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
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
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
Objective:To seek potential Chinese herbal medicine(CHM)for the treatment of coronavirus disease 2019(COVID-19)through the molecular docking of the medicine with SARS-CoV-23 CL hydrolytic enzyme and the angiotensin co...Objective:To seek potential Chinese herbal medicine(CHM)for the treatment of coronavirus disease 2019(COVID-19)through the molecular docking of the medicine with SARS-CoV-23 CL hydrolytic enzyme and the angiotensin converting enzymeⅡ(ACE2)as receptors,using computer virtual screening technique,so as to provide a basis for combination forecasting.Methods:The molecular docking of CHM with the SARS-Cov-23 CL hydrolase and the ACE2 converting enzyme,which were taken as the targets,was achieved by the Autodock Vina software.The CHM monomers acting on 3 CLpro and ACE2 receptors were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,the active ingredients were selected,and the key CHMs and compounds were speculated.Based on the perspective of network pharmacology,the chemical-target network was constructed,and the functional enrichment analysis of gene ontology and the pathway enrichment analysis of Kyoto encyclopedia of genes and genomes were carried out by DAVID to speculate about the mechanism of action of the core drug pairs.Results:There are6 small molecule compounds that have the optimal binding energy with the two target proteins.Among 238 potential anti-COVID-19 herbs screened in total,16 kinds of CHM containing the most active ingredients,and5 candidate anti-COVID-19 herbs that had been used in high frequency,as well as a core drug pair,namely,Forsythiae Fructus-Lonicerae Japonicae Flos were selected.Conclusion:The core drug pair of Forsythiae Fructus-Lonicerae Japonicae Flos containing multiple components and targets is easy to combine with 3 CLpro and ACE2,and exerts an anti-COVID-19 pneumonia effect through multi-component and multi-target,and plays the role of anti-COVID-19 pneumonia in multi-pathway.展开更多
Genetic,environmental and demographic factors contribute to the development of essential hypertension.Genetic polymorphism of Rennin-angiotensin-aldosterone system(RAAS)has been extensively studied to determine the ge...Genetic,environmental and demographic factors contribute to the development of essential hypertension.Genetic polymorphism of Rennin-angiotensin-aldosterone system(RAAS)has been extensively studied to determine the genetic susceptibility to hypertension.The insertion/deletion(I/D)angiotensin converting enzyme(ACE)polymorphism has been established as a cardiovascular risk factor in some population,but its association with essential hypertension is controversial.This study sought to determine the association of I/D polymorphism of the ACE gene in south Indian essential hypertensive subjects.A total of 208 clinically diagnosed essential hypertensive patients without any associated diseases and 220 healthy control subjects were included in this study.Distribution and allelic frequency of Insertion(I)and Deletion(D)polymorphism at the 287 base pair Alu repeat sequence in the intron 16 of ACE gene were analyzed.The distribution of II,ID,DD genotypes of ACE gene was 28.3%,32.6%and 38.9%respectively in essential hypertensive patients and to 53.6%,26.3%and 20%in controls.The allele frequency for D allele is 0.58 in essential hypertension as compared to 0.34 of control subjects.The genotype and allele frequency of ACE gene polymorphism is significantly differed in patients when compared to controls.In conclusion,the I/D polymorphism of ACE gene is associated with Indian essential hypertension.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
Objective: To explore the possible inhibitory potentials and mechanism by Mobola plum(Parinari curatellifolia) seeds crude methanol(CE) and flavonoid-rich(FE) extracts on angiotensin-1-converting enzyme(ACE Ⅰ).Method...Objective: To explore the possible inhibitory potentials and mechanism by Mobola plum(Parinari curatellifolia) seeds crude methanol(CE) and flavonoid-rich(FE) extracts on angiotensin-1-converting enzyme(ACE Ⅰ).Methods: The sensitivity and kinetic model of inhibition of CE and FE on ACE Ⅰ using N-[3-(2-furyl)-acryloyl]-Phe-Gly-Gly as enzyme substrate for ACE Ⅰ was evaluated by Michealis Menten approach. The inhibition mechanism was explored from Lineweaver–Burk model and IC_(50) was determined from Cheng–Prusoff empirical analysis.Results: The IC_(50) of CE and FE were 13.54 and 39.38 mg/m L, respectively. Both extracts exhibited mixed type inhibition with the inhibitory constant(K_i) of CE was between0.38 and 0.37 mg/m L while that of FE showed a two-fold increase(1.62 mg/mL and0.28 mg/mL). FE on ACE Ⅰ demonstrated positive cooperativity with a Hill's coefficient of1.89.Conclusions: The study reveals the superior ACE Ⅰ inhibitory potential of CE over FE and suggest that mixed inhibition pattern of the enzyme might be the underlying mechanism of antihypertensive activity.展开更多
