RESUMEN

The endothelial cells (ECs) make up the inner lining of blood vessels, acting as a barrier separating the blood and the tissues in several organs. ECs maintain endothelium integrity by controlling the constriction and relaxation of the vasculature, blood fluidity, adhesion, and migration. These actions of ECs are efficiently coordinated via an intricate signaling network connecting receptors, and a wide range of cellular macromolecules. ECs are naturally quiescent i.e.; they are not stimulated and do not proliferate. Upon infection or disease, ECs become activated, and this alteration is pivotal in the pathogenesis of a spectrum of human neurological, cardiovascular, diabetic, cancerous, and viral diseases. Considering the central position that ECs play in disease pathogenesis, therapeutic options have been targeted at improving ECs integrity, assembly, functioning, and health. The dietary intake of flavonoids present in citrus fruits has been associated with a reduced risk of endothelium dysfunction. Naringenin (NGN) and Naringin (NAR), major flavonoids in grapefruit, tomatoes, and oranges possess anti-inflammatory, antioxidant properties, and cell survival potentials, which improve the health of the vascular endothelium. In this review, we provide a comprehensive summary and present the advances in understanding of the mechanisms through which NGN and NAR modulate the biomarkers of vascular dysfunction and protect the endothelium against unresolved inflammation, oxidative stress, atherosclerosis, and angiogenesis. We also provide perspectives and suggest further studies that will help assess the efficacy of citrus flavonoids in the therapeutics of human vascular diseases.

RESUMEN

Bacteriophages (phages), as natural antibacterial agents, are being rediscovered because of the growing threat of multi- and pan-drug-resistant bacterial pathogens globally. However, with an estimated 1031 phages on the planet, finding the right phage to recognize a specific bacterial host is like looking for a needle in a trillion haystacks. The host range of a phage is primarily determined by phage tail fibers (or spikes), which initially mediate reversible and specific recognition and adsorption by susceptible bacteria. Recent significant advances at single-molecule and atomic levels have begun to unravel the structural organization of tail fibers and underlying mechanisms of phage-host interactions. Here, we discuss the molecular mechanisms and models of the tail fibers of the well-characterized T4 phage's interaction with host surface receptors. Structure-function knowledge of tail fibers will pave the way for reprogramming phage host range and will bring future benefits through more-effective phage therapy in medicine. Furthermore, the design strategies of tail fiber engineering are briefly summarized, including machine-learning-assisted engineering inspired by the increasingly enormous amount of phage genetic information.

Asunto(s)

Bacteriófagos , Bacteriófagos/fisiología , Especificidad del Huésped , Virión , Proteínas Portadoras , Antibacterianos

RESUMEN

Dengue virus and Zika virus are mosquito-borne, single-stranded, positive-sense RNA viruses that belong to the Flaviviridae family. Both the viruses are closely related and have similarities with other flaviviruses. Dengue virus (DENV) causes a severe febrile illness with fever, joint pain, and rash leading to a life-threatening condition in severe cases. While Zika virus (ZIKV) primarily causes mild fever, it can be passed from a pregnant mother to her fetus, resulting in severe birth defect microcephaly and even causing a rare autoimmune disease-Guillain-Barre syndrome. To date, there are no approved DENV and ZIKA vaccines available, except a Dengue vaccine (Dengvaxia, Sanofi Pasteur Inc., Lyon, France) recently approved to be used only for 9-16 years of age groups living in endemic areas and having a previous record of confirmed dengue infection. There are several potential vaccine candidates in the clinical trials based on multiple vaccine platforms, such as live attenuated, subunit, nucleic acid, and viral vector-based vaccines. In the current review, we have focused exclusively on the nucleic acid vaccine platform and discussed the progress of all the DNA/RNA vaccine candidates under preclinical and clinical studies for DENV and ZIKA viruses. Additionally, we have described a brief history of the emergence of these flaviviruses, major structural similarities between them, prominent vaccine targets, and the mechanism of virus entry and infection.