes,metabolic syndrome,and metabolic-associated fatty liver disease(MAFLD),COVID-19 has gained much attention.The metabolic syndrome's hepatic manifestation,MAFLD,carries a significant risk of type-2-diabetes.The link between the above two conditions has also drawn increasing consideration since MAFLD is intricately linked to the obesity epidemic.Independent of the metabolic syndrome,MAFLD may impact the severity of the viral infections,including COVID-19 or may even be a risk factor.An important question is whether the present COVID-19 pandemic has been fueled by the obesity and MAFLD epidemics.Many liver markers are seen elevated in COVID-19.MAFLD patients with associated comorbid conditions like obesity,cardiovascular disease,renal disease,malignancy,hypertension,and old age are prone to develop severe disease.There is an urgent need for more studies to determine the link between the two conditions and whether it might account for racial differences in the mortality and morbidity rates linked to COVID-19.The role of innate and adaptive immunity alterations in MAFLD patients may influence the severity of COVID-19.This review investigates the implications of COVID-19 on liver injury and disease severity and viceversa.We also addressed the severity of COVID-19 in patients with prior MAFLD and its potential implications and therapeutic administration in the clinical setting.展开更多
Gastrointestinal(GI)symptoms,such as diarrhea,abdominal pain,vomiting,and anorexia,are frequently observed in patients with coronavirus disease 2019(COVID-19).However,the pathophysiological mechanisms connecting these...Gastrointestinal(GI)symptoms,such as diarrhea,abdominal pain,vomiting,and anorexia,are frequently observed in patients with coronavirus disease 2019(COVID-19).However,the pathophysiological mechanisms connecting these GI symptoms to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections remain elusive.Previous studies indicate that the entry of SARS-CoV-2 into intestinal cells leads to downregulation of angiotensin converting enzyme 2(ACE2)receptors resulting in impaired barrier function.While intestinal ACE2 functions as a chaperone for the amino acid transporter B0AT1,the B0AT1/ACE2 complex within the intestinal epithelium acts as a regulator of gut microbiota composition and function.Alternations to the B0AT1/ACE2 complex lead to microbial dysbiosis through increased local and systemic immune responses.Previous studies have also suggested that altered serotonin metabolism may be the underlying cause of GI disorders involving diarrhea.The findings of elevated plasma serotonin levels and high fecal calprotectin in COVID-19 patients with diarrhea indicate that the viral infection evokes a systemic inflammatory response that specifically involves the GI.Interestingly,the elevated proinflammatory cytokines correlate with elevated serotonin and fecal calprotectin levels further supporting the evidence of GI inflammation,a hallmark of functional GI disorders.Moreover,the finding that rectal swabs of COVID-19 patients remain positive for SARS-CoV-2 even after the nasopharynx clears the virus,suggests that viral replication and shedding from the GI tract may be more robust than that of the respiratory tract,further indicating fecal-oral transmission as another important route of viral spread.This review summarized the evidence for pathophysiological mechanisms(impaired barrier function,gut inflammation,altered serotonin metabolism and gut microbiota dysbiosis)underlying the GI symptoms in patients with COVID-19.展开更多
The novel coronavirus,severe acute respiratory syndrome-corona virus-2(SARSCoV-2),is a topic of great interest currently in the medical field due to the significant morbidity and mortality associated with it.There is ...The novel coronavirus,severe acute respiratory syndrome-corona virus-2(SARSCoV-2),is a topic of great interest currently in the medical field due to the significant morbidity and mortality associated with it.There is immense curiosity about this virus as knowledge about it is limited from pathogenesis,host related factors and the variable effect it has on different patient populations.Though it has claimed fame due to its ability to compromise the respiratory system,it possess the capability to infect other organs as well including the liver.It is important for clinicians to recognize that the virus can result in multi-organ dysfunction as well.Presentation with gastrointestinal symptoms and involvement of the liver can be subtle and can be misdiagnosed.Those with preexisting liver disease may be more susceptible as well as those who are immunosuppressed or have other co-morbidities.This review article provides a brief overview of some of the information that is available so far with regards to how the liver is impacted by the coronavirus.展开更多
