Rational design of multi-epitope-based vaccine by exploring all dengue virus serotypes proteome: an immunoinformatic approach.

Millions of people's lives are being devastated by dengue virus (DENV), a severe tropical and subtropical illness spread by mosquitoes and other vectors. Dengue fever may be self-limiting like a common cold or can rapidly progress to catastrophic dengue hemorrhagic fever or dengue shock syndrome. With four distinct dengue serotypes (DENV1-4), each with the potential to contain antibody-boosting complicated mechanisms, developing a dengue vaccine has been an ambitious challenge. Here, we used a computational pan-vaccinomics-based vaccine design strategy (reverse vaccinology) for all 4 DENV serotypes acquired from different regions of the world to develop a new and safe vaccine against DENV. Consequently, only five mapped epitopes from all the 4 serotypes were shown to be extremely effective for the construction of multi-epitope vaccine constructs. The suggested vaccine construct V5 from eight vaccine models was thus classified as an antigenic, non-allergenic, and stable vaccine model. Moreover, molecular docking and molecular dynamics simulation was performed for the V5 vaccine candidate against the HLAs and TRL2 and 4 immunological receptors. Later, the vaccine sequence was transcribed into the cDNA to generate an expression vector for the Escherichia coli K12 strain. Our research suggests that this vaccine design (V5) has promising potential as a dengue vaccine. However, further experimental analysis into the vaccine's efficacy might be required for the V5 proper validation to combat all DENV serotypes.

Delineating multi-epitopes vaccine designing from membrane protein CL5 against all monkeypox strains: a pangenome reverse vaccinology approach.

The recently identified monkeypox virus (MPXV or mpox) is a zoonotic orthopox virus that infects humans and causes diseases with traits like smallpox. The world health organization (WHO) estimates that 3-6% of MPXV cases result in death. As it might impact everyone globally, like COVID, and become the next pandemic, the cure for this disease is important for global public health. The high incidence and disease ratio of MPXV necessitates immediate efforts to design a unique vaccine candidate capable of addressing MPXV diseases. Here, we used a computational pan-genome-based vaccine design strategy for all currently reported 19 MPXV strains acquired from different regions of the world. Thus, this study's objective was to develop a new and safe vaccine candidate against MPXV by targeting the membrane CL5 protein; identified after the pangenome analysis. Proteomics and reverse vaccinology have covered up all of the MPXV epitopes that would usually stimulate robust host immune responses. Following this, only two mapped (MHC-I, MHC-II, and B-cell) epitopes were observed to be extremely effective that can be used in the construction of CL5 protein vaccine candidates. The suggested vaccine (V5) candidate from eight vaccine models was shown to be antigenic, non-allergenic, and stable (with 213 amino acids). The vaccine's candidate efficacy was evaluated by using many in silico methods to predict, improve, and validate its 3D structure. Molecular docking and molecular dynamics simulations further reveal that the proposed vaccine candidate ensemble has a high interaction energy with the HLAs and TRL2/4 immunological receptors under study. Later, the vaccine sequence was used to generate an expression vector for the E. coli K12 strain. Further study uncovers that V5 was highly immunogenic because it produced robust primary, secondary, and tertiary immune responses. Eventually, the use of computer-aided vaccine designing may significantly reduce costs and speed up the process of developing vaccines. Although, the results of this research are promising, however, more research (experimental; in vivo, and in vitro studies) is needed to verify the biological efficacy of the proposed vaccine against MPXV.Communicated by Ramaswamy H. Sarma.

Investigating the role of Kinesin family in lung adenocarcinoma via integrated bioinformatics approach.

Lung cancer is the leading cause of mortality from cancer worldwide. Lung adenocarcinoma (LUAD) is a type of non-small cell lung cancer (NSCLC) with highest prevalence. Kinesins a class of motor proteins are shown to be involved in carcinogenesis. We conducted expression, stage plot and survival analyses on kinesin superfamily (KIF) and scrutinized the key prognostic kinesins. Genomic alterations of these kinesins were studied thereafter via cBioPortal. A protein-protein interaction network (PPIN) of selected kinesins and 50 closest altering genes was constructed followed by gene ontology (GO) term and pathway enrichment analyses. Multivariate survival analysis based on CpG methylation of selected kinesins was performed. Lastly, we conducted tumor immune infiltration analysis. Our results found KIF11/15/18B/20A/2C/4A/C1 to be significantly upregulated and correlated with poor survival in LUAD patients. These genes also showed to be highly associated with cell cycle. Out of our seven selected kinesins, KIFC1 showed the highest genomic alteration with highest number of CpG methylation. Also, CpG island (CGI) cg24827036 was discovered to be linked to LUAD prognosis. Therefore, we deduced that reducing the expression of KIFC1 could be a feasible treatment strategy and that it can be a wonderful individual prognostic biomarker. CGI cg24827036 can also be used as a therapy site in addition to being a great prognostic biomarker.

