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.

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 N99% 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.

SummaryThe rDNA region of eukaryotes has the immense potential to resolve the evolutionary and phylogeny problems using molecular markers. As evident from the present review, ITS region data is considered for interpretation of inter and intra-specifi c variations of 136 studies of 33 families including 78 genus and 114 species affecting individuals worldwide. Along with ITS-1 and ITS-2 region in 29 studies 18S region, in 38 studies 28S region and in 43 studies mitochondrial genes (COI and NDI) were also analyzed. Three new genera (Allobilharzia gen. nov., Caulanus gen. nov., and Latuterus gen. nov.) and 49 new species were discovered. Only 47 studies expressed variations at intra-specifi c and inter-specifi c level in complete ITS region, ITS-1 and ITS-2 rDNA sequences due to differences in nucleotide positions. According to the fi ndings ITS region is more reliable and precise marker for demarcation and identifi cation of species in combination of other DNA markers. Major studies were involved around the parasites of families Fasciolidae, Schistosomatidae, Opisthorchidae, Paragonimidae and Paramphistomidae, Clinostomidae, Diplostomidae, Haploporidae, among others infecting humans, farm animals, birds, fi shes, reptiles and amphibians on the clinical basis. In future, molecular and bioinformatics aspects based on genetic variations will lead to explore the untouched areas of trematodes.

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.

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Osteo-Arthritis (OA) is a disease of joints affecting the normal functions of joint and causes physical disability. Many factors are responsible for development of osteoarthritis including over age, obesity, gender, drug abuse, over load on joints and genetic factors. OA causes health problems and impairs the quality of life with increased economic burden across the world. Apart from the pro-inflammatory role of cytokine Interleukin-1 (IL-1) in osteoarthritis, Tumor necrosis factor-alpha (TNF-α) is also involved in the progression of osteoarthritis. Members of TNF family are secreted from lymphocytes and natural killer cells but in OA patients it is also secreted from chondrocyte cells to influence the catabolic processes in Extra Cellular Matrix (ECM) by inducing the activity of matrix metaloproteinases (MMPs). In promoter region, most of the Single nucleotide polymorphisms (SNPs) of TNF-α located on -863, -857, -308, and -238. These SNPs are involved in various diseases including OA, rheumatoid Arthritis, systemic lupus erythematosus etc. Significance association of SNP -G308A of the TNF-α gene in OA has been observed in various studies. Aim of this mini review is to conclude the fundamental roles of TNF-α cytokine in patients with OA.

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