We retrospectively investigated 68 parturients with or without COVID-19 undergone emergency cesarean section with combined spinal-epidural anesthesia(CSEA)from a single tertiary university hospital in Wuhan,China.The ...We retrospectively investigated 68 parturients with or without COVID-19 undergone emergency cesarean section with combined spinal-epidural anesthesia(CSEA)from a single tertiary university hospital in Wuhan,China.The cases were divided into 2 groups:patients with COVID-19 pneumonia(Group 1)and cases without COVID-19 pneumonia(Group 2).The patients in Group 1 were later divided into 2 groups:patients with low-angiotensin converting enzyme(ACE)(Group 3)and patients with normal-ACE(Group 4).The ACE levels,blood pressure and anesthesia management between the patients of Group 1 and Group 2,Group 3 and Group 4 were recorded as the primary outcome.The secondary outcome included perioperative symptoms,laboratory parameters and vital signs.Compared with Group 2,the patients in Group 1 had different ACE level and lower blood pressure after CSEA.Compared with Group 4,the patients in Group 3 showed lower SBP after CSEA(127 vs.130 mm Hg,p=0.028),accompanied with more partus matures and younger age(28 vs.32 years,p=0.007).ACE may be a possible biomarker to predict the anesthesia effects on patients with COVID-19 infections undergoing emergency cesarean delivery.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
The coronavirus disease 2019(COVID-19), which is caused by SARS-CoV-2, has become a worldwide public health crisis. Published clinical data from China and other countries have shown a much higher risk of developing CO...The coronavirus disease 2019(COVID-19), which is caused by SARS-CoV-2, has become a worldwide public health crisis. Published clinical data from China and other countries have shown a much higher risk of developing COVID-19 and dying from the disease among the elderly, especially among those who had preexisting hypertension, cardiovascular diseases(CVD) and diabetes mellitus[1].展开更多
Renin-Angiotensin System (RAS) is involved with hypertension and other cardiovascular diseases. However, the association of RAS components to cancer still causes suspicion. To try to clarify this, here we aimed to sho...Renin-Angiotensin System (RAS) is involved with hypertension and other cardiovascular diseases. However, the association of RAS components to cancer still causes suspicion. To try to clarify this, here we aimed to show this association for three important components: Angiotensin Converting Enzyme 1 (ACE1), Angiotensin Type 1 Receptor (AGTR1) and Angiotensin Type 2 Receptor (AGTR2). The first articles show that association of RAS components with cancer dates back to the 70’s. ECA1 and AGTR1 have close association with cancer and ACE1 inhibitors or AGTR1 blockers are candidates to treatment of some tumors. Moreover, the action of AGTR2 is still controversial, but most studies show that the increased expression of AGTR2 can attack the cancer cells. In breast cancer, these components have also been widely studied and many works have shown that the correlation exists. Therefore specific target using these RAS components could be a beneficial, novel therapy to various tumors.展开更多
BACKGROUND Vasoplegia is a common complication of cardiac surgery but its causal relationship with preoperative use of renin angiotensin system(RAS)blockers[angiotensin converting enzyme inhibitors(ACEIs)and angiotens...BACKGROUND Vasoplegia is a common complication of cardiac surgery but its causal relationship with preoperative use of renin angiotensin system(RAS)blockers[angiotensin converting enzyme inhibitors(ACEIs)and angiotensin receptor blockers(ARB)]is still debated.AIM To update and summarize data on the effect of preoperative use of RAS blockers on incident vasoplegia.METHODS All published studies from MEDLINE,EMBASE,and Web of Science providing relevant data through January 13,2021 were identified.A random-effects metaanalysis method was used to pool estimates,and post-cardiac surgery shock was differentiated from vasoplegia.RESULTS Ten studies reporting on a pooled population of 15672 patients(none looking at ARBs exclusively)were included in the meta-analysis.All were case-control studies.Use of ACEIs was associated with an increased risk of vasoplegia[pooled adjusted odds ratio(Aor)of 2.06,95%CI:1.45-2.93]and increased inotropic/vasopressor support requirement(pooled aOR 1.19,95%CI:1.10-1.29).Post-cardiac surgery shock was increased in the presence of left ventricular dysfunction(pooled aOR 2.32,95%CI:1.60-3.36;I249%)but not increased by the use of beta blockers(pooled aOR 0.78,95%CI:0.36-1.69;I277%).Two randomized control trials(RCTs),not eligible for the meta-analysis,did not show an association between continuation of RAS blockers and vasoplegia.CONCLUSION Preoperative continuation of ACEIs is associated with an increased need for inotropic support postoperatively and with an increased risk of vasoplegia in observational studies but not in RCTs.The absence of a consensus definition of vasoplegia should lead to the use of perioperative cardiovascular monitoring when designing RCTs to better understand this discrepancy.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
