Insight on Cardiac Chronobiology and Latest Developments of Chronotherapeutic Antihypertensive Interventions for Better Clinical Outcomes.

Cardiac circadian rhythms are an important regulator of body functions, including cardiac activities and blood pressure. Disturbance of circadian rhythm is known to trigger and aggravate various cardiovascular diseases. Thus, modulating the circadian rhythm can be used as a therapeutic approach to cardiovascular diseases. Through this work, we intend to discuss the current understanding of cardiac circadian rhythms, in terms of quantifiable parameters like BP and HR. We also elaborate on the molecular regulators and the molecular cascades along with their specific genetic aspects involved in modulating circadian rhythms, with specific reference to cardiovascular health and cardiovascular diseases. Along with this, we also presented the latest pharmacogenomic and metabolomics markers involved in chronobiological control of the cardiovascular system along with their possible utility in cardiovascular disease diagnosis and therapeutics. Finally, we reviewed the current expert opinions on chronotherapeutic approaches for utilizing the conventional as well as the new pharmacological molecules for antihypertensive chronotherapy.

Exploring the frostbite healing potential of hyaluronic acid based hydrogel of Manuka honey through in-silico antithrombotic and anti-platelet studies of major phytoconstituents and in-vivo evaluation in Wistar rat model.

OBJECTIVE: Development of Frostbite healing hydrogel of Manuka honey and hyaluronic acid. SIGNIFICANCE: Frostbite is a cold-induced ischemic vascular injury non-responsive to most of the wound healing products. Thrombus-induced ischemia is the main cause of frostbite-related necrosis. Hyaluronic acid is known to possess significant antithrombotic and wound healing activity. Moreover, Manuka Honey is also rich in flavonoids and polyphenols with potential antithrombotic activity. These two agents were together utilized to develop a frostbite healing formulation. METHODS: In-silico antithrombotic efficacy of major phytoconstituents of Manuka honey was evaluated using in-silico-docking studies against Tissue plasminogen activator and Cyclooxygenase-1 protein. Further in-vivo frostbite healing evaluation was carried out in Wistar rats, by inducing frostbite with a supercooled rod. RESULTS: The results indicate that major leptosin and other major phytoconstituent of Manuka honey has significant antithrombotic property. The hydrogel formulation of HA and MH possess significant antimicrobial efficacy. The wound contraction studies and histopathological evaluation reveals that the hydrogel also has a good frostbite healing activity showing complete wound healing within an 18-day period. The findings of the western blotting studies suggest that the hydrogel acts by VEGF- NRF-2 pathway. CONCLUSION: This result implies that the prepared hydrogel can serve as an effective frostbite healing formulation.

The Source of Rag5-Mediated Resistance to Soybean Aphids Is Located in the Stem.

The soybean aphid (Aphis glycines) continues to threaten soybean production in the United States. A suite of management strategies, such as planting aphid-resistant cultivars, has been successful in controlling soybean aphids. Several Rag genes (resistance against A. glycines) have been identified, and two are currently being deployed in commercial soybean cultivars. However, the mechanisms underlying Rag-mediated resistance are yet to be identified. In this study, we sought to determine the nature of resistance conferred by the Rag5 gene using behavioral, molecular biology, physiological, and biochemical approaches. We confirmed previous findings that plants carrying the Rag5 gene were resistant to soybean aphids in whole plant assays, and this resistance was absent in detached leaf assays. Analysis of aphid feeding behaviors using the electrical penetration graph technique on whole plants and detached leaves did not reveal differences between the Rag5 plants and Williams 82, a susceptible cultivar. In reciprocal grafting experiments, aphid populations were lower in the Rag5/rag5 (Scion/Root stock) chimera, suggesting that Rag5-mediated resistance is derived from the shoots. Further evidence for the role of stems comes from poor aphid performance in detached stem plus leaf assays. Gene expression analysis revealed that biosynthesis of the isoflavone kaempferol is upregulated in both leaves and stems in resistant Rag5 plants. Moreover, supplementing with kaempferol restored resistance in detached stems of plants carrying Rag5. This study demonstrates for the first time that Rag5-mediated resistance against soybean aphids is likely derived from stems.

Frostbite: Current status and advancements in therapeutics.

Frostbite is a severe ischemic injury which occurs due to the tissue vascular damage after sub-zero temperature tissue exposure. Deep frostbite can result in necrosis and may need amputation of affected tissue. Though a serious injury, it is not very well understood, and further scientific exploration is needed. This work explores the current understanding of the pathophysiology of frostbite. We reviewed the current status of the diagnostics, the drugs, the therapies and the surgical practices for prevention and management of frostbite. Advances in nanotechnology and drug delivery had improved the therapeutic outcomes significantly. This review also explored the latest advancements and researches done for development of newer therapeutics and diagnostics for frostbite care.

Graphene Family of Nanomaterials: Reviewing Advanced Applications in Drug delivery and Medicine.

Graphene in nano form has proven to be one of the most remarkable materials. It has a single atom thick molecular structure and it possesses exceptional physical strength, electrical and electronic properties. Applications of the Graphene Family of Nanomaterials (GFNs) in different fields of therapy have emerged, including for targeted drug delivery in cancer, gene delivery, antimicrobial therapy, tissue engineering and more recently in more diseases including HIV. This review seeks to analyze current advances of potential applications of graphene and its family of nano-materials for drug delivery and other major biomedical purposes. Moreover, safety and toxicity are the major roadblocks preventing the use of GFNs in therapeutics. This review intends to analyze the safety and biocompatibility of GFNs along with the discussion on the latest techniques developed for toxicity reduction and biocompatibility enhancement of GFNs. This review seeks to evaluate how GFNs in future will serve as biocompatible and useful biomaterials in therapeutics.

Differential biological effects of dehydroepiandrosterone (DHEA) between mouse (B16F10) and human melanoma (BLM) cell lines.

Dehydroepiandrosterone (DHEA) is a weak androgen and had been shown to have anti-cancer, anti-adipogenic and anti-inflammatory effects on mouse and other rodent models, but not on humans, suggesting a systemic level difference between mouse and human. Our previous study on DHEA biological functions involving a variety of cell lines, suggested that the functional differences between mouse and human existed even at the cellular level. Hence, using mouse and human melanoma cell models, in-vitro effects of DHEA on cell growth, mechanism of cell death and mechanism of DHEA action were studied. Results indicated a differential biological effects of DHEA between mouse and human melanoma cell lines. These in-vitro studies also suggested that the differential biological effects observed between these two cell lines could be due to the difference in the way DHEA was processed or metabolized inside the cell.