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Cells Jan 2023The novel coronavirus, SARS-CoV-2, rapidly spread worldwide, causing an ongoing global pandemic. While the respiratory system is the most common site of infection, a... (Review)
Review
The novel coronavirus, SARS-CoV-2, rapidly spread worldwide, causing an ongoing global pandemic. While the respiratory system is the most common site of infection, a significant number of reported cases indicate gastrointestinal (GI) involvement. GI symptoms include anorexia, abdominal pain, nausea, vomiting, and diarrhea. Although the mechanisms of GI pathogenesis are still being examined, viral components isolated from stool samples of infected patients suggest a potential fecal-oral transmission route. In addition, viral RNA has been detected in blood samples of infected patients, making hematologic dissemination of the virus a proposed route for GI involvement. Angiotensin-converting enzyme 2 (ACE2) receptors serve as the cellular entry mechanism for the virus, and these receptors are particularly abundant throughout the GI tract, making the intestine, liver, and pancreas potential extrapulmonary sites for infection and reservoirs sites for developing mutations and new variants that contribute to the uncontrolled spread of the disease and resistance to treatments. This transmission mechanism and the dysregulation of the immune system play a significant role in the profound inflammatory and coagulative cascades that contribute to the increased severity and risk of death in several COVID-19 patients. This article reviews various potential mechanisms of gastrointestinal, liver, and pancreatic injury.
Topics: Humans; COVID-19; SARS-CoV-2; Liver; Intestines; Pancreas
PubMed: 36672197
DOI: 10.3390/cells12020262 -
Cell Stem Cell Jul 2020SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19...
SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. We present an experimental platform comprised of cell and organoid derivatives from human pluripotent stem cells (hPSCs). A Spike-enabled pseudo-entry virus infects pancreatic endocrine cells, liver organoids, cardiomyocytes, and dopaminergic neurons. Recent clinical studies show a strong association with COVID-19 and diabetes. We find that human pancreatic beta cells and liver organoids are highly permissive to SARS-CoV-2 infection, further validated using adult primary human islets and adult hepatocyte and cholangiocyte organoids. SARS-CoV-2 infection caused striking expression of chemokines, as also seen in primary human COVID-19 pulmonary autopsy samples. hPSC-derived cells/organoids provide valuable models for understanding the cellular responses of human tissues to SARS-CoV-2 infection and for disease modeling of COVID-19.
Topics: Angiotensin-Converting Enzyme 2; Animals; Autopsy; Betacoronavirus; COVID-19; Cell Line; Coronavirus Infections; Hepatocytes; Humans; Induced Pluripotent Stem Cells; Liver; Mice; Models, Biological; Organoids; Pancreas; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; SARS-CoV-2; Tropism; Virus Internalization
PubMed: 32579880
DOI: 10.1016/j.stem.2020.06.015 -
Scientific Reports Apr 2023In slowly progressive type 1 diabetes mellitus (SPIDDM), the pancreas shows sustained islet inflammation, pancreatitis, pancreatic acinar cell metaplasia/dysplasia...
In slowly progressive type 1 diabetes mellitus (SPIDDM), the pancreas shows sustained islet inflammation, pancreatitis, pancreatic acinar cell metaplasia/dysplasia (ADM), and intraepithelial neoplasia (PanIN), a precancerous lesion. The mechanisms underlying these changes remain unclear. The presence of enterovirus (EV) encoded-capsid protein 1 (VP1) and -2A protease (2A) and the innate immune responses of the pancreas were studied using immunohistochemistry and in situ hybridization in 12 SPIDDM and 19 non-diabetic control pancreases. VP1, 2A, and EV-RNA were detected in islets and the exocrine pancreas in all SPIDDM pancreases. Innate immune receptor, melanoma differentiation-associated gene 5 (MDA5), and interferon (IFN)-beta1 were intensified in the islets of SPIDDM patients with short disease duration. However, expressions of MDA5 and IFN-beta1were suppressed in those with longer disease duration. CD3 T cell infiltration was observed in the VP1- and insulin-positive islets (insulitis) and exocrine acinar cells. CD11c dendritic cells (DCs) in islets were scarce in long-term SPIDDM. This study showed the consistent presence of EV, suggesting an association with inflammatory changes in the endocrine and exocrine pancreas in SPIDDM. Suppressed expressions of MDA5 and IFN-beta1, as well as decreased numbers of DCs in the host cells, may contribute to persistent EV infection and induction of ADM/PanIN lesions, which may potentially provide a scaffold for pancreatic neoplasms.
