This study is presenting an effective method of inducing liver fibrosis by CCL4 as a toxin in two different breeds of rat models.

The objective of this study was to determine the epidemiologic characteristics of patients with liver cirrhosis.

As the incidence of inflammatory bowel diseases (IBD) increases in the newly industrialized countries, the health and financial burden of disease also increase. These changes make the role of IBD biomarkers further crucial. Serum calprotectin, as a novel blood-based biomarker of IBD, has been investigated in several investigations. Yet, there is no consensus regarding its clinical utility. We searched the electronic database, including PubMed, EMBASE, Scopus, and Web of Science up to the end of 2018 to find how serum calprotectin associates with the disease characteristics in IBD. The search terms included: inflammatory bowel diseases, IBD, Crohn Diseases (CD), Ulcerative Colitis (UC), calprotectin, serum, and blood. Based on our review, a biomarker role has been suggested for serum calprotectin in IBD, as significant associations were found between serum calprotectin and disease burden, prognosis, and relapse. A complementary role to fecal calprotectin has also been suggested for serum calprotectin. On the other hand, considering a significant correlation between serum calprotectin and serum CRP, but not fecal calprotectin, serum calprotectin could be more representative of systemic inflammation than an intestinal inflammation. Consequently, further researches are needed to unwrap the potential of serum calprotectin as a blood-based biomarker in IBD.

A number of cagPAI genes in the Helicobacter pylori genome are considered the most evolved genes under a diversifying selection and evolutionary pressure. Among them, cagI and cagN are described as a part of the two different-operon of cagPAI that are involved in the T4SS machinery, but the definite association of these factors with clinical manifestations is still unclear. A total of 70 H. pylori isolates were obtained from different gastroduodenal patients. All isolates were examined for the presence of primary H. pylori virulence genes by PCR analysis. Direct DNA sequence analysis was performed for the cagI and cagN genes. The results were compared with the reference strain. The cagI, cagN, cagA, cagL, vacA s1m1, vacA s1m2, vacA s2m2, babA2, sabA, and dupA genotypes were detected in 80, 91.4, 84, 91.4, 32.8, 42.8, 24.4, 97.1, 84.3, and 84.3% of the total isolates, respectively. The most variable codon usage in cagI was observed at residues 20-25, 55-60, 94, 181-199, 213-221, 241-268, and 319-320, while the most variable codon usage in CagN hypervariable motif (CagNHM) was observed at residues 53 to 63. Sequencing data analysis of cagN revealed a hypothetical hexapeptide motif (EAKDEN/K) in residues of 278-283 among six H. pylori isolates, which needs further studies to evaluate its putative function. The present study demonstrated a high prevalence of cagI and cagN genes among Iranian H. pylori isolates with gastroduodenal diseases. Furthermore, no significant correlation between cagI and cagN variants and clinical diseases was observed in the present study. However, all patients had a high prevalence of cagPAI genes including cagI, cagN, cagA, and cagL, which indicates more potential role of these genes in disease outcome.

In the current study, we analysised only the articles that investigate serum proteome profile of cirrhosis patients or HCC patients versus healthy controls.

Genetic variability in cagL gene especially within the Helicobacter pylori CagL hypervariable motif (CagLHM) may affect the development of gastric cancer. Therefore, this study was conducted to investigate the association of CagL diversity with clinical outcomes and with H pylori virulence markers. A total of 126 patients with different gastric diseases including non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), gastric erosion (GE), and gastric cancer (GC) were enrolled. H pylori was cultured from gastric biopsies, and the isolates were screened for the presence of cagL, cagA, vacA, babA2, sabA, and cagPAI integrity by PCR. The amino acid polymorphisms of cagL were analyzed using DNA sequencing. We isolated 61 (48.4%) H pylori strains from 36 NUD, eight PUD, 12 GE, and five GC patients. Almost all isolates were cagL positive (97%), and their RGD, RHS, and SKIIVK motifs were highly conserved. Among 10 CagLHM variants identified, NEIGQ and NKIGQ were detected as the most prevalent sequences. Interestingly, a significant association was found between the presence of NKMGK and PUD (P = 0.002). Notably, the NEIGQ isolates with multiple C-type EPIYA repeat that carried intact cagPAI correlated with disease risk for PUD, GE, and GC (P = 0.021). In conclusion, we identified novel variants of H pylori CagLHM sequences in Iranian population such as NKMGK, which was associated with disease risk for PUD. Further studies using a large number of strains are required to better clarify the function of certain CagLHM motifs in gastric carcinogenesis and disease outcome.

