Data mining and structural analysis for multi-tissue regeneration potential of BMP-4 and activator drugs.

Despite substantial progress in surgery, managing multi-tissue injuries is strenuous to accomplish and requires a multi-staged serial treatment of individual tissues. Stimulated regeneration affects the complete structural and functional repair of both hard and soft tissues post-injury and thus serves as an attractive therapeutic option to target multi-tissue injuries. This study utilized data mining and structural analysis to identify a target that has the ability to evoke healing of the two most commonly injured tissues i.e., bone and muscle, and stimulate the inherent vascular connectivity between the tissues. To find out the multipotential molecule the gene expression profile from GSE34747 was extracted and processed to identify the differentially expressed genes (DEGs). The DEGs were then subjected to gene ontology enrichment analysis to filter out a target that is likely to regulate the multi-tissue regeneration. Further, STITCH and PubChem databases were screened to determine a stimulatory drug against the identified target molecule. Finally, the binding affinity and stability of the potential drug candidate(s) against the target were analysed by molecular docking and molecular dynamics simulation. The results revealed that bone morphogenetic protein-4 (BMP-4) was associated with the regulation of the multiple regeneration processes. The computational screening results suggested Retinoic acid and Torularhodin as potential drug candidates for the stimulation of BMP-4. Both drugs demonstrated slightly different but stable interactions with BMP-4, suggesting that the identified drug candidates are likely to serve as potential leads to further enhance tissues regeneration.Communicated by Ramaswamy H. Sarma.

Threat, challenges, and preparedness for future pandemics: A descriptive review of phylogenetic analysis based predictions.

For centuries the world has been confronted with many infectious diseases, with a potential to turn into a pandemic posing a constant threat to human lives. Some of these pandemics occurred due to the emergence of new disease or re-emergence of previously known diseases with a few mutations. In such scenarios their optimal prevention and control options were not adequately developed. Most of these diseases are highly contagious and for their timely control, knowledge about the pathogens and disease progression is the basic necessity. In this review, we have presented a documented chronology of the earlier pandemics, evolutionary analysis of the infectious disease with pandemic potential, the role of RNA, difficulties in controlling pandemics, and the likely pathogens that could trigger future pandemics. In this study, the evolutionary history of the pathogens was identified by carrying out phylogenetic analysis. The percentage similarity between different infectious diseases is critically analysed for the identification of their correlation using online sequence matcher tools. The Baltimore classification system was used for finding the genomic nature of the viruses. It was observed that most of the infectious pathogens rise from their animal hosts with some mutations in their genome composition. The phylogenetic tree shows that the single-stranded RNA diseases have a common origin and many of them are having high similarity percentage. The outcomes of this study will help in the identification of potential pathogens that can cause future pandemics. This information will be helpful in the development of early detection techniques, devising preventive mechanism to limit their spread, prophylactic measures, Infection control and therapeutic options, thereby, strengthening our approach towards global preparedness against future pandemics.

Therapeutics effect of mesenchymal stromal cells in reactive oxygen species-induced damages.

Reactive Oxygen Species are chemically unstable molecules generated during aerobic respiration, especially in the electron transport chain. ROS are involved in various biological functions; any imbalance in their standard level results in severe damage, for instance, oxidative damage, inflammation in a cellular system, and cancer. Oxidative damage activates signaling pathways, which result in cell proliferation, oncogenesis, and metastasis. Since the last few decades, mesenchymal stromal cells have been explored as therapeutic agents against various pathologies, such as cardiovascular diseases, acute and chronic kidney disease, neurodegenerative diseases, macular degeneration, and biliary diseases. Recently, the research community has begun developing several anti-tumor drugs, but these therapeutic drugs are ineffective. In this present review, we would like to emphasize MSCs-based targeted therapy against pathologies induced by ROS as cells possess regenerative potential, immunomodulation, and migratory capacity. We have also focused on how MSCs can be used as next-generation drugs with no side effects.

COVID-19 and its Therapeutics: Special Emphasis on Mesenchymal Stem Cells Based Therapy.

The novel virus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) caused the Corona Virus Disease-2019 (COVID-19) outbreak in Wuhan, Hubei province of China. This virus disseminated rapidly and reached to an unprecedented pandemic proportion in more than 213 nations with a large number of fatalities. The hypersecretion of pro-inflammatory cytokines is the main cause of mortality and morbidity due to COVID-19, therefore strategies that avert the cytokine storm may play a crucial role in abating the severity of COVID-19. This review highlights the minute details of SARS-CoV-2, its genomic organization, genomic variations within structural and non-structural proteins and viral progression mechanism in human beings. The approaches like antiviral strategies are discussed, including drugs that obstruct viral propagation and suppress the pro-inflammatory cytokines. This compilation emphasizes Mesenchymal Stem Cells (MSCs) based therapy alone or in combination with other therapeutics as an attractive curative approach for COVID-19 pandemic. The MSCs and its secretome, including antimicrobial peptides (AMPs) have various capabilities, for instance, immunomodulation, regeneration, antimicrobial properties, potential for attenuating the cytokine storm and bare minimum chances of being infected with SARS-CoV-2 virus. The immunomodulatory property of MSCs affects inflammatory state and regulates immune response during SARS-CoV-2 infection. However, as of now, there is no WHO-approved MSCs based therapy for the treatment of COVID-19 infection. Graphical abstract.