Silk fibroin/vitreous humor hydrogel scaffold modified by a carbodiimide crosslinker for wound healing.

Natural-derived biomaterials can be used as substrates for the growth, proliferation, and differentiation of cells. In this study, bovine vitreous humor as a biological material was cross-linked to silk fibroin with different concentration ratios to design a suitable substrate for corneal tissue regeneration. The cross-linked samples were evaluated with different analyses such as structural, physical (optical, swelling, and degradation), mechanical, and biological (viability, cell adhesion) assays. The results showed that all samples had excellent transparency, especially those with higher silk fibroin content. Increasing the ratio of vitreous humor to silk fibroin decreased mechanical strength and increased swelling and degradation, respectively. There was no significant difference in the toxicity of the samples, and with the increase in vitreous humor ratio, adhesion and cell proliferation increased. Generally, silk fibroin with vitreous humor can provide desirable characteristics as a transparent film for corneal wound healing.

Network Cluster Analysis of PPI and Phenotype Ontology for Type 1 Diabetes Mellitus.

Background: Our knowledge of Type 1 Diabetes Mellitus (T1DM) etiology is incomplete; however, the pathogenesis of the disease includes T-cell-mediated destruction of ß-cells. Objective: The present study aimed to investigate the key gene pathways and co-expression networks in T1DM disease. Material and Methods: TIDM-associated genes were identified from 13 databases, enrichment of pathways annotated with functional annotations, and analysis of protein-protein network interactions. Next, functional modules and transcription factor networks were constructed. The analysis of gene co-expression networks was conducted to discover associated pivotal modules. Results: A total of 172 expressed genes and four variants (SNP) were filtered in the of T1DM disease; pathway enrichment analysis identified key pathways, such as inflammatory bowel disease, type I diabetes mellitus, cytokine-cytokine receptor interaction, Th17 cell differentiation, JAK-STAT signaling pathway, and graft-versus-host disease. A weighted correlation network analysis revealed one module that was strongly correlated with T1DM. Functional annotation revealed that the module was mainly enriched in pathways such as T cell activation, regulation of immune system process, and response to the organic substance. IRF2, IRF4, IRF8, and CDX2 were regulated in the module at a significant level. Conclusion: The study identified IL-2 as a significant T1DM hotspot and highlighted the role of hub genes and transcription factors in the autoimmune disease, offering potentials for treatment and prevention.

Molecular Dynamics Simulation of Antimicrobial Peptide CM15 in Staphylococcus Aureus and Escherichia coli Model Bilayer Lipid.

Background: In animals and plants, antimicrobial peptides (AMPs) are crucial components of defense mechanisms, as they play a crucial role in innate immunity, which protects hosts from pathogenic bacteria. The CM15 has attracted considerable interest as a novel antibiotic against gram-negative and positive pathogens. Objective: The aim of this study was to investigate the permeation potential of the CM15 with membrane bilayers of Staphylococcus aureus and Escherichia coli. Material and Methods: The bilayer membranes of Escherichia coli and Staphylococcus aureus were modelled with the resemblance in lipid composition to its biological sample. This study followed Protein-Membrane Interaction (PMI) through successive applications of molecular dynamics simulation by GROMACS and CHARMM36 force field for two sets of 120-ns simulations. Results: Significant results were obtained from analyzing the trajectory of the unsuccessful insertion of CM15 during simulation. Our data suggested that Lysine residues in CM15 and Cardiolipins in membrane leaflets play a crucial role in stability and interaction terms. Conclusion: The obtained results strengthen the insertion possibility through the toroidal model, which should consider for further studies on AMPs interaction.

Promoting ß-cells function by the recapitulation of in vivo microenvironmental differentiation signals.

The study aims to transdifferentiate rat bone marrow-derived mesenchymal stem cells (BM-MSCs) more efficiently into islet-like cells and encapsulate and transplant them with vital properties like stability, proliferation, and metabolic activity enhanced for the treatment of T1DM. Trans-differentiation of BM-MCs into islet-like cells induced by high glucose concentration combined with Nicotinamide, ꞵ-Mercaptoethanol, ꞵ-Cellulin, and IGF-1. Glucose challenge assays and gene expression profiles were used to determine functionality. Microencapsulation was performed using the vibrating nozzle encapsulator droplet method with a 1% alginate concentration. Encapsulated ꞵ-cells were cultured in a fluidized-bed bioreactor with 1850 µL/min fluid flow rates and a superficial velocity of 1.15 cm/min. The procedure was followed by transplanting transdifferentiated cells into the omentum of streptozotocin (STZ)-induced diabetic Wistar rats. Changes in weight, glucose, insulin, and C-peptide levels were monitored for 2 months after transplantation. PDX1, INS, GCG, NKx2.2, NKx6.1, and GLUT2 expression levels revealed the specificity of generated ß-cells with higher viability (about 20%) and glucose sensitivity about twofold more. The encapsulated ß-cells decreased the glucose levels in STZ-induced rats significantly (P < 0.05) 1 week after transplantation. Also, the weight and levels of insulin and C-peptide reached the control group. In contrast to the treated, the sham group displayed a consistent decline in weight and died when loss reached > 20% at day ~ 55. The coated cells secrete significantly higher amounts of insulin in response to glucose concentration changes. Enhanced viability and functionality of ß-cells can be achieved through differentiation and culturing, a promising approach toward insulin therapy alternatives.