BACKGROUND The respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has evolved into a multi-organ disorder,with longterm effects known as post-acute sequelae of SARS-CoV-2 infect...BACKGROUND The respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has evolved into a multi-organ disorder,with longterm effects known as post-acute sequelae of SARS-CoV-2 infection or long coronavirus disease(COVID).AIM To examine the current knowledge and outcomes of long-term neurological and gastrointestinal(GI)symptoms in adult cohorts,including United States minority populations.METHODS PubMed and Google Scholar were searched using relevant terms,and data from five studies were analyzed,comprising 27383 patients with persistent neurological and GI sequelae.RESULTS The main symptoms included anxiety,depression,dysphagia,headache,vomiting,nausea,gastroesophageal reflux,fatigue,and abdominal pain.Patients with comorbidities and metabolic syndromes were at higher risk for long COVID.While most patients were European Americans,there was a need for further study on African Americans.CONCLUSION The underlying causes of these symptoms remain unclear,warranting more investigation into the long-term impact of the SARS-CoV-2 on different populations.展开更多
Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The suscep...Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of BU.Different susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary research.Methods:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in urine.The urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed proteins.Screening for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase pathways.Based on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU conditioning.Conclusions:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC injury.Using GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers.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
Originating from Wuhan in China,coronavirus disease 2019(COVID-19)spread globally within months and was declared a pandemic by World Health Organization in March 2020,making it one of the biggest healthcare calamities...Originating from Wuhan in China,coronavirus disease 2019(COVID-19)spread globally within months and was declared a pandemic by World Health Organization in March 2020,making it one of the biggest healthcare calamities of our time.As more data on COVID-19 infection became available,what was initially thought to be a simple respiratory illness was found to be more complex.Many extra-pulmonary manifestations are now frequently reported for COVID-19 in available literature,most commonly gastrointestinal and hepatopancreatobiliary manifestations.Due to early scarcity of data,extra pulmonary manifestations were initially overlooked and may have contributed to nosocomial spread of the infection.Practitioners,especially gastroenterologists,who frequently encounter patients with these symptoms,need to be aware of them.This can not only help minimize the nosocomial spread,ensure safety of provider but also help conserve already stretched-thin healthcare resources.A tremendous amount of COVID-19 related literature is getting added to the growing pool every day,making it difficult for providers to follow.The aim of our review is to summarize the available evidence for gastrointestinal and hepatopancreatobiliary manifestations of COVID-19.We here briefly discussed the possible pathophysiologic mechanism for these manifestations and summarized the recommendations put forward by multiple gastrointestinal societies regarding safe and effective clinical practice during the ongoing pandemic.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
Natural products are great treasure troves for the discovery of bioactive components.Current bioassay guided fractionation for identification of bioactive components is time-and workload-consuming.In this study,we pro...Natural products are great treasure troves for the discovery of bioactive components.Current bioassay guided fractionation for identification of bioactive components is time-and workload-consuming.In this study,we proposed a robust and convenient strategy for deciphering the bioactive profile of natural products by mass spectral molecular networking combined with rapid bioassay.As a proof-of-concept,the strategy was applied to identify angiotensin converting enzyme(ACE)inhibitors of Fangjihuangqi decoction(FJHQD),a traditional medicine clinically used for the treatment of heart failure.The chemical profile of FJHQD was comprehensively revealed with the assistance of tandem mass spectral molecular networking,and a total of 165 compounds were identified.With characterized constituents,potential clinical applications of FJHQD were predicted by Bioinformatics Analysis Tool for Molecular mech ANism of Traditional Chinese Medicine,and a range of cardiovascular related diseases were significantly enriched.ACE inhibitory activities of FJHQD and its constituents were then investigated with an aggregation-induced emission based fluorescent probe.FJHQD exhibited excellent ACE inhibitory effects,and a bioactive molecular network was established to elucidate the ACE inhibitory profile of constituents in FJHQD.This bioactive molecular network provided a panoramic view of FJHQD’s ACE inhibitory activities,which demonstrated that flavones from Astragali Radix and Glycyrrhizae Radix et Rhizoma,saponins from Astragali Radix,and sesquiterpenoids from Atractylodis Macrocephalae Rhizoma were principal components responsible for this effect of FJHQD.Among them,four novel ACE inhibitors were the first to be reported.Our study indicated that the proposed strategy offers a useful approach to uncover the bioactive profile of traditional medicines and provides a pragmatic workflow for exploring bioactive components.展开更多
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.
