Epigenetic modifications in solid tumor metastasis in people of African ancestry.

This review focuses on the critical role of epigenetic modifications in solid tumor metastasis, particularly in people of African ancestry. Epigenetic alterations, such as DNA methylation, histone modifications, alterations in non-coding RNAs, and mRNA methylation, significantly influence gene expression, contributing to cancer development and progression. Despite the primary focus on populations of European, American, and Asian descent in most cancer research, this work emphasizes the importance of studying the unique genetic and epigenetic landscapes of African populations for a more inclusive approach in understanding and treating cancer. Insights from this review have the potential to pave the way for the development of effective, tailored treatments, and provide a richer resource for understanding cancer progression and metastasis. Specific focus was placed on the role of DNA methylation, histone modifications, non-coding RNAs, and mRNA methylation in solid tumor metastasis, including how these modifications contribute to the regulation of tumor suppressor genes and oncogenes, influence cellular pathways and signaling, and interact with the immune system. Moreover, this review elaborates on the development of epigenetic-targeted therapeutic strategies and the current advances in this field, highlighting the promising applications of these therapies in improving outcomes for African ancestry populations disproportionately affected by certain types of cancer. Nevertheless, this work acknowledges the challenges that lie ahead, particularly the under-representation of African populations in cancer genomic and epigenomic studies and the technical complications associated with detecting subtle epigenetic modifications. Emphasis is placed on the necessity for more inclusive research practices, the development of more robust and sensitive methods for detecting and interpreting epigenetic changes, and the understanding of the interplay between genetic and epigenetic variations. The review concludes with an optimistic outlook on the future of epigenetic research in People of African ancestry, urging the concerted efforts of researchers, clinicians, funding agencies, and policymakers to extend the benefits of this research to all populations.

Africa (COVID-19) Vaccine Technology Transfer: Where Are We?

The rampant spread of the COVID-19 infection poses a grave and formidable challenge to global healthcare, with particular concern to the inhabitants of the African continent. In response to these pressing concerns, different strategies have been employed to combat the emergence of this insidious disease, encompassing crucial measures such as physical distancing, the utilization of face masks, meticulous hand hygiene, and widespread vaccination campaigns. Nevertheless, the economic realities faced by numerous African nations, characterized by their classification as "low-income countries (LICs)", present a formidable barrier to accessing and distributing approved vaccines to their populations. Moreover, it is essential to discuss the hesitancy of the European Union (EU) in releasing intellectual property rights associated with the transfer of vaccine technology to Africa. While the EU has been a key player in global efforts to combat the pandemic, there has been reluctance in sharing valuable knowledge and resources with African countries. This hesitancy raises concerns about equitable vaccine access and the potential for a prolonged health crisis in Africa. This review underscores the urgent imperative and need of establishing localized vaccine development and production facilities within Africa, necessitating the active involvement of governments and collaborative partnerships to achieve this crucial objective. Furthermore, this review advocates for the exploration of viable avenues for the transfer of vaccine technology as a means to facilitate equitable vaccine access across the African continent and also the cruciality and the need for the EU to reconsider its stance and actively engage in transferring vaccine technology to Africa through sharing intellectual property. The EU can contribute to the establishment of localized vaccine production facilities on the continent, which will not only increase vaccine availability but also promote self-sufficiency and resilience in the face of future health emergencies.

Proteome based analysis of circulating SARS-CoV-2 variants: approach to a universal vaccine candidate.

The discovery of the first infectious variant in Wuhan, China, in December 2019, has posed concerns over global health due to the spread of COVID-19 and subsequent variants. While the majority of patients experience flu-like symptoms such as cold and fever, a small percentage, particularly those with compromised immune systems, progress from mild illness to fatality. COVID-19 is caused by a RNA virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our approach involved utilizing immunoinformatic to identify vaccine candidates with multiple epitopes and ligand-binding regions in reported SARS-CoV-2 variants. Through analysis of the spike glycoprotein, we identified dominant epitopes for T-cells and B-cells, resulting in a vaccine construct containing two helper T-cell epitopes, six cytotoxic T-cell epitopes, and four linear B-cell epitopes. Prior to conjugation with adjuvants and linkers, all epitopes were evaluated for antigenicity, toxicity, and allergenicity. Additionally, we assessed the vaccine Toll-Like Receptors complex (2, 3, and 4). The vaccine construct demonstrated antigenicity, non-toxicity, and non-allergenicity, thereby enabling the host to generate antibodies with favorable physicochemical characteristics. Furthermore, the 3D structure of the B-cell construct exhibited a ProSA-web z-score plot with a value of -1.71, indicating the reliability of the designed structure. The Ramachandran plot analysis revealed that 99.6% of the amino acid residues in the vaccine subunit were located in the high favored observation region, further establishing its strong candidacy as a vaccination option.