Bacteriostatic Potency of Fe2O3 Against Enterococcus faecalis in Synergy with Antibiotics by DDST Method.

BACKGROUND: In this study, bacteriostatic potency of the Iron oxide nanoparticles against Enterococcus faecalis (E. faecalis) (a clinical sample and the ATCC11700 strain) was investigated. METHODS: Nanoparticles' bacteriostatic concentration was determined and used to appraise the characteristics of the Iron Oxide (Fe2O3) against the isolates. Antimicrobial examinations with 108 cfu.ml -1 were performed at the baseline. Due to evaluation level of potency, after performing Minimum Inhibitory Concentration (MIC), the assessment of death kinetic and susceptibility constant of nanoparticles was done by suspension at two MICs in 0 to 360 min treatment time. RESULTS: Fe2O3 nanoparticles in size range of 10-50 nm demonstrated the most effective susceptibility reaction against E. faecalis and ATCC11700 strain in Z=78.125 ml/µg -1 and 39.0625 ml/µg -1, respectively. The kinetic reaction of E. faecalis against Fe2O3 suspension was supposed to be decreased through the elapse of treatment time, whereas increased concentration was along with bacteria growth after a certain time. So, the efficient concentration of nanoparticles was applied with semi-sensitive and antibiotic resistant for both strains. However, synergism of Fe2O3 nanoparticles with Ceftazidime and Clindamycin revealed a higher susceptibility compared with Fe2O3nanoparticles alone against E. faecalis. CONCLUSION: The experimental results reveal that Fe2O3 has a strong antimicrobial effect at a certain concentration over the time so could potentially be used for bacterial inhibition and this feature will be strengthened in combination with antibiotics.

Structural characterization of PPTI, a kunitz-type protein from the venom of Pseudocerastes persicus.

The main purpose of this report is to investigate the structural property and new potential function of PPTI (Pseudocerastes Persicus Trypsin Inhibitor), a kunitz-type protein with inhibitory effect against trypsin proteolytic activity. Besides kunitz-type serine protease inhibitors, PPTI shows clear-cut similarities with dendrotoxins (DTXs), the other kunitz-type protein subfamily. The most important reason is the presence of functionally important residues of DTXs at correspondingly the same positions in PPTI. As such, we proposed the new ability of PPTI for inhibiting voltage-gated potassium channels and consequently its dual functionality. At first, we determined the solution structure of PPTI via Nuclear Magnetic Resonance (NMR) spectroscopy. Then by homology modeling, we constructed the model structure of trypsin-PPTI complex to confirm the same interaction pattern as trypsin-BPTI at complex interface. Finally, by Brownian dynamics (BD) simulations of PPTI NMR derived ensemble structure as ligand against homology model of human Kv1.1 potassium channel as receptor, we evaluated the potential DTX-like activity of PPTI. The results of our study support the proposed dual functionality of PPTI.

Kinetics activity of Yersinia Intermedia Against ZnO Nanoparticles Either Synergism Antibiotics by Double-Disc Synergy Test Method.

BACKGROUND: Bacterial resistance to the commonly used antibacterial agents is an increasing challenge in the medicine, and a major problem for the health care systems; the control of their spread is a constant challenge for the hospitals. OBJECTIVES: In this study, we have investigated the antimicrobial activity of the Zinc Oxide nanoparticles against clinical sample; Yersinia intermedia bacteria. MATERIALS AND METHODS: Nanoparticle susceptibility constants and death kinetic were used to evaluate the antimicrobial characteristics of the Zinc Oxide (ZnO) against the bacteria. Antimicrobial tests were performed with 108 cfu.mL-1 at baseline. At first, Minimum Inhibitory Concentration (MIC) of ZnO was determined and then nanoparticle suspension at one and two times of the MIC was used for death kinetic and susceptibility constant assay at 0 to 360 min treatment time. RESULTS: ZnO nanoparticles with size ranging from 10 to 30 nm showed the highest susceptibility reaction against Y. intermedia (Z=39.06 mL.µg-1). The process of Y. intermedia death in ZnO suspension was assumed to follow the first-order kinetics and the survival ratio of bacteria decreased with the increasing treatment time. An increased concentration of the nanoparticle was seen to enhance the bactericidal action of the nanoparticle. Then we performed the best ratio of the nanoparticles on semi-sensitive and resistance antibiotic for the bacteria. However, based on experimental results, synergy of ZnO nanoparticles and Oxacilin was determined and Y. intermedia showed a higher sensitivity compared to the ZnO nanoparticles alone. CONCLUSIONS: The results of the present study illustrates that ZnO has a strong antimicrobial effect and could potentially be employed to aid the bacterial control. It could also improve- antibacterial effects in combination with the antibiotics.