Gut microbiota dysbiosis is intimately associated with development of non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Nevertheless, the gut microbial community during the course of NAFLD and NASH is yet to be comprehensively profiled. This study evaluated alterations in fecal microbiota composition in Iranian patients with NAFLD and NASH compared with healthy individuals. This cross-sectional study enrolled 15 NAFLD, 15 NASH patients, and 20 healthy controls, and their clinical parameters were examined. The taxonomic composition of the fecal microbiota was determined by sequencing the V3-V4 region of 16S rRNA genes of stool samples. Compared to the healthy controls, NAFLD and NASH patients presented reduced bacterial diversity and richness. We noticed a reduction in the relative abundance of Bacteroidota and a promotion in the relative abundance of Proteobacteria in NAFLD and NASH patients. L-histidine degradation I pathway, pyridoxal 5'-phosphate biosynthesis I pathway, and superpathway of pyridoxal 5'-phosphate biosynthesis and salvage were more abundant in NAFLD patients than in healthy individuals. This study examined fecal microbiota dysbiosis in NAFLD and NASH patients and presented consistent results to European countries. These condition- and ethnicity-specific data could provide different diagnostic signatures and therapeutic targets.

The aim of this study was to evaluate and compare three available methods for mitochondrial isolation from a human cell line to predict the best method for each probable application.

Considering the global increase in the prevalence of hepatic fibrosis and ineffective disease treatment, novel therapies are urgently needed. The current study is focused on comparing the therapeutic effects of mesenchymal stem cells (MSC)/imatinib combination therapy to single (MSCs or imatinib) therapy, in a rat model of carbon tetrachloride (CCL4)-induced liver fibrosis. Using rats, hepatic fibrosis was induced by injection of CCL4. Rats were divided into 5 groups: CCL4-induced hepatic fibrosis, phosphate buffered saline (PBS) treatment (vehicle control), Bone marrow-MSCs (BM_MSCs), imatinib, and bone marrow-MSCs/imatinib co-treatment. The therapeutic impact of these approaches was determined using histopathology, sirius-red staining, serum markers, and qRT-PCR for over expression of matrix components. IHC and Western blot were conducted for further confirmation of the results. Single treatment with MSCs or imatinib and the combination therapy, all significantly reduced serum levels of ALT, AST, and ALP concomitant with down-regulation of α-SMA, pro-collagen I, pro-collagen III, collagen IV, and laminin. A significant reduction of ECM components deposits and a decrease in α-SMA expression were detected in all treatment groups. Pathological observations demonstrated that 20% and 40% of the rats in the MSC and MSC/imatinib group were in grade F0 respectively, while 80% of the rats of the imatinib group were in grade 2. Even though all treatment strategies studied resulted in an equally potent reduction in the mRNA and protein expression levels of pro-fibrotic markers, in aspect of pathological observations, our results demonstrate the highest therapeutic potential of utilizing combination of BM-MSCs and imatinib.

Akkermansia muciniphila, as a member of the gut microbiota, has been proposed as a next-generation probiotic. Liver fibrosis is the main determinant of liver dysfunction and mortality in patients with chronic liver disease. In this study, we aimed to determine the beneficial effects of live and pasteurized A. muciniphila and its extracellular vesicles (EVs) on the prevention of liver fibrosis. The response of hepatic stellate cells (HSCs) to live and pasteurized A. muciniphila and its EVs was examined in quiescent, lipopolysaccharide (LPS)-activated LX-2 cells. Liver fibrosis was induced in 8-week-old C57BL/6 mice, using a high-fat diet (HFD) and carbon tetrachloride (CCl4) administration for 4 weeks. The mice were concomitantly treated via oral gavage with three forms of bacteria. The relative expression of different fibrosis and inflammatory markers was assessed in the tissues. Histological markers, serum biochemical parameters, and cytokine production were also analyzed, and their correlations with the relative abundance of targeted fecal bacteria were examined. All A. muciniphila preparations exhibited protective effects against HSC activation; however, EVs showed the greatest activity in HSC regression. Oral gavage with A. muciniphila ameliorated the serum biochemical and inflammatory cytokines and improved liver and colon histopathological damages. The relative expression of fibrosis and inflammatory biomarkers was substantially attenuated in the tissues of all treated mice. The composition of targeted stool bacteria in the live A. muciniphila group was clearly different from that in the fibrosis group. This study indicated that A. muciniphila and its derivatives could successfully protect against HFD/CCl4-induced liver injury. However, further studies are needed to prove the beneficial effects of A. muciniphila on the liver. IMPORTANCE Akkermansia muciniphila, as a member of the gut microbiota, has been proposed as a next-generation probiotic. Liver fibrosis is the main determinant of liver dysfunction and mortality in patients with chronic liver disease. In this study, we aimed to determine the beneficial effects of live and pasteurized A. muciniphila and its extracellular vesicles (EVs) on the prevention of liver fibrosis. The results of the present study indicated that oral administration of live and pasteurized A. muciniphila and its EVs could normalize the fecal targeted bacteria composition, improve the intestinal permeability, modulate inflammatory responses, and subsequently prevent liver injury in HFD/CCl4-administered mice. Following the improvement of intestinal and liver histopathology, HFD/CCl4-induced kidney damage and adipose tissue inflammation were also ameliorated by different A. muciniphila treatments.