From December 31st,2019,a novel highly pathogenic coronavirus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread worldwide,reaching at present the dimension of a pandemic.In addition to damaging th...From December 31st,2019,a novel highly pathogenic coronavirus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread worldwide,reaching at present the dimension of a pandemic.In addition to damaging the lungs,SARS-CoV-2 may also damage the heart and this is corroborated by the evidence that cardiovascular comorbidities are associated with a higher mortality and poor clinical outcomes in patient infected by the virus.During the infection myocardial injury,myocarditis and arrhythmias have also been reported,but the pathophysiological mechanisms of these complications are yet to be understood.Great attention is also being posed on the potential beneficial/harmful role of angiotensin converting enzyme(ACE)inhibitors,as far as the virus binds to ACE2 to infect cells,but evidences lack.Furthermore,SARS-CoV-2 can also affect the aspect of acute coronary syndromes,not only because these two distinct pathological entities share pathogenic aspects(such as the systemic inflammatory state and cytokine release),but also and above all for the consequences that the need to contain the infection has on the management of cardiological urgencies.The aim of this review was therefore to summarize the relationship between the virus and the cardiovascular system.展开更多
The recent COVID-19 pandemic poses a global health emergency.Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor-human angiotensin converting enzyme 2(A...The recent COVID-19 pandemic poses a global health emergency.Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor-human angiotensin converting enzyme 2(ACE2).Here,by using lentivirus based pseudotypes bearing spike protein,we demonstrated that entry of SARS-CoV-2 into host cells was dependent on clathrin-mediated endocytosis,and phosphoinositides played essential roles during this process.In addition,we showed that the intracellular domain and the catalytic activity of ACE2 were not required for efficient virus entry.Finally,we showed that the current predominant Delta variant,although with high infectivity and high syncytium formation,also entered cells through clathrin-mediated endocytosis.These results provide new insights into SARS-CoV-2 cellular entry and present proof of principle that targeting viral entry could be an effective way to treat different variant infections.展开更多
Alzheimer’s disease(AD)has emerged as a key comorbidity of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).The morbidity and mortality of COVID-19 are elevated ...Alzheimer’s disease(AD)has emerged as a key comorbidity of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).The morbidity and mortality of COVID-19 are elevated in AD due to multiple pathological changes in AD patients such as the excessive expression of viral receptor angiotensin converting enzyme 2 and pro-inflammatory molecules,various AD complications including diabetes,lifestyle alterations in AD,and drug-drug interactions.Meanwhile,COVID-19 has also been reported to cause various neurologic symptoms including cognitive impairment that may ultimately result in AD,probably through the invasion of SARS-CoV-2 into the central nervous system,COVID-19-induced inflammation,long-term hospitalization and delirium,and post-COVID-19 syndrome.In addition,the COVID-19 crisis also worsens behavioral symptoms in uninfected AD patients and poses new challenges for AD prevention.In this review,we first introduce the symptoms and pathogenesis of COVID-19 and AD.Next,we provide a comprehensive discussion on the aggravating effects of AD on COVID-19 and the underlying mechanisms from molecular to social levels.We also highlight the influence of COVID-19 on cognitive function,and propose possible routes of viral invasion into the brain and potential mechanisms underlying the COVID-19-induced cognitive impairment.Last,we summarize the negative impacts of COVID-19 pandemic on uninfected AD patients and dementia prevention.展开更多