Topics: Humans; Enterovirus; Diabetes Mellitus, Type 1; Pancreas; Enterovirus Infections; Pancreas, Exocrine; Antigens, Viral; Islets of Langerhans
PubMed: 37117225
DOI: 10.1038/s41598-023-33011-7 -
Journal of Endocrinological... Mar 2022Coronavirus Disease 2019 (COVID-19) severity and Diabetes mellitus affect each other bidirectionally. However, the cause of severe acute respiratory syndrome coronavirus...
PURPOSE
Coronavirus Disease 2019 (COVID-19) severity and Diabetes mellitus affect each other bidirectionally. However, the cause of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection on the incidence of diabetes is unclear. In the SARS-CoV-2-infected cells, host microRNAs (miRNAs) may target the native gene transcripts as well as the viral genomic and subgenomic RNAs. Here, we investigated the role of miRNAs in linking Diabetes to SARS-CoV-2 infection in the human pancreas.
METHODS
Differential gene expression and disease enrichment analyses were performed on an RNA-Seq dataset of human embryonic stem cell-derived (hESC) mock-infected and SARS-CoV-2-infected pancreatic organoids to obtain the dysregulated Diabetes-associated genes. The miRNA target prediction for the Diabetes-associated gene transcripts and the SARS-CoV-2 RNAs has been made to determine the common miRNAs targeting them. Minimum Free Energy (MFE) analysis was done to identify the miRNAs, preferably targeting SARS-CoV-2 RNAs over the Diabetes-associated gene transcripts.
RESULTS
The gene expression and disease enrichment analyses of the RNA-Seq data have revealed five biomarker genes, i.e., CP, SOCS3, AGT, PSMB8 and CFB that are associated with Diabetes and get significantly upregulated in the pancreas following SARS-CoV-2-infection. Four miRNAs, i.e., hsa-miR-298, hsa-miR-3925-5p, hsa-miR-4691-3p and hsa-miR-5196-5p, showed preferential targeting of the SARS-CoV-2 genome over the cell's Diabetes-associated messenger RNAs (mRNAs) in the human pancreas.
CONCLUSION
Our study proposes that the differential targeting of the Diabetes-associated host genes by the miRNAs may lead to diabetic complications or new-onset Diabetes that can worsen the condition of COVID-19 patients.
Topics: 3' Untranslated Regions; 5' Untranslated Regions; COVID-19; Comorbidity; Diabetes Mellitus; Gene Expression Regulation; Humans; MicroRNAs; Pancreas; RNA, Messenger; RNA, Viral; SARS-CoV-2
PubMed: 34669152
DOI: 10.1007/s40618-021-01693-3 -
Transplant Infectious Disease : An... Apr 2021Data on the risk factors and outcome of intra-abdominal fungal infections (IAFI) following simultaneous pancreas-kidney transplantation (PKT) are scarce.
BACKGROUND
Data on the risk factors and outcome of intra-abdominal fungal infections (IAFI) following simultaneous pancreas-kidney transplantation (PKT) are scarce.
MATERIALS/METHODS
A retrospective monocentric study was conducted on all patients who underwent simultaneous PKT from January 2007 to December 2016. Deep sites positive cultures for fungi during the first post-transplantation year were collected. Clinical, radiological, and microbiological data of proven and probable invasive fungal infections were analysed.
RESULTS
Among sixteen PKT patients, 15 were included. Seven patients (47%) developed an invasive fungal infection, exclusively IAFI (six proven, one probable). The proven IAFI included four peritonitis, one pancreatic necrosis with infected hematoma, and one patient with positive preservation fluid only (PF). Candida albicans (n = 4) was the most prevalent species (associated with Galactomyces candidus in one case), C glabrata, C dubliniensis, and C krusei were found in one case each. Three patients had either a positive direct examination and/or culture for renal or pancreatic PF and the culture of PF was positive for the same species that caused IAFI. IAFIs were significantly associated with pancreatic graft arterial thrombosis (5/7 vs 0/8, P = .007) and fungal contamination of PF (3/7 vs 0/8, P = .008). Among patients with IAFI, all required an early surgical revision post-transplantation [1-18 days] and six had early or delayed pancreatic graft removal. One patient died in the first post-transplant year.
