Deferoxamine preconditioning to restore impaired HIF-1α-mediated angiogenic mechanisms in adipose-derived stem cells from STZ-induced type 1 diabetic rats

Objectives: Both excessive and insufficient angiogenesis are associated with progression of diabetic complications, of which poor angiogenesis is an important feature. Currently, adipose-derived stem cells (ADSCs) are considered to be a promising source to aid therapeutic neovascularization. However, functionality of these cells is impaired by diabetes which can result from a defect in hypoxia-inducible factor-1 (HIF-1), a key mediator involved in neovascularization. In the current study, we sought to explore effectiveness of pharmacological priming with deferoxamine (DFO) as a hypoxia mimetic agent, to restore the compromised angiogenic pathway, with the aid of ADSCs derived from streptozotocin (STZ)-induced type 1 diabetic rats ('diabetic ADSCs'). Materials and methods: Diabetic ADSCs were treated with DFO and compared to normal and non-treated diabetic ADSCs for expression of HIF-1α, VEGF, FGF-2 and SDF-1, at mRNA and protein levels, using qRT-PCR, western blotting and ELISA assay. Activity of matrix metalloproteinases -2 and -9 were measured using a gelatin zymography assay. Angiogenic potential of conditioned media derived from normal, DFO-treated and non-treated diabetic ADSCs were determined by in vitro (in HUVECs) and in vivo experiments including scratch assay, three-dimensional tube formation testing and surgical wound healing models. Results: DFO remarkably enhanced expression of noted genes by mRNA and protein levels and restored activity of matrix metalloproteinases -2 and -9. Compromised angiogenic potential of conditioned medium derived from diabetic ADSCs was restored by DFO both in vitro and in vivo experiments. Conclusion: DFO preconditioning restored neovascularization potential of ADSCs derived from diabetic rats by affecting the HIF-1α pathway. © 2015 John Wiley & Sons Ltd

Electrochemical properties of single-crystalline Mn3O4 nanostructures and their capacitive performance in basic electrolyte

Single-crystalline Mn3O4 square-shaped nanostructures have been successfully synthesized by hydrothermal method without using any surfactant. The as-prepared products were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), Transmission electron microscopy (TEM) and High Resolution transmission electron microscopy (HRTEM). To assess the potential properties of nanostructures, galvanostatic charging-discharging and cyclic voltammetry measurements were performed for their use in supercapacitors. The Mn3O4 nanoarchitectures used as supercapacitor electrode in 1mol L-1 KOH electrolyte have a specific capacitance value of 355.5 F g-1 at a low current density of 0.35 A.g-1. The device still retain 85.08% of its initial capacitance afterwards 2000 cycles at a current density of 5 A.g-1. The as-synthesized Mn3O4 nanostructures exhibited a good rate capability and stability for electrochemical properties. These results indicate their potential application as electrode material for high performance supercapacitor in basic medium. � 2016 The Authors

Keratins and epidermolysis bullosa simplex

Keratin intermediate filaments play an important role in maintaining the integrity of the skin structure. Understanding the importance of this subject is possible with the investigation of keratin defects in epidermolysis bullosa simplex (EBS). Nowadays, in addition to clinical criteria, new molecular diagnostic methods, such as next generation sequencing, can help to distinguish the subgroups of EBS more precisely. Because the most important and most commonly occurring molecular defects in these patients are the defects of keratins 5 and14 (KRT5 and KRT14), comprehending the nature structure of these proteins and their involved processes can be very effective in understanding the pathophysiology of this disease and providing new and effective therapeutic platforms to treat it. Here, we summarized the various aspects of the presence of KRT5 and KRT14 in the epidermis, their relation to the incidence and severity of EBS phenotypes, and the processes with which these proteins can affect them. © 2018 Wiley Periodicals, Inc

A novel succinate dehydrogenase type B mutation in an Iranian family. Its genetic and clinical evaluation

Succinate Dehydrogenase-B (SDH-B) gene mutations constitute one of the most frequent forms of hereditary paragangliomas (PGL). Genetic study is advised in all cases for the evaluation of tumour behaviour, the selection of optimal management and the surveillance of the first degree relatives. There are limited data on the genetic characteristics of patients with PGLs from Middle East countries, and to our knowledge this is the first study from Iran. We present the clinical and genetic characteristics of a 29-year old woman who presented with hypertension secondary to a para-aortic PGL. She was shown to have a novel mutation in the SDH-B gene and her family was subsequently screened. We also emphasize the problems in diagnosing and treating patients in this region. © 2014 Hellenic Endocrine Society. All rights reserved

Field Research Is Essential to Counter Virological Threats

The interface between humans and wildlife is changing and, with it, the potential for pathogen introduction into humans has increased. Avian influenza is a prominent example, with an ongoing outbreak showing the unprecedented expansion of both geographic and host ranges. Research in the field is essential to understand this and other zoonotic threats. Only by monitoring dynamic viral populations and defining their biology in situ can we gather the information needed to ensure effective pandemic preparation.</p

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

On the prediction of the mechanical properties of ultrafine grain Al-TiO2 nanocomposites using a modified long-short term memory model with beluga whale optimizer

Mechanical properties of fine grain nanocomposites differ from those of conventional composites due to the in situ effect caused by the addition of nanoparticle reinforcement and the complexity of strengthening mechanisms, which make their prediction using conventional analytical and numerical model is relatively difficult. Therefore, this work presents a rapid reliable machine learning model based on long-short term memory model modified with beluga whale optimizer to predict the mechanical properties of ultrafine grain Al-TiO2 nanocomposite manufactured using accumulative roll bonding (ARB). The mechanical properties were evaluated using tensile tests and correlated with the composite microstructure and hardness. Experimentally, it was demonstrated that the tensile strength increases with increasing the number of ARB passes until a plateau was achieved due to the uniform distribution of TiO2 nanoparticles inside the composite and the saturation of grain refinement in the Al matrix. The maximum tensile achieved was 270 MPa for composite containing 3% TiO2 nanoparticles after 5 ARB passes compared to 90.5 MPa for the raw Al. The proposed model was able to predict the yield and ultimate strengths, elongation, and hardness for all the produced composites tested with excellent accuracy reaching R2 equal 0.9955, 0.9952, 0.9859, and 0.9975, respectively, which is way better than other models