Nanophase materials are promising alternative implant materials in tissue engineering. Here we report for the first time the large-scale direct growth of nanostructured bioactive titanates on ...three-dimensional (3D) microporous Ti-based metal (NiTi and Ti) scaffolds via a facile low temperature hydrothermal treatment. The nanostructured titanates show characteristics of 1D nanobelts/nanowires on a nanoskeleton layer. Besides resembling cancelous bone structure on the micro/macroscale, the 1D nanostructured titanate on the exposed surface is similar to the lowest level of hierarchical organization of collagen and hydroxyapatite. The resulting surface displays superhydrophilicity and favors deposition of hydroxyapatite and accelerates cell attachment and proliferation. The remarkable simplicity of this process makes it widely accessible as an enabling technique for applications from engineering materials treatment including energy-absorption materials and pollution-treatment materials to biotechnology.
Summary
Background
The rs738409 GG variant in patatin‐like phospholipase 3 (PNPLA3) is associated with non‐alcoholic fatty liver disease (NAFLD) and disease severity. However, it remains unclear if ...it contributes to the development of NAFLD through affecting dietary pattern.
Aim
To examine the association among PNPLA3 gene polymorphism, dietary pattern, metabolic factors and NAFLD.
Methods
Liver fat and fibrosis were assessed by proton‐magnetic resonance spectroscopy and transient elastography in 920 subjects from a population screening project (251 had NAFLD). Dietary nutrient intake was recorded using a locally validated food‐frequency questionnaire.
Results
The prevalence of GG genotype in NAFLD subjects was 20.7%, compared to 10.6% in controls (P < 0.001). Macronutrient intake was similar among subjects with different PNPLA3 genotypes. The presence of G allele was a predictor of NAFLD independent of nutrient intake and other metabolic factors (adjusted odds ratio to CC: CG, 2.00; GG, 2.68). In subjects without metabolic syndrome, G allele was even more closely correlated with NAFLD diagnosis (adjusted odds ratio to CC: CG, 2.22; GG, 3.39). The prevalence of NAFLD was only 12% in subjects with CC genotype and no metabolic syndrome, and increased to 34% in those with GG genotype and no metabolic syndrome. While NAFLD subjects had significantly lower fibre intake, there was no significant interaction between PNPLA3 and dietary pattern.
Conclusions
The G allele in PNPLA3 rs738409 increases the risk of NAFLD in the general population, especially in subjects without metabolic syndrome, independent of dietary pattern and metabolic factors.
Summary
Background
Patients with non‐alcoholic steatohepatitis (NASH) have increased intestinal permeability and small intestine bacterial overgrowth.
Aims
To test the hypothesis that endotoxemia is ...associated with non‐alcoholic fatty liver disease (NAFLD) in the general population, and to study dietary factors associated with endotoxemia.
Methods
Nine hundred and twenty adults were randomly selected from the government's census database and underwent proton‐magnetic resonance spectroscopy to assess hepatic steatosis. Endotoxemia was assessed using the limulus amebocyte lysate, lipopolysaccharide‐binding protein (LBP) and EndoCab immunoglobulin G (IgG) assays.
Results
Two hundred and sixty‐three (29%) subjects had NAFLD. Subjects with NAFLD had slightly higher LBP (P < 0.001) and EndoCab IgG (P = 0.013) levels. EndoCab IgG remained an independent factor associated with intrahepatic triglycerides after adjusting for other metabolic factors. Among 565 subjects without NAFLD at baseline who had repeated assessment at a median interval of 47 months, 78 (13.8%) developed incident NAFLD and they also had higher LBP (P = 0.016). Moreover, LBP was associated with insulin resistance and dyslipidaemia, and modestly increased with the cytokeratin‐18 fragment level but not liver stiffness measurement by transient elastography. Although total energy consumption and individual macronutrients were not associated with endotoxemia, current drinkers (mostly <140 g/week) had lower endotoxin, EndoCab IgG and fetuin‐A levels than nondrinkers.
Conclusions
Endotoxin markers are associated with NAFLD in the general population, but do not have a major effect on NASH and fibrosis. People with modest alcohol consumption have lower serum endotoxin. This may partly explain the lower risk of NAFLD and NASH in modest drinkers in previous observational studies.
