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Duchenne muscular dystrophy (DMD) is a lethal muscle-wasting disease caused by the lack of dystrophin in muscle fibers that is currently without curative treatment. Mesoangioblasts (MABs) are multipotent progenitor cells that can differentiate to a myogenic lineage and that can be used to express Dystrophin upon transplantation into muscles, in autologous gene therapy approaches. However, their fate in the muscle environment remains poorly characterized. Here, we investigated the differentiation fate of MABs following their transplantation in DMD murine muscles using a mass cytometry strategy. This allowed the identification and isolation of a fraction of MAB-derived cells presenting common properties with satellite muscle stem cells. This analysis also indicated that most cells did not undergo a myogenic differentiation path once in the muscle environment, limiting their capacity to restore dystrophin expression in transplanted muscles. We therefore assessed whether MAB treatment with cytokines and growth factors prior to engraftment may improve their myogenic fate. We identified a combination of such signals that ameliorates MABs capacity to undergo myogenic differentiation in vivo and to restore dystrophin expression upon engraftment in myopathic murine muscles., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Deficiency in ferrochelatase (FECH), the last enzyme in the heme biosynthetic pathway, leads to an accumulation of protoporphyrin IX (PPIX) that causes a severely painful phototoxic reaction of the skin in patients with erythropoietic protoporphyria (EPP). Besides phototoxicity of the skin, EPP patients often present with symptoms of iron deficiency in form of a microcytic and hypochromic anemia with low serum iron and ferritin. In addition, elevated aminolevulinic acid synthase 2 (ALAS2) both at the mRNA and protein levels have been observed among EPP patients. ALAS is the first enzyme in the pathway and exists in two isoforms, whereby the isoform 2 (ALAS2) is expressed exclusively in erythropoiesis. The mRNA of ALAS2 contains an iron response element (IRE) at its 5'UTR. When iron is limited, iron response element binding protein 2 (IRP2) binds to the IRE of ALAS2 mRNA and suppresses its translation. In this study, we demonstrated that iron deprivation increased the amount of ALAS2 mRNA as well as the ratio of ALAS2 to FECH mRNAs in cultured erythroleukemic K562 cells. At the protein level, however, iron deprivation in the cell line caused reductions in both enzymes as shown by the Western blot analysis. A comparable increase in the ratio of ALAS2 to FECH mRNAs was also found in EPP patients indicating an imbalance in heme biosynthesis. As iron cannot be completely missing from an organism, we assume that in EPP patients, a certain amount of ALAS2 mRNA is translated despite a partial deficiency of FECH. The increase in ALAS2 enzyme contributes to the accumulation in PPIX in the patients. Targeted inhibition of ALAS2 could therefore be a treatment option for EPP., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The present study focuses on fabrication and characterisation of porous composite scaffold containing hydroxyapatite (HAP), chitosan, and gelatin with an average pore size of 250-1010 nm for improving wound repair and regeneration by Electrospinning method. From the results of X -Ray Diffraction (XRD) study, the peaks correspond to crystallographic structure of HAP powder. The presence of functional group bonds of HAP powder, Chitosan and scaffold was studied using Fourier Transform Infrared Spectroscopy (FTIR). The surface morphology of the scaffold was observed using Scanning Electron Microscope (SEM). The Bioactivity of the Nano composite scaffolds was studied using simulated body fluid solution at 37 ± 1°C. The biodegradability test was studied using Tris-Buffer solution for the prepared nanocomposites [nano Chitosan, nano Chitosan gelatin, Nano based Hydroxyapatite Chitosan gelatin]. The cell migration and potential biocompatibility of nHAP-chitosan-gelatin scaffold was assessed via wound scratch assay and were compared to povedeen as control. Cytocompatibility evaluation for Vero Cells using wound scratch assay showed that the fabricated porous nanocomposite scaffold possess higher cell proliferation and growth than that of povedeen. Thus, the study showed that the developed nanocomposite scaffolds are potential candidates for regenerating damaged cell tissue in wound healing process.

