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1.
Sci Rep ; 10(1): 5189, 2020 03 23.
Article in English | MEDLINE | ID: covidwho-1454803

ABSTRACT

Stapled hemorrhoidopexy has a few advantages such as less postoperative pain and faster recovery compared with conventional hemorrhoidectomy. There are two major devices used for stapled hemorrhoidopexy, PPH stapler (Ethicon EndoSurgery) and DST stapler (Covidien). This study was conducted to investigate the postoperative outcomes among patients with grade III and IV hemorrhoids who underwent hemorrhoidopexy with either of these two devices. A total of 242 consecutive patients underwent stapled hemorrhoidopexy with either PPH stapler (110 patients) or DST stapler (132 patients) at a single center in 2017. We performed a retrospective case-control study to compare the short-term postoperative outcomes and the complications between these two groups. After matching the cases in terms of age, gender, and the grade of hemorrhoids, there were 100 patients in each group (PPH versus DST). There were no significant differences in the postoperative visual analog scale (VAS) score and analgesic usage. Among complications, the incidence of anorectal stricture was significantly higher in the DST group (p = 0.02). Evaluation of the mucosal specimen showed that the total surface area, the muscle/mucosa ratio and the surface area of the muscle were also significantly higher in the DST group (p = 0.03). Further analysis of the DST group demonstrated that patients with anorectal stricture after surgery are younger than patients without anorectal stricture, and higher muscle/mucosa ratio (p = 0.03) and a higher surface area of the muscle (p = 0.03) also measured in the surgical specimen. The two devices provide similar outcomes of postoperative recovery. Patients who underwent DST stapled hemorrhoidopexy had a higher incidence rate of stricture, larger area of muscle excision, and higher muscle/mucosa ratio in the surgical specimen. Further investigation is warranted for a better understanding of the correlation between muscle excision and anorectal stricture.


Subject(s)
Hemorrhoidectomy/instrumentation , Hemorrhoids/surgery , Surgical Staplers , Acetaminophen/therapeutic use , Anal Canal/pathology , Analgesics/therapeutic use , Anus Diseases/etiology , Constriction, Pathologic/etiology , Equipment Design , Female , Hemorrhage/etiology , Humans , Intestinal Mucosa/pathology , Isoxazoles/therapeutic use , Male , Middle Aged , Organ Size , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Postoperative Complications/etiology , Retrospective Studies , Treatment Outcome , Urinary Retention/etiology
2.
Mucosal Immunol ; 14(6): 1381-1392, 2021 11.
Article in English | MEDLINE | ID: covidwho-1366810

ABSTRACT

The SARS-CoV-2 pandemic has so far claimed over three and a half million lives worldwide. Though the SARS-CoV-2 mediated disease COVID-19 has first been characterized by an infection of the upper airways and the lung, recent evidence suggests a complex disease including gastrointestinal symptoms. Even if a direct viral tropism of intestinal cells has recently been demonstrated, it remains unclear, whether gastrointestinal symptoms are caused by direct infection of the gastrointestinal tract by SARS-CoV-2 or whether they are a consequence of a systemic immune activation and subsequent modulation of the mucosal immune system. To better understand the cause of intestinal symptoms we analyzed biopsies of the small intestine from SARS-CoV-2 infected individuals. Applying qRT-PCR and immunohistochemistry, we detected SARS-CoV-2 RNA and nucleocapsid protein in duodenal mucosa. In addition, applying imaging mass cytometry and immunohistochemistry, we identified histomorphological changes of the epithelium, which were characterized by an accumulation of activated intraepithelial CD8+ T cells as well as epithelial apoptosis and subsequent regenerative proliferation in the small intestine of COVID-19 patients. In summary, our findings indicate that intraepithelial CD8+ T cells are activated upon infection of intestinal epithelial cells with SARS-CoV-2, providing one possible explanation for gastrointestinal symptoms associated with COVID-19.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Duodenum/immunology , Immunity, Mucosal , Intestinal Diseases/immunology , Intestinal Mucosa/immunology , Intraepithelial Lymphocytes/immunology , Lymphocyte Activation , SARS-CoV-2/immunology , Adult , Aged , Animals , Apoptosis , CD8-Positive T-Lymphocytes/virology , COVID-19/pathology , COVID-19/virology , Case-Control Studies , Cell Proliferation , Chlorocebus aethiops , Duodenum/pathology , Duodenum/virology , Female , Host-Pathogen Interactions , Humans , Intestinal Diseases/pathology , Intestinal Diseases/virology , Intestinal Mucosa/pathology , Intestinal Mucosa/virology , Intraepithelial Lymphocytes/virology , Male , Re-Epithelialization , SARS-CoV-2/pathogenicity , Vero Cells , Viral Load
3.
Front Immunol ; 12: 708149, 2021.
Article in English | MEDLINE | ID: covidwho-1337643

