message stringlengths 4 10.2k | message_type stringclasses 3 values | message_id int64 0 2 | conversation_id int64 48.9k 898k | cluster float64 4 4 | __index_level_0__ int64 146k 2.69M |
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Answer this question truthfully | instruction | 0 | 48,879 | 4 | 146,227 |
Angiotensin-converting enzyme 2 (ACE2), is a primary receptor for SARS-CoV-2 entry into cells, mostly presents in renal tubular epithelial cells as well as lungs and heart. Kidney injury following COVID-19 infection is less frequent than severe lung injury, however ACE2: ACE ratio is higher in the kidneys compared to the respiratory system. (1:1 in the kidneys VS 1:20 in the respiratory system) After SARS-CoV-2 enters through the nasal cavity, it may travel to the kidneys and enter the bloodstream leading to severe inflammatory response activation and cytokine storm. Cytokine induced AKI may occur due to intrarenal inflammation, hyperpermeability of vessels, hypovolemia and cardiomyopathy, leading to cardiorenal syndrome type 1 that is characterized by third space volume overload such as pleural effusion, edema and intravascular volume loss (hypovolemia) and hypotension. cardiomyopathy and COVID-19-associated myocarditis can lead to hypotension and reduction in renal perfusion. The major cytokine is IL-6, which induces inflammation and lung endothelial cell injury, leading to ARDS and hypoxia that subsequently cause renal tubular cell injury and AKI.
Other Cytokine releasing factors in critically ill patients with COVID-19 include: Extracorporeal membrane oxygenation (ECMO) Mechanical ventilation Continuous renal replacement therapy
To conclude, COVID-19 -associated AKI can occur as a result of: Sepsis and cytokine storm Hypovolemia and Hypotension Hypoxemia Blood clots formation due to hypercoagulable state, leading to impaired blood flow in the renal arterioles. | output | 1 | 48,879 | 4 | 146,228 |
What is the association between COVID-19 and acute kidney injury? | input | 2 | 48,879 | 4 | 146,229 |
Answer this question truthfully | instruction | 0 | 49,907 | 4 | 149,311 |
Angiotensin-converting enzyme 2 and Dipeptidyl peptidase have been implicated in the uptake of SARS-Cov and MERS-CoV Several studies have indicated that viral S-protein RBD interacts with host ACE2 receptor. S protein changes thus make the human cells permissive to SARS-CoV and SARS-CoV-2 infection ACE2: ACE ratio is higher in the kidneys compared to the respiratory system. (1:1 in the kidneys VS 1:20 in the respiratory system).These receptors are found in the proximal tubules of kidney SARS-CoV2 spike(S) protein is cleaved and activated by transmembrane serine protease family (TMPRSS) after attaching to angiotensin-converting enzyme 2 (ACE2) receptors. This allows the virus to release fusion peptide that aides in membrane fusion..
There is a possibility of association between MHC class I(HLA A, B & C) with incidence of COVID-19 infection as well as severity of complications. HLA-B*46:01 gene product is believed to show lowest binding to SARS-CoV-2 indicating decreased viral presentation to immune system. Whereas HLA-B*15:03 shows increased affinity to SARS-CoV-2 leading to higher likelihood in developing immunity.
Acute Kidney Injury has been reported in patients with COVID-19 infection along with presence of proteinuria, hematuria. In a case observation, 4 out of 7 patients had AKI which may indicate that renal transplant patients are at higher risk AKI on being infected with COVID-19 whereas only 29% AKI was seen in critically ill patients of general population. Acute Kidney Injury seen in COVID-19 infection can be from the cytotropic effect (Uptake of SARS-Cov-2 virus into proximal tubule cells is possible explanation for the AKI seen in COVID patients ) of the viral particles as well as systemic inflammatory response induced by the cytokines. Patients admitted with severe disease, acute respiratory distress syndrome (ARDS) or in patients admitted to ICU have a higher incidence of AKI.. Other possible reasons that can play a role in AKI development, are multi-organ failure resulting in acute tubular necrosis (ATN), volume reduction causing prerenal ATN, high fever, drug toxicity, hypotension, and contrast exposure.
Pro-inflammatory cytokine levels are elevated in the COVID-19 infection and there is activation of T-cell response. There is higher cytokine levels and there is occurrence of cytokine storm in severe cases. In cytokine storm the, the immune system damages the healthy tissue rather than virus. According to an autopsy report of six patients, the light microscopy indicated CD68+ macrophage infiltration of the tubulointerstitium and severe ATN. The tubules showed complement 5b-9 deposition in all six cases, but deposition in glomeruli and capillaries were seldom seen. Some CD8+ T lymphocyte cells and CD56+ (natural killer) cells were seen in kidney tissue
The overall presentation of COVID-19 in renal transplant patients is similar to that in general population.However, the renal transplant recipients are at remain at higher risk to catch COVID-19 and develop severe complications due to chronic immunosuppressed state which is implicated in various viral infections such as cytomegalovirus, herpes zoster, norovirus infectionsetc.
