A computational approach to analyzing the functional and structural impacts of Tripeptidyl-Peptidase 1 missense mutations in neuronal ceroid lipofuscinosis.

Neuronal ceroid-lipofuscinosis (NCLs) are a group of severe neurodegenerative conditions, most likely present in infantile, late infantile, juvenile, and adult-onset forms. Their phenotypic characteristics comprise eyesight damage, reduced motor activity and cognitive function, and sometimes tend to die in the initial stage. In recent studies, NCLs have been categorized into at least 14 genetic collections (CLN1-14). CLN2 gene encodes Tripeptidyl peptidase 1 (TPP1), which affects late infantile-onset form. In this study, we retrieved a mutational dataset screening for TPP1 protein from various databases (ClinVar, UniProt, HGMD). Fifty-six missense mutants were enumerated with computational methods to perceive the significant mutants (G475R and G501C) and correlated with clinical and literature data. A structure-based screening method was initiated to understand protein-ligand interaction and dynamic simulation. The docking procedure was performed for the native (3EDY) and mutant (G473R and G501C) structures with Gemfibrozil (gem), which lowers the lipid level, decreases the triglycerides amount in the blood circulation, and controls hyperlipidemia. The Native had an interaction score of -5.57 kcal/mol, and the mutants had respective average binding scores of -6.24 (G473R) and - 5.17 (G501C) kcal/mol. Finally, molecular dynamics simulation showed that G473R and G501C mutants had better flexible and stable orientation in all trajectory analyses. Therefore, this work gives an extended understanding of both functional and structural levels of influence for the mutant form that leads to NCL disorder.

An integrated management (Ayurveda and Modern medicine) of accidental burn injury: A case study.

Burn injuries are frequent, horrifying, and life-threatening conditions that are still challenging to cure. Complications like scarring, keloid formation, and contractures are the main challenges for the treating surgeon. The Ayurvedic classics explain different treatment modalities for the management of burn wounds, like oral medicines, topical applications prepared with herbal medicines, ghee, oil, and typical wound dressing techniques like Patraadaana (wound covering with medicinal leaves), and fumigation therapy, etc. Here we report a case of accidental burn injury with a TBSA of 27% First degree (superficial) and 15% second degree (deep partial-thickness) burns with complaints of fever and burning sensation at the burn site. On the basis of the symptoms listed in the classical texts of Ayurveda, the case was diagnosed as Pramadadagdha (accidental burn). To properly manage the burn wound, an integrated therapy strategy was designed. Ropanaghrita (medicated ghee) was applied locally, followed by the application of Tinospora cordifolia leaves to cover the wound, fumigation therapy, and oral medications to hasten wound healing and reduce infection. In the first seven days, modern medicine was used as emergency care in addition to Ayurvedic management. Within 60 days of receiving treatment, the burn wound had entirely healed, and the patient was able to resume her regular work activities. In the current situation, the combined strategy produced encouraging burn management outcomes.