The metabolic fingerprint of chronic hepatitis C progression: Metabolome shifts and cutting-edge diagnostic options.

Hepatitis C virus infection causes chronic diseases such as cirrhosis and hepatocellular carcinoma. Metabolomics research has been shown to be linked to pathophysiologic pathways in liver illnesses. The aim of this study was to investigate the serum metabolic profile of patients with chronic hepatitis C (CHC) infection and to identify underlying mechanisms as well as potential biomarkers associated with the disease. Nuclear magnetic resonance (NMR) was used to evaluate the sera of 83 patients with CHC virus and 52 healthy control volunteers (NMR). Then, multivariate statistical analysis was used to find distinguishing metabolites between the two groups. Sixteen out of 40 metabolites including include 3-HB, betaine, carnitine, creatinine, fucose, glutamine, glycerol, isopropanol, lysine, mannose, methanol, methionine, ornithine, proline, serine, and valine-were shown to be significantly different between the CHC and normal control (NC) groups (variable importance in projection >1 and p < 0.05). All the metabolic perturbations in this disease are associated with pathways of Glycine, serine, and threonine metabolism, glycerolipid metabolism, arginine and proline metabolism, aminoacyl-tRNA biosynthesis, cysteine and methionine metabolism, alanine, aspartate, and glutamate metabolism. Multivariate statistical analysis constructed using these expressed metabolites showed CHC patients can be discriminated from NCs with high sensitivity (90%) and specificity (99%). The metabolomics approach may expand the diagnostic armamentarium for patients with CHC while contributing to a comprehensive understanding of disease mechanisms.

Association of MMP7 T > C Gene Variant (rs10502001) and Expression in Chronic Obstructive Pulmonary Disease.

Patients with chronic obstructive pulmonary disease (COPD) have obstructed airflow through their lungs. Single nucleotide polymorphisms in matrix metalloproteinases (MMPs) genes and the risk of COPD have been the subject of numerous studies, with conflicting results. This investigation was conducted to determine whether the MMP7 (T>C) gene variant (rs10502001) was associated with an increased risk of COPD. A case-control study was conducted with 360 subjects (180 healthy controls and 180 COPD cases). The polymerase chain reaction (PCR)-restriction fragment length polymorphism method was used to genotype the SNP rs1050200. mRNA expression of MMP7 was performed using RT-PCR. The genotypic/allelic frequencies and carriage rates of rs10502001 (T>C) polymorphism were evaluated in 180 each of healthy controls and COPD cases. Cases have higher TC/CC genotype frequencies than controls. The "CC" genotype was found to be significantly associated with increased COPD risk (p = 0.016). The "C" allele frequency was higher in cases than in controls and showed significant association with COPD (p = 0.005). The carriage rate frequencies of T(-) and C(+) were significantly higher in cases than in controls (p = 0.031 and 0.047, respectively). MMP7 expression was significantly upregulated (p = 0.001) in COPD cases as compared with the controls. In addition, comparisons of MMP7 expression between the COPD cases with different genotypes showed that the "CC" genotype cases had significantly higher expression than those with "TT" genotype. The present findings showed statistically significant correlation of MMP7 (T>C) polymorphism and expression with COPD. Therefore, MMP7 responsible for degradation of elastin has been strongly linked to the progression of COPD.

TNF-α and MMPs mediated mucus hypersecretion induced by cigarette smoke: An in vitro study.

Cigarette smoke is one of the leading causes of oxidative stress due to high levels of free radicals, which in turn leads to the degradation of alveolar cell walls and development of emphysema. Cigarette smoking has been linked to chronic bronchitis, Chronic Obstructive Pulmonary Disease (COPD) and lung cancer as well. The aim of the present study was to observe the effect of cigarette smoke extract (CSE) on TNF-α and MMPs mediated mucus hypersecretion in A549 cell line. The MTT experiments showed that CSE caused a dose-dependent decline in the level of viability of A549 cells. In addition, AO/PI and Mitotracker Red staining assays demonstrated that CSE caused the A549 cells to undergo apoptosis. This was determined by observing the reduction in mitochondrial membrane potential. CSE was found to be responsible for the formation of intracellular ROS, which was observed by DCFDA staining through fluorescence microscopy. Approximately 65% migration rate was decreased in 20% CSE exposed cells. CSE exposure led to the significantly increased mRNA levels of TNF-α, MMP-7, and MMP-12, in comparison to the control cells. Additionally, the expression of MUC5AC and MUC5B was provoked by CSE as well. Human epithelial cells are stimulated by TNF-α and MMPs secreted mucus, as shown by expression of MUC5AC and MUC5B. CSE could induce mucus in lungs through TNF-α and MMPs mediated pathways.