COVID-19 Pathophysiology | output | 1 | 49,907 | 4 | 149,312 |
What is the full form of GDS? | input | 2 | 49,907 | 4 | 149,313 |
Question: is this a 2) strong advice, 1) weak advice 0) no advice? | instruction | 0 | 68,977 | 4 | 206,521 |
This is no advice | output | 1 | 68,977 | 4 | 206,522 |
The lung seems to be the target organ for SARS-CoV-2, and patients may develop acute lung injury and ARDS upon infection. | input | 2 | 68,977 | 4 | 206,523 |
Question: is this a 2) strong advice, 1) weak advice 0) no advice? | instruction | 0 | 71,454 | 4 | 213,952 |
This is no advice | output | 1 | 71,454 | 4 | 213,953 |
The tropism of SARS-CoV-2 for angiotensin converting enzyme 2 receptors expressed on endothelial cells seems to result in endothelial cell activation and apoptosis. | input | 2 | 71,454 | 4 | 213,954 |
Please summerize the given abstract to a title | instruction | 0 | 77,265 | 4 | 231,385 |
Murine-β-coronavirus-induced neuropathogenesis sheds light on CNS pathobiology of SARS-CoV2 | output | 1 | 77,265 | 4 | 231,386 |
The pandemic caused by SARS-CoV-2 has caused widespread infection and significant mortality across the globe Combined virology perspective of SARS-CoV-2 with a deep-rooted understanding of pathophysiological and immunological processes underlying the clinical manifestations of COVID-19 is of prime importance The characteristic symptom of COVID-19 is respiratory distress with diffused alveolar damage, but emerging evidence suggests COVID-19 might also have neurologic consequences Dysregulated homeostasis in the lungs has proven to be fatal, but one cannot ignore that the inability to breathe might be due to defects in the respiratory control center of the brainstem While the mechanism of pulmonary distress has been documented in the literature, awareness of neurological features and their pathophysiology is still in the nascent state This review makes references to the neuro-immune axis and neuro-invasive potential of SARS-CoV and SARS-CoV2, as well as the prototypic H-CoV strains in human brains Simultaneously, considerable discussion on relevant experimental evidence of mild to severe neurological manifestations of fellow neurotropic murine-β-CoVs (m-CoVs) in the mouse model will help understand the underpinning mechanisms of Neuro-COVID In this review, we have highlighted the neuroimmunopathological processes in murine CoVs While MHV infection in mice and SARS-CoV-2 infection in humans share numerous parallels, there are critical differences in viral recognition and viral entry These similarities are highlighted in this review, while differences have also been emphasized Though CoV-2 Spike does not favorably interact with murine ACE2 receptor, modification of murine SARS-CoV2 binding domain or development of transgenic ACE-2 knock-in mice might help in mediating consequential infection and understanding human CoV2 pathogenesis in murine models While a global animal model that can replicate all aspects of the human disease remains elusive, prior insights and further experiments with fellow m-β-CoV-induced cause-effect experimental models and current human COVID-19 patients data may help to mitigate the SARS-CoV-2-induced multifactorial multi-organ failure | input | 2 | 77,265 | 4 | 231,387 |
Please summerize the given abstract to a title | instruction | 0 | 77,337 | 4 | 231,601 |
Is Gut Involvement a Cause or Effect of COVID-19? | output | 1 | 77,337 | 4 | 231,602 |
Digestive disorder symptoms in COVID-19 may be similar in form to post-infectious functional gastrointestinal disorder (PI-FGID). To cause clinical effects, SARS-CoV-2 must reach the bowels and gastric hypochlorhydria may facilitate such transit. Asian elderly are predisposed to greater infection rate and severity of COVID-19, and the high prevalence of gastric atrophy and intake of proton-pump inhibitor in this aged group might explain the risk. Persistence shedding of SARS-CoV-2 in stools indicates that faecal transmission should not be disregarded. Gut involvement in COVID-19 is mediated by angiotensin-converting enzyme 2 (ACE2) receptor, which serves as the entry point for SARS-CoV-2 in the small bowel. ACE2 dysregulation has an impact on the homeostasis of gut microbiota and altered inflammatory response. Liver injury is variable in COVID-19 and is likely a result of by-stander effects rather than actual viropathic process. Further research is needed to understand if gut involvement is a cause or effect of SARS-CoV-2. | input | 2 | 77,337 | 4 | 231,603 |
Please summerize the given abstract to a title | instruction | 0 | 77,412 | 4 | 231,826 |
Air contamination with SARS-CoV-2 in the operating room | output | 1 | 77,412 | 4 | 231,827 |
Angiotensin converting enzyme 2 (ACE2) is a target cell receptor for internalization and proliferation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). When ACE2-highly expressed tissues are manipulated, SARS-CoV-2 containing aerosols may be generated. Normal breathing and speaking are capable of producing aerosols so mask ventilation, suction of airway tract and bucking during tracheal intubation and extubation are clinical procedures capable of significant aerosol production. Whilst no data have been reported on the distribution of SARS-CoV-2 in the operating room (OR), contamination in the OR can be estimated from the intensive care unit (ICU) data. ICU data showed that SARS-CoV-2 was detected on all types of surface and in air within about 4 m from coronavirus disease 2019 (COVID-19) patients. High concentrations of SARS-CoV-2 was detected in the personal protective equipment (PPE) removal room and medical staff office. Submicron virus-laden aerosols could result from resuspension of particles containing SARS-CoV-2 sticking the PPE surface; removal could produce the initial velocity. Supermicron virus-laden aerosol could come from floor deposited SARS-CoV-2, which were carried across different areas by medical staff (e.g., shoe). Knowledge of aerosol generation and distribution in the OR will aid the design of strategies to reduce transmission risk. | input | 2 | 77,412 | 4 | 231,828 |
Please summerize the given abstract to a title | instruction | 0 | 77,436 | 4 | 231,898 |
Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging | output | 1 | 77,436 | 4 | 231,899 |
A 2018 report from the American Heart Association shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin–angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, and heart failure, among others. It has been suggested that ACE inhibitors can alleviate the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that genetic variants of the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases, while other variants are associated with reduced risk of AD. In mice, ACE overexpression in the brain reduces symptoms of the AD model systems. Thus, we find two opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin–angiotensin system; (2) amyloid-degrading enzyme that hydrolyzes beta-amyloid, reducing amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to AD to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during midlife, leading to age-related later events. | input | 2 | 77,436 | 4 | 231,900 |
