The rapid expansion of the available genomic data continues to greatly impact biomedical science and medicine. Fulfilling the clinical potential of genetic discoveries requires the development of therapeutics that can specifically modulate the expression of disease-relevant genes. RNA-based drugs, including short interfering RNAs and antisense oligonucleotides, are particularly promising examples of this newer class of biologics. For over two decades, researchers have been trying to overcome major challenges for utilizing such RNAs in a therapeutic context, including intracellular delivery, stability, and immune response activation. This research is finally beginning to bear fruit as the first RNA drugs gain FDA approval and more advance to the final phases of clinical trials. Furthermore, the recent advent of CRISPR, an RNA-guided gene-editing technology, as well as new strides in the delivery of messenger RNA transcribed in vitro, have triggered a major expansion of the RNA-therapeutics field. In this review, we discuss the challenges for clinical translation of RNA-based therapeutics, with an emphasis on recent advances in delivery technologies, and present an overview of the applications of RNA-based drugs for modulation of gene/protein expression and genome editing that are currently being investigated both in the laboratory as well as in the clinic.

/pdf/advances-in-the-delivery-of-rna-therapeutics-from-concept-to-3ws5q1y8fv.pdf

Advances in the delivery of RNA therapeutics: from concept to clinical reality.

Inflammasome Priming in Sterile Inflammatory Disease.

MicroRNAs (miRNAs) are small noncoding RNAs that broadly affect cellular and physiological function in all multicellular organisms. Here, the role of miRNAs in neuroinflammation is considered. miRNAs are 21- to 23-oligonucleotide RNAs that regulate translation of specific RNAs by binding to complementary regulatory RNA sequences, thereby causing mRNA degradation or sequestration. More than 5000 miRNAs likely exist in humans, and each miRNA binds an average of 200 RNAs. Specific immunomodulatory miRNAs can regulate a set of RNAs in a coordinated manner, suggesting that effective miRNA-based therapeutic manipulations for neuroinflammatory conditions may be revealed. For instance, miRNAs that preferentially inhibit translation of many cellular anti-inflammatory proteins could drive a pro-inflammatory response. Key pro-inflammatory ( miR-155, miR-27b, miR-326), anti-inflammatory ( miR-124, miR-146a, miR-21, miR-223), and mixed immunomodulatory ( let-7 family) miRNAs regulate neuroinflammation in various pathologies, including spinal cord injury, multiple sclerosis, ischemic stroke, and Alzheimer's disease. miRNAs represent a newly revealed layer of physiological complexity, the therapeutic benefits of which remain to be fully explored and exploited. In this review, we discuss the role of miRNAs in neuroinflammatory regulation and discuss how controlling miRNAs could alter cellular machinery to improve neuroinflammatory dynamics.

https://journals.sagepub.com/doi/pdf/10.1177/1073858417721150

MicroRNAs: Roles in Regulating Neuroinflammation:

The decline of oxygen tension in the tissues below the physiological demand leads to the hypoxic adaptive response. This physiological consequence enables cells to recover from this cellular insult. Understanding the cellular pathways that mediate recovery from hypoxia is therefore critical for developing novel therapeutic approaches for cardiovascular diseases and cancer. The master regulators of oxygen homeostasis that control angiogenesis during hypoxia are hypoxia-inducible factors (HIFs). HIF-1 and HIF-2 function as transcriptional regulators and have both unique and overlapping target genes, whereas the role of HIF-3 is less clear. HIF-1 governs the acute adaptation to hypoxia, whereas HIF-2 and HIF-3 expressions begin during chronic hypoxia in human endothelium. When HIF-1 levels decline, HIF-2 and HIF-3 increase. This switch from HIF-1 to HIF-2 and HIF-3 signaling is required in order to adapt the endothelium to prolonged hypoxia. During prolonged hypoxia, the HIF-1 levels and activity are reduced, despite the lack of oxygen-dependent protein degradation. Although numerous protein factors have been proposed to modulate the HIF pathways, their application for HIF-targeted therapy is rather limited. Recently, the miRNAs that endogenously regulate gene expression via the RNA interference (RNAi) pathway have been shown to play critical roles in the hypoxia response pathways. Furthermore, these classes of RNAs provide therapeutic possibilities to selectively target HIFs and thus modulate the HIF switch. Here, we review the significance of the microRNAs on the relationship between the HIFs under both physiological and pathophysiological conditions.

/pdf/mirnas-regulate-the-hif-switch-during-hypoxia-a-novel-7emhz52dg2.pdf

miRNAs regulate the HIF switch during hypoxia: a novel therapeutic target.

In recent years, the link between regulatory microRNAs (miRNAs) and diseases has been the object of intensive research miRNAs have emerged as key mediators of metabolic processes, playing crucial roles in maintaining/altering physiological processes, including energy balance and metabolic homeostasis Altered miRNAs expression has been reported in association with obesity, both in animal and human studies Dysregulation of miRNAs may affect the status and functions of different tissues and organs, including the adipose tissue, pancreas, liver, and muscle, possibly contributing to metabolic abnormalities associated with obesity and obesity-related diseases More recently, the discovery of circulating miRNAs easily detectable in plasma and other body fluids has emphasized their potential as both endocrine signaling molecules and disease indicators In this review, the status of current research on the role of miRNAs in obesity and related metabolic abnormalities is summarized and discussed

/pdf/role-of-micrornas-in-obesity-and-obesity-related-diseases-1yflxm1sf2.pdf

Role of microRNAs in obesity and obesity-related diseases

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression in diverse biological process. They act as intracellular mediators that are necessary for various biological processes. MicroRNAs targeting pathways of human disease provide a new and potential powerful candidate for therapeutic intervention against various pathological conditions. Even though, the information about miRNA biology has significantly enriched but we still do not completely understand the mechanism of miRNA gene regulation. Various groups across the globe and pharmaceutical companies are conducting research and developments to explore miRNA based therapy and build a whole new area of miroRNA therapeutics. Consequently, few miRNAs have entered the preclinical and clinical stage and soon might be available in the market for use in humans.

