Repurposing the Antibacterial Activity of Etoposide─A Chemotherapeutic Drug in Combination with Eggshell-Derived Hydroxyapatite.

Drug repurposing has been gaining increasing interest recently due to the reduction in development cost and reduced development timelines. Here, we report the antibacterial activity of the anticancer drug etoposide investigated in combination with the eggshell-derived hydroxyapatite (EHA). Hydroxyapatite (HA) is a well-known bioactive material with enhanced osteoconductivity and possesses superior drug delivery properties. In the present work, we have synthesized etoposide-loaded EHA by the wet precipitation method. The physicochemical characterization of the samples confirmed the composition and amount of drug encapsulation. Screening for antibacterial activity confirmed the antibacterial effect of etoposide against Staphylococcus aureus. Biofilm formation test on pristine and etoposide-loaded samples showed the inhibition of biofilm formation on etoposide loading, which was further studied by confocal laser scanning microscopy (CLSM) and colony forming units (CFUs). It has been found that etoposide-loaded HA exhibited a sustained release of the drug upto 168 h. Analysis of the inhibition mechanism of etoposide against S. aureus revealed damage to the cell membrane and has been quantified using flow cytometry by the uptake of propidium iodide. Etoposide-loaded eggshell-derived HA (EHA-ET) exhibited excellent bioactivity and cytocompatibility against mouse fibroblast cells (L929) and supressed the growth of osteosarcoma cells (MG-63). Our studies reveal that the EHA-ET has a great potential for treating osteosarcoma and osteomyelitis.

Mechanisms contributing to adverse outcomes of COVID-19 in obesity.

A growing amount of epidemiological data from multiple countries indicate an increased prevalence of obesity, more importantly central obesity, among hospitalized subjects with COVID-19. This suggests that obesity is a major factor contributing to adverse outcome of the disease. As it is a metabolic disorder with dysregulated immune and endocrine function, it is logical that dysfunctional metabolism contributes to the mechanisms behind obesity being a risk factor for adverse outcome in COVID-19. Emerging data suggest that in obese subjects, (a) the molecular mechanisms of viral entry and spread mediated through ACE2 receptor, a multifunctional host cell protein which links to cellular homeostasis mechanisms, are affected. This includes perturbation of the physiological renin-angiotensin system pathway causing pro-inflammatory and pro-thrombotic challenges (b) existent metabolic overload and ER stress-induced UPR pathway make obese subjects vulnerable to severe COVID-19, (c) host cell response is altered involving reprogramming of metabolism and epigenetic mechanisms involving microRNAs in line with changes in obesity, and (d) adiposopathy with altered endocrine, adipokine, and cytokine profile contributes to altered immune cell metabolism, systemic inflammation, and vascular endothelial dysfunction, exacerbating COVID-19 pathology. In this review, we have examined the available literature on the underlying mechanisms contributing to obesity being a risk for adverse outcome in COVID-19.

Comparison of eri and tasar silk fibroin scaffolds for biomedical applications.

The cultivated silk, mulberry, is being used as biomaterial in different forms. Eri, tasar and muga are some of the known wild silk varieties. The studies on biomedical applications of electrospun mats produced from these wild silks are limited though few studies on eri silk are available. In this work, comparison was made between eri and tasar silk fibroin scaffolds for biomedical application. The scaffolds were produced from eri silk fibroin (ESF) and tasar silk fibroin (TSF) by electrospinning method and they were treated with ethanol to improve dimensional stability. Ethanol treatment increased the crystallinity% of both ESF and TSF scaffolds. The crystallinity percentage of the ESF and TSF scaffolds was found to be 46.7 and 42.8 % respectively. Thermal stability was higher for ESF than that of TSF scaffold. The hemolytic % of ESF and TSF scaffolds was found to be 1.3 and 7.7 % respectively. The platelet adhesion on the surface of ESF scaffold was lower than that found on TSF scaffold. Better fibroblast cell attachment, binding and spreading was found on the ESF scaffold. The cell viability on ESF scaffold was 83.78 % and in TSF was 78.01 % for 48 h. The results showed that ESF electrospun scaffold can be considered as a better biomaterial for biomedical applications compared to that of TSF scaffold.

Bioactivity Studies of ß-Lactam Derived Polycyclic Fused Pyrroli-Dine/Pyrrolizidine Derivatives in Dentistry: In Vitro, In Vivo and In Silico Studies.

The antibacterial activity of ß-lactam derived polycyclic fused pyrrolidine/pyrrolizidine derivatives synthesized by 1, 3-dipolar cycloaddition reaction was evaluated against microbes involved in dental infection. Fifteen compounds were screened; among them compound 3 showed efficient antibacterial activity in an ex vivo dentinal tubule model and in vivo mice infectious model. In silico docking studies showed greater affinity to penicillin binding protein. Cell damage was observed under Scanning Electron Microscopy (SEM) which was further proved by Confocal Laser Scanning Microscope (CLSM) and quantified using Flow Cytometry by PI up-take. Compound 3 treated E. faecalis showed ROS generation and loss of membrane integrity was quantified by flow cytometry. Compound 3 was also found to be active against resistant E. faecalis strains isolated from failed root canal treatment cases. Further, compound 3 was found to be hemocompatible, not cytotoxic to normal mammalian NIH 3T3 cells and non mutagenic. It was concluded that ß-lactam compound 3 exhibited promising antibacterial activity against E. faecalis involved in root canal infections and the mechanism of action was deciphered. The results of this research can be further implicated in the development of potent antibacterial medicaments with applications in dentistry.