Design and Characterization of a Multistage Peptide-Based Vaccine Platform to Target Mycobacterium tuberculosis Infection.

The complex immunopathology ofMycobacterium tuberculosis(Mtb) is one of the main challenges in developing a novel vaccine against this pathogen, particularly regarding eliciting protection against both active and latent stages. Multistage vaccines, which contain antigens expressed in both phases, represent a promising strategy for addressing this issue, as testified by the tuberculosis vaccine clinical pipeline. Given this approach, we designed and characterized a multistage peptide-based vaccine platform containing CD4+ and CD8+ T cell epitopes previously validated for inducing a relevant T cell response against Mtb. After preliminary screening, CFP10 (32-39), GlfT2 (4-12), HBHA (185-194), and PPE15 (1-15) were selected as promising candidates, and we proved that the PM1 pool of these peptides triggered a T cell response in Mtb-sensitized human peripheral blood mononuclear cells (PBMCs). Taking advantage of the use of thiol-maleimide chemoselective ligation, we synthesized a multiepitope conjugate (Ac-CGHP). Our results showed a structure-activity relationship between the conjugation and a higher tendency to fold and assume an ordered secondary structure. Moreover, the palmitoylated conjugate (Pal-CGHP) comprising the same peptide antigens was associated with an enhanced cellular uptake in human and murine antigen-presenting cells and a better immunogenicity profile. Immunization study, conducted in BALB/c mice, showed that Pal-CGHP induced a significantly higher T cell proliferation and production of IFNγ and TNFα over PM1 formulated in the Sigma Adjuvant System

Some Energy Inequalities for Two-Body Problems and Helium Dimer

It is shown that the energy of two particles in 2D (2 dimensions) is always less or equal than energy in 1D, and the energy in 3D can be less or greater than in 2D. The application to the important case of helium 4 dimer shows that this molecule may have only in 2D at least one bound excited stat

Effects of zofenopril on arterial stiffness in hypertension patients

Angiotensin-converting enzyme inhibitors (ACEIs) reduce arterial stiffness beyond their antihypertensive effect. Studies showed that sulfhydryl ACEIs have the antioxidative potential to improve endothelial function, which might have a clinical effect on arterial distensibility. However, there are no studies that directly compare the effects of sulfhydryl (zofenopril) and non-sulfhydryl ACEIs (enalapril) on arterial stiffness. Therefore, this prospective study aims to compare the effects of enalapril and zofenopril on arterial stiffness and oxidative stress in both short- and long-term treatment of arterial hypertension (AH). Baseline and post-treatment peripheral and central arterial pressure indices, augmentation index (Aix), aortic pulse wave velocity (ao-PWV), serum levels of oxidized low-density cholesterol lipoprotein, LDL and uric acid (UA) were measured. The results showed that acute treatment with zofenopril, in contrast to enalapril, significantly decreased peripheral and central Aix (p < 0.001). Chronic treatment with zofenopril showed a superior effect over enalapril on the reduction of the peripheral systolic arterial pressure with reduction of ao-PWV (p = 0.004), as well as a reduction in peripheral Aix (p = 0.021) and central Aix (p = 0.021). Therefore, this study indicates that zofenopril has beneficial effects on the reduction of arterial stiffness compared to enalapril. It has potent clinical efficacy in AH treatment and further studies should compare its safety and long-term efficacy to other AH drugs that would aid clinicians in treating AH and other various cardiovascular diseases that have arterial stiffness as a common denominator