Angiogenesis in Inflammatory Bowel Disease

Angiogenesis is an important component of pathogenesis of inflammatory bowel disease (IBD). Chronic inflammation and angiogenesis are two closely related processes. Chronic intestinal inflammation is dependent on angiogenesis and this angiogenesis is modulated by immune system in IBD. Angiogenesis is a very complex process which includes multiple cell types, growth factors, cytokines, adhesion molecules, and signal transduction. Lymphangiogenesis is a new research area in the pathogenesis of IBD. While angiogenesis supports inflammation via leukocyte migration, carrying oxygen and nutrients, on the other hand, it has a major role in wound healing. Angiogenic molecules look like perfect targets for the treatment of IBD, but they have risk for serious side effects because of their nature

Pathogenesis and Mechanisms of SARS-CoV-2 Infection in the Intestine, Liver, and Pancreas

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

Phenotypic and genotypic spectrum of Turkish patients with isovaleric acidemia

Dursun, Ali/0000-0003-1104-9902; Ozturk-Hismi, Burcu/0000-0001-7146-0248; Ozgul, Riza Koksal/0000-0002-0283-635XWOS: 000343331200010PubMed: 25220015We aim to investigate the genetic basis of isovaleryl-CoA dehydrogenase (IVD) gene mutations and genotype-phenotype correlations in Turkish patients. Accordingly, bi-directional sequencing was performed to screen 26 patients with isovaleric acidemia (IVA). Nine novels (c.145delC, c.234 + 3G > C, c.506_507insT, p.Glu85Gln, p.Met147Val, p.Ala268Val, p.Ile287Met, p.Gly346Asp and p.Arg382Trp) and six previously reported (c.456 + 2T > C, p.Arg21His, p.Arg21Pro, p.Arg363Cys, p.Arg363His p.Glu379Lys) pathogenic mutations were identified. Pathogenicity of the novel mutations was supported using computational programs. No clear genotype-phenotype correlation could be determined. One of the cases with the novel c.234 + 3G > C mutation has portoseptal liver fibrosis, the clinical condition that was first reported for IVA. This study is the first comprehensive report from Turkey related to IVA genetics that provides information about the high number of disease-causing novel mutations. (C) 2014 Elsevier Masson SAS. All rights reserved.[DPT-1206400603]; [TUBITAK-111S217]This study was funded by the DPT-1206400603 and TUBITAK-111S217 projects

The effectiveness of small heterodimer partner and FGF 19 levels in prediction of perinatal morbidity in intrahepatic cholestasis of pregnancy

© 2022 Informa UK Limited, trading as Taylor & Francis Group.Fibroblast growth factor 19 (FGF19) and small heterodimer partner (SHP) are molecules responsible for controlling serum bile acid levels. We designed this study for evaluating the effects of FGF 19 and SHP in intrahepatic cholestasis of pregnancy (ICP). Fifty-six pregnant women having ICP and 20 healthy pregnant women were included in the study. The patients were followed up until delivery in terms of pregnancy-related morbidity/mortality. Serum FGF 19 and SHP levels were determined by enzyme-linked immunosorbent assay (ELISA). Serum FGF 19 and SHP levels were significantly higher in the patient group compared to the control group (p:.04, p:.003, respectively). In ROC analysis, SHP level above 1995 ng/L was found effective in predicting the need for neonatal intensive care unit (ICU) follow-up with 53.8% sensitivity and 77.8% specificity. High SHP levels were correlated with perinatal morbidity, mortality and neonatal ICU hospitalisation.Impact StatementWhat is already known on this subject? Itching, elevated serum transaminase and serum total bile acid (TBA) levels are the most important clinical and biochemical findings of intrahepatic cholestasis of pregnancy (ICP). Fibroblast growth factor 19 (FGF19) and small heterodimer partner (SHP) are molecules–responsible for controlling serum bile acid levels. ICP is associated with preterm labour, asphyxia, foetal distress, stillbirth and preeclampsia. What do the results of this study add? Serum FGF 19 and SHP levels were significantly higher in the patient group compared to the control group. High SHP level was found effective in predicting the need for neonatal intensive care unit and showed a negative correlation with birth week and birth weight. What are the implications of these findings for clinical practice and/or further research? Checking SHP levels can help to predict perinatal mortality and morbidity. Treatments to be developed through the mechanism of action of FGF 19 and SHP can be promising in the treatment of ICP and other cholestatic liver diseases

Changes in Liver Tissue Trace Element Concentrations During Hepatitis B Viral Infection Treatment