A Comparative Analysis of the APRI, FIB4, and FibroScan Score in Evaluating the Severity of Chronic Liver Disease in Chronic Hepatitis B Patients in India.

Background and aims Non-invasive assessment methods to assess liver fibrosis are important tools where FibroScan or liver biopsy is not accessible. The aim of this study is to assess the efficacy and performance of the fibrosis index based on four factors (FIB-4) and aspartate transaminase-to-platelet ratio index (APRI) to evaluate liver fibrosis against FibroScan for the stages of liver fibrosis in patients of chronic liver disease due to chronic hepatitis B (CHB). Methods This was a cross-sectional study conducted in a tertiary care center in Uttar Pradesh, India, and the patients were enrolled between 2017 and 2020. During the study period, 520 patients with a confirmed diagnosis of chronic hepatitis B virus (HBV) infection were selected. Laboratory blood testing and FibroScan were performed in all patients with CHB. APRI and FIB-4 were calculated using a standard formula involving laboratory parameters. Result The performance of FIB-4 scores are nearly similar to APRI, with area under the curve (AUC) 0.753, (95% CI) (0.711-0.795) (p<0.0001) for ≥F2 fibrosis (significant fibrosis) and even better 0.851 (0.815-0.887) (p<0.0001) for the F4 fibrosis (cirrhosis) group. Both the tests are proven good to diagnose fibrosis but FIB-4 has more area under the receiver operating characteristic (AUROC) than APRI in each set, thus FIB-4 is considered better than APRI. Conclusions APRI and FIB-4 scores showed good performance in detecting patients without liver fibrosis as compared with FibroScan. Based on this study, FibroScan can be avoided in patients examined for the diagnosis of mild fibrosis and cirrhosis in the source constrained area.

Previous history of surgery in females and roadside shaving in males are the commonest risk factors for hepatitis C infection: A cross-sectional retrospective study.

BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) is a causative agent of hepatitis C disease of the liver. We have analysed the major risk factors including demographic, clinical and genotypic distribution among HCV seropositive patients and their distribution in Uttar Pradesh, India. METHODS: This study was conducted by a questionnaire-based proforma, filled in Hepatobiliary Clinic, Department of Medicine, King Georg's Medical University, Lucknow, from 2014 to 2017. Demographic, clinical and laboratory data were recorded. Seropositivity was demonstrated through an anti-HCV IgG ELISA kit. Positive patients were further examined for HCV RNA by RT-PCR. RESULTS: A total of 31,440 patients attended the hepatobiliary clinic. Among these, 310 (0.99%) patients were confirmed for HCV infection and there was no significant difference between males and females (50.3% vs. 49.7%). Previous surgery (49.0%), dental extraction (41.0%) and roadside shaving (38.1%) were the major risk factors for HCV infection. We also observed that previous surgery 143/154 (92.9%) in female and roadside shaving 118/156 (75.6%) in male was the commonest factor for HCV, however; dental extraction was comparable among male and female (65 [51.8%] vs 62 [48.2%], P value = 0.818). HCV RNA genotype 3 (81.6%) was the most frequent followed by 3a (11.3%), 3b (5.8%), 1 (0.7%) and 4 (0.7%). In the district-wise analysis, frequent cases were included from Lucknow with previous surgery and dental extraction as the commonest risk factor. INTERPRETATION AND CONCLUSIONS: Previous surgery among female and roadside shaving among males are the commonest risk factors for HCV. This study suggests a powerful and strict guideline, to avoid HCV infection.

APRI and FIB-4 performance to assess liver fibrosis against predefined Fibroscan values in chronic hepatitis C virus infection.

BACKGROUNDS AND AIMS: Chronic hepatitis C (CHC) infection can leads to chronic liver disease, fibrosis, then cirrhosis, and, finally, hepatocellular carcinoma (HCC); moreover, it is the most common indication for liver transplantation. Liver biopsy is still the gold standard method for the staging of liver fibrosis as it is an invasive procedure with complications. There are some noninvasive methods such as fibroscan that are now the investigation of choice; FIB-4 and aminotransferase to platelet ratio index (APRI) are other noninvasive tools to assess liver fibrosis by using aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelet count, and age. This study aims to evaluate the efficacy and performance of FIB-4 and APRI against fibroscan in patients infected with the hepatitis C virus. METHOD: It is a cross-sectional study that was conducted in a tertiary health care center in Uttar Pradesh, India, from January 2017 to January 2020. Fibroscan was done for all patients. A blood sample was used to determine AST, ALT, and platelet count. FIB-4 and APRI were calculated from laboratory data. RESULT: 187 of the 487 patients in the study have F0-F1 fibrosis, 69 have F2, 53 have F3 fibrosis, and 178 have cirrhosis. Based on receiver operating characteristic (ROC) analysis, single optimum cut-offs for diagnosing significant fibrosis and cirrhosis were 1.2 for APRI and 2.25 for FIB-4. CONCLUSIONS: Compared with Fibroscan, APRI and FIB-4 showed good performance in detecting the patients without liver fibrosis as well as satisfactory performance in detecting significant fibrosis. These scores should be used in combination with other noninvasive scores for an accurate assessment of liver fibrosis.