ABSTRACT

Microbial translocation (MT) and intestinal damage (ID) are poorly explored in COVID-19. Aims were to assess whether alteration of gut permeability and cell integrity characterize COVID-19 patients, whether it is more pronounced in severe infections and whether it influences the development of subsequent bloodstream infection (BSI). Furthermore, we looked at the potential predictive role of TM and ID markers on Intensive Care Unit (ICU) admission and in-hospital mortality. Over March-July 2020, 45 COVID-19 patients were enrolled. Markers of MT [LPB (Lipopolysacharide Binding Protein) and EndoCab IgM] and ID [I-FABP (Intestinal Fatty Acid Binding Protein)] were evaluated at COVID-19 diagnosis and after 7 days. As a control group, age- and gender-matched healthy donors (HDs) enrolled during the same study period were included. Median age was 66 (56-71) years. Twenty-one (46.6%) were admitted to ICU and mortality was 22% (10/45). Compared to HD, a high degree of MT and ID was observed. ICU patients had higher levels of MT, but not of ID, than non-ICU ones. Likewise, patients with BSI had lower EndoCab IgM than non-BSI. Interestingly, patients with high degree of MT and low ID were likely to be admitted to ICU (AUC 0.822). Patients with COVID-19 exhibited high level of MT, especially subjects admitted to ICU. COVID-19 is associated with gut permeability.


Subject(s)
COVID-19/metabolism , Intestinal Mucosa/metabolism , SARS-CoV-2/physiology , Acute-Phase Proteins/metabolism , Aged , Biomarkers/metabolism , COVID-19/diagnosis , COVID-19/mortality , COVID-19/pathology , Carrier Proteins/metabolism , Disease Progression , Fatty Acid-Binding Proteins/metabolism , Female , Humans , Intensive Care Units , Intestinal Mucosa/pathology , Male , Membrane Glycoproteins/metabolism , Middle Aged , Predictive Value of Tests , Prognosis , Survival Analysis , Tight Junctions/metabolism
4.
J Virol ; 95(18): e0085321, 2021 08 25.
Article in English | MEDLINE | ID: covidwho-1299218

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus causing acute intestinal infection in pigs, with high mortality often seen in neonatal pigs. The newborns rely on innate immune responses against invading pathogens because of lacking adaptive immunity. However, how PEDV disables the innate immunity of newborns toward severe infection remains unknown. We found that PEDV infection led to reduced expression of histone deacetylases (HDACs), especially HDAC1, in porcine IPEC-J2 cells. HDACs are considered important regulators of innate immunity. We hypothesized that PEDV interacts with certain host factors to regulate HDAC1 expression in favor of its replication. We show that HDAC1 acted as a negative regulator of PEDV replication in IPEC-J2 cells, as shown by chemical inhibition, gene knockout, and overexpression. A GC-box (GCCCCACCCCC) within the HDAC1 promoter region was identified for Sp1 binding in IPEC-J2 cells. Treatment of the cells with Sp1 inhibitor mithramycin A inhibited HDAC1 expression, indicating direct regulation of HDAC1 expression by Sp1. Of the viral proteins that were overexpressed in IPEC-J2 cells, the N protein was found to be present in the nuclei and more inhibitory to HDAC1 transcription. The putative nuclear localization sequence 261PKKNKSR267 contributed to its nuclear localization. The N protein interacted with Sp1 and interfered with its binding to the promoter region, thereby inhibiting its transcriptional activity for HDAC1 expression. Our findings reveal a novel mechanism of PEDV evasion of the host responses, offering implications for studying the infection processes of other coronaviruses. IMPORTANCE The enteric coronavirus porcine epidemic diarrhea virus (PEDV) causes fatal acute intestinal infection in neonatal pigs that rely on innate immune responses. Histone deacetylases (HDACs) play important roles in innate immune regulation. Our study found PEDV suppresses HDAC1 expression via the interaction of its N protein and porcine Sp1, which identified a novel mechanism of PEDV evasion of the host responses to benefit its replication. This study suggests that other coronaviruses, including SARS-CoV and SARS-CoV-2, also make use of their N proteins to intercept the host immune responses in favor of their infection.