文摘The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has triggered a widespread outbreak since December 2019.The SARS-CoV-2 infection-related illness has been dubbed the coronavirus disease 2019(COVID-19)by the World Health Organization.Asymptomatic and subclinical infections,a severe hyperinflammatory state,and mortality are all examples of clinical signs.After attaching to the angiotensin converting enzyme 2(ACE2)receptor,the SARSCoV-2 virus can enter cells through membrane fusion and endocytosis.In addition to enabling viruses to cling to target cells,the connection between the spike protein(S-protein)of SARS-CoV-2 and ACE2 may potentially impair the functionality of ACE2.Blood pressure is controlled by ACE2,which catalyzes the hydrolysis of the active vasoconstrictor octapeptide angiotensin(Ang)II to the heptapeptide Ang-(1-7)and free L-Phe.Additionally,Ang I can be broken down by ACE2 into Ang-(1-9)and metabolized into Ang-(1-7).Numerous studies have demonstrated that circulating ACE2(cACE2)and Ang-(1-7)have the ability to restore myocardial damage in a variety of cardiovascular diseases and have antiinflammatory,antioxidant,anti-apoptotic,and anti-cardiomyocyte fibrosis actions.There have been some suggestions for raising ACE2 expression in COVID-19 patients,which might be used as a target for the creation of novel treatment therapies.With regard to this,SARS-CoV-2 is neutralized by soluble recombinant human ACE2(hrsACE2),which binds the viral S-protein and reduces damage to a variety of organs,including the heart,kidneys,and lungs,by lowering Ang II concentrations and enhancing conversion to Ang-(1-7).This review aims to investigate how the presence of SARS-CoV-2 and cACE2 are related.Additionally,there will be discussion of a number of potential therapeutic approaches to tip the ACE/ACE-2 balance in favor of the ACE-2/Ang-(1-7)axis.
文摘Extracellular vesicles(EVs)are membranous vesicular structures released from almost all eukaryotic cell types under different physiological or pathological conditions.Growing evidence demonstrates that EVs can serve as mediators of intercellular communication between donor and recipient cells or microorganism-infected and noninfected cells.Coronavirus disease 2019(COVID-19)disease is caused by infection of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)of host cells in the respiratory system and various extra-pulmonary tissue/organs,resulting in complications of multiple organ systems.As the cell surface receptor,angiotensin-converting enzyme 2(ACE2)mediates cellular entry of SARS-CoV-2 into the host cells in patients with COVID-19.Recent studies have found that ACE2 can be released with EVs,which have been shown to interfere with the entry of the virus into host cells and thus may be involved in COVID-19 pathophysiology.In addition,ACE2,neprilysin(NEP),and thimet oligopeptidase(TOP)are the key enzymes that regulate angiotensin metabolism by converting angiotensin II or angiotensin I to angiotensin 1-7,the latter of which has protective effects in counterbalancing the harmful effects of angiotensin II in COVID-19 disease.This review summarizes the recent research progress regarding EV-associated ACE2,NEP,and TOP and the perspectives of their potential involvement in the pathophysiology of COVID-19 disease.
文摘The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the virus responsible for coronavirus disease 2019(COVID-19),enters affected cells through the angiotensin-converting enzyme 2(ACE2)receptor,which is highly expressed in type II alveolar cells,enterocytes,and cholangiocytes.SARS-CoV-2 infection causes fever,dry cough,and breathing difficulty,which can progress to respiratory distress due to interstitial pneumonia,and hepatobiliary injury due to COVID-19 is increasingly recognized.The hepatobiliary injury may be evident at presentation of the disease or develop during the disease progression.The development of more severe clinical outcomes in patients with chronic liver diseases(CLD)with or without cirrhosis infected with SARS-CoV-2 has not been elucidated.Moreover,there is limited data related to common medications that affect the disease severity of COVID-19 patients.Additionally,ACE2 receptor expression of hepatobiliary tissue related to the disease severity also have not been clarified.This review summarized the current situation regarding the clinical outcomes of COVID-19 patients with chronic liver diseases who were treated with common medications.Furthermore,the association between ACE2 receptor expression and disease severity in these patients is discussed.
