A multi-epitope based vaccine against the surface proteins expressed in cyst and trophozoite stages of parasite Entamoeba histolytica.

Entamoeba histolytica, an anaerobic parasite, infects humans and other primates and causes fatal diseases, such as amebiasis, amebic liver abscesses, and many others. Thousands of people are infected and dying due to the need for a proper protective cure, especially in poor sanitizing regions, such as Latin America, Asia, and Africa. Around 10% of the world population is infected by E. histolytica every year. Consequently, novel preventive approaches are required to eliminate the threats of the parasite. A designed vaccine targeting the exposed proteins that are common between cyst and trophozoite stages of the parasite's life cycle would be an effective way to repress the impact of the parasite. Therefore, an in silico bioinformatics approach was performed to design an effective vaccine targeting surface proteins common between both stages of the parasite's life cycle using B-cell and T-cell epitopes. The epitopes derived from the conserved portions of the proteins and their corresponding isomers specific to the parasite suggested that the vaccine could benefit cross-protection. Furthermore, the three-dimensional structure of the designed vaccine was modelled, refined, and validated using multiple bioinformatics tools. The physiological properties and solubility were also predicted using different algorithmic tools and found to be highly soluble in nature. The vaccine was found interactcted with TLR immune receptors, and the stability was observed via dynamics simulation. Codon optimization and cloning were performed for expression analysis. Immune simulation prediction anticipated significant immune responses with a high IgG and IgM antibodies expression, Th and Tc cells population, B-cell population, memory cells, INF-γ, and IL-2 cytokines. Therefore, the constructed multi-epitope putative vaccine can effectively neutralize the parasite's harmful effects.

High-impact opportunities to address ischemia: a focus on heart and circulatory research.

Myocardial ischemic injury and its resolution are the key determinants of morbidity or mortality in heart failure. The cause and duration of ischemia in patients vary. Numerous experimental models and methods have been developed to define genetic, metabolic, molecular, cellular, and pathophysiological mechanisms, in addition to defining structural and functional deterioration of cardiovascular performance. The rapid rise of big data, such as single-cell analysis techniques with bioinformatics, machine learning, and neural networking, brings a new level of sophistication to our understanding of myocardial ischemia. This mini-review explores the multifaceted nature of ischemic injury in the myocardium. We highlight recent state-of-the-art findings and strategies to show new directions of high-impact approach to understanding myocardial tissue remodeling. This next age of heart and circulatory physiology research will be more comprehensive and collaborative to uncover the origin, progression, and manifestation of heart failure while strengthening novel treatment strategies.

The polymorphic landscape analysis of GATA1 exons uncovered the genetic variants associated with higher thrombocytopenia in dengue patients.

The current study elucidated an association between gene variants and thrombocytopenia through the investigation of the exonic polymorphic landscape of hematopoietic transcription factor-GATA1 gene in dengue patients. A total of 115 unrelated dengue patients with dengue fever (DF) (N = 91) and dengue hemorrhagic fever (DHF) (N = 24) were included in the study. All dengue patients were confirmed through detection of NS1 antigen, IgM, and IgG antibodies against the dengue virus. Polymerase chain reaction using specific primers amplified the exonic regions of GATA1 while Sanger sequencing and chromatogram analyses facilitated the identification of variants. Variants G>A (at chX: 48792009) and C>A (at chX: 4879118) had higher frequency out of 13 variants identified (3 annotated and 10 newly recognized). Patients carrying either nonsynonymous or synonymous variants had significantly lower mean values of platelets compared to those harboring the reference nucleotides (NC_000023.11). Further analyses revealed that the change in amino acid residue leads to the altered three-dimensional structure followed by interaction with neighboring residues. Increased stability of the protein due to substitution of serine by asparagine (S129N at chX: 48792009) may cause increased rigidity followed by reduced structural flexibility which may ultimately disturb the dimerization (an important prerequisite for GATA1 to perform its biological activity) process of the GATA1 protein. This, in turn, may affect the function of GATA1 followed by impaired production of mature platelets which may be reflected by the lower platelet counts in individuals with such variation. In summary, we have identified new variants within the GATA1 gene which were found to be clinically relevant to the outcome of dengue patients and thus, have the potential as candidate biomarkers for the determination of severity and prognosis of thrombocytopenia caused by dengue virus. However, further validation of this study in a large number of dengue patients is warranted. Trial Registration: number SLCTR/2019/037.