Subject(s)
Coronavirus Infections/veterinary , Epithelial Cells/virology , Histone Deacetylase 1/antagonists & inhibitors , Intestinal Mucosa/virology , Sp1 Transcription Factor/metabolism , Swine Diseases/virology , Viral Nonstructural Proteins/metabolism , Virus Replication , Animals , Cells, Cultured , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Epithelial Cells/metabolism , Epithelial Cells/pathology , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Porcine epidemic diarrhea virus/pathogenicity , Sp1 Transcription Factor/genetics , Swine , Swine Diseases/metabolism , Swine Diseases/pathology , Viral Nonstructural Proteins/genetics
5.
Front Immunol ; 12: 672808, 2021.
Article in English | MEDLINE | ID: covidwho-1236674

ABSTRACT

The anti-inflammatory role of extra-adrenal glucocorticoid (GC) synthesis at epithelial barriers is of increasing interest with regard to the search for alternatives to synthetic corticosteroids in the therapy of inflammatory disorders. Despite being very effective in many situations the use of synthetic corticosteroids is often controversial, as exemplified in the treatment of influenza patients and only recently in the current COVID-19 pandemic. Exploring the regulatory capacity of locally produced GCs in balancing immune responses in barrier tissues and in pathogenic disorders that lead to symptoms in multiple organs, could provide new perspectives for drug development. Intestine, skin and lung represent the first contact zones between potentially harmful pathogens or substances and the body, and are therefore important sites of immunoregulatory mechanisms. Here, we review the role of locally produced GCs in the regulation of type 2 immune responses, like asthma, atopic dermatitis and ulcerative colitis, as well as type 1 and type 3 infectious, inflammatory and autoimmune diseases, like influenza infection, psoriasis and Crohn's disease. In particular, we focus on the role of locally produced GCs in the interorgan communication, referred to as gut-skin axis, gut-lung axis or lung-skin axis, all of which are interconnected in the pathogenic crosstalk atopic march.


Subject(s)
Glucocorticoids/immunology , Intestinal Mucosa/immunology , Lung/immunology , Skin/immunology , Anti-Inflammatory Agents , Autoimmune Diseases/immunology , Autoimmune Diseases/pathology , Dermatitis, Atopic/immunology , Dermatitis, Atopic/pathology , Epithelium/immunology , Glucocorticoids/biosynthesis , Humans , Inflammation , Intestinal Mucosa/pathology , Lung/pathology , Skin/pathology
6.
Diagn Pathol ; 16(1): 40, 2021 May 05.
Article in English | MEDLINE | ID: covidwho-1216913