文摘The emergence of coronavirus disease-2019 induced by a newly identified bcoronavirus, namely severe acute respiratory syndrome coronavirus 2(SARSCoV-2) has constituted a public health emergency. Even though it was considered a zoonotic disease, the virus has also spread among humans via respiratory secretions. The expression and distribution of angiotensin converting enzyme type 2(ACE2) in various human organs might also show other possible infection routes. High ACE2 ribonucleic acid expression has been identified in the gastrointestinal tract(GI) indicating its importance as a possible infection pathway of SARS-CoV-2. ACE2 induces viral entry into the host and most importantly has been found to be associated with the function of the gut. Its deficiency has been implicated in several pathologies such as colorectal inflammation. The renin-angiotensin system(RAS) is an essential regulatory cascade operating both at a local tissue level and at the systemic or circulatory level. The RAS may be important in the pathogenesis of chronic liver disease and is associated with the up-regulation of ACE2. Thus, the aim of this review is firstly, the analysis of some important general and genome characteristics of SARS-CoV-2 and secondly, and most importantly, to focus on the utility of ACE2 receptors in both SARS-CoV-2 replication and pathogenesis, especially in the GI tract.
文摘Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)seems to employ two routes of entrance to the host cell;via membrane fusion(with the cells expressing both angiotensin converting enzyme 2(ACE2)and transmembrane peptidase/serine subfamily member 2/4(TMPRSS2/4))or via receptor-mediated endocytosis(to the target cells expressing only ACE2).The second mode is associated with cysteine cathepsins(probably cathepsin L)involvement in the virus spike protein(S protein)proteolytic activation.Also furin might activate the virus S protein enabling it to enter cells.Gastrointestinal tract(GIT)involvement in SARS-CoV-2 infection is evident in a subset of coronavirus disease 2019(COVID-19)patients exhibiting GIT symptoms,such as diarrhea,and presenting viral-shedding in feces.Considering the abundance and co-localization of ACE2 and TMPRSS2 in the lower GIT(especially brush-border enterocytes),these two receptors seem to be mainly involved in SARS-CoV-2 invasion of the digestive tract.Additionally,in vitro studies have demonstrated the virions capability of infection and replication in the human epithelial cells lining GIT.However,also furin and cysteine cathepsins(cathepsin L)might participate in the activation of SARS-CoV-2 spike protein contributing to the virus invasiveness within GIT.Moreover,cathepsin L(due to its involvement in extracellular matrix components degradation and remodeling,the processes enhanced during SARS-CoV-2-induced inflammation)might be responsible for the dysregulation of absorption/digestion functions of GIT,thus adding to the observed in some COVID-19 patients symptoms such as diarrhea.
基金Supported by Päivikki and Sakari Sohlberg Foundationthe Eye Foundation+2 种基金the Glaucoma Research Foundation Luxthe Competitive Research Funding of Tampere University Hospital,No.9S072and the Foundation for Clinical Chemistry Research.
文摘The renin-angiotensin system(RAS) regulates blood pressure(BP) homeostasis, systemic fluid volume and electrolyte balance. The RAS cascade includes over twenty peptidases, close to twenty angiotensin peptides and at least six receptors. Out of these, angiotensin Ⅱ, angiotensin converting enzyme 1 and angiotensin Ⅱ type 1 receptor(AngⅡ-ACE1-AT1R) together with angiotensin(1-7), angiotensin converting enzyme 2 and Mas receptor(Ang(1-7)-ACE2-Mas R) are regarded as the main components of RAS. In addition to circulating RAS, local RA-system exists in various organs. Local RA-systems are regarded as tissue-specific regulatory system accounting for local effects and long term changes in different organs. Many of the central components such as the two main axes of RAS: AngⅡ-ACE1-AT1 R and Ang(1-7)-ACE2-Mas R, have been identified in the human eye. Furthermore, it has been shown that systemic antihypertensive RAS- inhibiting medications lower intraocular pressure(IOP). These findings suggest the crucial role of RAS not only in the regulation of BP but also in the regulation of IOP, and RAS potentially plays a role in the development of glaucoma and antiglaucomatous drugs.