Direct evidence-based approaches are vital to evaluating newly proposed theories on the persistence of soil organic carbon and establishing the contributions of abiotic and biotic controls. Our primary goal was to directly identify the mechanisms of organic carbon stabilization in native-state, free soil microaggregates without disrupting the aggregate microstructure using scanning transmission x-ray microscopy coupled with near edge x-ray absorption fine structure spectroscopy (STXM-NEXAFS). The influence of soil management practices on microaggregate associated-carbon was also assessed. Free, stable soil microaggregates were collected from a tropical agro-ecosystem in Cruz Alta, Brazil. The long-term experimental plots (>25 years) comparing two tillage systems: no-till and till with a complex crop rotation. Based on simultaneously collected multi-elemental associations and speciation, STXM-NEXAFS successfully provided submicron level information on organo-mineral associations. Simple organic carbon sources were found preserved within microaggregates; some still possessing original morphology, suggesting that their stabilization was not entirely governed by the substrate chemistry. Bulk analysis showed higher and younger organic carbon in microaggregates from no-till systems than tilled systems. These results provide direct submicron level evidence that the surrounding environment is involved in stabilizing organic carbon, thus favoring newly proposed concepts on the persistence of soil organic carbon.

Duchenne muscular dystrophy (DMD) is a lethal muscle-wasting disease currently without cure. We investigated the use of the PiggyBac transposon for full-length dystrophin expression in murine mesoangioblast (MABs) progenitor cells. DMD murine MABs were transfected with transposable expression vectors for full-length dystrophin and transplanted intramuscularly or intra-arterially into mdx/SCID mice. Intra-arterial delivery indicated that the MABs could migrate to regenerating muscles to mediate dystrophin expression. Intramuscular transplantation yielded dystrophin expression in 11%-44% of myofibers in murine muscles, which remained stable for the assessed period of 5 months. The satellite cells isolated from transplanted muscles comprised a fraction of MAB-derived cells, indicating that the transfected MABs may colonize the satellite stem cell niche. Transposon integration site mapping by whole-genome sequencing indicated that 70% of the integrations were intergenic, while none was observed in an exon. Muscle resistance assessment by atomic force microscopy indicated that 80% of fibers showed elasticity properties restored to those of wild-type muscles. As measured in vivo, transplanted muscles became more resistant to fatigue. This study thus provides a proof-of-principle that PiggyBac transposon vectors may mediate full-length dystrophin expression as well as functional amelioration of the dystrophic muscles within a potential autologous cell-based therapeutic approach of DMD., (Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

We report the detailed gross, histopathological and immunohistochemical study of Strobilocercus fasciolaris infection, the metacestodal stage of Taenia taeniaeformis, in the liver of laboratory Wistar rats. Necropsy examination of seventeen rats revealed transparent or white or cream to clear, thick walled cysts, 1 to 97 in number, measuring about 2mm to 12mm on one or many of the liver lobes and containing strobilocercus of Taenia taeniaeformis. Histopathological examination revealed the presence of the cross-section of larva surrounded by a thick fibrous capsule and moderate infiltration of lymphocytes, plasma cells and a few eosinophils. Fatty degeneration of hepatocytes, gastric mucosal hyperplasia, distended gastric glands and marked increase in the mucosal epithelial cells and goblet cells in the duodenum were also observed. Contamination of feed and bedding materials seems to be the probable source in these naturally infected rats., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Spontaneous coronary artery dissection (SCAD) is a rare cause of non-atherosclerotic acute coronary syndrome (ACS). As it is more commonly seen in young women, the diagnosis can be missed. Current evidence is based on case reports and retrospective studies with no consensus recommendations on immediate management and long-term follow-up. We present a case series of four patients to outline clinical presentation, prognosis and long-term management of this rare clinical entity., (Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.)

Relative quantification of algC gene expression was evaluated in the multidrug resistant strain Acinetobacter baumannii AIIMS 7 biofilm (3 to 96 h, on polystyrene surface) compared to the planktonic counterparts. Comparison revealed differential algC expression pattern with maximum 81.59-fold increase in biofilm cells versus 3.24-fold in planktonic cells (P < 0.05). Expression levels strongly correlated with specific biofilm stages (scale of 3 to 96 h), coinciding maximum at initial surface attachment stage (9 h) and biofilm maturation stage (48 h). Cloning, heterologous expression, and bioinformatics analyses indicated algC gene product as the bifunctional enzyme phosphomannomutase/phosphoglucomutase (PMM/PGM) of ∼ 53 kDa size, which augmented biofilms significantly in algC clones compared to controls (lacking algC gene), further localized by scanning electron microscopy. Moreover, molecular dynamics analysis on the three-dimensional structure of PMM/PGM (simulated up to 10 ns) revealed enzyme structure as stable and similar to that in P. aeruginosa (synthesis of alginate and lipopolysaccharide core) and involved in constitution of biofilm EPS (extracellular polymeric substances). Our observation on differential expression pattern of algC having strong correlation with important biofilm stages, scanning electron-microscopic evidence of biofilm augmentation taken together with predictive enzyme functions via molecular dynamic (MD) simulation, proposes a new basis of A. baumannii AIIMS 7 biofilm development on inanimate surfaces.

