DNA-binding activity in the excretory-secretory products of Trichinella pseudospiralis (Nematoda: Trichinelloidea)

A novel DNA-binding peptide of Mr approximately 30 kDa was documented for the first time in the excretory-secretory (E-S) products of the infective-stage larvae of Trichinella pseudospiralis. Larvae recovered from muscles of infected mice were maintained for 48 h in DMEM medium. E-S products of worms extracted from the medium were analysed for DNA-binding activity by the electrophoretic mobility shift assay (EMSA). Multiple DNA-protein complexes were detected. A comparison of the Mr of proteins in the complexes indicated that they could bind to the target DNA as a dimer, tetramer or multiples of tetramers. Site selection and competition analysis showed that the binding has a low specificity. A (G/C-rich)-gap-(G/T-rich)-DNA sequence pattern was extracted from a pool of degenerate PCR fragments binding to the E-S products. Results of immunoprecipitation and electrophoretic mobility supershift assay confirmed the authenticity of the DNA-binding protein as an E-S product.published_or_final_versio

Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution

Activation-induced deoxycytidine deaminase (AID) generates antibody diversity in B cells by initiating somatic hypermutation (SHM) and class-switch recombination (CSR) during transcription of immunoglobulin variable (IgV) and switch region (IgS) DNA. Using single-molecule FRET, we show that AID binds to transcribed dsDNA and translocates unidirectionally in concert with RNA polymerase (RNAP) on moving transcription bubbles, while increasing the fraction of stalled bubbles. AID scans randomly when constrained in an 8 nt model bubble. When unconstrained on single-stranded (ss) DNA, AID moves in random bidirectional short slides/hops over the entire molecule while remaining bound for ~5 min. Our analysis distinguishes dynamic scanning from static ssDNA creasing. That AID alone can track along with RNAP during transcription and scan within stalled transcription bubbles suggests a mechanism by which AID can initiate SHM and CSR when properly regulated, yet when unregulated can access non-Ig genes and cause cancer

S-maltoheptaose targets syndecan-bound effectors to reduce smoking-related neutrophilic inflammation.

Cigarette smoke induces injury and neutrophilic inflammation in the airways of smokers. The stability and activity of inflammatory effectors, IL8 and neutrophil elastase (NE), can be prolonged by binding to airway heparan sulfate (HS)/syndecan-1, posing risk for developing chronic obstructive pulmonary disease(COPD). We hypothesize that antagonizing HS/syndecan-1 binding of the inflammatory effectors could reduce smoking-related neutrophil-mediated airway inflammation. Analysis of bronchoalveolar lavage fluid(BALF) of COPD patients found both total and unopposed NE levels to be significantly higher among smokers with COPD than non-COPD subjects. Similar NE burden was observed in smoke-exposed rats compared to sham air controls. We chose sulfated-maltoheptaose(SM), a heparin-mimetic, to antagonize HS/sydecan-1 binding of the inflammatory mediators in airway fluids and lung tissues of the smoke-exposed rat model. Airway treatment with SM resulted in displacement of CINC-1 and NE from complexation with bronchio-epithelial HS/syndecan-1, dissipating the chemokine gradient for neutrophil flux across to the bronchial lumen. Following SM displacement of NE from shed HS/syndecan-1 in bronchial fluids, NE became accessible to inhibition by α1-antitrypsin endogenous in test samples. The antagonistic actions of SM against syndecan-1 binding of NE and CINC-1 in smoke-exposed airways suggest new therapeutic opportunities for modulating airway inflammation in smokers with SM delivery.published_or_final_versio

Anatomic variations of neurovascular structures of the ankle in relation to arthroscopic portals: a cadaveric study of Chinese subjects.

PURPOSE: To investigate anatomic variations of neurovascular structures in the ankle and the safety margin for arthroscopic portals. METHODS: 11 left and 12 right ankles from 8 female and 15 male fresh cadavers of Chinese ethnicity aged 53 to 88 (mean, 68) years were used. The ankle was standardised in a plantigrade position, zero-degree inversion, and neutral rotation. Four ankle portals, namely anteromedial (AM), anterolateral (AL), posteromedial (PM) and posterolateral (PL), were identified using 23-gauge needles. Skin and subcutaneous fat were dissected from the underlying fascia to visualise neurovascular structures. Distances were measured from: (1) the AM portal to the saphenous vein and nerve and its branches, (2) the AL portal to branches of the superficial peroneal nerves, of which the lateral one was labelled as the intermediate dorsal cutaneous branch and the medial one as the medial dorsal cutaneous branch, (3) the PM portal to the posterior tibial neurovascular bundles, and (4) the PL portal to the sural nerve. RESULTS: The distances from (1) the AM portal to branches of the great saphenous vein and nerve, and (2) the AL portal to the intermediate dorsal cutaneous branch of the superficial peroneal nerve were short and may be an anatomic hazard. Variations were significant among the cadavers in terms of distances of the portals to the neurovascular structures. CONCLUSION: In Chinese cadavers, variations of neurovascular structures are significant. Care must be taken to avoid inadvertent injury during ankle arthroscopy.published_or_final_versio

Infrapatellar fat pad adipose-derived stem cells co-cultured with articular chondrocytes from osteoarthritis patients exhibit increased chondrogenic gene expression.