CONCLUSION
IAFI is a common complication in PKT, associated with pancreatic graft thrombosis or fungal contamination of the graft PF, and can sometimes lead to pancreatic detransplantation.
Topics: Geotrichum; Humans; Kidney Transplantation; Mycoses; Pancreas; Retrospective Studies; Risk Factors
PubMed: 33047447
DOI: 10.1111/tid.13486 -
Journal of Nippon Medical School =... 2015
Topics: Aged; Ancylostomatoidea; Animals; Diagnosis, Differential; Hookworm Infections; Host-Parasite Interactions; Humans; Male; Mustelidae; Pancreas
PubMed: 26823028
DOI: 10.1272/jnms.82.264 -
Frontiers in Cellular and Infection... 2023
Topics: Humans; Pancreatitis; Acute Disease; Pancreas; Infections
PubMed: 37026058
DOI: 10.3389/fcimb.2023.1175195 -
The Journal of General Virology Dec 2005The pathogenesis of coxsackie B virus (CVB) infections is generally studied in mice by intraperitoneal (i.p.) injection, whereas the gastrointestinal tract is the...
The pathogenesis of coxsackie B virus (CVB) infections is generally studied in mice by intraperitoneal (i.p.) injection, whereas the gastrointestinal tract is the natural porte d'entrée in humans. The present study was undertaken to compare systematically the influence of infection route on morbidity and pathology. Swiss Albino mice were infected with CVB3 (Nancy) at different doses (5 x 10(3), 5 x 10(5), 5 x 10(7), 5 x 10(9) TCID50), given either i.p. or orally. Virus could be isolated from several organs (heart, spleen and pancreas), indicating systemic infection, irrespective of the infection route. Virus titres were 1-2 logs higher after i.p. infection, but kinetics were largely independent of infection route. Organs became negative for virus isolation after 21 days, with the exception of spleen tissue, which remained positive for up to 49 days. Thereafter, virus was detected only by immunohistochemistry and PCR up to 98 days post-infection (oral route). Histopathology showed mild inflammation and necrosis in heart tissue of all mice during the acute phase, with repair at later stages. Strikingly, pancreatic lesions were confined to the exocrine pancreas and observed only after i.p. infection. Under all experimental conditions, the pancreatic islets were spared. In contrast, immunohistochemistry showed the presence of viral VP1, protein 3A and alpha interferon (IFN-alpha) in exocrine as well as endocrine pancreas of all mice, irrespective of route and dose of infection. It is concluded that infection via the oral route protects the pancreas from damage, but not from infection, a process in which IFN-alpha is not the only factor involved.
Topics: Administration, Oral; Animals; Cell Line; Chlorocebus aethiops; Coxsackievirus Infections; Disease Models, Animal; Enterovirus B, Human; Heart; Immunohistochemistry; Inflammation; Injections, Intraperitoneal; Interferon-alpha; Intestine, Small; Mice; Mice, Inbred ICR; Myocardium; Necrosis; Pancreas; Polymerase Chain Reaction; RNA, Viral; Spleen; Viral Proteins
PubMed: 16298972
DOI: 10.1099/vir.0.81249-0 -
Gastroenterology Dec 2021
Topics: AIDS-Related Opportunistic Infections; Adult; Anti-Bacterial Agents; Anti-HIV Agents; Biopsy, Fine-Needle; Endosonography; Host-Pathogen Interactions; Humans; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Pancreas; Pancreatitis; Tomography, X-Ray Computed
PubMed: 33915172
DOI: 10.1053/j.gastro.2021.04.052 -
Hong Kong Medical Journal = Xianggang... Apr 2021
Topics: COVID-19; Exocrine Pancreatic Insufficiency; Humans; Pancreas; Pancreatic Function Tests; SARS-CoV-2
PubMed: 33843611
DOI: 10.12809/hkmj209056