Please summerize the given abstract to a title | instruction | 0 | 77,925 | 4 | 233,365 |
An overview of preclinical animal models for SARS-CoV-2 pathogenicity | output | 1 | 77,925 | 4 | 233,366 |
Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused millions of fatalities globally since its origin in November 2019. The SARS-CoV-2 shares 79 and 50 per cent genome similarity with its predecessors, severe SARS-CoV and Middle East respiratory syndrome (MERS) coronavirus, all belonging to the same genus, Betacoronavirus. This relatively new virus has stymied the effective control of COVID-19 pandemic and caused huge social and economic impact worldwide. The FDA-approved drugs were re-purposed to reduce the number of fatalities caused by SARS-CoV-2. However, controversy surrounds about the efficacy of these re-purposed antiviral drugs against SARS-CoV-2.This necessitates the identification of new drug targets for SARS-CoV-2. Hence, the development of pre-clinical animal model is warranted. Such animal models may help us gain better understanding of the pathophysiology of SARS-CoV-2 infection and will be effective tools for the evaluation and licensure of therapeutic strategies against SARS-CoV-2. This review provides a summary of the attempts made till to develop a suitable animal model to understand pathophysiology and effectiveness of therapeutic agents against SARS-CoV-2. | input | 2 | 77,925 | 4 | 233,367 |
Please summerize the given abstract to a title | instruction | 0 | 77,980 | 4 | 233,530 |
Potential pathogenesis of severe acute respiratory syndrome coronavirus 2 | output | 1 | 77,980 | 4 | 233,531 |
A review The emergence of novel coronavirus pneumonia which was named as coronavirus disease 2019 (COVID-19) by the World Health Organization, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a serious threat to public health Notably, COVID-19 has rapidly spread around the world and large amount of people have been infected There is imminent need to investigate the pathogenesis of SARS-CoV-2 and develop effective therapeutic strategies to contain the epidemic The spike (S) protein of SARS-CoV-2 mediates viral entry into target cells, with S1 subunit binding to a cellular receptor and S2 subunit fusing viral and host membranes Angiotensin-converting enzyme 2 (ACE2), previously known as a cell receptor of severe acute respiratory syndrome coronavirus (SARS-CoV), is putatively responsible for mediating COVID-19 In this review, we detail our current understanding of the interaction between S protein and ACE2 in the process of virus infection and the potential pathogenesis of SARS-CoV-2, which has critical implications for exploring the potential therapeutic strategies for COVID-19 | input | 2 | 77,980 | 4 | 233,532 |
Please summerize the given abstract to a title | instruction | 0 | 77,998 | 4 | 233,584 |
Renin-angiotensin system blockers, risk of SARS-CoV-2 infection and outcomes fromCoViD-19: systematic review and meta-analysis | output | 1 | 77,998 | 4 | 233,585 |
AIMS: This meta-analysis provides summary odds ratio (OR) estimates for associations between treatment with (vs. without) renin-angiotensin system (RAS) blockers and risk of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and coronavirus disease 2019 (CoViD-19) severity (including case-fatality) in patients with hypertension, and in all patients (irrespective of hypertension). METHODS AND RESULTS: PubMed, EMBASE, Web of Science, Google Scholar, medRxiv and SSRN were searched (May 02, 2020 to August 12, 2020) for non-randomised observational CoViD-19 studies. Event/patient numbers were extracted, comparing ACE inhibitor/ARB treatment (and each separately), to treatment with neither drug, for the outcomes: (a) Likelihood of SARS-CoV-2 infection; (b) CoViD-19 severity (including hospitalisation, Intensive Therapy Unit (ITU), ventilation); (c) Case-fatality. Risk of bias was assessed (ROBINS-I). Random-effects meta-analysis estimates were pooled. Eighty six studies including 459,755 patients (103,317 with hypertension), were analysed. In patients with hypertension, ACE inhibitor or ARB treatment was not associated with a greater likelihood of SARS-CoV-2 infection in 60,141 patients (OR 1.06, 95% CI 0.99-1.14), hospitalisation in 5,925 patients (OR 0.90, 0.62-1.31), ITU in 7,218 patients (OR 1.06, 0.73-1.56), ventilation (or ITU/ventilation/death) in 13,163 patients (OR 0.91, 0.72-1.15) or case-fatality in 18,735 patients with 2,893 deaths (OR 0.75, 0.61-0.92). CONCLUSION: ACE inhibitors and ARBs appear safe in the context of SARS-CoV-2 infection and should not be discontinued. PROSPERO registration number: CRD42020186996. | input | 2 | 77,998 | 4 | 233,586 |
Please summerize the given abstract to a title | instruction | 0 | 78,035 | 4 | 233,695 |
Air pollution particulate matter as a potential carrier of SARS-CoV-2 to the nervous system and/or neurological symptom enhancer: arguments in favor | output | 1 | 78,035 | 4 | 233,696 |
Entry receptor for SARS-CoV-2 is expressed in nasal epithelial cells, and nasal delivery pathway can be a key feature of transmission. Here, a possibility of interaction of SARS-CoV-2 with air pollution particulate matter (PM) was considered. It was shown in our recent studies that water-suspended plastic and wood smoke aerosol PM and carbon-containing nanoparticles from burning organics can interact with the plasma membrane of brain nerve terminals presumably due to their lipid components. COVID-19 patients have neurological symptoms, viral particles were found in the brain, SARS-CoV-2 enters the cells via fusion of lipid viral envelope with the plasma membranes of infected cells, and so viral envelop can contain lipid components of the host neuronal membranes. Therefore, interaction of SARS-CoV-2 envelope with PM is possible in water surrounding. After drying, PM can serve as a carrier for transmission of SARS-CoV-2 immobilized at their surface. Moreover, PM and SARS-CoV-2 per se can enter human organism during nasal inhalation, and they both use the same nose-to-brain delivery pathways moving along axons directly to the brain, influencing the nervous system and exocytosis/endocytosis in nerve cells. Thus, PM can aggravate neurological symptoms of SARS-CoV-2 and vice versa, due to their identical nose-to-brain delivery mechanism and possible interference of neuronal effects. In addition, different types of PM because of their ability to interact with the plasma membranes of nerve cells can facilitate unspecific SARS-CoV-2 entrance to the cells, and can influence envelope features of SARS-CoV-2. Detailed studies are required to analyze interaction of SARS-CoV-2 with PM. | input | 2 | 78,035 | 4 | 233,697 |
Please summerize the given abstract to a title | instruction | 0 | 78,057 | 4 | 233,761 |