ABSTRACT

AIMS: Patients with COVID-19 can also have enteric symptoms. Here we analyzed the histopathology of intestinal detachment tissue from a patient with COVID-19. METHODS: The enteric tissue was examined by hematoxylin & eosin stain, PAS (Periodic acid-Schiff) staining, Gram staining, Ziehl-Neelsen stain and Grocott's Methenamine Silver (GMS) Stain. The distribution of CD3, CD4, CK20 and CD68, cytomegalovirus (CMV) and Herpes Simplex Virus (HSV) antigen were determined by immunohistochemistry. In situ hybridization (ISH) of SARS-CoV-2 and Epstein-Barr virus-encoded small RNA (EBER) were also performed. RESULTS: We observed mucosal epithelium shedding, intestinal mucosal erosion, focal inflammatory necrosis with hemorrhage, massive neutrophil infiltration, macrophage proliferation accompanied by minor lymphocyte infiltration. Fungal spores and gram positive cocci but not mycobacteria tuberculosis were identified. Immunohistochemistry staining showed abundant CD68+ macrophages but few lymphocytes infiltration. HSV, CMV and EBV were negative. ISH of SARS-CoV-2 RNA showed positive signal which mostly overlapped with CD68 positivity. CONCLUSIONS: The in situ detection of SARS-CoV-2 RNA in intestinal macrophages implicates a possible route for gastrointestinal infection. Further study is needed to further characterize the susceptibility of enteric cells to SARS-CoV-2 infection.


Subject(s)
COVID-19/pathology , Gastrointestinal Diseases/pathology , Intestinal Mucosa/pathology , Macrophages/virology , RNA, Viral/isolation & purification , SARS-CoV-2/isolation & purification , Aged , Biomarkers/metabolism , COVID-19/diagnosis , COVID-19/immunology , COVID-19/microbiology , COVID-19 Testing , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/immunology , Gastrointestinal Diseases/microbiology , Humans , Immunohistochemistry , In Situ Hybridization , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Macrophages/metabolism , Male
7.
Stem Cell Reports ; 16(4): 940-953, 2021 04 13.
Article in English | MEDLINE | ID: covidwho-1180038

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease 2019 (COVID-19) usually results in respiratory disease, but extrapulmonary manifestations are of major clinical interest. Intestinal symptoms of COVID-19 are present in a significant number of patients, and include nausea, diarrhea, and viral RNA shedding in feces. Human induced pluripotent stem cell-derived intestinal organoids (HIOs) represent an inexhaustible cellular resource that could serve as a valuable tool to study SARS-CoV-2 as well as other enteric viruses that infect the intestinal epithelium. Here, we report that SARS-CoV-2 productively infects both proximally and distally patterned HIOs, leading to the release of infectious viral particles while stimulating a robust transcriptomic response, including a significant upregulation of interferon-related genes that appeared to be conserved across multiple epithelial cell types. These findings illuminate a potential inflammatory epithelial-specific signature that may contribute to both the multisystemic nature of COVID-19 as well as its highly variable clinical presentation.


Subject(s)
COVID-19/pathology , Colon/pathology , Intestinal Mucosa/pathology , Organoids/pathology , Cell Line , Colon/virology , Epithelial Cells/virology , Humans , Induced Pluripotent Stem Cells/cytology , Inflammation/virology , Intestinal Mucosa/virology , Models, Biological , Organoids/cytology , Organoids/virology , SARS-CoV-2 , Virus Replication/physiology
8.
Mucosal Immunol ; 14(3): 566-573, 2021 05.
Article in English | MEDLINE | ID: covidwho-1091501

ABSTRACT

Viral infections with SARS-CoV-2 can cause a multi-facetted disease, which is not only characterized by pneumonia and overwhelming systemic inflammatory immune responses, but which can also directly affect the digestive system and infect intestinal epithelial cells. Here, we review the current understanding of intestinal tropism of SARS-CoV-2 infection, its impact on mucosal function and immunology and summarize the effect of immune-suppression in patients with inflammatory bowel disease (IBD) on disease outcome of COVID-19 and discuss IBD-relevant implications for the clinical management of SARS-CoV-2 infected individuals.