Background: Venous thromboembolism (VTE) is a prevalent disease with potential serious consequences. Idraparinux and idrabiotaparinux are two kinds of long-acting pentasaccharides. Evidence has shown that idraparinux and idrabiotaparinux are effective anticoagulants. However, up to now, there is no consensus on whether they are better than other anticoagulation methods for long-term VTE treatment., Objective: To evaluate the effect of idraparinux or idrabiotaparinux versus other anticoagulation methods for long-term VTE treatment., Methods: We searched Cochrane Central Register of Controlled Trials, PubMed, Embase, Web of science, clinical trial registry web sites (clinical trials,WHO clinical trial registry), Googlescholar, PubMed related articles and companies' web sites electronically up to Dec 30(th), 2012 and manually searched the reference lists and conference proceedings. Only randomized controlled trial (RCT) involving adult patients comparing idraparinux and/or idrabiotaparinux versus other anticoagulation methods for long-term VTE treatment was included. Two reviewers evaluated the studies and extracted data independently. Pooled risk ratios (RRs) were calculated as outcome measures and Revman 5.2 software was used to analyze data. Our primary efficacy and safety outcomes were the recurrent VTE and major bleeding rates., Results: We included four RCTs and involved 8584 participants on idraparinux or idrabiotaparinux versus standard warfarin for VTE treatment from 9364 references. We did not perform meta-analysis on the VTE rate because of the significant heterogeneity. We used the fixed effect model to analyze the safety outcomes and demonstrated that idraparinux or idrabiotaparinux decreased major bleeding rate significantly (RR 0.73, 95% CI 0.54 to 0.98, P = 0.04) but had a trend to increase the all cause mortality (RR 1.26, 95% CI 1.00 to 1.57, P = 0.05) compared with warfarin., Conclusions: Until now there is not sufficient evidence to clarify whether idraparinux or idrabiotaparinux is as effective and safe as the standard warfarin treatment for VTE treatment.

The cardiofaciocutaneous (CFC) syndrome is a condition of sporadic occurrence, with patients showing multiple congenital anomalies and mental retardation and characteristic dysmorphic features. We, thus, report a rare case of this syndrome in a 1-year-old child who presented with typical features of CFC syndrome.

Release of extracellular DNA (eDNA) was observed during in vitro growth of a clinical strain of Acinetobacter baumannii. Membrane vesicles (MV) of varying diameter (20-200 nm) containing DNA were found to be released by transmission electron microscopy (TEM) and atomic force microscopy (AFM). An assessment of the characteristics of the eDNA with respect to size, digestion pattern by DNase I/restriction enzymes, and PCR-sequencing, indicates a high similarity with genomic DNA. Role of eDNA in static biofilm formed on polystyrene surface was evaluated by biofilm augmentation assay using eDNA available in different preparations, for example, whole cell lysate, cell-free supernatant, MV suspension, and purified eDNA. Biofilm augmentation was seen up to 224.64%, whereas biofilm inhibition was 59.41% after DNase I treatment: confirming that eDNA facilitates biofilm formation in A. baumannii. This is the first paper elucidating the characteristics and role of eDNA in A. baumannii biofilm, which may provide new insights into its pathogenesis.

A 27-year-old healthy man presented with non-itchy hyperpigmented skin lesions involving the trunk of duration 3 years. Examination revealed numerous coalescing, rough, slightly elevated brownish papules involving large areas of back, chest, and abdomen. There were no other cutaneous or systemic findings. Cutaneous biopsy was suggestive of verruca plana, which confirmed our clinical diagnosis. Here, we report this case of verruca plana due to its rare extensive involvement and unusual site in a non-immunocompromised individual.

Background: The advent of highly active antiretroviral therapy (HAART) has changed the scenario of human immunodeficiency virus (HIV) infection. HIV patients in India have now access to generic HAART and this is the first report describing oral lesions in patients on HAART from our country., Methods: Oral lesions were studied in HIV seropositive patients (n = 50 on HAART and n = 50 not on HAART) attending a tertiary HIV referral care centre in India and patients on HAART were followed up., Results: There was a difference in the occurrence of oral candidiasis (OC) between HAART and non-HAART participants (8%, 24%; P < 0.05). Pseudomembranous candidiasis was 4% and 18% in HAART and non-HAART groups respectively (P < 0.05). In patients with CD4 count 200, pigmentation was 43.8% in the HAART group and 14.8% in the non-HAART group (P < 0.05)., Conclusion: The prevalence of OC in patients who had access to HAART was less when compared with those who did not have access to HAART.