Oxidative stress and mitochondrial transfer: A new dimension towards ocular diseases.

Ocular cells like, retinal pigment epithelium (RPE) is a highly specialized pigmented monolayer of post-mitotic cells, which is located in the posterior segment of the eye between neuro sensory retina and vascular choroid. It functions as a selective barrier and nourishes retinal visual cells. As a result of high-level oxygen consumption of retinal cells, RPE cells are vulnerable to chronic oxidative stress and an increased level of reactive oxygen species (ROS) generated from mitochondria. These oxidative stress and ROS generation in retinal cells lead to RPE degeneration. Various sources including mtDNA damage could be an important factor of oxidative stress in RPE. Gene therapy and mitochondrial transfer studies are emerging fields in ocular disease research. For retinal degenerative diseases stem cell-based transplantation methods are developed from basic research to preclinical and clinical trials. Translational research contributions of gene and cell therapy would be a new strategy to prevent, treat and cure various ocular diseases. This review focuses on the effect of oxidative stress in ocular cell degeneration and recent translational researches on retinal degenerative diseases to cure blindness.

Emerging Biosensors for Oral Cancer Detection and Diagnosis-A Review Unravelling Their Role in Past and Present Advancements in the Field of Early Diagnosis.

Oral cancer is a serious concern to people all over the world because of its high mortality rate and metastatic spread to other areas of the body. Despite recent advancements in biomedical research, OC detection at an early stage remains a challenge and is complex and inaccurate with conventional diagnostics procedures. It is critical to study innovative approaches that can enable a faster, easier, non-invasive, and more precise diagnosis of OC in order to increase the survival rate of patients. In this paper, we conducted a review on how biosensors might be an excellent tool for detecting OC. This review covers the strategies that use different biosensors to target various types of biomarkers and focuses on biosensors that function at the molecular level viz. DNA biosensors, RNA biosensors, and protein biosensors. In addition, we reviewed non-invasive electrochemical methods, optical methods, and nano biosensors to analyze the OC biomarkers present in body fluids such as saliva and serum. As a result, this review sheds light on the development of ground-breaking biosensors for the early detection and diagnosis of OC.

Management of tibial shaft fractures with closed intra medullary interlocking nail among Indians.

It is of interest to document data on the well Reamed Intramedullary Nailing in Isolated Tibial Diaphyseal Fractures without Fibular Osteotomy among Indians. 120 patients with isolated tibial diaphyseal fractures were treated with IMIL nail (84 closed fractures, 16 type I open fractures, and 20 type II open fractures) were involved in this study. Research was carried out over a five-and-a-half-year period, from July 2013 to December 2018.According to Johner and Wruh's criteria, good functional findings were achieved in 70% of patients, better operational results in 15%, reasonable functional results in 5%, and poor functional results in 10% of cases after surgery. The percentage of union in the present analysis was 90%. The average time for union was 5 months, with 84 fractures healing before 5 months. Intramedullary Interlocking Nailing reduces length of stay in hospital, lowers the financial load, and promotes early return to work without the need for further surgical treatment such as partial fibular osteotomy.

Management of tendinopathies among south Indians using collagen II peptide, glucosamine and vitamin C.

Tendinopathy is a multi-factorial, broad spectrum of tendon disorder, characterized by activity-related chronic tendon pain and local tenderness. The point of this study was to assess the adequacy of a nutritional supplement containing Glucosamine, type II collagen and vitamin C on the clinical and auxiliary advancement of tendinopathies. The prospective study was Hospital based randomized control trail comparing the efficacy of collage 2 peptide, glucosamine and vitamin c with placebo in various tendinopathies. All diagnosed patients willing for the treatment attending Konaseema Institute of Medical Sciences during period of 2017-2019 were selected with regular follow up of 2nd week, 2nd month & 6 month. The statistics and visualizations of various observations made in the entire study which include a total of 80 patients with various tendinopathies. 60 of them were given collagen 2, glucosamine and vitamin c (cases) and 20 were given placebo (controls). At the end of 6 months almost 90% patients relieved completely of pain. The duration of maximum benefit to reach is almost around 24 weeks. These are seen more commonly to affect non-athletes rather than athletes.

Design and Development of Mycobacterium tuberculosis Lysine ɛ-Aminotransferase Inhibitors for Latent Tuberculosis Infection.

Lysine ɛ-aminotransferase (LAT) is a protein involved in lysine catabolism, and it plays a significant role during the persistent/latent phase of Mycobacterium tuberculosis (MTB), as observed by its up-regulation by ~40-fold during this stage. We have used the crystal structure of MTB LAT in external aldimine form in complex with its substrate lysine as a template to design and identify seven lead compounds with IC50 ranging from 18.06 to > 90 µm. We have synthesized 21 compounds based on the identified lead, and compound 21 [2,2'-oxybis(N'-(4-fluorobenzylidene)acetohydrazide)] was found to be the most active with MTB LAT IC50 of 0.81 ± 0.03 µm. Compound 21 also showed a 2.3 log reduction in the nutrient-starved MTB model and was more potent than standard isoniazid and rifampicin at the same dose level of 10 µg/mL.

Benzothiazinone-piperazine derivatives as efficient Mycobacterium tuberculosis DNA gyrase inhibitors.

BACKGROUND AND OBJECTIVES: Bacterial DNA topoisomerases are unique in maintaining the DNA topology for cell viability. Mycobacterium tuberculosis (MTB) DNA gyrase, a sole type II topoisomerase has a larger scope as a target for developing novel therapeutics. In this study, an effort was made towards the design and synthesis of benzothiazinone-piperazine hybrid analogues to obtain the possibility of it to lead development through the molecular hybridization technique. METHODS: A five-step scheme was followed to obtain a series of 36 benzothiazinone-piperazine derivatives and to evaluate them for MTB DNA gyrase inhibition, antimycobacterial and cytotoxicity studies. RESULTS: Compound N-(4-chlorophenyl)-4-(6-nitro-4-oxo-4H-benzo[e][1,3]thiazin-2-yl)piperazine-1-carbothioamide (18) showed greater inhibitory potential with an IC50 of 0.51 ± 0.16 µM in the DNA supercoiling assay of MTB with a moderate anti-tubercular activity of 4.41 µM. The compound even passed the safety profile of eukaryotic cell cytotoxicity with a 1.81% inhibition in the RAW 264.7 cell line at 100 µM concentration. CONCLUSIONS: This study describes the discovery of benzothiazinone as gyrase inhibitors with potent MTB MIC and inhibitory profiles of the gyrase enzyme with less cytotoxic effect. Furthermore, it is believed that this class of compounds has the potential to be further developed as an anti-TB drug candidate.

Development of 5-nitrothiazole derivatives: identification of leads against both replicative and latent Mycobacterium tuberculosis.

Twenty eight 5-nitrothiazole derivatives were synthesized and evaluated for in vitro activities against Mycobacterium tuberculosis (MTB), cytotoxicity against HEK 293T. Among the compounds, 5-nitro-N-(5-nitrothiazol-2-yl)furan-2-carboxamide (20) was found to be the most active compound in vitro with MICs of 5.48 µM against log-phase culture of MTB and also non-toxic up to 100 µM.