The very low-density lipoprotein receptor (VLDLR) plays an important role in the development of hepatic steatosis. In this study, we investigated the role of Peroxisome Proliferator-Activated Receptor (PPAR)β/δ and fibroblast growth factor 21 (FGF21) in hepatic VLDLR regulation.

Inflammation plays a critical role in the promotion of hepatocyte damage and liver fibrosis. In recent years the protective role of Akkermansia muciniphila, a next-generation beneficial microbe, has been suggested for metabolic and inflammatory disorders. In this study, we aimed to evaluate the effects of live and pasteurized A. muciniphila and its extra cellular vesicles (EVs) on inflammatory markers involved in liver fibrosis in a mouse model of a high-fat diet (HFD)/carbon tetrachloride (CCl4)-induced liver injury. Firstly, the responses of hepatic stellate cells (HSCs) to live and pasteurized A. muciniphila and its EVs were examined in the quiescent and LPS-activated LX-2 cells. Next, the anti-inflammatory effects of different forms of A. muciniphila were examined in the mouse model of HFD/CCl4-induced liver injury. The gene expression of various inflammatory markers was evaluated in liver, colon, and white adipose tissues. The cytokine secretion in the liver and white adipose tissues was also measured by ELISA. The results showed that administration of live and pasteurized A. muciniphila and its EVs leads to amelioration in HSCs activation. Based on data obtained from the histopathological analysis, an improvement in gut health was observed through enhancing the epithelium and mucosal layer thickness and strengthening the intestinal integrity in all treatments. Moreover, live A. muciniphila and its EVs had inhibitory effects on liver inflammation and hepatocytes damage. In addition, the tissue cytokine production and inflammatory gene expression levels revealed that live A. muciniphila and its EVs had more pronounced anti-inflammatory effects on liver and adipose tissues. Furthermore, EVs had better effects on the modulation of gene expression related to TLRs, PPARs, and immune response in the liver. In conclusion, the present results showed that oral administration of A. muciniphila and its derivatives for four weeks could enhance the intestinal integrity and anti-inflammatory responses of the colon, adipose, and liver tissues and subsequently prevent liver injury in HFD/CCL4 mice.

The present study aims to evaluate the prognostic value of liver-related laboratory parameters in COVID-19.

Hepatitis viruses are infectious agents that can infect liver and cause inflammation. The infection triggers immune response against infected cells that leads to the destruction of hepatic cells. This destruction has two consequences: leaking ALT and AST liver enzymes which increases during the course of disease and accumulation of bilirubin- a red pigmented compound released from dead red cells- which causes the yellow coloration of eyes and skin. These viruses transmit through diverse routes i.e. blood transfusion, sexual contacts and consuming water or food contaminated by feces. Enteric hepatitis viruses use the latter route for transmission; hence their outbreaks are more common in underdeveloped countries. There are currently two distinguished enteric hepatitis viruses, hepatitis A and hepatitis E. These viruses belong to different family of viruses and their epidemiological characteristics are different. These infections can be diagnosed by an ELISA for IgM antibody. A vaccine has been developed in last decade of twentieth century for hepatitis A virus, which is administered mostly in the developed world i.e. U.S and Japan. Treatment for these infections is mostly supportive; however, in the case of fulminant hepatitis the liver transplantation might be necessary.