文摘People across the world are affected by the"coronavirus disease 2019(COVID-19)",brought on by the"SARS-CoV type-2 coronavirus".Due to its high incidence in individuals with diabetes,metabolic syndrome,and metabolic-associated fatty liver disease(MAFLD),COVID-19 has gained much attention.The metabolic syndrome's hepatic manifestation,MAFLD,carries a significant risk of type-2-diabetes.The link between the above two conditions has also drawn increasing consideration since MAFLD is intricately linked to the obesity epidemic.Independent of the metabolic syndrome,MAFLD may impact the severity of the viral infections,including COVID-19 or may even be a risk factor.An important question is whether the present COVID-19 pandemic has been fueled by the obesity and MAFLD epidemics.Many liver markers are seen elevated in COVID-19.MAFLD patients with associated comorbid conditions like obesity,cardiovascular disease,renal disease,malignancy,hypertension,and old age are prone to develop severe disease.There is an urgent need for more studies to determine the link between the two conditions and whether it might account for racial differences in the mortality and morbidity rates linked to COVID-19.The role of innate and adaptive immunity alterations in MAFLD patients may influence the severity of COVID-19.This review investigates the implications of COVID-19 on liver injury and disease severity and viceversa.We also addressed the severity of COVID-19 in patients with prior MAFLD and its potential implications and therapeutic administration in the clinical setting.
文摘Gastrointestinal(GI)symptoms,such as diarrhea,abdominal pain,vomiting,and anorexia,are frequently observed in patients with coronavirus disease 2019(COVID-19).However,the pathophysiological mechanisms connecting these GI symptoms to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections remain elusive.Previous studies indicate that the entry of SARS-CoV-2 into intestinal cells leads to downregulation of angiotensin converting enzyme 2(ACE2)receptors resulting in impaired barrier function.While intestinal ACE2 functions as a chaperone for the amino acid transporter B0AT1,the B0AT1/ACE2 complex within the intestinal epithelium acts as a regulator of gut microbiota composition and function.Alternations to the B0AT1/ACE2 complex lead to microbial dysbiosis through increased local and systemic immune responses.Previous studies have also suggested that altered serotonin metabolism may be the underlying cause of GI disorders involving diarrhea.The findings of elevated plasma serotonin levels and high fecal calprotectin in COVID-19 patients with diarrhea indicate that the viral infection evokes a systemic inflammatory response that specifically involves the GI.Interestingly,the elevated proinflammatory cytokines correlate with elevated serotonin and fecal calprotectin levels further supporting the evidence of GI inflammation,a hallmark of functional GI disorders.Moreover,the finding that rectal swabs of COVID-19 patients remain positive for SARS-CoV-2 even after the nasopharynx clears the virus,suggests that viral replication and shedding from the GI tract may be more robust than that of the respiratory tract,further indicating fecal-oral transmission as another important route of viral spread.This review summarized the evidence for pathophysiological mechanisms(impaired barrier function,gut inflammation,altered serotonin metabolism and gut microbiota dysbiosis)underlying the GI symptoms in patients with COVID-19.
文摘The novel coronavirus,severe acute respiratory syndrome-corona virus-2(SARSCoV-2),is a topic of great interest currently in the medical field due to the significant morbidity and mortality associated with it.There is immense curiosity about this virus as knowledge about it is limited from pathogenesis,host related factors and the variable effect it has on different patient populations.Though it has claimed fame due to its ability to compromise the respiratory system,it possess the capability to infect other organs as well including the liver.It is important for clinicians to recognize that the virus can result in multi-organ dysfunction as well.Presentation with gastrointestinal symptoms and involvement of the liver can be subtle and can be misdiagnosed.Those with preexisting liver disease may be more susceptible as well as those who are immunosuppressed or have other co-morbidities.This review article provides a brief overview of some of the information that is available so far with regards to how the liver is impacted by the coronavirus.