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.
基金Supported by the Fundamental Research Funds for the Central Central University,Scientific Research Project on Prevention and Treatment Emergency in Novel Coronavirus(No.20720200034)。
文摘Objective:To seek potential Chinese herbal medicine(CHM)for the treatment of coronavirus disease 2019(COVID-19)through the molecular docking of the medicine with SARS-CoV-23 CL hydrolytic enzyme and the angiotensin converting enzymeⅡ(ACE2)as receptors,using computer virtual screening technique,so as to provide a basis for combination forecasting.Methods:The molecular docking of CHM with the SARS-Cov-23 CL hydrolase and the ACE2 converting enzyme,which were taken as the targets,was achieved by the Autodock Vina software.The CHM monomers acting on 3 CLpro and ACE2 receptors were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,the active ingredients were selected,and the key CHMs and compounds were speculated.Based on the perspective of network pharmacology,the chemical-target network was constructed,and the functional enrichment analysis of gene ontology and the pathway enrichment analysis of Kyoto encyclopedia of genes and genomes were carried out by DAVID to speculate about the mechanism of action of the core drug pairs.Results:There are6 small molecule compounds that have the optimal binding energy with the two target proteins.Among 238 potential anti-COVID-19 herbs screened in total,16 kinds of CHM containing the most active ingredients,and5 candidate anti-COVID-19 herbs that had been used in high frequency,as well as a core drug pair,namely,Forsythiae Fructus-Lonicerae Japonicae Flos were selected.Conclusion:The core drug pair of Forsythiae Fructus-Lonicerae Japonicae Flos containing multiple components and targets is easy to combine with 3 CLpro and ACE2,and exerts an anti-COVID-19 pneumonia effect through multi-component and multi-target,and plays the role of anti-COVID-19 pneumonia in multi-pathway.
文摘Genetic,environmental and demographic factors contribute to the development of essential hypertension.Genetic polymorphism of Rennin-angiotensin-aldosterone system(RAAS)has been extensively studied to determine the genetic susceptibility to hypertension.The insertion/deletion(I/D)angiotensin converting enzyme(ACE)polymorphism has been established as a cardiovascular risk factor in some population,but its association with essential hypertension is controversial.This study sought to determine the association of I/D polymorphism of the ACE gene in south Indian essential hypertensive subjects.A total of 208 clinically diagnosed essential hypertensive patients without any associated diseases and 220 healthy control subjects were included in this study.Distribution and allelic frequency of Insertion(I)and Deletion(D)polymorphism at the 287 base pair Alu repeat sequence in the intron 16 of ACE gene were analyzed.The distribution of II,ID,DD genotypes of ACE gene was 28.3%,32.6%and 38.9%respectively in essential hypertensive patients and to 53.6%,26.3%and 20%in controls.The allele frequency for D allele is 0.58 in essential hypertension as compared to 0.34 of control subjects.The genotype and allele frequency of ACE gene polymorphism is significantly differed in patients when compared to controls.In conclusion,the I/D polymorphism of ACE gene is associated with Indian essential hypertension.
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Objective: To explore the possible inhibitory potentials and mechanism by Mobola plum(Parinari curatellifolia) seeds crude methanol(CE) and flavonoid-rich(FE) extracts on angiotensin-1-converting enzyme(ACE Ⅰ).Methods: The sensitivity and kinetic model of inhibition of CE and FE on ACE Ⅰ using N-[3-(2-furyl)-acryloyl]-Phe-Gly-Gly as enzyme substrate for ACE Ⅰ was evaluated by Michealis Menten approach. The inhibition mechanism was explored from Lineweaver–Burk model and IC_(50) was determined from Cheng–Prusoff empirical analysis.Results: The IC_(50) of CE and FE were 13.54 and 39.38 mg/m L, respectively. Both extracts exhibited mixed type inhibition with the inhibitory constant(K_i) of CE was between0.38 and 0.37 mg/m L while that of FE showed a two-fold increase(1.62 mg/mL and0.28 mg/mL). FE on ACE Ⅰ demonstrated positive cooperativity with a Hill's coefficient of1.89.Conclusions: The study reveals the superior ACE Ⅰ inhibitory potential of CE over FE and suggest that mixed inhibition pattern of the enzyme might be the underlying mechanism of antihypertensive activity.