Regulatory effects of ketogenic diet on the inflammatory response in obese Saudi women.

Objective: In recent years, the use of a ketogenic diet (KD) against obesity has gained popularity in KSA. This study was designed to determine the impact of KD on anthropometric indices and on the abnormal regulation of inflammatory activities in obese Saudi women. Moreover, we investigated the potential of beta-hydroxybutyrate (BHB) supplementation on the inhibition of pro-inflammatory activities. Methods: We enrolled 31 Saudi women (aged, 35.3 ± 8.4 years) with an average BMI of 33.96 ± 4.44 kg/m2 underwent an 8-week KD (8KD) from January to March 2021. Changes in anthropometric measurements were collected at baseline and after 4-8 weeks of intervention. Compliance with the dietary regimen was monitored weekly by plasma BHB level. Results: Twenty-nine females commenced the diets and 23 completed the study (a 79% completion rate). In comparison to pre-intervention, the 8KD resulted in a significant increase in the levels of plasma BHB (P < 0.001) throughout the duration of the trial. This was accompanied by a significant reduction in weight loss (7.7 kg ± 11.3; P < 0.001), BMI, waist circumference (P < 0.001), and levels of the inflammatory cytokine IL-1ß (P < 0.001). Conclusions: An 8-week KD was found to be useful in producing a positive impact on anthropometric indices, biochemical and inflammatory processes. This study indicated that the intake of a KD by obese Saudi women induced the release of BHB in the blood without stimulation of an overall starvation response. This may be useful to alleviate the severity of chronic inflammatory disorders associated with obesity.

Effect of Tea Saponins on Rumen Microbiota and Rumen Function in Qinchuan Beef Cattle.

Antibiotics can promote livestock growth but have side effects, so the search for safe and effective alternatives to antibiotics is urgent. This study aimed to evaluate the effect of supplementing cattle feed with tea saponins on ruminal bacteria and fungi. Sixteen Qinchuan beef cattle with a live body weight of 250 ± 10 kg were divided into four groups (four animals in each group) using a completely randomized experimental design. Four different levels of tea saponins were provided to the Qinchuan cattle as treatments, including 0 g/cattle per day control, CON), 10 g/cattle per day (low-level, LT), 20 g/cattle per day (medium-level, MT) and 30 g/cattle per day (high-level, HT). The pre-feeding period was 10 days and the official period was 80 days in this experiment. After 90 days of feeding, the rumen fluid from sixteen Qinchuan beef cattle was collected using an oral stomach tube for evaluating changes in ruminal microbiota and rumen fermentation parameters. Results indicate that the total VFAs and proportions of propionate in the LT group was significantly higher than that in the CON and HT groups (p < 0.05). For ruminal bacteria, results indicate that the Chao1 index of the MT group was significantly lower than the CON and HT groups (p < 0.05). The phyla Bacteroidetes and Firmicutes were found to be the most abundant in all treatment groups, with the LT group having significantly increased relative abundances of Proteobacteria, Actinobacteria and Ascomycota at the phylum level (p < 0.05). The relative abundance of Bacteroides was found to be relatively lower in the LT, MT and HT treatment groups compared with the CON treatment group at the genus level (p < 0.05). For ruminal fungi, the LT treatment group was found to have higher relative abundances of Saccharomyces and Aspergillus, and lower relative abundances of Succiniclasticum and Bacteroides at the at the phylum level (p < 0.05). Compared with the CON treatment group, a significant increase in the relative abundance of Saccharomyces and Aspergillus were observed in the LT treatment group at the genus level (p < 0.05). PICRUSt analyses identified pathways associated with Xenobiotic biodegradation and metabolism and glycolysisIII to be significantly enriched in the LT and HT treatment groups (p < 0.05). These findings could provide insights on how tea saponins may influence ruminal bacteria and fungi, providing a theoretical basis for replacing antibiotics with tea saponins for promoting growth in cattle.

Bacteriophage Therapy as an Application for Bacterial Infection in China.

Antibiotic resistance has emerged as a significant issue to be resolved around the world. Bacteriophage (phage), in contrast to antibiotics, can only kill the target bacteria with no adverse effect on the normal bacterial flora. In this review, we described the biological characteristics of phage, and summarized the phage application in China, including in mammals, ovipara, aquatilia, and human clinical treatment. The data showed that phage had a good therapeutic effect on drug-resistant bacteria in veterinary fields, as well as in the clinical treatment of humans. However, we need to take more consideration of the narrow lysis spectrum, the immune response, the issues of storage, and the pharmacokinetics of phages. Due to the particularity of bacteriophage as a bacterial virus, there is no unified standard or regulation for the use of bacteriophage in the world at present, which hinders the application of bacteriophage as a substitute for antibiotic biological products. We aimed to highlight the rapidly advancing field of phage therapy as well as the challenges that China faces in reducing its reliance on antibiotics.