Bioinformatics analysis of structural protein to approach a vaccine candidate against Vibrio cholerae infection.

The bacteria Vibrio cholerae causes cholera, an acute diarrheal infection that can lead to dehydration and even death. Over 100,000 people die each year as a result of epidemic diseases; vaccination has emerged as a successful strategy for combating cholera. This study uses bioinformatics tools to create a multi-epitope vaccine against cholera infection using five structural polyproteins from the V. cholerae (CTB, TCPA, TCPF, OMPU, and OMPW). The antigenic retrieved protein sequence were analyzed using BCPred and IEDB bioinformatics tools to predict B cell and T cell epitopes, respectively, which were then linked with flexible linkers together with an adjuvant to boost it immunogenicity. The construct has a theoretical PI of 6.09, a molecular weight of 53.85 kDa, and an estimated half-life for mammalian reticulocytes in vitro of 4.4 h. These results demonstrate the construct's longevity. The vaccine design was docked against the human toll-like receptor (TLR) to evaluate compatibility and effectiveness; also other additional post-vaccination assessments were carried out on the designed vaccine. Through in silico cloning, its expression was determined. The results show that it has a CAI value of 0.1 and GC contents of 58.97% which established the adequate expression and downstream processing of the vaccine construct, and our research demonstrated that the multi-epitope subunit vaccine exhibits antigenic characteristics. Additionally, we carried out an in silico immunological simulation to examine the immune reaction to an injection. Our results strongly suggest that the vaccine candidate on further validation would induce immune response against the V. cholerae infection.

Immunoinformatics design of multi-epitope peptide for the diagnosis of Schistosoma haematobium infection.

Schistosoma haematobium has been identified as a significant cause of urogenital disease, as well as a risk factor for bladder cancer and HIV/AIDS. The parasites are obtained trans-dermally by swimming or wading in contaminated freshwater, and they are also transmitted to humans by freshwater snails. The organisms infect the vasculature of the gastrointestinal or genitourinary tracts. Worms live in blood vessels and lay eggs that become embedded in the bladder wall, causing chronic immune-mediated disease and squamous cell carcinoma growth. The primary goal of this research is to predict and design a novel synthetic protein containing multiple immunodominant B cell epitopes using three schistosome proteins: XP-012801068.2, XP-012801892.2, and XP-012793835.2 softwares were used to analyze the proteins' primary, secondary, and tertiary structures (BepiPred, BcPred).The B cell construct was then evaluated using I-TASSER server, and physicochemical properties, as well as homology modeling of the 3 D structure of the protein, was obtained. In silico analyses revealed regions with high immunogenicity. For XP-012801068.2, three epitopes are found between residues 292-334, 3-22, and 314-333; for XP-012801892.2, three epitopes are found in the residues 184-236, 81-100, and 329-348 for XP-012793835.2, four epitopes are found in the residues 185-222, 469-512, 649-713, and 338-357. The construct's has an average length of 308 bp, instability index of 49.96, theoretical PI of 4.2 and a C score -1.59. Furthermore, these parameters analyzed reveals that the constructed multi-epitope peptide has the potential to provide a theoretical basis for the development of a Schistosoma haematobium diagnostic kit.Communicated by Ramaswamy H. Sarma.

Bioinformatics Designing and Molecular Modelling of a Universal mRNA Vaccine for SARS-CoV-2 Infection.

At this present stage of COVID-19 re-emergence, designing an effective candidate vaccine for different variants of SARS-CoV-2 is a study worthy of consideration. This research used bioinformatics tools to design an mRNA vaccine that captures all the circulating variants and lineages of the virus in its construct. Sequences of these viruses were retrieved across the six continents and analyzed using different tools to screen for the preferable CD8+ T lymphocytes (CTL), CD4+ T lymphocytes (HTL), and B-cell epitopes. These epitopes were used to design the vaccine. In addition, several other co-translational residues were added to the construct of an mRNA vaccine whose molecular weight is 285.29686 kDa with an estimated pI of 9.2 and has no cross affinity with the human genome with an estimated over 68% to cover the world population. It is relatively stable, with minimal deformability in its interaction with the human innate immune receptor, which includes TLR 3 and TLR 9. The overall result has proven that the designed candidate vaccine is capable of modulating cell-mediated immune responses by activating the actions of CD4+ T cells, natural killer cells, and macrophages, and displayed an increased memory T cell and B cell activities, which may further be validated via in vivo and in vitro techniques.