scholarly journals The scRNA-seq Expression Profiling of the Receptor ACE2 and the Cellular Protease TMPRSS2 Reveals Human Organs Susceptible to SARS-CoV-2 Infection

Author(s):  
Jing Qi ◽  
Yang Zhou ◽  
Jiao Hua ◽  
Liying Zhang ◽  
Jialin Bian ◽  
...  

COVID-19 patients always develop multiple organ dysfunction syndromes other than lungs, suggesting the novel virus SARS-CoV-2 also invades other organs. Therefore, studying the viral susceptibility of other organs is important for a deeper understanding of viral pathogenesis. Angiotensin-converting enzyme II (ACE2) is the receptor protein of SARS-CoV-2, and TMPRSS2 promotes virus proliferation and transmission. We investigated the ACE2 and TMPRSS2 expression levels of cell types from 31 organs to evaluate the risk of viral infection using single-cell RNA sequencing (scRNA-seq) data. For the first time, we found that the gall bladder and fallopian tube are vulnerable to SARS-CoV-2 infection. Besides, the nose, heart, small intestine, large intestine, esophagus, brain, testis, and kidney are also identified to be high-risk organs with high expression levels of ACE2 and TMPRSS2. Moreover, the susceptible organs are grouped into three risk levels based on the ACE2 and TMPRSS2 expression. As a result, the respiratory system, digestive system, and urinary system are at the top-risk level for SARS-CoV-2 infection. This study provides evidence for SARS-CoV-2 infection in the human nervous system, digestive system, reproductive system, respiratory system, circulatory system, and urinary system using scRNA-seq data, which helps in the clinical diagnosis and treatment of patients.

Author(s):  
Jing Qi ◽  
Yang Zhou ◽  
Jiao Hua ◽  
Liying Zhang ◽  
Jialin Bian ◽  
...  

SummaryBackgroundCOVID-19 caused by SARA-CoV-2 is a disaster sweeping over 200 countries, and more than 2,150,000 people are suffering from the disease and 140,000 people died. ACE2 is a receptor protein of SARS- CoV-2, and TMPRSS2 promotes virus proliferation and transmission. Some patients developed multiple organ dysfunction syndromes other than lungs. Therefore, studying the viral susceptibility of other organs is important for a deeper understanding of viral pathogenesis.MethodsThe advantage of scRNA-seq data is the identification of cell types by clustering the gene expression of cells. ACE2 and TMPRSS2 are highly expressed in AT2 of lungs, we compared the ACE2 and TMPRSS2 expression levels of cell types from 31 organs, with AT2 of lungs to evaluate the risk of the viral infection using scRNA-seq data.FindingsFor the first time, we found the brain, gall bladder, and fallopian tube are vulnerable to COVID-19 infection. Besides, the nose, heart, small intestine, large intestine, esophagus, testis and kidney are also identified to be high-risk organs with high expression levels of ACE2 and TMPRSS2. Moreover, the susceptible organs are grouped into three risk levels based on the TMPRSS2 expression. As a result, the respiratory system, digestive system and reproductive system are at the top-risk level to COVID-19 infection.InterpretationThis study provides evidence for COVID-19 infection in the human nervous system, digestive system, reproductive system, respiratory system, circulatory system and urinary system using scRNA-seq data, which helps for the clinical diagnosis and treatment of patients.


Author(s):  
RS Rakhmanov ◽  
ES Bogomolova ◽  
SA Razgulin ◽  
GG Bakhmudov ◽  
MKh Alikberov ◽  
...  

Background: Dental diseases and their sequelae promote comorbidity and polymorbidity. The objective of the study was to analyze the overall incidence including diseases of the oral cavity among contract military personnel. Materials: We conducted a retrospective analysis of the overall 5-year morbidity by ICD-10 categories among contract soldiers serving in Dagestan for 2012–2016. We estimated the incidence rate per 1,000 people by disease categories and subcategories (C00–C14, K01–K04 and K05–K14), the structure of morbidity, worktime losses due to sickness absence, and rates of diseases of the digestive system by subcategories K01-K04 and K05-K14. Results: With account for the diseases of the oral cavity, the proportion of leading diseases (diseases of the digestive system, respiratory system, musculoskeletal system and connective tissue) among the contact soldiers was 41.1 % and differed from the morbidity structure in the general population. The incidence rate of diseases of the digestive system was 1.6 times higher than that of diseases of the respiratory system, which was equal to that in the K01–K04 subcategory. In the category of diseases of the digestive system, the proportion of caries, its complications and other diseases of hard tissues of teeth reached 62.8 % and that of other diseases of the oral cavity – 17.4 %. As for worktime losses, the share of this category reached 8.1 %, of subcategories K01–K04 and K05–K14 – 0.7 % and 2.5 %, respectively. Having excluded the latter subcategories from the analysis, we found that the proportion of diseases of the digestive system became 4.3 times lower and they dropped to the sixth place. Conclusion: The proportion of diseases of the digestive system, when including and excluding diseases of the oral cavity in the structure of general morbidity, was 18.7 % and 4.7 %, respectively, while diseases of the respiratory system, musculoskeletal system and circulatory system prevailed. It can be assumed that the problem of dental caries is interdisciplinary and its prevention is a common task of both dentists and hygienists.