Role of Ecologic ACE I/D Polymorphism Data Towards Prediction of COVID-19 Epidemiology | output | 1 | 78,057 | 4 | 233,762 |
COVID-19 displays marked variability in the clinical course as well as regional epidemiology. Abnormalities in RAAS system especially stemming from genetic variability in ACE and ACE2 expression (including ACE I/D polymorphism) have been proposed to explain underlying pathogenesis and variability in SARS-CoV-2 infection. In a meta-regression data set of 30 countries, we found significant associations of ACE I/D ratio and COVID-19 prevalence, deaths and recovery rate but not when adjusted for possible confounders. This ecological study suggests potential of ACE I/D data as predictive biomarker COVID-19 risk and severity in a population specific manner, subject to validation in large genetic epidemiological and functional studies. | input | 2 | 78,057 | 4 | 233,763 |
Please summerize the given abstract to a title | instruction | 0 | 78,060 | 4 | 233,770 |
COVID-19-related Genes in Sputum Cells in Asthma. Relationship to Demographic Features and Corticosteroids | output | 1 | 78,060 | 4 | 233,771 |
Rationale: Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 (angiotensin-converting enzyme 2), and TMPRSS2 (transmembrane protease serine 2) mediate viral infection of host cells. We reasoned that differences in ACE2 or TMPRSS2 gene expression in sputum cells among patients with asthma may identify subgroups at risk for COVID-19 morbidity.Objectives: To determine the relationship between demographic features and sputum ACE2 and TMPRSS2 gene expression in asthma.Methods: We analyzed gene expression for ACE2 and TMPRSS2, and for ICAM-1 (intercellular adhesion molecule 1) (rhinovirus receptor as a comparator) in sputum cells from 330 participants in SARP-3 (Severe Asthma Research Program-3) and 79 healthy control subjects.Measurements and Main Results: Gene expression of ACE2 was lower than TMPRSS2, and expression levels of both genes were similar in asthma and health. Among patients with asthma, male sex, African American race, and history of diabetes mellitus were associated with higher expression of ACE2 and TMPRSS2. Use of inhaled corticosteroids (ICS) was associated with lower expression of ACE2 and TMPRSS2, but treatment with triamcinolone acetonide did not decrease expression of either gene. These findings differed from those for ICAM-1, where gene expression was increased in asthma and less consistent differences were observed related to sex, race, and use of ICS.Conclusions: Higher expression of ACE2 and TMPRSS2 in males, African Americans, and patients with diabetes mellitus provides rationale for monitoring these asthma subgroups for poor COVID-19 outcomes. The lower expression of ACE2 and TMPRSS2 with ICS use warrants prospective study of ICS use as a predictor of decreased susceptibility to SARS-CoV-2 infection and decreased COVID-19 morbidity. | input | 2 | 78,060 | 4 | 233,772 |
Please summerize the given abstract to a title | instruction | 0 | 78,070 | 4 | 233,800 |
In vitro Characterisation of SARS-CoV-2 and Susceptibility of Domestic Ferrets (Mustela putorius furo). | output | 1 | 78,070 | 4 | 233,801 |
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an emerging virus that has caused significant human morbidity and mortality since its detection in late 2019. With the rapid emergence has come an unprecedented programme of vaccine development with at least 300 candidates under development. Ferrets have proven to be an appropriate animal model for testing safety and efficacy of SARS-CoV-2 vaccines due to quantifiable virus shedding in nasal washes and oral swabs. Here we outline our efforts early in the SARS-CoV-2 outbreak to propagate and characterise an Australian isolate of the virus in vitro and in an ex vivo model of human airway epithelium, as well as to demonstrate the susceptibility of domestic ferrets (Mustela putorius furo) to SARS-CoV-2 infection following intranasal challenge. | input | 2 | 78,070 | 4 | 233,802 |
Please summerize the given abstract to a title | instruction | 0 | 78,128 | 4 | 233,974 |
Angiotensin-converting enzyme 2 and COVID-19 in cardiorenal diseases | output | 1 | 78,128 | 4 | 233,975 |
The rapid spread of the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought into focus the key role of angiotensin-converting enzyme 2 (ACE2), which serves as a cell surface receptor required for the virus to enter cells. SARS-CoV-2 can decrease cell surface ACE2 directly by internalization of ACE2 bound to the virus and indirectly by increased ADAM17 (a disintegrin and metalloproteinase 17)-mediated shedding of ACE2. ACE2 is widely expressed in the heart, lungs, vasculature, kidney and the gastrointestinal (GI) tract, where it counteracts the deleterious effects of angiotensin II (AngII) by catalyzing the conversion of AngII into the vasodilator peptide angiotensin-(1-7) (Ang-(1-7)). The down-regulation of ACE2 by SARS-CoV-2 can be detrimental to the cardiovascular system and kidneys. Further, decreased ACE2 can cause gut dysbiosis, inflammation and potentially worsen the systemic inflammatory response and coagulopathy associated with SARS-CoV-2. This review aims to elucidate the crucial role of ACE2 both as a regulator of the renin-angiotensin system and a receptor for SARS-CoV-2 as well as the implications for Coronavirus disease 19 and its associated cardiovascular and renal complications. | input | 2 | 78,128 | 4 | 233,976 |
Please summerize the given abstract to a title | instruction | 0 | 78,487 | 4 | 235,051 |
Diltiazem inhibits SARS-CoV-2 cell attachment and internalization and decreases the viral infection in mouse lung | output | 1 | 78,487 | 4 | 235,052 |
The continuous emergence of severe acute respiratory coronavirus 2 (SARS-CoV-2) variants and the increasing number of breakthrough infection cases among vaccinated people support the urgent need for research and development of antiviral drugs. Viral entry is an intriguing target for antiviral drug development. We found that diltiazem, a blocker of the L-type calcium channel Ca(v)1.2 pore-forming subunit (Ca(v)1.2 α(1c)) and an FDA-approved drug, inhibits the binding and internalization of SARS-CoV-2, and decreases SARS-CoV-2 infection in cells and mouse lung. Ca(v)1.2 α(1c) interacts with SARS-CoV-2 spike protein and ACE2, and affects the attachment and internalization of SARS-CoV-2. Our finding suggests that diltiazem has potential as a drug against SARS-CoV-2 infection and that Ca(v)1.2 α(1c) is a promising target for antiviral drug development for COVID-19. | input | 2 | 78,487 | 4 | 235,053 |
Please summerize the given abstract to a title | instruction | 0 | 78,509 | 4 | 235,117 |
Pathological Post Mortem Findings in Lungs Infected With Sars-Cov 2. | output | 1 | 78,509 | 4 | 235,118 |