Subject(s)
COVID-19/complications , COVID-19/immunology , Host-Pathogen Interactions/immunology , Immunity, Mucosal , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/immunology , SARS-CoV-2/physiology , Biomarkers , COVID-19/diagnosis , COVID-19/virology , Humans , Immunity, Innate , Inflammatory Bowel Diseases/diagnosis , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Severity of Illness Index , Symptom Assessment , Viral Tropism , Virus Internalization
9.
EMBO Mol Med ; 13(4): e13191, 2021 04 09.
Article in English | MEDLINE | ID: covidwho-1068062

ABSTRACT

SARS-CoV-2, the agent that causes COVID-19, invades epithelial cells, including those of the respiratory and gastrointestinal mucosa, using angiotensin-converting enzyme-2 (ACE2) as a receptor. Subsequent inflammation can promote rapid virus clearance, but severe cases of COVID-19 are characterized by an inefficient immune response that fails to clear the infection. Using primary epithelial organoids from human colon, we explored how the central antiviral mediator IFN-γ, which is elevated in COVID-19, affects epithelial cell differentiation, ACE2 expression, and susceptibility to infection with SARS-CoV-2. In mouse and human colon, ACE2 is mainly expressed by surface enterocytes. Inducing enterocyte differentiation in organoid culture resulted in increased ACE2 production. IFN-γ treatment promoted differentiation into mature KRT20+ enterocytes expressing high levels of ACE2, increased susceptibility to SARS-CoV-2 infection, and resulted in enhanced virus production in infected cells. Similarly, infection-induced epithelial interferon signaling promoted enterocyte maturation and enhanced ACE2 expression. We here reveal a mechanism by which IFN-γ-driven inflammatory responses induce a vulnerable epithelial state with robust replication of SARS-CoV-2, which may have an impact on disease outcome and virus transmission.


Subject(s)
COVID-19/etiology , Interferon-gamma/immunology , Models, Immunological , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/immunology , COVID-19/pathology , Cell Differentiation/immunology , Colon/immunology , Colon/pathology , Colon/virology , Disease Susceptibility , Enterocytes/metabolism , Enterocytes/pathology , Enterocytes/virology , Gene Expression , Host Microbial Interactions/immunology , Humans , Interferon-gamma/administration & dosage , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Intestinal Mucosa/virology , Mice , Organoids/immunology , Organoids/pathology , Organoids/virology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Virus Replication/immunology
10.
mBio ; 12(1)2021 01 12.
Article in English | MEDLINE | ID: covidwho-1029053

ABSTRACT

Coronavirus disease 2019 (COVID-19), which has been declared a pandemic, has exhibited a wide range of severity worldwide. Although this global variation is largely affected by socio-medical situations in each country, there is also high individual-level variation attributable to elderliness and certain underlying medical conditions, including high blood pressure, diabetes, and obesity. As both elderliness and the aforementioned chronic conditions are often associated with an altered gut microbiota, resulting in disrupted gut barrier integrity, and gut symptoms have consistently been associated with more severe illness in COVID-19 patients, it is possible that dysfunction of the gut as a whole influences COVID-19 severity. This article summarizes the accumulating evidence that supports the hypothesis that an altered gut microbiota and its associated leaky gut may contribute to the onset of gastrointestinal symptoms and occasionally to additional multiorgan complications that may lead to severe illness by allowing leakage of the causative coronavirus into the circulatory system.


Subject(s)
COVID-19/pathology , Gastrointestinal Diseases/pathology , Gastrointestinal Microbiome , SARS-CoV-2/pathogenicity , COVID-19/complications , COVID-19/virology , Dysbiosis , Gastrointestinal Diseases/complications , Gastrointestinal Diseases/virology , Humans , Intestinal Mucosa/pathology , Intestinal Mucosa/virology , Severity of Illness Index
11.
J Virol ; 94(14)2020 07 01.
Article in English | MEDLINE | ID: covidwho-922525