A cutting-edge immunoinformatics approach for design of multi-epitope oral vaccine against dreadful human malaria.

Human malaria is a pathogenic disease mainly caused by Plasmodium falciparum, which was responsible for about 405,000 deaths globally in the year 2018. To date, several vaccine candidates have been evaluated for prevention, which failed to produce optimal output at various preclinical/clinical stages. This study is based on designing of polypeptide vaccines (PVs) against human malaria that cover almost all stages of life-cycle of Plasmodium and for the same 5 genome derived predicted antigenic proteins (GDPAP) have been used. For the development of a multi-immune inducer, 15 PVs were initially designed using T-cell epitope ensemble, which covered >99% human population as well as linear B-cell epitopes with or without adjuvants. The immune simulation of PVs showed higher levels of T-cell and B-cell activities compared to positive and negative vaccine controls. Furthermore, in silico cloning of PVs and codon optimization followed by enhanced expression within Lactococcus lactis host system was also explored. Although, the study has sound theoretical and in silico findings, the in vitro/in vivo evaluation seems imperative to warrant the immunogenicity and safety of PVs towards management of P. falciparum infection in the future.

Novel coronavirus (COVID-19) and its potential G.I. manifestation: A review.

The outbreak of the new coronavirus in Wuhan, Chinese Hubei City (COV-2) was also known as COVID-19 and has spread to more than 213 countries, zones or territories worldwide, and is an emergency of international public health with no antiviral drugs or vaccines; and, also, the presencouragement of the disease has become a global public health emergency. This novel coronavirus is now the seventh member of the coronaviridae family, known for infecting humans and showing evidence of causing gastric symptoms, and has the potential to be transmitted through the fecal-oral route according to a new report published online by physicians at Shanghai Jiao Tong University (Gastroenterology. 2020 March 3. doi: 10.1053/j.gastro. 2020.02.054). Here we identify the efforts to compile and disseminate the COVID-19 epidemiological information on Its potential G.I. Demonstration of news media and social networks, and few newspapers recently published. Physicians should know, how GI manifestation discussed in different publications to suspect CORONA virus infection in that patients who does not have any upper and lower respiratory tract symptom and intervein to discuss the disease severity and duration. It will increase the threshold of suspicion of physician toward Covid-19 disease.

Exploitation of reverse vaccinology and immunoinformatics as promising platform for genome-wide screening of new effective vaccine candidates against Plasmodium falciparum.

BACKGROUND: In the current scenario, designing of world-wide effective malaria vaccine against Plasmodium falciparum remain challenging despite the significant progress has been made in last few decades. Conventional vaccinology (isolate, inactivate and inject) approaches are time consuming, laborious and expensive; therefore, the use of computational vaccinology tools are imperative, which can facilitate the design of new and promising vaccine candidates. RESULTS: In current investigation, initially 5548 proteins of P. falciparum genome were carefully chosen for the incidence of signal peptide/ anchor using SignalP4.0 tool that resulted into 640 surface linked proteins (SLP). Out of these SLP, only 17 were predicted to contain GPI-anchors using PredGPI tool in which further 5 proteins were considered as malarial antigenic adhesins by MAAP and VaxiJen programs, respectively. In the subsequent step, T cell epitopes of 5 genome derived predicted antigenic adhesins (GDPAA) and 5 randomly selected known malarial adhesins (RSKMA) were analysed employing MHC class I and II tools of IEDB analysis resource. Finally, VaxiJen scored T cell epitopes from each antigen were considered for prediction of population coverage (PPC) analysis in the world-wide population including malaria endemic regions. The validation of the present in silico strategy was carried out by comparing the PPC of combined (MHC class I and II) predicted epitope ensemble among GDPAA (99.97%), RSKMA (99.90%) and experimentally known epitopes (EKE) of P. falciparum (97.72%) pertaining to world-wide human population. CONCLUSIONS: The present study systematically screened 5 potential protective antigens from P. falciparum genome using bioinformatics tools. Interestingly, these GDPAA, RSKMA and EKE of P. falciparum epitope ensembles forecasted to contain highly promiscuous T cell epitopes, which are potentially effective for most of the world-wide human population with malaria endemic regions. Therefore, these epitope ensembles could be considered in near future for novel and significantly effective vaccine candidate against malaria.