Search

Carboxypeptidase B (CPB) in Anopheles spp. breaks down blood and releases free amino acids, which promote Plasmodium sexual development in the mosquito midgut. Our goal was to computationally assess the inhibitory effectiveness of carboxypeptidase inhibitors obtained from tomato, potato (CPiSt), and leech against the Anopheles stephensi CPBAs1 and CPBAs2 enzymes. The tertiary structures of CPB inhibitors were predicted and their interaction mode with CPBAs1 and CPBAs2 were examined using molecular docking. Next, this data was compared with four licensed medications that are known to reduce the Anopheles' CPB activity. Molecular dynamics simulations were used to evaluate the stability of complexes containing CPiSt and its mutant form. Both CPiSt and its mutant form showed promise as possible candidates for further evaluations in the paratransgenesis technique for malaria control, based on the similar bindings of CPiSt and CPiSt-Mut to the active sites of CPBAs1 and CPBAs2, as well as their binding affinity in comparison to the drugs., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Cancer testis antigens (CTAs) are a family of proteins typically expressed in male testicles but overexpressed in various cancer cell types. Transmembrane Phosphatase with Tensin homology (TPTE) is expressed only in the testis of healthy individuals and is a member of the family of CTAs. The current study, for the first time, examined the significance of TPTE expression in prostate cancer (PCa) tissues by generating a novel antibody marker targeting TPTE protein., Methods: Polyclonal antibodies were prepared for TPTE-p1 and TPTE-p2 peptides, which are derived from the extracellular domains of TPTE. Anti-TPTE-p2 antibody was then used to study the extent and pattern of TPTE expression in 102 PCa and 48 benign prostatic hyperplasia (BPH) tissue samples by immunohistochemistry. The viability of cancer cell lines (PC-3 and MCF-7 cells) was also evaluated in the presence of anti-TPTE-p2 antibody using the MTT test., Results: The immunohistochemical analysis demonstrated a significant increase in cytoplasmic and membrane TPTE expression in the PCa samples compared to the BPH group (both P < 0.0001). Cytoplasmic TPTE expression was positively correlated with Gleason score and PSA levels (P = 0.03 and P = 0.001, respectively). Significant correlations were identified between the levels of PSA and perineural invasion and the membrane expression (P = 0.01, P = 0.04, respectively). Moreover, anti-TPTE-p2 antibody inhibited PC-3 and MCF-7 cells proliferation compared to the control group for 24 h (P < 0.001 and P = 0.001, respectively) as well as for 48 h (P = 0.001 and P = 0.001, respectively)., Conclusion: Our findings indicate that increased TPTE expression is associated with progression of disease. The ability of anti-TPTE-p2 antibody to recognize and target the TPTE protein makes it a potential biomarker to assess and/or target the PCa., (© 2024. The Author(s).)

The lack of effective medicines or vaccines, combined with climate change and other environmental factors, annually subjects a significant proportion of the world's inhabitants to the risk of dengue virus (DENV) infection. These conditions increase the likelihood of exposure to mosquito-borne diseases such as dengue fever. Hence, many research approaches tend to develop efficient vaccine candidates against the dengue virus. Therefore, we used immunoinformatics and bioinformatics to design a construction for developing a candidate vaccine against dengue virus serotypes. In this study, the in silico structure, containing the non-structural protein 1 region (NS1) (consensus and epitope), the envelope domain III protein (EDIII) as the structural part of the virus construction, and the bc-loop of envelope domain II (EDII) as the neutralizing and protected epitope, were employed. We utilized in silico tools to enhance the immunogenicity and effectiveness of dengue virus vaccine candidates. Evaluations included refining and validating physicochemical characteristics, B and T-cell epitopes, homology modeling, and the three-dimensional structure to assess the designed vaccine's quality. In silico results for tertiary structure prediction and validation revealed high-quality modeling for all vaccine constructs. Additionally, the instructed model demonstrated stability throughout molecular dynamics simulation. The results of the immune simulation suggested that the titers of IgG and IgM could be raised to desirable values following injection into in vivo models. It can be concluded that the designed construct effectively induce humoral and cellular immunity and can be proposed as effective vaccine candidate against four dengue serotypes.Communicated by Ramaswamy H. Sarma.