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.

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.

Antimicrobial activity of cationic peptides in endodontic procedures.

OBJECTIVES: The present study aimed to investigate the antimicrobial and biofilm inhibition activity of synthetic antimicrobial peptides (AMPs) against microbes such as Enterococcus faecalis, Staphylococcus aureus, and Candida albicans which are involved in endodontic infections. MATERIALS AND METHODS: Agar diffusion test was done to determine the activity of peptides. The morphological changes in E. faecalis and reduction in biofilm formation after treatment with peptides were observed using scanning electron microscope. The efficacy of peptides using an ex vivo dentinal model was determined by polymerase chain reaction and confocal laser scanning microscopy. Platelet aggregation was done to determine the biocompatibility of peptides. RESULTS: Among 11 peptides, two of the amphipathic cationic peptides were found to be highly active against E. faecalis, S. aureus, C. albicans. Efficacy results using dentinal tubule model showed significant reduction in microbial load at 400 µm depth. The peptides were also biocompatible. CONCLUSION: These results suggest that synthetic AMPs have the potential to be developed as antibacterial agents against microorganisms involved in dental infections and thus could prevent the spread and persistence of endodontic infections improving treatment outcomes and teeth preservation.

Electrospun eri silk fibroin scaffold coated with hydroxyapatite for bone tissue engineering applications.

Natural biomaterials such as collagen, silk fibroin, and chitosan, and synthetic biopolymers such as polylactic acid, polycaprolactone, polyglycolic acid, and their copolymers are being used as scaffold for tissue engineering applications. In the present work, a fibrous mat was electrospun from eri silk fibroin (ESF). A composite of hydroxyapatite (Hap) and the ESF scaffold was prepared by soaking the ESF scaffold in a solution of calcium chloride and then in sodium diammonium phosphate. The average tensile stress of the pure ESF and hydroxyapatite-coated ESF scaffold (ESF-Hap) was found to be 1.84 and 0.378 MPa, respectively. Pure ESF and ESF-Hap scaffolds were evaluated for their characteristics by a themogravimetric analyzer and Fourier transform infrared spectroscope. The crystallinity and thermal stability of the ESF-Hap scaffold were found to be more than that of uncoated eri silk nanofiber scaffold. The water uptake of the pure ESF and ESF-Hap scaffolds was found to be 69% and 340%, respectively, in distilled water as well as phosphate buffer saline. The hemolysis percentage of both scaffolds was less than 5%, which indicate their good blood compatibility. The cytocompatibility studied by 3-(4,5-dimethyl) thiazol-2-yl-2,5-dimethyl tetrazolium bromide assay showed that the scaffold is biocompatible. To assess cell attachment and growth on the scaffold, human mesenchymal stem cells were cultured on the scaffolds. The results from scanning electron microscopy and fluorescent microscopy showed a notable cellular growth and favorable morphological features. Hence, the ESF-Hap scaffold is better suited for cell growth than the pure ESF scaffold.