基金the National Natural Science Foundation of China(81771160)。
文摘We retrospectively investigated 68 parturients with or without COVID-19 undergone emergency cesarean section with combined spinal-epidural anesthesia(CSEA)from a single tertiary university hospital in Wuhan,China.The cases were divided into 2 groups:patients with COVID-19 pneumonia(Group 1)and cases without COVID-19 pneumonia(Group 2).The patients in Group 1 were later divided into 2 groups:patients with low-angiotensin converting enzyme(ACE)(Group 3)and patients with normal-ACE(Group 4).The ACE levels,blood pressure and anesthesia management between the patients of Group 1 and Group 2,Group 3 and Group 4 were recorded as the primary outcome.The secondary outcome included perioperative symptoms,laboratory parameters and vital signs.Compared with Group 2,the patients in Group 1 had different ACE level and lower blood pressure after CSEA.Compared with Group 4,the patients in Group 3 showed lower SBP after CSEA(127 vs.130 mm Hg,p=0.028),accompanied with more partus matures and younger age(28 vs.32 years,p=0.007).ACE may be a possible biomarker to predict the anesthesia effects on patients with COVID-19 infections undergoing emergency cesarean delivery.
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The coronavirus disease 2019(COVID-19), which is caused by SARS-CoV-2, has become a worldwide public health crisis. Published clinical data from China and other countries have shown a much higher risk of developing COVID-19 and dying from the disease among the elderly, especially among those who had preexisting hypertension, cardiovascular diseases(CVD) and diabetes mellitus[1].
文摘Renin-Angiotensin System (RAS) is involved with hypertension and other cardiovascular diseases. However, the association of RAS components to cancer still causes suspicion. To try to clarify this, here we aimed to show this association for three important components: Angiotensin Converting Enzyme 1 (ACE1), Angiotensin Type 1 Receptor (AGTR1) and Angiotensin Type 2 Receptor (AGTR2). The first articles show that association of RAS components with cancer dates back to the 70’s. ECA1 and AGTR1 have close association with cancer and ACE1 inhibitors or AGTR1 blockers are candidates to treatment of some tumors. Moreover, the action of AGTR2 is still controversial, but most studies show that the increased expression of AGTR2 can attack the cancer cells. In breast cancer, these components have also been widely studied and many works have shown that the correlation exists. Therefore specific target using these RAS components could be a beneficial, novel therapy to various tumors.
文摘BACKGROUND Vasoplegia is a common complication of cardiac surgery but its causal relationship with preoperative use of renin angiotensin system(RAS)blockers[angiotensin converting enzyme inhibitors(ACEIs)and angiotensin receptor blockers(ARB)]is still debated.AIM To update and summarize data on the effect of preoperative use of RAS blockers on incident vasoplegia.METHODS All published studies from MEDLINE,EMBASE,and Web of Science providing relevant data through January 13,2021 were identified.A random-effects metaanalysis method was used to pool estimates,and post-cardiac surgery shock was differentiated from vasoplegia.RESULTS Ten studies reporting on a pooled population of 15672 patients(none looking at ARBs exclusively)were included in the meta-analysis.All were case-control studies.Use of ACEIs was associated with an increased risk of vasoplegia[pooled adjusted odds ratio(Aor)of 2.06,95%CI:1.45-2.93]and increased inotropic/vasopressor support requirement(pooled aOR 1.19,95%CI:1.10-1.29).Post-cardiac surgery shock was increased in the presence of left ventricular dysfunction(pooled aOR 2.32,95%CI:1.60-3.36;I249%)but not increased by the use of beta blockers(pooled aOR 0.78,95%CI:0.36-1.69;I277%).Two randomized control trials(RCTs),not eligible for the meta-analysis,did not show an association between continuation of RAS blockers and vasoplegia.CONCLUSION Preoperative continuation of ACEIs is associated with an increased need for inotropic support postoperatively and with an increased risk of vasoplegia in observational studies but not in RCTs.The absence of a consensus definition of vasoplegia should lead to the use of perioperative cardiovascular monitoring when designing RCTs to better understand this discrepancy.