Italy was the first European nation to be massively infected by SARS-COV 2. Up to the end of May 2020 more than thirty-three thousand deaths had been recorded in Italy with a large prevalence among males, those over 75 years of age, and in association with co-morbidities. We describe the lung pathological and immunohistochemical post-mortem findings at the autopsy of 9 patients who died of SARS-COV 2 associated disease. We found in the lung tissues of all patients histological changes consistent with diffuse alveolar damage in various evolution phases ranging from acute exudative to acute proliferative to fibrotic phase. Alveolar damage was associated a prominent involvement of the vascular component in both the interstitial capillaries and in the mid-size vessels, with capillary fibrin micro-thrombi, as well as organized thrombi even in medium sized arteries, in most cases not related to sources of embolism. Eosinophilic infiltrate was also seen, probably reactive to pharmacological treatment. Viral RNA of SARS-COV 2 was detected from the lung tissues of all the nine patients. Immunohistochemistry for the receptor of the SARS-COV 2, ACE2, and its priming activatorTMPRSS2 revealed that both proteins co-localize in airway cells. In particular, the ACE2 protein was expressed in both endothelial cells and alveolar type I and II pneumocytes in the areas of histological diffuse alveolar damage (DAD). Pneumocytes but not endothelial cells also expressed TMPRSS2. There are no distinctive histological features of SARS-COV 2 infection with respect to SARS-COV 1 and other DAD with different aetiology. The identification of the cause of death in course of SARS-COV 2 infection is more likely multi-factorial. This article is protected by copyright. All rights reserved. | input | 2 | 78,509 | 4 | 235,119 |
Please summerize the given abstract to a title | instruction | 0 | 78,589 | 4 | 235,357 |
17ß-Estradiol, a potential ally to alleviate SARS-CoV-2 infection | output | 1 | 78,589 | 4 | 235,358 |
Considering that female sexual hormones may modulate the inflammatory response and also exhibit direct effects on the cells of the immune system, herein, we intend to discuss the sex differences and the role of estradiol in modulating the lung and systemic inflammatory response, focusing on its possible application as a treatment modality for SARS-CoV-2 patients. COVID-19 patients develop severe hypoxemia early in the course of the disease, which is silent most of the time. Small fibrinous thrombi in pulmonary arterioles and a tumefaction of endothelial were observed in the autopsies of fatal COVID-19 cases. Studies showed that the viral infection induces a vascular process in the lung, which included vasodilation and endothelial dysfunction. Further, the proportions of CD4+ T and CD8+ T lymphocytes were strongly reduced in patients with severe SARS-CoV-2 infection. Estradiol is connected with CD4+ T cell numbers and increases T-reg cell populations, affecting immune responses to infection. It is known that estradiol exerts a protective effect on endothelial function, activating the generation of nitric oxide (NO) via endothelial nitric oxide synthase. Estrogen attenuates the vasoconstrictor response to various stimuli and induces vasodilation in the pulmonary vasculature during stress situations like hypoxia. It exerts a variety of rapid actions, which are initiated after its coupling with membrane receptors, which in turn, may positively modulate vascular responses in pulmonary disease and help to maintain microvascular flow. Direct and indirect mechanisms underlying the effects of estradiol were investigated, and the results point to a possible protective effect of estradiol against COVID-19, indicating that it may be considered as an adjuvant therapeutic element for the treatment of patients affected by the novel coronavirus. | input | 2 | 78,589 | 4 | 235,359 |
Please summerize the given abstract to a title | instruction | 0 | 78,590 | 4 | 235,360 |
Deceiving SARS-CoV-2 molecular-tropism clues - A combinational contemporary strategy | output | 1 | 78,590 | 4 | 235,361 |
Several attempts to control the dreadfulness of SARS-CoV-2 are still underway. Based on the literature evidences we have speculated a prospective contemporary remedy, which was categorized into Specificity, Remedy, and a Conveyor. In which, pros and cons were discussed and inferred the possible alternatives. (a) Specificity: Implicit to express the ACE2 receptors in conveyor cells to deceive SARS-CoV-2 frompreponetargets. (b) Remedy: As depletion of pulmonary surfactants causes strong acute respiratory distress syndrome, we propose an entity of a cost-effective artificialsurfactantsystem as a remedy to pulmonary complications. (c) Conveyor: We propose red blood cells (RBCs) as a conveyor with embedded artificial surfactant and protruding ACE2 receptors for the target-specific delivery. Overall we postulate focused insights by employing a combinational contemporary strategy to steer towards a prospective direction on combating SARS-CoV-2. | input | 2 | 78,590 | 4 | 235,362 |
Please summerize the given abstract to a title | instruction | 0 | 78,797 | 4 | 235,981 |
Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease | output | 1 | 78,797 | 4 | 235,982 |
The emergence of SARS-CoV-2 has created an international health crisis. Small animal models mirroring SARS-CoV-2 human disease are essential for medical countermeasure (MCM) development. Mice are refractory to SARS-CoV-2 infection due to low affinity binding to the murine angiotensin-converting enzyme 2 (ACE2) protein. Here we evaluated the pathogenesis of SARS-CoV-2 in male and female mice expressing the human ACE2 gene under the control of the keratin 18 promotor. In contrast to non-transgenic mice, intranasal exposure of K18-hACE2 animals to two different doses of SARS-CoV-2 resulted in acute disease including weight loss, lung injury, brain infection and lethality. Vasculitis was the most prominent finding in the lungs of infected mice. Transcriptomic analysis from lungs of infected animals revealed increases in transcripts involved in lung injury and inflammatory cytokines. In the lower dose challenge groups, there was a survival advantage in the female mice with 60% surviving infection whereas all male mice succumbed to disease. Male mice that succumbed to disease had higher levels of inflammatory transcripts compared to female mice. This is the first highly lethal murine infection model for SARS-CoV-2. The K18-hACE2 murine model will be valuable for the study of SARS-CoV-2 pathogenesis and the assessment of MCMs. | input | 2 | 78,797 | 4 | 235,983 |
Please summerize the given abstract to a title | instruction | 0 | 78,909 | 4 | 236,317 |
Angiotensin-converting enzyme 2 and kidney diseases in the era of coronavirus disease 2019 | output | 1 | 78,909 | 4 | 236,318 |