Author(s):  
G. I. Tikhonova ◽  
M. S. Bryleva ◽  
T. Yu. Gorchakova

Standardized mortality rates of the male population aged 15-59 in Monchegorsk, where the Kola mining and metallurgical company is located, were higher relative to the Murmansk region and Russia: from diseases of the circulatory system by 34.8% and 52.1%, respectively, from malignant neoplasms by 26.3% and 19.4%, from diseases of the digestive system by 59.0% and 36.3%.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wiruntita Chankeaw ◽  
Sandra Lignier ◽  
Christophe Richard ◽  
Theodoros Ntallaris ◽  
Mariam Raliou ◽  
...  

Abstract Background A number of studies have examined mRNA expression profiles of bovine endometrium at estrus and around the peri-implantation period of pregnancy. However, to date, these studies have been performed on the whole endometrium which is a complex tissue. Consequently, the knowledge of cell-specific gene expression, when analysis performed with whole endometrium, is still weak and obviously limits the relevance of the results of gene expression studies. Thus, the aim of this study was to characterize specific transcriptome of the three main cell-types of the bovine endometrium at day-15 of the estrus cycle. Results In the RNA-Seq analysis, the number of expressed genes detected over 10 transcripts per million was 6622, 7814 and 8242 for LE, GE and ST respectively. ST expressed exclusively 1236 genes while only 551 transcripts were specific to the GE and 330 specific to LE. For ST, over-represented biological processes included many regulation processes and response to stimulus, cell communication and cell adhesion, extracellular matrix organization as well as developmental process. For GE, cilium organization, cilium movement, protein localization to cilium and microtubule-based process were the only four main biological processes enriched. For LE, over-represented biological processes were enzyme linked receptor protein signaling pathway, cell-substrate adhesion and circulatory system process. Conclusion The data show that each endometrial cell-type has a distinct molecular signature and provide a significantly improved overview on the biological process supported by specific cell-types. The most interesting result is that stromal cells express more genes than the two epithelial types and are associated with a greater number of pathways and ontology terms.


1968 ◽  
Vol 46 (3) ◽  
pp. 321-327 ◽  
Author(s):  
M. A. Alikhan

Tbe circulatory system, lying in the mid-dorsal line of the body, consists of an oval heart, the opthalmic artery, and a dorsal abdominal artery.The digestive system comprises a wide, large alimentary tube and two pairs of digestive glands. An oesophagus, a proventriculus, midgut, and a short proctodacum or hindgut form the digestive tube. The digestive glands are very well developed and are beaded in form; each pair lies on either side of the alimentary canal.The reproductive organs are well developed in both sexes: in the male they consist of paired testes and their vas deferentia, and in the female paired bilobed ovaries and oviducts.A cerebral or supraoesophageal ganglion, a suboesophageal ganglion, and seven thoracic ganglia form the nervous system. The supraoesophageal ganglion is united with the suboesophageal ganglion by means of the circumoesophageal commissures, whereas the thoracic ganglia and suboesophageal ganglia are linked with each other by paired connectives.The gills and the tracheae are the organs of respiration. The gills are borne of the bases of the pleopods and are enclosed in the branchial chamber. The tracheae are located on the lateral lobes of the first two pleopods only.