ABSTRACT

Porcine deltacoronavirus (PDCoV) is an economically important enteropathogen of swine with worldwide distribution. PDCoV primarily infects the small intestine instead of the large intestine in vivo However, the underlying mechanism of PDCoV tropism to different intestinal segments remains poorly understood as a result of the lack of a suitable in vitro intestinal model that recapitulates the cellular diversity and complex functions of the gastrointestinal tract. Here, we established the PDCoV infection model of crypt-derived enteroids from different intestinal segments. Enteroids were susceptible to PDCoV, and multiple types of different functional intestinal epithelia were infected by PDCoV in vitro and in vivo We further found that PDCoV favorably infected the jejunum and ileum and restrictedly replicated in the duodenum and colon. Mechanistically, enteroids from different intestinal regions displayed a distinct gene expression profile, and the differential expression of primary viral receptor host aminopeptidase N (APN) instead of the interferon (IFN) responses determined the susceptibility of different intestinal segments to PDCoV, although PDCoV substantially elicited antiviral genes production in enteroids after infection. Additional studies showed that PDCoV infection significantly induced the expression of type I and III IFNs at the late stage of infection, and exogenous IFN inhibited PDCoV replication in enteroids. Hence, our results provide critical inputs to further dissect the molecular mechanisms of PDCoV-host interactions and pathogenesis.IMPORTANCE The zoonotic potential of the PDCoV, a coronavirus efficiently infecting cells from a broad range species, including porcine, chicken, and human, emphasizes the urgent need to further study the cell and tissue tropism of PDCoV in its natural host. Herein, we generated crypt stem cell-derived enteroids from porcine different intestinal regions, which well recapitulated the events in vivo of PDCoV infection that PDCoV targeted multiple types of intestinal epithelia and preferably infected the jejunum and ileum over the duodenum and colon. Mechanistically, we demonstrated that the expression of APN receptor rather than the IFN responses determined the susceptibility of different regions of the intestines to PDCoV infection, though PDCoV infection markedly elicited the IFN responses. Our findings provide important insights into how the distinct gene expression profiles of the intestinal segments determine the cell and tissue tropism of PDCoV.


Subject(s)
CD13 Antigens/genetics , Coronavirus Infections/veterinary , Coronavirus/physiology , Gene Expression Regulation, Viral , Host-Pathogen Interactions , Swine Diseases/metabolism , Swine Diseases/virology , Viral Tropism , Animals , Enterocolitis/metabolism , Enterocolitis/pathology , Enterocolitis/virology , Interferons/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Intestinal Mucosa/virology , Swine , Swine Diseases/pathology , Virus Replication
12.
Cell Mol Gastroenterol Hepatol ; 11(4): 935-948, 2021.
Article in English | MEDLINE | ID: covidwho-917333

ABSTRACT

BACKGROUND AND AIMS: The COVID-19 pandemic has spread worldwide and poses a severe health risk. While most patients present mild symptoms, descending pneumonia can lead to severe respiratory insufficiency. Up to 50% of patients show gastrointestinal symptoms like diarrhea or nausea, intriguingly associating with prolonged symptoms and increased severity. Thus, models to understand and validate drug efficiency in the gut of COVID-19 patients are of urgent need. METHODS: Human intestinal organoids derived from pluripotent stem cells (PSC-HIOs) have led, due to their complexity in mimicking human intestinal architecture, to an unprecedented number of successful disease models including gastrointestinal infections. Here, we employed PSC-HIOs to dissect SARS-CoV-2 pathogenesis and its inhibition by remdesivir, one of the leading drugs investigated for treatment of COVID-19. RESULTS: Immunostaining for viral entry receptor ACE2 and SARS-CoV-2 spike protein priming protease TMPRSS2 showed broad expression in the gastrointestinal tract with highest levels in the intestine, the latter faithfully recapitulated by PSC-HIOs. Organoids could be readily infected with SARS-CoV-2 followed by viral spread across entire PSC-HIOs, subsequently leading to organoid deterioration. However, SARS-CoV-2 spared goblet cells lacking ACE2 expression. Importantly, we challenged PSC-HIOs for drug testing capacity. Specifically, remdesivir effectively inhibited SARS-CoV-2 infection dose-dependently at low micromolar concentration and rescued PSC-HIO morphology. CONCLUSIONS: Thus, PSC-HIOs are a valuable tool to study SARS-CoV-2 infection and to identify and validate drugs especially with potential action in the gut.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , COVID-19/metabolism , Human Embryonic Stem Cells , Intestinal Mucosa , Organoids , SARS-CoV-2/physiology , Virus Replication/drug effects , Adenosine Monophosphate/pharmacology , Alanine/pharmacology , Caco-2 Cells , Human Embryonic Stem Cells/metabolism , Human Embryonic Stem Cells/pathology , Human Embryonic Stem Cells/virology , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Intestinal Mucosa/virology , Organoids/metabolism , Organoids/pathology , Organoids/virology
14.
Virology ; 552: 43-51, 2021 01 02.
Article in English | MEDLINE | ID: covidwho-843443