Approximately 350-400 million people in the world have Hbs Ag (hepatitis B virus surface antigen) positivity. In the international guidelines, the permanent suppression of replication in chronic hepatitis B virus (HBV) infection therapy is reported as the primary therapeutic goal. Trace elements play a key role in liver diseases. The aim of our study is to determine some trace element concentrations in the liver during HBV treatment periods. The measurement of 11 trace elements (manganese, lead, nickel, chromium, cadmium, iron, copper, zinc, silver, cobalt, and aluminum) was carried out by the method of inductively coupled plasma mass spectrometry in liver biopsy materials (before starting treatment and at the sixth month of the treatment period). There was an increase in zinc and copper concentrations in liver materials at the sixth month of treatment compared to the pre-treatment values (the median zinc value was 48.05g/g before treatment and 74.9g/g at 6months after initial treatment, p=0.035; median copper was 2.82g/g before treatment and 5.31g/g after 6months, p=0.002). General estimations indicated that zinc (p=0.002), iron (p=0.0244), copper (p=0.0003), and aluminum (p=0.0239) values may be effective in HAI (histological activity index) changes. Only iron levels could be at a very low level effective on the changes caused by fibrosis (p=0.0002). Liver tissue zinc and copper levels increased in parallel with the improvement of inflammation in antiviral-treated HBV patients. In addition, the levels of zinc and copper in the liver tissue can be useful markers for liver tissue damage detection

High prevalence of cerebral venous sinus thrombosis (CVST) as presentation of cystathionine beta-synthase deficiency in childhood: Molecular and clinical findings of Turkish probands

WOS: 000330013500010PubMed: 24211323Classical homocystinuria is the most commonly inherited disorder of sulfur metabolism, caused by the genetic alterations in human cystathionine beta-synthase (CBS) gene. In this study, we present comprehensive clinical findings and the genetic basis of homocystinuria in a cohort of Turkish patients. Excluding some CBS mutations, detailed genotype-phenotype correlation for different CBS mutations has not been established in literature. We aimed to make clinical subgroups according to main clinical symptoms and discussed these data together with mutational analysis results from our patients. Totally, 16 different mutations were identified; twelve of which had already been reported, and four are novel (p.N93Y, p.L251P, p.D281V and c.829-2A>T). The probands were classified into three major groups according to the clinical symptoms caused by these mutations. A psychomotor delay was the most common diagnostic symptom (n = 12, 46.2% neurological presentation), followed by thromboembolic events (n = 6, 23.1% vascular presentation) and lens ectopia, myopia or marfanoid features (n = 5, 19.2% connective tissue presentation). Pyridoxine responsiveness was 7.7%; however, with partial responsive probands, the ratio was 53.9%. In addition, five thrombophilic nucleotide changes including MTHFR c.677 C>T and c.1298 A>C, Factor V c.1691 G>A, Factor II c.20210 G>A, and SERPINE1 4G/5G were investigated to assess their contributions to the clinical spectrum. We suggest that the effect of these polymorphisms on clinical phenotype of CBS is not very clear since the distribution of thrombophilic polymorphisms does not differ among specific groups. This study provides molecular findings of 26 Turkish probands with homocystinuria and discusses the clinical presentations and putative effects of the CBS mutations. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved.State Planning Organization of Turkey [DPT2006K1206400603]This work was supported by a grant from the State Planning Organization of Turkey (Project number: DPT2006K1206400603)

Extracellular Vesicle Release Promotes Viral Replication during Persistent HCV Infection

Hepatitis C virus (HCV) infection promotes autophagic degradation of viral replicative intermediates for sustaining replication and spread. The excessive activation of autophagy can induce cell death and terminate infection without proper regulation. A prior publication from this laboratory showed that an adaptive cellular response to HCV microbial stress inhibits autophagy through beclin 1 degradation. The mechanisms of how secretory and degradative autophagy are regulated during persistent HCV infection is unknown. This study was performed to understand the mechanisms of viral persistence in the absence of degradative autophagy, which is essential for virus survival. Using HCV infection of a CD63-green fluorescence protein (CD63-GFP), labeled stable transfected Huh-7.5 cell, we found that autophagy induction at the early stage of HCV infection increased the degradation of CD63-GFP that favored virus replication. However, the late-stage of persistent HCV infection showed impaired autophagic degradation, leading to the accumulation of CD63-GFP. We found that impaired autophagic degradation promoted the release of extracellular vesicles and exosomes. The impact of blocking the release of extracellular vesicles (EVs) on virus survival was investigated in persistently infected cells and sub-genomic replicon cells. Our study illustrates that blocking EV and exosome release severely suppresses virus replication without effecting host cell viability. Furthermore, we found that blocking EV release triggers interferon lambda 1 secretion. These findings suggest that the release of EVs is an innate immune escape mechanism that promotes persistent HCV infection. We propose that inhibition of extracellular vesicle release can be explored as a potential antiviral strategy for the treatment of HCV and other emerging RNA viruses