In the decades since the discovery of angiotensin-converting enzyme 2 (ACE2), its protective role in terms of antagonizing activation of the classical renin-angiotensin system (RAS) axis has been recognized in clinical and experimental studies on kidney and cardiovascular diseases. The effects of ACE inhibitor/angiotensin type 1 receptor blockers (ACEi/ARBs) on ACE2-angiotensin-(1-7) (Ang-(1-7))-Mas receptor (MasR) axis activation has encouraged the use of such blockers in patients with kidney and cardiovascular diseases, until the emergence of coronavirus disease 2019 (COVID-19). The previously unchallenged functions of the ACE2-Ang-(1-7)-MasR axis and ACEi/ARBs are being re-evaluated in the era of COVID-19; the hypothesis is that ACEi/ARBs may increase the risk of severe acute respiratory syndrome coronavirus 2 infection by upregulating the human ACE2 receptor expression level. In this review, we examine ACE2 molecular structure, function (as an enzyme of the RAS), and distribution. We explore the roles played by ACE2 in kidney, cardiovascular, and pulmonary diseases, highlighting studies that defined the benefits imparted when ACEi/ARBs activated the local ACE2-Ang-(1-7)-MasR axis. Finally, the question of whether ACEi/ARBs therapies should be stopped in COVID-19-infected patients will be reviewed by reference to the available evidence. | input | 2 | 78,909 | 4 | 236,319 |
Please summerize the given abstract to a title | instruction | 0 | 79,266 | 4 | 237,388 |
Effect of different human tissue processing techniques on SARS-CoV-2 inactivation-review | output | 1 | 79,266 | 4 | 237,389 |
The safety of the tissue transplant recipient is a top priority for tissue banks, and the emergence of the new coronavirus SARS-CoV-2 has raised significant concerns about the risks of releasing tissue for clinical use. In the present study, we conducted a literature review about the potential infectivity of SARS-CoV-2 in different biological tissues and the influence of various tissue processing and sterilization procedures on viral inactivation. The search revealed that SARS-CoV-2 binds to the human angiotensin-converting enzyme receptor to penetrate human cells. These receptors are present in skin cells, musculoskeletal tissue, amniotic membranes, cardiovascular tissue and ocular tissues, including the cornea. In general, we found that coronaviruses are stable at low temperatures, and inactivated upon exposure to extreme heat and pH. Notably, gamma irradiation, which has already been employed to inactivate SARS and MERS, could be useful for sterilizing skin, amnion and musculoskeletal tissues against SARS-CoV-2. We conclude that due to the limited information about the effects of physical and chemical tissue processing methods on viral neutralization, rigorous donor screening is still essential for tissue transplant recipient safety. | input | 2 | 79,266 | 4 | 237,390 |
Please summerize the given abstract to a title | instruction | 0 | 79,312 | 4 | 237,526 |
Hypoxia inducible factors regulate infectious SARS-CoV-2, epithelial damage and respiratory symptoms in a hamster COVID-19 model | output | 1 | 79,312 | 4 | 237,527 |
Understanding the host pathways that define susceptibility to SARS-CoV-2 infection and disease are essential for the design of new therapies. Oxygen levels in the microenvironment define the transcriptional landscape, however the influence of hypoxia on virus replication and disease in animal models is not well understood. In this study, we identify a role for the hypoxic inducible factor (HIF) signalling axis to inhibit SARS-CoV-2 infection, epithelial damage and respiratory symptoms in Syrian hamsters. Pharmacological activation of HIF with the prolyl-hydroxylase inhibitor FG-4592 significantly reduced the levels of infectious virus in the upper and lower respiratory tract. Nasal and lung epithelia showed a reduction in SARS-CoV-2 RNA and nucleocapsid expression in treated animals. Transcriptomic and pathological analysis showed reduced epithelial damage and increased expression of ciliated cells. Our study provides new insights on the intrinsic antiviral properties of the HIF signalling pathway in SARS-CoV-2 replication that may be applicable to other respiratory pathogens and identifies new therapeutic opportunities. | input | 2 | 79,312 | 4 | 237,528 |
Please summerize the given abstract to a title | instruction | 0 | 79,379 | 4 | 237,727 |
Mild and severe SARS-CoV-2 infection induces respiratory and intestinal microbiome changes in the K18-hACE2 transgenic mouse model | output | 1 | 79,379 | 4 | 237,728 |
Transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths and declining economies around the world. K18-hACE2 mice develop disease resembling severe SARS-CoV-2 infection in a virus dose-dependent manner. The relationship between SARS-CoV-2 and the intestinal or respiratory microbiome is not fully understood. In this context, we characterized the cecal and lung microbiome of SARS-CoV-2 challenged K18-hACE2 transgenic mice in the presence or absence of treatment with the Mpro inhibitor GC376. Cecum microbiome showed decreased Shannon and Inv Simpson diversity index correlating with SARS-CoV-2 infection dosage and a difference of Bray-Curtis dissimilarity distances among control and infected mice. Bacterial phyla such as Firmicutes, particularly Lachnospiraceae and Oscillospiraceae, were significantly less abundant while Verrucomicrobiota, particularly the family Akkermansiaceae, were increasingly more prevalent during peak infection in mice challenged with a high virus dose. In contrast to the cecal microbiome, the lung microbiome showed similar microbial diversity among the control, low and high challenge virus groups, independent of antiviral treatment. Bacterial phyla in the lungs such as Bacteroidota decreased while Firmicutes and Proteobacteria were significantly enriched in mice challenged with a high dose of SARS-CoV-2. In summary, we identified changes in the cecal and lung microbiome of K18-hACE2 mice with severe clinical signs of SARS-CoV-2 infection. IMPORTANCE The COVID-19 pandemic has resulted in millions of deaths. The host’s respiratory and intestinal microbiome can affect directly or indirectly the immune system during viral infections. We characterized the cecal and lung microbiome in a relevant mouse model challenged with a low and high dose of SARS-CoV-2 in the presence or absence of an antiviral Mpro inhibitor, GC376. Decreased microbial diversity and taxonomic abundances of the phyla Firmicutes, particularly Lachnospiraceae, correlating with infection dosage was observed in the cecum. In addition, microbes within the family Akkermansiaceae were increasingly more prevalent during peak infection, which is observed in other viral infections. The lung microbiome showed similar microbial diversity to the control, independent of antiviral treatment. Decreased Bacteroidota and increased Firmicutes and Proteobacteria were observed in the lungs in a virus dose-dependent manner. These studies add to a better understanding of the complexities associated with the intestinal microbiome during respiratory infections. | input | 2 | 79,379 | 4 | 237,729 |
Please summerize the given abstract to a title | instruction | 0 | 79,639 | 4 | 238,507 |
