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.

Bismuth salts exert their activity within the upper gastrointestinal tract through action of luminal bismuth. Bismuth exerts direct bactericidal effect on Helicobacter pylori by different ways: forms complexes in the bacterial wall and periplasmic space, inhibits different enzymes, ATP synthesis, and adherence of the bacteria to the gastric mucosa. Bismuth also helps ulcer healing by acting as a barrier to the aggressive factors and increasing mucosal protective factors such as prostaglandin, epidermal growth factor, and bicarbonate secretion. To date, no resistance to bismuth has been reported. Also synergism between bismuth salts and antibiotics was present. It was shown that metronidazole and clarithromycin resistant H. pylori strains become susceptible if they are administered together with bismuth. Bismuth-containing quadruple therapy was recommended both by the Second Asia-Pacific Consensus Guidelines and by the Maastricht IV/Florence Consensus Report as an alternative first choice regimen to standard triple therapy, in areas with low clarithromycin resistance, and it is recommended as the first-line therapeutic option in areas with a high prevalence of clarithromycin resistance. Greater than 90% eradication success can be obtained by bismuth-containing quadruple therapy. Choosing bismuth as an indispensable part of first-line therapy is logical as both metronidazole and clarithromycin resistances can be overcome by adding bismuth to the regimen.

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.

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.

ST2, a specific ligand of interleukin 33, was described as a biomarker protein of inflammatory processes and overexpression of ST2 in ulcerative colitis (UC) was shown previously. We aimed to investigate the potential relationship of serum ST2 levels with the clinical, endoscopic and histopathological activity scores in UC and Crohn's disease (CD). Serum ST2 levels were determined in 143 patients with inflammatory bowel disease (IBD) (83 UC and 60 CD), in 50 healthy controls (HC), and in 32 patients with irritable bowel syndrome (IBS). Serum ST2 levels were elevated in IBD (56.8 (41.9–87.2) pg/mL) compared to HC and IBS (30.7 (20.2–54.3), p<0.001 and 39.9 (25.9–68.7) pg/mL, p=0.002, respectively). No significant difference was found between UC (54.2 (41.3–93.0) pg/mL) and CD (63.8 (42.7–88.4) pg/mL) and between IBS and HC. Serum ST2 levels were significantly increased in active UC compared to inactive UC (72.5 (44.1–99.5) vs 40.0 (34.7–51.6) pg/mL, p<0.001) and in active CD in comparison with inactive CD (63.8 (42.7–88.4) vs 48.4 (29.6–56.9) pg/mL, p=0.036). Patients with CD showing fistulizing behavior had significantly higher ST2 levels compared to patients with inflammatory and stricturing CD (p<0.001). Clinical activity scores of patients with UC and CD were correlated with serum ST2 levels (r=0.692, p<0.001 and r=0.242, p=0.043, respectively). Serum ST2 levels showed stepwise increases with the increasing histopathological scores of patients with UC and CD (p<0.001 for both). The present study highlights significant associations between ST2 and IBD presence and activity and demonstrates elevated serum ST2 levels in patients with active CD as a novel finding.

Background: Nonalcoholic fatty liver disease (NAFLD) includes a variety of histopathological findings ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which can only be differentiated by liver biopsy. There is yet no unique biomarker found to discriminate NASH from simple steatosis.We aimed to investigate the relationship of plasma pentraxin 3 (PTX3) and its main stimulant tumor necrosis factor alpha (TNF-α) with the degree of liver damage in NAFLD. Methods: Plasma PTX3 and TNF-α levels were measured in 70 patients with histologically verified NAFLD (56 with NASH, 14 with non-NASH) and 12 controls. Results: PTX3 and TNF-α levels were found significantly higher in the NAFLD group than in the control group (4.1 ± 2.3 vs. 1.3 ± 0.8 ng/mL, P < 0.001, and 7.6 ± 4.1 vs. 3.3 ± 1.3 pg/mL, P < 0.001 respectively) and in biopsy proven NASH subgroup than non-NASH subgroup (4.6 ± 2.2 vs. 2.2 ± 1.7 ng/mL, P = 0.001, and 8.3 ± 4.3 vs. 4.6 ± 1.6 pg/mL, P = 0.001 respectively). To discriminate NASH from non-NASH PTX3 had 91.1% sensitivity and 71.4% specificity at the cutoff value of 2.45 ng/mL. Plasma PTX3 levels showed correlation with NAFLD activity score, fibrosis stage and steatosis grade (r = 0.659, P < 0.001; r = 0.354, P < 0.01; and r = 0.455, P < 0.001, respectively). Conclusion: This study demonstrated markedly higher PTX3 levels in NAFLD patients compared with controls, and in biopsy proven NASH patients compared with non-NASH ones. Thus, in this cohort we showed that plasma PTX3 may be a promising biomarker for the presence of NASH.