Data Mining for Drug Repurposing and New Targets Identification for Radioprotection

Ionising radiation (IR) is responsible for various types of tissue injury leading to morbidity at low doses and mortality at high radiation exposure. Although many radioprotective and pharmacological agents are being tested for decreasing radiation injury, however, the availability of Amifostine as the only clinically used radioprotector with limited indication has prompted us to find out new potential molecules through drugs repurposing for protecting or decreasing radiation damage by data mining. In this work we have used text-mining based network generation approach to find out the gene targets of radioprotectors under evaluation by Agilent Literature Search app in Cytoscape. Extracted genes were evaluated for their association with radiation in Radiation Genes database. These genes were searched against therapeutic drugs and molecules under clinical trial in the Drug Gene Interaction database. We found that most of the radiation target genes were involved in cell death, proliferation, homeostasis, cell cycle and cancer pathways. Many of these genes were druggable and could be targeted by the drugs under clinical research, whereas there were few genes (new targets), which were never considered for radioprotective drug development. This study would likely help in repurposing of identified drugs for use in the event of radiation fallout, keeping in mind that no radiation medical countermeasure for acute radiation syndrome has been approved by the US FDA for use in humans. Results also revealed new target genes for drug targeting and indicates use of similar pipeline in other pathologies for drug repurposing and development

A Hypothetical Tool for Integrated Omics, Drugs and Clinical Stem Cell Data Analysis

Understanding the molecular basis of stem cell (SC) function is essential to regenerate damaged tissue due to various types of injuries and pathologies. However, there are bottlenecks that prevent the use of Stem cell in the treatment of wide range of diseases. Complete information regarding the control of gene expression in Stem cell is necessary to understand the regulation of Stem cell fates such as self-renewal, differentiation, migration/ homing and apoptosis. However, in the absence of multi-functional, single window tool for the analysis of various omics and drugs data related to Stem cell, the knowledge consolidation is missing to fully harness its potential. A tool which can integrate various databases, analysis software and gives a probable solution for Stem cell mediated regeneration of tissues using available therapeutic options would likely to help in reducing morbidity and mortality associated with various pathologies. This subsumes omics based repurposing of drugs for Stem cell guided tissue regeneration, which will be a boon for clinicians to treat various debilitating diseases/ malfunctions

Comparative genetic diversity analysis of oat (Avena sativa L.) by microsatellite markers and morphological rainfed expressions

Equivalence was appraised between phenotypic and molecular markers (ISSR) to analyze the genetic diversity of 20 high yielding genotypes representing different geographical zones of the world. A moderate range of genetic similarity (0.84 to 0.20) was observed on the basis of 20 inter-simple sequence repeats (ISSR) markers, where it was found high (0.995 – 0.204) on the basis of 7 primary morphological rainfed expression. Genotypes in morphological character based dendogram were clustered into their respective geographic groups, while a random grouping was observed in dendogram based on the ISSR markers. A negative correlation (r = -0.186) was found among morphological and molecular marker systems, but the latter was found effective in distinguishing the genotypes using specific band positions for them. The genotypic classification agreed closely with the grouping observed in ISSR based 3D analysis.Keywords: Avena sativa, diversity, inter-simple sequence repeats (ISSR), morphology, oat, relationshipAfrican Journal of Biotechnology Vol. 12(22), pp. 3414-342

Stem Cell Antigen CD34 In Native And Engineered Form Alter Its Binding Ability To Stromal Cells And Ligands: A Classical Example Of Clinical Benefits Of Therapeutic Genetic Engineering Of Stem Cells In Transplantation

CD34 is a highly glycosylated surface-expressed sialomucin and, because it is present on hematopoietic stem cells (HSCs), has demonstrated immense clinical utility in their enumeration in aphaeresis products, immunoaffinity purification for transplantation, and disease monitoring. The success of CD34 based reagents in identifying hematopoietic progenitors led to the assumption that CD34 is expressed on cells with regenerative potential and is sufficient for hematopoietic reconstitution in marrow-ablated recipients. However, its role has not been identified in substantial detail. 