Genome-wide analysis provides genetic evidence that ACE2 influences COVID-19 risk and yields risk scores associated with severe disease | output | 1 | 79,639 | 4 | 238,508 |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters human host cells via angiotensin-converting enzyme 2 (ACE2) and causes coronavirus disease 2019 (COVID-19). Here, through a genome-wide association study, we identify a variant (rs190509934, minor allele frequency 0.2–2%) that downregulates ACE2 expression by 37% (P = 2.7 × 10(−)(8)) and reduces the risk of SARS-CoV-2 infection by 40% (odds ratio = 0.60, P = 4.5 × 10(−)(13)), providing human genetic evidence that ACE2 expression levels influence COVID-19 risk. We also replicate the associations of six previously reported risk variants, of which four were further associated with worse outcomes in individuals infected with the virus (in/near LZTFL1, MHC, DPP9 and IFNAR2). Lastly, we show that common variants define a risk score that is strongly associated with severe disease among cases and modestly improves the prediction of disease severity relative to demographic and clinical factors alone. | input | 2 | 79,639 | 4 | 238,509 |
Please summerize the given abstract to a title | instruction | 0 | 79,664 | 4 | 238,582 |
A Single-Cell RNA Expression Map of Human Coronavirus Entry Factors | output | 1 | 79,664 | 4 | 238,583 |
To predict the tropism of human coronaviruses, we profile 28 SCARFs using scRNA-seq data from a wide range of healthy human tissues. SCARFs include cellular factors both facilitating and restricting viral entry. Among adult organs, enterocytes and goblet cells of small intestine and colon, kidney proximal tubule cells, and gallbladder basal cells appear permissive to SARS-CoV-2, consistent with clinical data. Our analysis also suggests alternate entry paths for SARS-CoV-2 infection of the lung, CNS, and heart. We predict spermatogonial cells and prostate endocrine cells, but not ovarian cells, are highly permissive to SARS-CoV-2, suggesting male-specific vulnerabilities. Early embryonic and placental development show a moderate risk of infection. The nasal epithelium is characterized by high expression of both promoting and restricting factors and a potential age-dependent shift in SCARF expression. Lastly, SCARF expression appears broadly conserved across primate organs examined. Our study establishes an important resource for investigations of coronavirus pathology. Funding: M.S. is supported by a Presidential Postdoctoral Fellowship from Cornell University. V.B. is supported by a Career Development Fellowship at DZNE Tuebingen. Work on host-virus interactions in the Feschotte lab is funded by R35 GM122550 from the National Institutes of Health. Conflict of Interest: The authors declare that there is no conflict of interest. | input | 2 | 79,664 | 4 | 238,584 |
Please summerize the given abstract to a title | instruction | 0 | 79,669 | 4 | 238,597 |
Ace2, Tmprss2 and Furin Gene Expression in the Airways of People with Asthma - Implications for Covid-19 | output | 1 | 79,669 | 4 | 238,598 |
To-date, there has not been a clear signal suggesting that asthma or treatment with inhaled steroids are a risk factor for severe COVID-19 disease We have therefore explored ACE2 receptor mRNA expression, and co-factors for Sars-CoV-2 infectivity (TMPRSS2 and furin) in bronchial brushes and biopsies from people with asthma and healthy controls, and looked for relationships between asthma severity, Th2- and IL-17 dependent gene signatures, and clinical demographics (age, sex) We have looked at a cohort of 356 research participants from previously described studies The only significant association was a positive correlation between ACE2 and IL-17-dependent gene expression, and an inverse correlation between ACE2 and Th2-cytokine-dependent gene expression These data suggest that differences in ACE2, TMPRSS2 and furin epithelial and airway gene expression are unlikely to confer enhanced COVID-19 pneumonia risk in patients with asthma across all treatment intensities and severity | input | 2 | 79,669 | 4 | 238,599 |
Please summerize the given abstract to a title | instruction | 0 | 79,787 | 4 | 238,951 |
Short‐term effects of COVID‐19 on semen parameters: A multicenter study of 69 cases | output | 1 | 79,787 | 4 | 238,952 |
OBJECTIVE: COVID‐19, which is known to be caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is a global health problem that can cause multiorgan damage because of its use of the angiotensin‐converting enzyme 2 (ACE2) receptor in its pathophysiology. We aimed to investigate whether SARS‐CoV‐2 had a short‐term effect on spermatogenesis, which plays an important role in male reproductive health as it has abundant ACE2 expression in testicular tissue. MATERIAL AND METHODS: This multicenter study included 69 patients aged 20–45 years, who admitted to our hospitals between April 2020 and October 2020 with a history of a positive test result for SARS‐CoV‐2 based on the nasopharyngeal or oropharyngeal swab samples and had recovered from the disease at least three months earlier and who had undergone a spermiogram test in the hospital database within the last year before the onset of disease. The patients were divided into two groups according to their COVID‐19 symptoms being mild or moderate, depending on whether they had received home treatment or required hospitalization for oxygen therapy. Semen samples taken before and after COVID‐19 were compared within and between the groups in terms of sperm parameters. RESULTS: The mean age of the patients included in the study was 30.4±4.8 years in the mild symptomatic COVID‐19 group and 31.06±4.2 years in the moderate symptomatic group. When the spermiogram samples of the patients before and after COVID‐19 were evaluated, it was found that motility and vitality significantly decreased in the mild symptomatic group, while the decrease in all semen parameters was statistically significant in the moderate symptomatic group. CONCLUSION: Although the mechanism by which COVID‐19 causes testicular involvement remains uncertain, its short‐term results on spermatogenesis reveals that COVID‐19 negatively affects sperm parameters. | input | 2 | 79,787 | 4 | 238,953 |
Please summerize the given abstract to a title | instruction | 0 | 79,799 | 4 | 238,987 |
The differences in SARS-CoV and SARS-CoV-2 specific co-expression network mediated biological process in human gut enterocytes | output | 1 | 79,799 | 4 | 238,988 |