文摘From December 31st,2019,a novel highly pathogenic coronavirus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread worldwide,reaching at present the dimension of a pandemic.In addition to damaging the lungs,SARS-CoV-2 may also damage the heart and this is corroborated by the evidence that cardiovascular comorbidities are associated with a higher mortality and poor clinical outcomes in patient infected by the virus.During the infection myocardial injury,myocarditis and arrhythmias have also been reported,but the pathophysiological mechanisms of these complications are yet to be understood.Great attention is also being posed on the potential beneficial/harmful role of angiotensin converting enzyme(ACE)inhibitors,as far as the virus binds to ACE2 to infect cells,but evidences lack.Furthermore,SARS-CoV-2 can also affect the aspect of acute coronary syndromes,not only because these two distinct pathological entities share pathogenic aspects(such as the systemic inflammatory state and cytokine release),but also and above all for the consequences that the need to contain the infection has on the management of cardiological urgencies.The aim of this review was therefore to summarize the relationship between the virus and the cardiovascular system.
基金supported by the National Natural Science Foundation of China(81871662,82150201)Xi’an Jiaotong University Fund(xzy012019066 and xzy032020037)Xi’an Jiaotong University Health Science Center-Qinnong Bank Fund(QNXJTU-04&QNXJTU-07)。
文摘The recent COVID-19 pandemic poses a global health emergency.Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor-human angiotensin converting enzyme 2(ACE2).Here,by using lentivirus based pseudotypes bearing spike protein,we demonstrated that entry of SARS-CoV-2 into host cells was dependent on clathrin-mediated endocytosis,and phosphoinositides played essential roles during this process.In addition,we showed that the intracellular domain and the catalytic activity of ACE2 were not required for efficient virus entry.Finally,we showed that the current predominant Delta variant,although with high infectivity and high syncytium formation,also entered cells through clathrin-mediated endocytosis.These results provide new insights into SARS-CoV-2 cellular entry and present proof of principle that targeting viral entry could be an effective way to treat different variant infections.
基金This review was supported in part by research grants from the National Natural Science Foundation of China(No.91949204 and No.81830037 to J.Z.,No.81971145 and No.81901333 to X.X.,No.81801063 to Y.W.)Shanghai Sailing Program(No.19YF1451700 to X.X.)+1 种基金Clinical Research Fund from Shanghai Municipal Health Commission(No.20204Y0031 to Y.W.)Shanghai Blue Cross Brain Hospital Co.,Ltd.,and Shanghai Tongji University Education Development Foundation(No.000000381/2018108 to J.Z.).
文摘Alzheimer’s disease(AD)has emerged as a key comorbidity of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).The morbidity and mortality of COVID-19 are elevated in AD due to multiple pathological changes in AD patients such as the excessive expression of viral receptor angiotensin converting enzyme 2 and pro-inflammatory molecules,various AD complications including diabetes,lifestyle alterations in AD,and drug-drug interactions.Meanwhile,COVID-19 has also been reported to cause various neurologic symptoms including cognitive impairment that may ultimately result in AD,probably through the invasion of SARS-CoV-2 into the central nervous system,COVID-19-induced inflammation,long-term hospitalization and delirium,and post-COVID-19 syndrome.In addition,the COVID-19 crisis also worsens behavioral symptoms in uninfected AD patients and poses new challenges for AD prevention.In this review,we first introduce the symptoms and pathogenesis of COVID-19 and AD.Next,we provide a comprehensive discussion on the aggravating effects of AD on COVID-19 and the underlying mechanisms from molecular to social levels.We also highlight the influence of COVID-19 on cognitive function,and propose possible routes of viral invasion into the brain and potential mechanisms underlying the COVID-19-induced cognitive impairment.Last,we summarize the negative impacts of COVID-19 pandemic on uninfected AD patients and dementia prevention.