With the advent of the fact that CD34 binds adapter protein like CRK-L in cytosol and CD34 knock out studies identified a a signaling role, CD34 antigen has been proposed to play a signaling function. Since it is a sialomucin, a member of the group adhesion molecules, we attempted to identify a role by over-expreesing its gene in cell lines. We report here that CD34 and engineered forms (Ser306 & Tyr318) significantly regulates adhesion to stromal cells, like mesenchymal stem cells and bone marrow ligands. These enhance binding of cells overexpressing CD34 by upregulating integrins and we therefore propose that such cells may effectively potentiate the success of transplantation through greater homing if they are used for transfusion

VITAMIN C AND ITS ROLE IN BODY

Ascorbic acid or Vitamin C is very important in our body because of its antioxidant property. But the main problem; that vitamin C uses is to maintain the stability as well as its drug distribution system. Vitamin C also plays a protective role in diabetes, cancer, heavy metal toxicity or poisoning, etc. Vitamin C is found in many sources present in nature, including tomatoes, broccoli, etc. Many factors in the body, as well as outside the body, affect the content of vitamin C in the body or sources like the season, climate, and pollution affect the content in fruits and vegetables besides sex, age, pregnancy, lactation, etc. affect the vitamin C content in the body. It is extensively used in the common cold, wound healing process, cancer, heavy metal poisoning or toxicity, and even in men's fertility. In this article, we focused on the general aspects: its bioavailability, sources, its toxicity and deficiency, and factors affecting vitamin C level as well as its use in humans. In the last, we conclude, the excess or lack of Vitamin C, both conditions have affected the human body in a significant range. It plays a protective role against many disorders and is required for kids, men, women, and even old-aged patients

Tubercular myositis of infraspinatus: a rare clinical entity

Tuberculosis of the musculoskeletal system is generally confined to bones and joints. The surrounding soft tissue is secondarily infected. Tuberculous bursitis, tenosynovitis and primary pyomyositis are rarer manifestations of the disease. Of these, primary tuberculouspyomyositis is probably the rarest entity. We report a case of tubercular myositis of infraspinatus in an 8 year-old female who presented with pain, low grade fever, weight loss, anorexia, progressively increasing pain in the scapular region and restriction of movements. There was no history of trauma, diabetes, immunosuppression, corticosteroid usage, or renal failure. History of contact was present. Tenderness was present along the medial border of scapula and movements of upper extremity requiring movement of the scapula were painful and grossly restricted. MRI of the scapulothoracic region and shoulder revealed small amount of fluid along medial border of scapula with T2 hyperintensity of infraspinatus. Histopathology showed caseous necrosis, inflammatory cells and granulomatous cells suggestive of tuberculosis. Polymerase Chain Reaction for Mycobacterium tuberculosis was found to be positive. Patient was started on four-drug antitubercular treatment and regular dressings. The patient’s general condition improved and at 4 weeks post starting ATT, there was no pain and the patient was able to perform complete range of movement. This is probably the first reported case of tubercular myositis of infraspinatus in an immunocompetent patient without any identifiable focus elsewhere in the body. Rarity of the condition, presence of characteristic findings on MRI and histopathology make the case illustrative for young Orthopaedics surgeons.

Charcot’s Neuroarthropathy: A Case Report and Review of Literature

Charcot’s neuroarthropathy (CN) is a progressive disabling complication of diabetes mellitus, usually seen 10 years after diagnosis of diabetes. There is widespread destruction of affected joint and bones around it leading to severe deformity and loss of function. Its treatment may require multiple corrective surgeries or even amputation apart from application of cast, glycemic control and bisphosphonates. Here, we report such a case of CN, which was treated with multiple strategies aggressively to a good outcome

A case series of Stener’s lesion of the first metacarpophalangeal joint

Ulnar collateral ligament (UCL) injuries have a high prevalence however; these are usually being missed in the initial clinical evaluation. Depending on the chronicity of the injury there are two acronyms for UCL tear. One is the skier's thumb and the other is the gamekeeper's thumb. If the UCL of the first metacarpophalangeal joint (MCP joint) has a complete tear with entrapment of aponeurosis of adductor pollicis muscle between the MCP joint and torn ligament, is called a Stener’s lesion. This is a rare clinical entity that requires early surgical correction because of entrapment. The mechanism of injury is the coerced abduction of the thumb from the index finger, causing ligament tears or sprain with or without ensuing avulsion fracture. The incidence of Stener’s lesions associated with UCL rupture has been reported to be up to 52% per intra-operative finding. In Stener’s lesions, the UCL tears from the base of the proximal phalanx (PP) then retracts proximally and displaces superficial to the adductor pollicis. Here we are presenting four cases of Stener’s lesions, with the usefulness of magnetic resonance imaging (MRI) in diagnosing this entity, which can prevent possible long-term complications such as chronic pain, joint degeneration, and joint instability