ABSTRACT

This study focused on intestinal restitution including phenotype switching of absorptive enterocytes and the abundance of different enterocyte subtypes in weaned pigs after porcine epidemic diarrhea virus (PEDV) infection. At 10 days post-PEDV-inoculation, the ratio of villus height to crypt depth in both jejunum and ileum had restored, and the PEDV antigen was not detectable. However, enterocytes at the villus tips revealed epithelial-mesenchymal transition (EMT) in the jejunum in which E-cadherin expression decreased while expression of N-cadherin, vimentin, and Snail increased. Additionally, there was reduced expression of actin in microvilli and Zonula occludens-1 (ZO-1) in tight junctions. Moreover, the protein concentration of transforming growth factor ß1 (TGFß1), which mediates EMT and cytoskeleton alteration, was increased. We also found a decreased number of Peyer's patch M cells in the ileum. These results reveal incomplete restitution of enterocytes in the jejunum and potentially impaired immune surveillance in the ileum after PEDV infection.


Subject(s)
Coronavirus Infections/veterinary , Enterocytes/pathology , Epithelial-Mesenchymal Transition , Gastroenteritis, Transmissible, of Swine/pathology , Peyer's Patches/pathology , Porcine epidemic diarrhea virus/pathogenicity , Animals , Cadherins/metabolism , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Gastroenteritis, Transmissible, of Swine/immunology , Gastroenteritis, Transmissible, of Swine/virology , Ileum/immunology , Ileum/pathology , Intestinal Mucosa/pathology , Jejunum/immunology , Jejunum/pathology , Microvilli/pathology , Swine , Tight Junctions/pathology , Transforming Growth Factor beta1/metabolism , Weaning
18.
Int J Mol Sci ; 21(15)2020 Jul 24.
Article in English | MEDLINE | ID: covidwho-699380

ABSTRACT

Sarcopenia in patients with liver cirrhosis (LC) has been attracting much attention these days because of the close linkage to adverse outcomes. LC can be related to secondary sarcopenia due to protein metabolic disorders and energy metabolic disorders. LC is associated with profound alterations in gut microbiota and injuries at the different levels of defensive mechanisms of the intestinal barrier. Dysbiosis refers to a state in which the diversity of gut microbiota is decreased by decreasing the bacterial species and the number of bacteria that compose the gut microbiota. The severe disturbance of intestinal barrier in LC can result in dysbiosis, several bacterial infections, LC-related complications, and sarcopenia. Here in this review, we will summarize the current knowledge of the relationship between sarcopenia and dysbiosis in patients with LC.


Subject(s)
Bacterial Infections , Dysbiosis , Gastrointestinal Microbiome , Liver Cirrhosis , Sarcopenia , Bacterial Infections/etiology , Bacterial Infections/metabolism , Bacterial Infections/microbiology , Bacterial Infections/pathology , Dysbiosis/etiology , Dysbiosis/metabolism , Dysbiosis/microbiology , Dysbiosis/pathology , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Liver Cirrhosis/complications , Liver Cirrhosis/metabolism , Liver Cirrhosis/microbiology , Liver Cirrhosis/pathology , Sarcopenia/etiology , Sarcopenia/metabolism , Sarcopenia/microbiology , Sarcopenia/pathology
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