Author(s):  
Sergey Aleksandrovich Kuzmin ◽  
Lyubov Kuzminichna Grigorieva ◽  
Kargla Amanzhulovna Izbagambetova

In the context of the reform of the Armed Forces of the Russian Federation, the issues of recruiting troops with healthy, physically developed and mentally stable young conscripts are of paramount importance. Only citizens "A" - fit for military service and "B" fit for military service with minor restrictions are subject to conscription. When analyzing the results of medical examination of persons of military age, it was found that over the studied period of time, fitness for military service for health reasons decreased by 3.8% (from 78.3% in 2016 to 74.5% in 2020). However, despite the general decrease in fitness for military service, there is an increase in the fitness for military service "A" by 13.5% (from 23.4% in 2016 to 36.9% in 2020). Every year, during the period of work of the draft commissions, a significant number of citizens (more than 10%) were sent for additional examination to medical organizations. As a rule, the examination of conscripts was carried out on an outpatient basis (up to 85%) and much less often in an inpatient setting (up to 15%). The first place was occupied by diseases of the musculoskeletal system and connective tissue, which accounted for 24.9%. Mental and behavioral disorders ranked second with an indicator of 18.7%. The third place was taken by diseases of the circulatory system - 14.9%. Diseases of the eye and adnexa ranked fourth - 8.2%. Diseases of the digestive system were less common, accounting for only 4.5%. Thus, in total, the listed diseases accounted for 71.2% and were the main ones in determining the fitness of conscripts for military service for health reasons.


Author(s):  
Rajesh Kumar ◽  
Seetha Harilal ◽  
Sabitha M ◽  
Leena K Pappachan ◽  
P R Roshni ◽  
...  

: SARS-CoV-2, the novel coronavirus and the causative organism of Covid-19 pandemic wreaked havoc worldwide producing asymptomatic to symptomatic cases leading to significant morbidity and mortality even after infection. Most of the countries reported a mortality rate of 2-3 % majorly due to cardiorespiratory failures. Recent studies highlighted the neurological involvement playing a key role in cardiorespiratory failures and other symptoms such as headache, anosmia, and ageusia observed in Covid-19 patients. Studies suggests SARS-CoV-2 entry via olfactory epithelium (OE) and the expression of type 2 transmembrane serine protease (TMPRSS2) in addition to angiotensin converting enzyme 2 (ACE2) can facilitate SARS-CoV-2 neurotropism. The virus can either travel via peripheral blood vessel causing endothelial dysfunction, triggering coagulation cascade and multiple organ dysfunction or reach the systemic circulation and take a different route to the blood brain barrier (BBB), disrupting the BBB causing neuroinflammation or neuronal excitotoxicity resulting in the development of encephalitis, encephalopathy, seizures, and strokes. SARS-CoV-2 invasion on brain stem is believed to be responsible for the cardiorespiratory failures observed in Covid-19 patients. Apart from viral invasion via hematogenous route, SARS-CoV-2 neural invasion via PNS nerve terminal, resulting in viral replication and retrograde transportation to soma leading to invasion of the CNS including the brain producing neurological manifestations of the disease either in the initial stages or during the course of the disease and even in a long period post infection in many cases. The ACE2 receptors are expressed in the brain and glial cells and SARS-CoV-2 acts via neuronal as well as non-neuronal pathway. But the exact cell types involved and how they can trigger inflammatory pathways need further in-depth study for the development of targeted therapy.


2014 ◽  
Vol 19 (10) ◽  
pp. 1402-1408 ◽  
Author(s):  
Stephanie D. Cole ◽  
Janna S. Madren-Whalley ◽  
Albert P. Li ◽  
Russell Dorsey ◽  
Harry Salem

In vitro models that accurately and rapidly assess hepatotoxicity and the effects of hepatic metabolism on nonliver cell types are needed by the U.S. Department of Defense and the pharmaceutical industry to screen compound libraries. Here, we report the first use of high content analysis on the Integrated Discrete Multiple Organ Co-Culture (IdMOC) system, a high-throughput method for such studies. We cultured 3T3-L1 cells in the presence and absence of primary human hepatocytes, and exposed the cultures to 4-aminophenol and cyclophosphamide, model toxicants that are respectively detoxified and activated by the liver. Following staining with calcein-AM, ethidium homodimer-1, and Hoechst 33342, high content analysis of the cultures revealed four cytotoxic endpoints: fluorescence intensities of calcein-AM and ethidium homodimer-1, nuclear area, and cell density. Using these endpoints, we observed that the cytotoxicity of 4-aminophenol in 3T3-L1 cells in co-culture was less than that observed for 3T3-L1 monocultures, consistent with the known detoxification of 4-aminophenol by hepatocytes. Conversely, cyclophosphamide cytotoxicity for 3T3-L1 cells was enhanced by co-culturing with hepatocytes, consistent with the known metabolic activation of this toxicant. The use of IdMOC plates combined with high content analysis is therefore a multi-endpoint, high-throughput capability for measuring the effects of metabolism on toxicity.


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