Background: Ceria (CeO2) is the focus of constant and diverse research interest due to its wide industrial applications. In particular, ceria-based mixed oxides with nanostructures exhibit better catalytic properties owing to high specific surface area, improved sintering properties and high oxygen storage-release characteristics in comparison to the individual bulk materials. This work is aimed at analyzing the significance of doping in the ceria lattice to enhance CO and soot oxidation activity over a series of CeO2-La2O3, CeO2-Sm2O3, CeO2-Eu2O3 and CeO2-Gd2O3 mixed oxides. Keywords: Ceria, solid solutions, CO oxidation, soot oxidation, redox property, H2-TPR.
HIV/AIDS pandemic is one of the leading cause of death worldwide and a matter of serious concern to the scientific world. Most of new HIV infections spread through heterosexual mode and leads to HIV-1 induced immune system activation. This renders infected individuals more susceptible to HIV-1 pathogenesis and opportunistic infections. Hence, preventing HIV infections at early stages and neutralising its effect on host cells is essential in combating AIDS epidemic.
Methods
Human haemoglobin derived peptide, named HbAHP-25, was designed in silico against CD4 binding domain of gp120 by molecular docking methods. HbAHP-25 was characterised for its inhibitory activity on various strains of HIV-1 in PBMCs in the presence and absence of seminal plasma and vaginal fluid. Specificity of action of HbAHP-25 was determined by HIV-1 pseudotyped assays. Immunofluorescence, Multiplex Cytokine assay and Dual Chamber assays were performed to evaluate safety of HbAHP-25 and its role in modulating immune response to HIV.
Results
HbAHP-25 has significant anti-HIV activity against various strains of HIV-1 in a dose dependent fashion. HbAHP-25 binds to a site proximal to CD4 binding site on gp120, has partial epitope similarity with VRC01 on gp120 and inhibits gp120-CD4 interaction. Flow cytometery analysis showed that HbAHP-25 specifically binds to gp120 expressing HL2/3 cells. HbAHP-25 inhibits HIV-1 and doesn’t inhibit HIV-1 pseudotyped virus from entering cells. Further, HbAHP-25 didn’t affect cell viability even at higher concentrations; nor did it have any effect on epithelial monolayer integrity. HbAHP-25 doesn’t elicit any pro-inflammatory response and protects cells from HIV induced inflammation. Results indicate that HbAHP-25 prevents HIV-1 from activating NF-kB pathway, thus limiting its ability to induce cytokines.
Conclusion
HbAHP-25 protects cells from HIV-1 entry and HIV-1 induced inflammation by binding proximal to CD4 binding site of gp120. HbAHP-25 maintained good safety profile and can be a potential molecule for pre-clinical development of prophylactic/anti-HIV drug.
The herb Evolvulus nummularius (L). L generally grown as an ornamental plant. This herb has found many applications in traditional folk medicine. There was however insufficient scientific data to back its safety to be used on humans. Methanolic extract of E. nummularius was used to check for its safety as a vaginal microbicide through various safety tests such as cell viability using MTT assay on three female genital tract epithelial cell lines, vaginal (VK2/E6E7), endocervical (End1/E6E7) and endometrial (HEC-1-A). Quantification of hemolytic activity was done on human red blood cells (RBCs). Determination of cellular integrity was checked by transepithelial electrical resistance (TER) assay and permeability by fluorescent microsphere assay. At 24 hours, application of the extract for cell viability assay showed extensive cell death with cell disruption. IC50 of VK2/E6E7 and HEC-1-A cells were found to be 2 mg/ml, IC50of End1/E6E7 was 1 mg/ml. For hemolytic assay, with treatment of the extract for one hour did not show hemolysis till the concentration of 2.5mg/ml. In TER and microsphere permeability assays, polarized HEC-1-A monolayer 24 hours post treatment had significant drop in TER and enhanced fluorescence from passage of microspheres implying disruption of the epithelial monolayer. The study revealed the crude methanolic extract appeared to be toxic towards human RBCs and female genital tract epithelial cells. Due to its toxic nature, its direct applications to the human vaginal tissue in vivo should be done with caution. Keywords: Medicinal plants; Microbicide; Evolvulus nummularius (L). L; MTT assay; Transepithelial electrical resistance; Fluorescent microsphere assay. Â Â
The global increase in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and sexually transmitted infections (STIs) has led to the introduction of barrier methods, such as condoms. However, drawbacks associated with condoms, such as men being reluctant to use them and women being unable to negotiate their use, have led to the search for better and acceptable alternatives, namely the microbicides. These are gel formulations that, when used prior to sexual intercourse, protect against the transmission of HIV and other STIs. However, after observing the side-effects of nonoxynol-9, a component of the microbicidal formulations available on the market, the focus has shifted to natural available compounds demonstrating the preferred protective effects. Antimicrobial peptides (AMPs) are one such group of compounds present in a wide range of organisms from bacteria to humans. The existing 750 or so, low-molecular-weight, cationic charged peptides are classified into five major groups based on their three-dimensional structure obtained by nuclear magnetic resonance studies. The hypothesized mode of action seems to be the interaction of the positively charged peptides with the negatively charged phospholipids present on the surface of the cell membrane. Various studies have demonstrated the effect of several AMPs, namely, defensins, protegrins, cathelicidins, cecropins, polyphemusins, magainins and melittins, against various STI-causing pathogens and HIV/herpes simplex virus, both in vitro and in vivo. The contraceptive efficacies of magainin and nisin in vitro and in vivo are worth mentioning. We believe these peptides are suitable candidates in the development of newer mechanism-based microbicides in future.
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