An immuno-informatics approach for annotation of hypothetical proteins and multi-epitope vaccine designed against the Mpox virus.

A worrying new outbreak of Monkeypox (Mpox) in humans is caused by the Mpox virus (MpoxV). The pathogen has roughly 28 hypothetical proteins of unknown structure, function, and pathogenicity. Using reliable bioinformatics tools, we attempted to analyze the MpoxV genome, identify the role of hypothetical proteins (HPs), and design a potential candidate vaccine. Out of 28, we identified seven hypothetical proteins using multi-server validation with high confidence for the occurrence of conserved domains. Their physical, chemical, and functional characterizations, including molecular weight, theoretical isoelectric point, 3D structures, GRAVY value, subcellular localization, functional motifs, antigenicity, and virulence factors, were performed. We predicted possible cytotoxic T cell (CTL), helper T cell (HTL) and linear and conformational B cell epitopes, which were combined in a 219 amino acid multiepitope vaccine with human ß defensin as a linker. This multi-epitopic vaccine was structurally modelled and docked with toll-like receptor-3 (TLR-3). The dynamical stability of the vaccine-TLR-3 docked complexes exhibited stable interactions based on RMSD and RMSF tests. Additionally, the modelled vaccine was cloned in-silico in an E. coli host to check the appropriate expression of the final vaccine built. Our results might conform to an immunogenic and safe vaccine, which would require further experimental validation.Communicated by Ramaswamy H. Sarma.

A review on enhanced microplastics derived from biomedical waste during the COVID-19 pandemic with its toxicity, health risks, and biomarkers.

The COVID-19 pandemic led to the explosion of biomedical waste, a global challenge to public health and the environment. Biomedical waste comprising plastic can convert into microplastics (MPs, < 5 mm) by sunlight, wave, oxidative and thermal processes, and biodegradation. MPs with additives and contaminants such as metals are also hazardous to many aquatic and terrestrial organisms, including humans. Bioaccumulation of MPs in organisms often transfers across the trophic level in the global food web. Thus, this article aims to provide a literature review on the source, quantity, and fate of biomedical waste, along with the recent surge of MPs and their adverse impact on aquatic and terrestrial organisms. MPs intake (ingestion, inhalation, and dermal contact) in humans causing various chronic diseases involving multiple organs in digestive, respiratory, and reproductive systems are surveyed, which have been reviewed barely. There is an urgent need to control and manage biomedical waste to shrink MPs pollution for reducing environmental and human health risks.

The Role of miR-29s in Human Cancers-An Update.

MicroRNAs (miRNAs) are small non-coding RNAs that directly bind to the 3' untranslated region (3'-UTR) of the target mRNAs to inhibit their expression. The miRNA-29s (miR-29s) are suggested to be either tumor suppressors or oncogenic miRNAs that are strongly dysregulated in various types of cancer. Their dysregulation alters the expression of their target genes, thereby exerting influence on different cellular pathways including cell proliferation, apoptosis, migration, and invasion, thereby contributing to carcinogenesis. In the present review, we aimed to provide an overview of the current knowledge on the miR-29s biological network and its functions in cancer, as well as its current and potential applications as a diagnostic and prognostic biomarker and/or a therapeutic target in major types of human cancer.

An updated review on the role of the CXCL8-CXCR1/2 axis in the progression and metastasis of breast cancer.

Chronic inflammation is a major factor in tumor growth and progression. Cancer cells secrete C-X-C chemokine ligand 8 (CXCL8) along with its receptor C-X-C chemokine receptor 1 (CXCR1) and chemokine receptor 2 (CXCR2). It plays a significant role in the activation and trafficking of inflammatory mediators, tumor proliferation and interferes in breast cancer development by controlling cell adhesion, proliferation, migration, and metastasis. This axis also plays a significant role in driving different cancers and melanomas, including breast cancer progression, by controlling stem cell masses. Few small-molecule CXCR1/2 inhibitors and CXCL8 releasing inhibitors have been identified in the past two decades that bind these receptors in their inactive forms and blocks their signaling as well as the biological activities associated with inflammation. Inhibitors of certain inflammatory molecules are projected to be more efficient in different inflammatory diseases. Preclinical trials indicate that patients may be benefitted from combined treatment with targeted drugs, chemotherapies, and immunotherapies. Thus, targeting the CXCL8-CXCR1/2 signaling axis in breast cancer could be a promising approach for its therapeutics. This review examines the roles of the CXCL8-CXCR1/2 signaling axis and how it is implicated in the tumor microenvironment in breast cancer. In addition, we also discuss the potential role of the CXCL8-CXCR1/2 axis in targeted therapeutics for breast cancer.

MiR-21 in the Cancers of the Digestive System and Its Potential Role as a Diagnostic, Predictive, and Therapeutic Biomarker.

MicroRNAs (miRNAs) are small non-coding RNAs. They can regulate the expression of their target genes, and thus, their dysregulation significantly contributes to the development of cancer. Growing evidence suggests that miRNAs could be used as cancer biomarkers. As an oncogenic miRNA, the roles of miR-21 as a diagnostic and prognostic biomarker, and its therapeutic applications have been extensively studied. In this review, the roles of miR-21 are first demonstrated via its different molecular networks. Then, a comprehensive review on the potential targets and the current applications as a diagnostic and prognostic cancer biomarker and the therapeutic roles of miR-21 in six different cancers in the digestive system is provided. Lastly, a brief discussion on the challenges for the use of miR-21 as a therapeutic tool for these cancers is added.

Toxicity and biomarkers of micro-plastic in aquatic environment: a review.

Microplastics (MPs; <5 mm) are found in all aquatic environments. Due to harmful impacts, MPs pose a great threat to the aquatic ecology. Therefore, this review aims to provide an overview of the risk, bioavailability, and toxicity of MPs in aquatic organisms. Various factors affecting MPs bioavailability and level of risks at cellular and molecular level on aquatic organisms are comprehensively discussed. More specifically biomarkers for antioxidant response (superoxide dismutase, catalase, glutathione peroxidase, reductase, and glutathione S-transferase), neurotoxic impairment (acetylcholinesterase), lysosomal activity alteration, and genotoxicity have been discussed in detail. Biomarkers are powerful tool in the monitoring programme, but the collection of literature on biomarkers for MPs is limited. Thus, here we demonstrate how to evaluate MPs impact, in monitoring programme, on organisms using biomarkers in aquatic environment. This review would broaden the existing knowledge on the toxic effect and biomarkers of MPs and offer research priorities for future studies.