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BACKGROUND The respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has evolved into a multi-organ disorder,with longterm effects known as post-acute sequelae of SARS-CoV-2 infection or long coronavirus disease(COVID).AIM To examine the current knowledge and outcomes of long-term neurological and gastrointestinal(GI)symptoms in adult cohorts,including United States minority populations.METHODS PubMed and Google Scholar were searched using relevant terms,and data from five studies were analyzed,comprising 27383 patients with persistent neurological and GI sequelae.RESULTS The main symptoms included anxiety,depression,dysphagia,headache,vomiting,nausea,gastroesophageal reflux,fatigue,and abdominal pain.Patients with comorbidities and metabolic syndromes were at higher risk for long COVID.While most patients were European Americans,there was a need for further study on African Americans.CONCLUSION The underlying causes of these symptoms remain unclear,warranting more investigation into the long-term impact of the SARS-CoV-2 on different populations.
基金National Natural Scientific Foundation of ChinaGrant/Award Number:81972975+2 种基金National Human Diseases Animal Model Resource CenterNational Science Foundation for Young Scientists of ChinaGrant/Award Number:81703170。
文摘Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of BU.Different susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary research.Methods:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in urine.The urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed proteins.Screening for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase pathways.Based on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU conditioning.Conclusions:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC injury.Using GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers.
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.
文摘Originating from Wuhan in China,coronavirus disease 2019(COVID-19)spread globally within months and was declared a pandemic by World Health Organization in March 2020,making it one of the biggest healthcare calamities of our time.As more data on COVID-19 infection became available,what was initially thought to be a simple respiratory illness was found to be more complex.Many extra-pulmonary manifestations are now frequently reported for COVID-19 in available literature,most commonly gastrointestinal and hepatopancreatobiliary manifestations.Due to early scarcity of data,extra pulmonary manifestations were initially overlooked and may have contributed to nosocomial spread of the infection.Practitioners,especially gastroenterologists,who frequently encounter patients with these symptoms,need to be aware of them.This can not only help minimize the nosocomial spread,ensure safety of provider but also help conserve already stretched-thin healthcare resources.A tremendous amount of COVID-19 related literature is getting added to the growing pool every day,making it difficult for providers to follow.The aim of our review is to summarize the available evidence for gastrointestinal and hepatopancreatobiliary manifestations of COVID-19.We here briefly discussed the possible pathophysiologic mechanism for these manifestations and summarized the recommendations put forward by multiple gastrointestinal societies regarding safe and effective clinical practice during the ongoing pandemic.
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.
基金financially supported by the National Key R&D Program of China(Grant No.:2018YFC1704502)the National Natural Science Foundation of China(Grant No.:81603268)the National Natural Science Foundation of China(Grant No.:81822047)
文摘Natural products are great treasure troves for the discovery of bioactive components.Current bioassay guided fractionation for identification of bioactive components is time-and workload-consuming.In this study,we proposed a robust and convenient strategy for deciphering the bioactive profile of natural products by mass spectral molecular networking combined with rapid bioassay.As a proof-of-concept,the strategy was applied to identify angiotensin converting enzyme(ACE)inhibitors of Fangjihuangqi decoction(FJHQD),a traditional medicine clinically used for the treatment of heart failure.The chemical profile of FJHQD was comprehensively revealed with the assistance of tandem mass spectral molecular networking,and a total of 165 compounds were identified.With characterized constituents,potential clinical applications of FJHQD were predicted by Bioinformatics Analysis Tool for Molecular mech ANism of Traditional Chinese Medicine,and a range of cardiovascular related diseases were significantly enriched.ACE inhibitory activities of FJHQD and its constituents were then investigated with an aggregation-induced emission based fluorescent probe.FJHQD exhibited excellent ACE inhibitory effects,and a bioactive molecular network was established to elucidate the ACE inhibitory profile of constituents in FJHQD.This bioactive molecular network provided a panoramic view of FJHQD’s ACE inhibitory activities,which demonstrated that flavones from Astragali Radix and Glycyrrhizae Radix et Rhizoma,saponins from Astragali Radix,and sesquiterpenoids from Atractylodis Macrocephalae Rhizoma were principal components responsible for this effect of FJHQD.Among them,four novel ACE inhibitors were the first to be reported.Our study indicated that the proposed strategy offers a useful approach to uncover the bioactive profile of traditional medicines and provides a pragmatic workflow for exploring bioactive components.