AIM: The variable results in clinical trials of adipose tissue-derived stem cells (ASCs) for chondral defects may be due to the different ex vivo culture conditions of the ASCs which are implanted to treat the lesions. We sought to determine the optimal in vitro chondrocyte co-culture condition that promotes infrapatellar fat pad-derived (IFPD) ASC chondrogenic gene expression in a novel co-culture combination. METHODS: In our study, we utilized an in vitro autologous co-culture of IFPD ASCs and articular chondrocytes derived from Kellgren-Lawrence Grade III/IV osteoarthritic human knee joints at ASC-to-chondrocyte seeding log ratios of 1:1, 10:1, and 100:1. Gene expression following in vitro co-culture was quantified by RT-qPCR with a panel comprising COL1A1, COL2A1, COL10A1, L-SOX5, SOX6, SOX9, ACAN, HSPG2, and COMP for chondrogenic gene expression. RESULTS: The chondrogenic gene expression profiles from co-cultures were greater than would be expected from an expression profile modeled from chondrocyte and ASC-only monocultures. Additionally, chondrogenic gene expression decreased with increasing ASC-to-chondrocyte seeding ratios. CONCLUSIONS: These findings provide insight into the mechanisms underlying clinical ASC therapies and signifies that IFPD ASCs pre-conditioned by chondrocyte co-culture may have improved chondrogenic potential for cartilage repair. This model can help further understand IFPD ASCs in chondral and osteochondral repair and the chondrogenic pathways involved. Video Abstract

Risk factors, clinical features and prognosis of perioperative stroke in adults

INTRODUCTION: Perioperative stroke (POS) is an uncommon but severe surgical complication. No widely accepted guidelines for risk prediction or management have been established. Its prevention depends on knowledge about the nature of this disease. METHODS: A total of 36 cases and equal number of controls in Hong Kong West Cluster hospitals were recruited over 43 months. Peri- and intra-operative features were compared and characteristics of POS were described. RESULTS: Atrial fibrillation, diabetes mellitus (DM), and history of stroke were identified as risk factors (P=0.017, 0.002, and 0.003, respectively). Prolonged aortic occlusion (P=0.018) and bypass (P=0.002) contributed in cardiac surgery. Only few BP parameters, but not consistently all, were significant; 78% POS were infarcts. Watershed infarction related to hypotension was uncommon. Beta-blocker use seemed to bare protective effect. Blood loss and haemoglobin levels did not correlate to POS. Three-month mortality rate was 36%. CONCLUSION: Optimal DM control and cardioversion before elective OT, perioperative anticoagulation in AF and old stroke patients, and beta-blockers may be preventive measures for POS. Role of hypotension in POS aetiology is debatable.published_or_final_versionThe 15th Medical Research Conference; Department of Medicine, The University of Hong Kong, Hong Kong, 16 January 2010. In Hong Kong Medical Journal, 2010, v. 16 suppl. 1, p. 13, abstract no.

Sirt1 attenuates kidney disorders in male offspring due to maternal high-fat diet

© 2019, MDPI AG. All rights reserved. Maternal obesity has been associated with kidney disorders in male offspring. Our previous studies have demonstrated that Sirtuin (SIRT)1, an essential regulator of metabolic stress responses, is suppressed in the offspring as the result of maternal high-fat diet (HFD) consumption, which is likely to underpin the adverse metabolic and renal outcomes. To examine if SIRT1 overexpression or activation early in life can protect the offspring kidney, wild-type (WT) and transgenic (Tg) offspring were born to the same diet-induced obese female C57BL/6 mice through breeding with hemizygous SIRT1-transgenic (Tg) male mice and examined for renal pathological changes. In separate experiments, SIRT1 activator SRT1720 (25 mg/kg/2 days i.p) was administrated in WT offspring over 6 weeks of postnatal high-fat diet exposure. The results show that offspring born to obese dams have increased kidney weight, higher levels of renal triglycerides, and increased expression of oxidative stress, inflammatory, and fibrotic markers, as well as increased albuminuria compared to offspring of control dams. Both SIRT1 overexpression and SRT1720 treatment attenuated renal lipid contents and expression of lipogenesis, oxidative stress, and inflammatory markers; however, fibrosis was modestly reduced and albuminuria was not affected. The findings suggest that SIRT1 therapy can ameliorate some pathological mechanisms of kidney programming due to maternal obesity but may not be sufficient to prevent the resulting chronic kidney injury

Novel Hybrid Au/Fe3O4 Magnetic Octahedron-like Nanoparticles with Tunable Size

published_or_final_versio

De novo transcriptome analysis of Perna viridis highlights tissue-specific patterns for environmental studies

published_or_final_versio

Synthesis and Morphology Control of Gold/Iron oxide Magnetic Nanocomposites via a Simple Aqueous Method

published_or_final_versio