Discovery of Tropomyosin Receptor Kinase Inhibitors as New Generation Anticancer Agents: A Review.

BACKGROUND: The tropomyosin receptor kinases (TRKs) are crucial for many cellular functions, such as growth, motility, differentiation, and metabolism. Abnormal TRK signalling contributes to a variety of human disorders, most evidently cancer. Comprehensive genomic studies have found numerous changes in the genes that code for TRKs like MET, HER2/ErbB2, and EGFR, among many others. Precision medicine resistance, relapse occurring because of the protein point mutations, and the existence of multiple molecular feedback loops are significant therapeutic hurdles to the long-term effectiveness of TRK inhibitors as general therapeutic agents for the treatment of cancer. OBJECTIVE: This review is carried out to highlight the role of tropomyosin receptor kinase in cancer and the function of TRK inhibitors in the intervention of cancer. METHODS: Literature research has been accomplished using Google Scholar and databases like ScienceDirect, WOS, PubMed, SciFinder, and Scopus. RESULTS: In this review, we provide an overview of the main molecular and functional properties of TRKs and their inhibitors. It also discusses how these advancements have affected the development and use of novel treatments for malignancies and other conditions caused by activated TRKs. Several therapeutic strategies, including the discovery and development of small-molecule TRK inhibitors belonging to various chemical classes and their activity, as well as selectivity towards the receptors, have been discussed in detail. CONCLUSION: This review will help the researchers gain a fundamental understanding of TRKs, how this protein family works, and the ways to create chemical moieties, such as TRK inhibitors, which can serve as tailored therapies for cancer.

Safety and feasibility of pulmonary rehabilitation in patients hospitalized with post-COVID-19 fibrosis: A feasibility study.

BACKGROUND: Emerging data suggest a spectrum of pulmonary complications from COVID-19, ranging from dyspnea to difficult ventilator weaning and fibrotic lung damage. Prolonged hospitalization is known to significantly affect activity levels, impair muscle strength and reduce cardiopulmonary endurance. OBJECTIVE: To assess the feasibility and safety of inpatient pulmonary rehabilitation (PR) and to explore effects on functional capacity, physical performance, fatigue levels, and functional status. DESIGN: A prospective feasibility study. SETTING: Inpatient unit of a tertiary care hospital. PARTICIPANTS: Twenty-five hospitalized patients diagnosed with post-COVID-19 fibrosis referred for PR. INTERVENTION: Individualized PR intervention including breathing exercises, positioning, strengthening, functional training, and ambulation twice a day for 6 days a week. OUTCOME MEASURES: One-minute sit-to-stand test (STST), Short Physical Performance Battery (SPPB), Fatigue Assessment Scale (FAS), and Post-COVID-19 Functional Status Scale (PCFS). RESULTS: Twenty-five participants (19 males, 6 females) with a mean age of 54.2 ± 13.4 years were enrolled. Sixteen completed the two-point assessment after undergoing in-patient PR of mean duration 14.8 ± 9 days. PR led to a significant improvement in all functional outcomes that is, STST (from 7.1 ± 4.3 repetitions to 14.2 ± 2.1 repetitions, SPPB (from 5 ± 2.8 to 9.4 ± 1.5), FAS (from 33.3 ± 10.8 to 25.8 ± 4.7) at the p ≤ .001, and PCFS (from 3.6 ± 0.9 to 2.9 ± 1.2, p ≤ .05). CONCLUSION: Early initiation of PR for hospitalized patients with COVID-19 fibrosis was safe, well tolerated, and feasible and may improve functional status.

Draft Genome Sequence of the Methyl Parathion (Pesticide) Degrading Bacterium Pseudomonas spp. MR3.

Pseudomonas spp. MR3 was isolated from the surrounding soil of pesticide manufacturing industries of Ankleshwar, Gujarat. Under laboratory conditions these microbes were able to degrade up to 500 ppm of methyl parathion within 72 h. Genome sequencing of Pseudomonas spp. MR3 was carried out inIon Torrent (PGM), next generation sequencer. The data obtained revealed 1,268 contigs with genome size of 2.99 Mb and G + C content of 60.9 %. The draft genome sequence of strain MR3 will be helpful in studying the genetic pathways involved in the degradation of several pesticides.