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The regulatory paradigm in cardiac hypertrophy involves alterations in gene expression that is mediated by chromatin remodeling. Various data suggest that class I and class II histone deacetylases (HDACs) play opposing roles in the regulation of hypertrophic pathways. To address this, we tested the effect of magnesium valproate (MgV), an HDAC inhibitor with 5 times more potency on class I HDACs. Cardiac hypertrophy was induced by partial abdominal aortic constriction in Wistar rats, and at the end of 6 weeks, we evaluated hypertrophic, hemodynamic, and oxidative stress parameters, and mitochondrial DNA concentration. Treatment with MgV prevented cardiac hypertrophy, improved hemodynamic functions, prevented oxidative stress, and increased mitochondrial DNA concentration. MgV treatment also increased the survival rate of the animals as depicted by the Kaplan-Meier curve. Improvement in hypertrophy due to HDAC inhibition was further confirmed by HDAC mRNA expression studies, which revealed that MgV decreases expression of pro-hypertrophic HDAC (i.e., HDAC2) without altering the expression of anti-hypertrophic HDAC5. Selective class I HDAC inhibition is required for controlling cardiac hypertrophy. Newer HDAC inhibitors that are class I inhibitors and class II promoters can be designed to obtain 'pan' or 'dual' natural HDAC 'regulators'. [ABSTRACT FROM AUTHOR]

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Identification of biologically active small molecules for further optimization into candidate drugs has been challenging because of ethnic variations and hence could not capture full diversity of regulation seen in native cells. Biomarkers commonly utilized earlier in drug development and drug discovery included biochemical surrogate markers, enzymes, receptors and genes. Of late, application of stem cell research, novel biomarkers like microRNAs, extracellularRNAs, circulating tumour cells have emerged for non-invasive diagnostics as well as target identification in drug discovery. Translational research using precision medicine is one of the main strategies being evolved recently worldwide by the industry in the drug discovery. Precision medicine aims to integrate both clinical and molecular information and provides biomarkers to better understand the biological basis of disease and therefore select them as better disease targets. The 21st century will be remembered for coronavirus disease 2019 (COVID-19) pandemic although over 80 years are yet to come. Just two years of the COVID-19 have brought a number of transitions. For pharmaceutical companies there are number of opportunities emerging. There is now a wave of innovation and launching of generation of entrepreneurs. The 'Biopharma Revolution' is one of the major transformation that is in the forefront for the medical and pharmaceutical world in the form of Biomolecules, Biosystems, Biomachines, and Biocomputing. Coupled with these, many new strategies have evolved in the drug discovery and Diagnostics like Gene Therapy; Precision Medicine based on biomarkers; Stem cell Therapy, Crisper Technology, and Molecular Diagnostics. Currently in the Pharmaceutical sciences especially Pharmaceutics most common area of research is the nanotechnology, Fourth Industrial Revolution is combination of first three industrial revolutions in the world that has given robotics or automation. Theranostics is one such revolution that integrates therapywith diagnosis in one systemto achieve accurate treatment of disease like cancer. It has attracted tremendous interest, and has been recognized as a potential breakthrough in overcoming the challenges of conventional oncotherapy. Nanotheranostics is yet anothersort of novel and revolutionary strategies that has emergedfor accurate diagnosis of the site of cancer and the treatment to the right and accurate site in the body. It started with the biomarker based drug precision medicine but the same principles are utilized Nanopharmaceutical Scientists could realize that Nanoparticles are ideal candidates as carriers for theranostic agents, which is attributed to their extraordinary physicochemical properties, including nanoscale sizes, functional properties, prolonged blood circulation, active or passivetumor targeting, specific cellular uptake, and in some cases, excellent optical properties that ideally meet the needs of phototherapy and imaging at the same time. The development of nanotechnology based diagnostics and therapeutics, now known as Nanotheranostics has become a reality, and is now in the transition stage of "bench to bedside." Significant progress has been made in this nanotheranostics and has greatly assisted traditional therapies to provide therapeutic optionsas like "cocktail" mixingvarious nanotechnology, diagnostics and treatment modalities openingan exciting field of research in pharmaceutical sciences. [ABSTRACT FROM AUTHOR]

Purpose: Recent investigations have shown that phytochemical antioxidants can scavenge free radicals and prevent various diseases like cataract. The objective of the present study was to assess the efficacy of theTephrosia purpureain preventing these changes in the lens of selenite-induced cataract models. Materials and methods: Cataract was induced by a single injection of sodium selenite (4 mg/kg, s.c.) to 9-day-old Sprague–Dawley rat pups. The treatment with different extracts ofT. purpureawas started on 10th day and continued for 30 days in pups pretreated with sodium selenite. The animals were treated orally with either quercetin (1 mg/kg), flavonoid rich fraction (40 mg/kg) or alcohol extract (300 mg/kg) ofT. purpurea. Cataract was visualized after 30 days. Encapsulated lenses were analyzed for reduced glutathione and malondialdehyde. Lenses were also analyzed for total protein, insoluble protein, total nitrite, calcium levels, protein sulfhydryl content as well as for the activities of superoxide dismutase and Ca2+-ATPase. Results: Morphological examination of the rat lenses revealed normal transparent lens with minimal or partial nuclear opacity in control whereas dense opacity developed in rat lens treated with selenite. Both the extracts ofT. purpureaproduced reduction in nuclear opacity as well as improvement in the insoluble proteins, protein sulfhydryl, total nitrite, calcium levels and Ca2+-ATPase activity in lenses. The extracts decreased malondialdehyde levels but also prevented the loss of reduced glutathione levels. Conclusion: Our data suggests therapeutic potential ofT. purpureafor the treatment of cataract. [ABSTRACT FROM AUTHOR]