MicroRNA therapeutics: Discovering novel targets and developing specific therapy.

Antioxidants are known to play a vital role in inhibiting and scavenging free radicals, thus, provide immunity to human body against various infections and chronic diseases. Nowadays the modern research is moving towards plant based “Natural antioxidants” due to their safety, easy availability and better curative value. So the main reason of the present study was to assess the in-vitro antioxidant activity of the extracts of Allium cepa which is a very commonly used food worldwide. Aim: Estimation of in-vitro antioxidant activity of the Allium cepa extract. Study Design: Red onions were purchased from the market, washed in water to remove the dust and then dried for 20 days. The methanol and aqueous extracts of the bulb were prepared and investigated for their antioxidant activity. Methodology: The methanol and aqueous extracts of the bulb were prepared and investigated for their antioxidant activity by using FeCl3, DPPH, Superoxide scavenging and FRAP methods. The total phenolic content was determined by Folin-Ciocalteu reagent. Results: The total phenolic content showed a higher value (47 mg/100 ml) in the aqueous extract compared to (41 mg/100 ml) in the methanol extract. The antioxidant activity of aqueous extract by using FeCl3, DPPH, Superoxide scavenging and FRAP methods were found to be 13.1%, 23%, 33%, 21.7% and that of methanol extract were 17.5%, 35.5%, 37.8%, 38.7% respectively. Conclusion: From the above study it has been concluded that, both extracts showed an important antioxidant activity. However the methanol extract proved to have higher antioxidant activity. It was Short Communication Kaur et al.; JOCAMR, 1(1): 1-5, 2016; Article no.JOCAMR.26718 2 further observed that the phenolic content was higher in the aqueous extract of Allium cepa. Further study will be conducted to isolate the active components responsible for the activity.

/pdf/antioxidant-potential-of-most-commonly-used-vegetable-onion-4pzeqvcur8.pdf

Antioxidant Potential of Most Commonly Used Vegetable - Onion (Allium cepa L.)

Background: Endangered plant “Kakoli” is important component of Ashtwarga group of plants and anti-aging Ayurvedic preparations. Due to limited supply of original plant, official substitutes and common adulterants are being used by drug manufacturers. There is a need to identify a marker compound that could differentiate original plant from substitutes and common adulterants. Objective: To isolate and characterize the marker compound from roots of this plant. Material and methods: The extract of plant root was prepared in methanol and marker compound was isolated from methanol extract through column chromatography by using silica gel (60–120 mesh size) in glass column (1000mm x 50mm). The compound was obtained in fractions numbered 990-1550 and isolated by cutting and pooling of TLC plate of compound having Rf = 0.52 by the use of mobile phase toluene: ethyl acetate: formic acid (9.5: 0.5: 0.1 v/v/v). Compound was characterized by using IR, NMR, Mass and UV spectroscopy. Results: The methanol extract was blackish brown in color and showed the presence of alkaloids, terpenoids, phytosterols, flavonoids, phenolics and amino acid. The isolated compound was found to be colorless terpenoid needle with m.p. 168-171°C; [α]D +62.8° (c 1.0,CHCl3). Spectral analysis confirmed presence of lupenone. Conclusion: In present study lupenone was isolated for the first time from Kakoli. None of adulterants and substitutes of Kakoli are reported to have lupenone hence can be used as marker for identification as well as differentiation of the plant from official substitutes and common adulterants.

Isolation of lupenone (18-Lupen-3-one) from Roscoea purpurea root extract

Despite breakthroughs in medical sciences, drug development remains a time-consuming, expensive, challenging, and inefficient process with a high failure rate for novel therapeutic discoveries. Bioinformatics analysis can speed up drug target identification, drug candidate screening, and refining, but it can also help characterise adverse effects and anticipate drug resistance. Integrated genomics, proteomics, and bioinformatics have resulted in potent new tactics for resolving numerous biochemical problems and establishing new methodologies that result in new biomedical products. As a result, a new research trend emerged to demonstrate the mechanism of therapeutic action, forecast drug resistance, and uncover biomarkers for various disorders. The development of new medications is a complicated procedure. There are two basic approaches to drug design: ligand-based drug design and structure-based drug design. The study of protein structure and function was essential for drug development. Current techniques based on combinatorial approaches such as proteomics, genomics, bioinformatics, molecular docking, and mass spectrometry were applied. This article provides an overview of the combinatorial techniques of proteomics, genomics, and bioinformatics that aid in understanding the drug-creation process.

Gunpreet Kaur

Papers

MicroRNA therapeutics: Discovering novel targets and developing specific therapy.

Antioxidant Potential of Most Commonly Used Vegetable - Onion (Allium cepa L.)

Isolation of lupenone (18-Lupen-3-one) from Roscoea purpurea root extract

Bioinformatics Paradigms in Drug Discovery and Drug Development.

Fast track development of Fisetin and Naringenin based economic antianxiety drug using Docking tools.