This systematic review and meta-analysis study was conducted to estimate the pooled prevalence of CD in low and high risk groups in this region. Following keywords were searched in the Medline, PubMed, Scopus, Web of Science and Cochrane database according to the MeSH terms; celiac disease, prevalence, high risk population and Asian-Pacific region. Prevalence studies published from January 1991 to March 2018 were selected. Prevalence of CD with 95% confidence interval (CI) was calculated using STATA software, version 14. The pooled sero-prevalence of CD among low risk group in Asia-Pacific region was 1.2% (95% CI 0.8-1.7%) in 96,099 individuals based on positive anti-tissue transglutaminase (anti-t-TG Ab) and/or anti-endomysial antibodies (EMA). The pooled prevalence of biopsy proven CD in Asia-Pacific among high and low risk groups was 4.3% (95% CI 3.3-5.5%) and 0.61% (95% CI 0.4-0.8%) in 10,719 and 70,344 subjects, respectively. In addition, the pooled sero-prevalence and prevalence of CD in general population was significantly higher in children compared with adults and it was significantly greater in female vs. male (P < 0.05). Our results suggest high risk individuals of CD are key group that should be specifically targeted for prevention and control measures, and screening may prove to have an optimal cost-benefit ratio.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with no medical treatment proven to improve survival and postpone liver transplantation. Previous studies have shown the effectiveness of fibrates in primary biliary cholangitis. The current study prospectively evaluated the effect of fenofibrate on PSC patients. We administered 200 mg of fenofibrate to PSC patients in the intervention arm and a placebo in the control arm once per day for 6 months and evaluated liver biochemistries (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, bilirubin, and albumin) and the Mayo Risk Score at the start and end of the study. The primary endpoint was defined as a reduction greater than 50% or normalization of ALP levels. Secondary endpoints were an improvement in the Mayo Risk Score and serum bilirubin levels. Thirty patients were included (19 female, 11 male, 40.2 ± 9.2 years old), all under treatment with Ursodeoxycholic acid prior to this study. ALP and ALT levels significantly decreased in the fenofibrate group, by 64.7% (mean difference = 557, p = 0.004, 95% CI = 208.72, 905.27) and 52.78%, (p = 0.006), respectively. The primary endpoint was achieved in 66.7% of patients (10 in 15) in the fenofibrate group versus 20% of patients (3 in 15) in the placebo group (p = 0.009). Other endpoints were not met. As studies have demonstrated lower levels of ALP may improve outcomes for PSC, our study resulted in significantly lower levels of ALP in the fenofibrate group, which could translate into better disease prognosis in PSC.

The influence of microsatellite instability (MSI) on the prognosis of colorectal cancer (CRC) requires more investigation. We assessed the role of MSI status in survival of individuals diagnosed with primary colorectal cancer. In this retrospective cross-sectional study the MSI status was determined in 158 formalin-fixed paraffin-embedded tumors and their matched normal tissues from patients who underwent curative surgery. Cox proportional hazard modeling was performed to assess the clinical prognostic significance. In this study we found that MSI-H tumors were predominantly located in the colon versus rectum (p = 0.03), associated with poorer differentiation (p = 0.003) and TNM stage II/III of tumors (p = 0.02). In CRC patients with stage II, MSI-L cases showed significantly poorer survival compared with patients who had MSI-H or MSS tumors (p = 0.04). This study indicates that MSI-L tumors correlate with poorer clinical outcome in patients with stage II tumors (p = 0.04) or in tumors located in the colon (p = 0.02). MSI-L characterizes a distinct subgroup of CRC patients who have a poorer outcome. This study suggests that MSI status in CRC, as a clinical prognostic marker, is dependent on other factors, such as tumor stage and location.

Colorectal cancer (CRC) is the second cause of cancer-related deaths worldwide. There have been several studies reporting the proximal tumor shift, especially in Western countries. In the present study, we investigated the clinicopathologic and anatomical distributions of colorectal tumors in Iranian CRC patients.

Clostridioides difficile infection (CDI) is a major cause of morbidity among patients with inflammatory bowel disease (IBD). Diagnostic biomarkers for early detection of CDI are needed in clinical practice. The relationship between serum procalcitonin and CDI in IBD patients has not been investigated so far. Therefore, we aimed to evaluate the usefulness of measuring serum procalcitonin level to detect CDI in patients with the flare of IBD.

Pancreatic cancer is one of the deadliest cancers with short-term survival rates. Trends for pancreatic cancer incidence and mortality varied considerably in the world. To date, the causes of pancreatic cancer are not known sufficiently, although certain risk factors have been identified such as, smoking, obesity, life style, diabetes mellitus, alcohol, dietary factors and chronic pancreatitis. Since there are no current screening recommendations for pancreatic cancer, primary prevention is very important. Therefore, up-to-date statistics on pancreatic cancer occurrence and outcome are essential for the primary prevention of this disease. Due to the lack of information on epidemiology of pancreatic cancer in most Asian countries, and limited of statistics and registration system in this area, we conducted a systematic review study to evaluate the most recent data concerning epidemiology of pancreatic cancer in Asia-Pacific region. In this review we focused on collected recent data on incidence, mortality, survival and risk factors of pancreatic cancer in this region. In addition, we reviewed and used the data of GLOBOCAN 2012 in this paper to complete the information as a source of compiling pancreatic cancer incidence and mortality rate.