Novel coronavirus SARS-CoV-2 was recently outbreak worldwide causes severe acute respiratory syndrome along with gastrointestinal symptoms for some infected patients. Information on detail pathogenesis, host immune responses and responsible biological pathways are limited. Therefore, infection specific host gut responses and dietary supplements to neutralize immune inflammation demand extensive research. This study aimed to find differences in global co-expression protein-protein interaction sub-network and enriched biological processes in SARS-CoV and SARS-CoV-2 infected gut enterocytes cell line. Attempts have also been made to predict some dietary supplements to boost human health. The SARS-CoV and SARS-CoV-2 infected differential express proteins were integrated with the human protein interaction network and co-expression subnetworks were constructed. Common hubs of these sub-networks reshape central cellular pathways of metabolic processes, lipid localization, hypoxia response to decrease oxygen level and transport of bio-molecules. The major biological process enriched in the unique hub of SARS-CoV-2 significantly differ from SARS-CoV, related to interferon signaling, regulation of viral process and influenza-A enzymatic pathway. Predicted dietary supplements can improve SARS-CoV-2 infected person''s health by boosting the host immunity/reducing inflammation. To the best of our knowledge this is the first report on co-expression network mediated biological process in human gut enterocytes to predict dietary supplements/compounds. | input | 2 | 79,799 | 4 | 238,989 |
Please summerize the given abstract to a title | instruction | 0 | 79,804 | 4 | 239,002 |
The Impact of Angiotensin Converting Enzyme Inhibition and/or Angiotensin Receptor Blockade on Tissue Expression of the SARS‐CoV‐2 Receptor ACE2 in Mice | output | 1 | 79,804 | 4 | 239,003 |
The angiotensin‐converting enzyme 2 (ACE2) is an established receptor and entry point for the novel SARS‐CoV‐2 coronavirus, as the spike protein on the viral envelope binds the ACE2 receptor. Published histological profiling revealed ACE2 to be highly expressed on human lung alveolar epithelial cells and on enterocytes of the small intestine, as well as on arterial and venous endothelial cells. Given the widespread abundance of ACE2 across tissues, there has been much speculation regarding whether ACE inhibitors (ACEi) and/or Angiotensin Receptor Blockers (ARB) might alter tissue ACE2 expression and thereby change the risk of transmission or development of severe complications. Therefore, the aim of this ongoing study is to measure the impact of ACEi and ARB singly and in combination versus placebo control on tissue distribution of ACE2 in male and female mice. A factorial design was employed with the following exposures: ACEi (lisinopril, 10 mg/kg/day), ARB (losartan, 10 mg/kg/day), both drugs, or water control. Drugs were delivered via drinking water. C57BL/6J Mice were 8 weeks of age at the start of the experiment. After 21 days of treatment, four mice (two males and two females) from each treatment group were euthanized, followed by perfusion and tissue collection. 12 more untreated mice were combined with the placebo group to increase the sample size of this reference group to 16 (8 males, 8 females). ACE2 protein abundance in brain, kidney, liver, lung, and small intestine was measured by ELISA (Abcam) and normalized to BCA‐measured total protein. Two‐way ANOVA was performed to test for differences in ACE2 levels by organ or sex among untreated mice; Mann‐Whitney tests were performed to compare each drug treatment group to the control group. Among untreated mice, ACE2 levels differed by organ (p < 0.01), but there were no differences between males and females for a given organ (p = 0.20). Males and females were combined for subsequent analyses. After 21 days of treatment, ACEi, ARB, and the combination therapy lowered ACE2 tissue abundance compared to untreated mice in the brain (ACEi p = 0.04; ARB p = 0.04; ACEi+ARB p = 0.01), kidney (ACEi p = 0.03; ARB p = 0.02; ACEi+ARB p = 0.02), and lung (ACEi p = 0.01; ARB p = 0.01; ACEi+ARB p = 0.01). ACEi, but not ARB or combination therapy, lowered ACE2 tissue abundance in the liver (p = 0.02). None of the treatments changed ACE2 tissue abundance in the small intestine. These results indicate that ACEi, ARB, or combination therapy reduces levels of ACE2, the SARS‐CoV‐2 receptor, in key tissues affected by the virus, including lung, kidney, and brain. An ongoing validation study will evaluate ACE2 protein and gene expression at earlier time points, as well as after discontinuation of treatment. These results will provide valuable insight into the risk or potential benefit of starting or stopping ACEi, ARB, or combination therapy during the COVID‐19 pandemic. | input | 2 | 79,804 | 4 | 239,004 |
Please summerize the given abstract to a title | instruction | 0 | 79,820 | 4 | 239,050 |
Genetic Models | output | 1 | 79,820 | 4 | 239,051 |
Genetically altered rat and mouse models have been instrumental in the functional analysis of genes in a physiological context. In particular, studies on the renin-angiotensin system (RAS) have profited from this technology in the past. In this review, we summarize the existing animal models for the protective axis of the RAS consisting of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7)(Ang-(1-7), and its receptor Mas. With the help of models with altered expression of the components of this axis in the brain and cardiovascular organs, its physiological and pathophysiological functions have been elucidated. Thus, novel opportunities for therapeutic interventions in cardiovascular diseases were revealed targeting ACE2 or Mas. | input | 2 | 79,820 | 4 | 239,052 |
Please summerize the given abstract to a title | instruction | 0 | 79,840 | 4 | 239,110 |
FXR inhibition reduces ACE2 expression, SARS-CoV-2 infection and may improve COVID-19 outcome | output | 1 | 79,840 | 4 | 239,111 |
Prevention of SARS-CoV-2 entry in cells through the modulation of viral host receptors, such as ACE2, could represent a new therapeutic approach complementing vaccination. However, the mechanisms controlling ACE2 expression remain elusive. Here, we identify the farnesoid X receptor (FXR) as a direct regulator of ACE2 transcription in multiple COVID19-affected tissues, including the gastrointestinal and respiratory systems. We demonstrate that FXR antagonists, including the over-the-counter compound z-guggulsterone (ZGG) and the off-patent drug ursodeoxycholic acid (UDCA), downregulate ACE2 levels, and reduce susceptibility to SARS-CoV-2 infection in lung, cholangiocyte and gut organoids. We then show that therapeutic levels of UDCA downregulate ACE2 in human organs perfused ex situ and reduce SARS-CoV-2 infection ex vivo. Finally, we perform a retrospective study using registry data and identify a correlation between UDCA treatment and positive clinical outcomes following SARS-CoV-2 infection, including hospitalisation, ICU admission and death. In conclusion, we identify a novel function of FXR in controlling ACE2 expression and provide evidence that this approach could be beneficial for reducing SARS-CoV-2 infection, thereby paving the road for future clinical trials. | input | 2 | 79,840 | 4 | 239,112 |
Please summerize the given abstract to a title | instruction | 0 | 79,902 | 4 | 239,296 |
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