Melting dynamics of hafnium clusters are investigated using a novel approach based on the idea of the chemical similarity index. Ground state configurations of small hafnium clusters are first derived using Basin-Hopping and Genetic Algorithm in the parallel tempering mode, employing the COMB potential in the energy calculator. These assumed ground state structures are verified by using the Low Lying Structures (LLS) method. The melting process is carried out either by using the direct heating method or prolonged simulated annealing. The melting point is identified by a caloric curve. However, it is found that the global similarity index is much more superior in locating premelting and total melting points of hafnium clusters.
Malaria is a life-threatening disease caused by the Plasmodium sp. parasite. Infection results in heightened pro-inflammatory response which contributes to the pathophysiology of the disease. To mitigate the overwhelming cytokine response, host-directed therapy is a plausible approach. Glycogen synthase kinase-3β (GSK3β), a serine/threonine kinase plays a pivotal role in the regulation of inflammatory response during pathogenic infections. The present study was conducted to investigate the chemo-suppressive and cytokine-modulating effects of insulin administration in malaria-infected mice and the involvement of GSK3β. Intraperitoneal administrations of 0.3 and 0.5 U/kg body weight insulin each for four consecutive days into Plasmodium berghei NK65 (PbN)-infected mice resulted in chemo-suppression exceeding 60% and improved median survival time of infected mice (20.5 days and 19 days respectively compared to 15.5 days for non-treated control). Western analysis revealed that pGSK3β (Ser9) intensity in brain samples from insulin-treated (0.3 and 0.5 U/kg body weight) infected mice each were 0.6 and 2.2 times respectively than that in control. In liver samples, pGSK3β (Ser9) intensity from insulin-treated infected mice were significantly higher (4.8 and 16.1 fold for 0.3 and 0.5 U/kg bw respectively) than that in control. Insulin administration decreased both brain and liver pNF-κB p65 (Ser536) intensities (to 0.8 and 0.6 times for 0.3 U/kg bw insulin; and to 0.2 and 0.1 times for 0.5 U/kg bw insulin respectively compared to control). Insulin treatment (0.5 U/kg bw) also significantly decreased the serum levels of pro-inflammatory cytokines (TNF-α (3.3 times) and IFN-γ (4.9 times)) whilst significantly increasing the levels of anti-inflammatory cytokines (IL-4 (4.9 fold) and IL-10 (2.1 fold)) in PbN-infected mice. Results from this study demonstrated that the cytokinemodulating effects of insulin at least in part involve inhibition of GSK3β and consequent inhibition of the activation of NF-κB p65 suggesting insulin as a potential adjunctive therapeutic for malaria.
Glottic insufficiency is one of the voice disorders affecting all demographics. Due to the incomplete closure of the vocal fold, there is a risk of aspiration and ineffective phonation. Current treatments for glottic insufficiency include nerve repair, reinnervation, implantation and injection laryngoplasty. Injection laryngoplasty is favored among these techniques due to its cost-effectiveness and efficiency. However, research into developing an effective injectable for the treatment of glottic insufficiency is currently lacking. Therefore, this study aims to develop an injectable gelatin (G) hydrogel crosslinked with either 1-ethyl-3-(3-dimethylaminpropyl)carbodiimide hydrochloride) (EDC) or genipin (gn). The gelation time, biodegradability and swelling ratio of hydrogels with varying concentrations of gelatin (6-10% G) and genipin (0.1-0.5% gn) were investigated. Some selected formulations were proceeded with rheology, pore size, chemical analysis and in vitro cellular activity of Wharton's Jelly Mesenchymal Stem Cells (WJMSCs), to determine the safety application of the selected hydrogels, for future cell delivery prospect. 6G 0.4gn and 8G 0.4gn were the only hydrogel groups capable of achieving complete gelation within 20 min, exhibiting an elastic modulus between 2 and 10 kPa and a pore size between 100 and 400 μm. Moreover, these hydrogels were biodegradable and biocompatible with WJMSCs, as > 70% viability were observed after 7 days of in vitro culture. Our results suggested 6G 0.4gn and 8G 0.4gn hydrogels as potential cell encapsulation injectates. In light of these findings, future research should focus on characterizing their encapsulation efficiency and exploring the possibility of using these hydrogels as a drug delivery system for vocal fold treatment.
Glottic insufficiency is widespread in the elderly population and occurs as a result of secondary damage or systemic disease. Tissue engineering is a viable treatment for glottic insufficiency since it aims to restore damaged nerve tissue and revitalize aging muscle. After injection into the biological system, injectable biomaterial delivers cost- and time-effectiveness while acting as a protective shield for cells and biomolecules. This article focuses on injectable biomaterials that transport cells and biomolecules in regenerated tissue, particularly adipose, muscle, and nerve tissue. We propose Wharton's Jelly mesenchymal stem cells (WJMSCs), induced pluripotent stem cells (IP-SCs), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor-1 (IGF-1) and extracellular vesicle (EV) as potential cells and macromolecules to be included into biomaterials, with some particular testing to support them as a promising translational medicine for vocal fold regeneration.