nSARS-Cov-2, pulmonary edema and thrombosis: possible molecular insights using miRNA-gene circuits in regulatory networks.

BACKGROUND: Given the worldwide spread of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (nSARS-CoV-2) infection pandemic situation, research to repurpose drugs, identify novel drug targets, vaccine candidates have created a new race to curb the disease. While the molecular signature of nSARS-CoV-2 is still under investigation, growing literature shows similarity among nSARS-CoV-2, pulmonary edema, and thromboembolic disorders due to common symptomatic features. A network medicine approach is used to to explore the molecular complexity of the disease and to uncover common molecular trajectories of edema and thrombosis with nSARS-CoV-2. RESULTS AND CONCLUSION: A comprehensive nSARS-CoV-2 responsive miRNA: Transcription Factor (TF): gene co-regulatory network was built using host-responsive miRNAs and it's associated tripartite, Feed-Forward Loops (FFLs) regulatory circuits were identified. These regulatory circuits regulate signaling pathways like virus endocytosis, viral replication, inflammatory response, pulmonary vascularization, cell cycle control, virus spike protein stabilization, antigen presentation, etc. A unique miRNA-gene regulatory circuit containing a consortium of four hub FFL motifs is proposed to regulate the virus-endocytosis and antigen-presentation signaling pathways. These regulatory circuits also suggest potential correlations/similarity in the molecular mechanisms during nSARS-CoV-2 infection, pulmonary diseases and thromboembolic disorders and thus could pave way for repurposing of drugs. Some important miRNAs and genes have also been proposed as potential candidate markers. A detailed molecular snapshot of TGF signaling as the common pathway, that could play an important role in controlling common pathophysiologies among diseases, is also put forth. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s41544-020-00057-y.

Role of miRNAs in hypoxia-related disorders.

Hypoxia is a complex pathophysiological condition. The physiological and molecular responses to this stress have been extensively studied. However, the management of its ill effects still poses a challenge to clinicians. MicroRNAs (miRNAs) are short non-coding RNA molecules that control post-transcriptional gene expression. The regulatory role of miRNAs in hypoxic environments has been studied in many hypoxia-related disorders, however a comprehensive compilation and analysis of all data and the significance of miRNAs in hypoxia adaption is still lacking. This review summarizes the miRNAs related to various hypoxia-related disorders and highlights the computational approaches to study them. This would help in designing novel strategies toward efficient management of hypoxia-related disorders.

Purification and crystallization of coconut globulin cocosin from Cocos nucifera.

Cocosin is a legume class reserve protein found in coconut endosperm. Using coconut endosperm, two methods of purification were done. Crystallization was achieved by vapor diffusion (hanging drop) method using MPD, PEG 3350 and PEG 4000 as precipitants. X-ray diffraction data to 3.5-A resolution were collected using Mar345 image plate detector system. Crystals of cocosin grown under 20% MPD, are rhombohedral with space group R3 and cell dimensions a=92.829 A, b=92.829 A, c=215.290 A.

Degradation of (+)-catechin by Acinetobacter calcoaceticus MTC 127.

Acinetobacter calcoaceticus MTC 127 was able to grow on catechin and protocatechuic acid (PCA) as sole carbon source. Cells induced with catechin oxidized catechin and PCA at rates higher than cells of uninduced cultures. Two aromatic compounds, PCA and phloroglucinol carboxylic acid (PGCA) were isolated from culture filtrate of cells grown in catechin and characterized by infrared spectrometry and high performance thin-layer chromatography. Moreover, A. calcoaceticus MTC 127 produced high levels of PCA compared to PGCA in the degradation of catechin. Based upon these results, a pathway for the degradation of (+)-catechin in A. calcoaceticus MTC 127 is proposed. Enzymes extracted from catechin-induced culture showed catechin oxygenase (cox) and protocatechuate 3,4-dioxygenase (pcd) activities. Catechin oxygenase was purified by column chromatography and SDS-PAGE analysis showed a single band with an apparent molecular weight of 47 kDa.

Recombinant heat shock protein 60 (Hsp60/GroEL) of Salmonella enterica serovar Typhi elicits cross-protection against multiple bacterial pathogens in mice.

Heat shock proteins (HSPs) or stress proteins are recognized as protective antigens against a wide range of bacterial diseases. Conservation of HSPs across different life forms also appears to contribute to the antigenicity of these proteins. Due to their high sequence homology, there exists an immunological cross-recognition between different bacterial species. In the present study, we evaluated the efficacy of recombinant GroEL of Salmonella enterica serovar Typhi as a vaccine candidate against various bacterial pathogens viz.; Shigella dysenteriae type I, Shigella flexneri, Shigella boydii, enteropathogenic Escherichia coli (EPEC), Klebsiella pneumoniae and Pseudomonas aeruginosa. In vitro serum bactericidal assay (SBA) with GroEL antisera showed 50-55% inhibition of cells of Shigella Spp., 65-75% of E. coli, 60-65% of K. pneumoniae, 45-50% of P. aeruginosa. In in vivo experiments, mice immunized with GroEL protein of S. Typhi showed 60-65% protection against S. flexneri, S. dysenteriae type I, S. boydii. Similarly 75-80% protection was observed against enteropathogenic E. coli, 70-80% against K. pneumoniae. 50% of mice survived the lethal infection against P. aeruginosa. Organ burden and histopathological studies also revealed significant reduction of bacterial infection. This study shows the cross-protective efficacy of recombinant GroEL of S. Typhi which could lead to the development of a single vaccine candidate protective against multiple bacterial pathogens.