Abstract Magnesium and its alloys may potentially be applied as degradable metallic materials in orthopaedic implantations due to their degradability and resemblance to human cortical bone. However, ...the high corrosion rate and accumulation of hydrogen gas upon degradation hinders its clinical application. In this study, we adopt a new approach to control the corrosion rate by coating a controllable polymeric membrane fabricated by polycaprolactone and dichloromethane onto magnesium alloys, in which the pore size was controlled during the manufacturing process. The addition of the polymeric membrane was found to reduce the degradation rate of magnesium, and the bulk mechanical properties were shown to be maintained upon degradation. The in-vitro studies indicated good cytocompatibility of eGFP and SaOS-2 osteoblasts with the polymer-coated samples, which was not observed for the uncoated samples. The in-vivo study indicated that the uncoated sample degraded more rapidly than that of the polymer-coated samples. Although new bone formation was found on both samples, as determined by Micro-CT, higher volumes of new bone were observed on the polymer-coated samples. Histological analysis indicated no inflammation, necrosis or hydrogen gas accumulation on either of the samples during degradation. Collectively, these data suggest that the use of polymeric membrane may be potentially applied for future clinical use.
Background
The generation of IgE‐mediated food allergy in humans is silent and only diagnosed upon manifestation of clinical symptoms. While experimental models have been used to investigate some ...mechanisms of allergic sensitization, the generation of humoral immunity and memory remains to be elucidated. Here, we defined the evolution of allergen‐specific B‐cell responses during epicutaneous sensitization to foods.
Methods
Wild‐type and genetic knockout animals, and drug or antibody strategies for cell depletion and immunoglobulin signaling blockade were used to investigate epicutaneous sensitization and disease progression; we analyzed allergen‐specific germinal centers and IgG1+ memory B cells by flow cytometry, evaluated humoral responses, and determined clinical reactivity (anaphylaxis).
Results
Epicutaneous sensitization caused microscopic skin damage, inflammation, and recruitment of activated dendritic cells to the draining lymph nodes. This process generated allergen‐specific IgG1+ germinal center B cells, serum IgG1, and anaphylaxis that was mediated by the alternative pathway. Whether we used peanut and/or ovalbumin from the egg white for sensitization, the allergen‐specific IgG1+ memory compartment predominantly exhibited an immature, pro‐germinal center phenotype (PDL‐2−CD80−CD35+CD73+). Subsequent subclinical exposures to the allergen induced IgE+ germinal center B cells, serum IgE, and likely activated the classical pathway of anaphylaxis.
Conclusions
Our data demonstrate that IgG1+ B‐cell immunity against food allergens in epicutaneous sensitization precedes the generation of IgE responses. Therefore, the assessment of allergen‐specific cellular and humoral IgG1+ immunity may help to identify individuals at risk of developing IgE‐mediated food allergy and hence provide a window for therapeutic interventions.
IgG1+ B‐cell immunity against food allergens in epicutaneous sensitization precedes the generation of IgE responses. Immature, pro‐germinal centre, allergen‐specific IgG1+ memory B cells are formed at the incipient stages of skin sensitization to foods. The assessment of allergen‐specific cellular and humoral IgG1+ immunity may help to identify individuals at risk of developing IgE‐mediated food allergy.
Summary
Background
Little is known about the importance of liver fibrosis and fatty liver in HIV‐monoinfected individuals without hepatitis virus co‐infection, particularly among the Asian ...population.
Aim
To evaluate prevalence and risk factors for liver fibrosis and fatty liver in Asian HIV‐monoinfected individuals.
Methods
Eighty asymptomatic HIV‐monoinfected individuals (tested negative for HBV/HCV) were compared with 160 matched HIV‐uninfected healthy controls. Transient elastography and proton‐magnetic resonance spectroscopy (1H‐MRS) were performed to measure liver stiffness and hepatic steatosis respectively. Blood samples were analysed for metabolic profiles and markers of steatohepatitis (e.g. cytokeratin‐18).
Results
All HIV‐infected individuals (mean ± s.d. age 54 ± 11 years, male 93%, Chinese 94%; diagnosis median duration 8 (IQR 4–13 years) were stable on anti‐retrovirals (PI‐based 58.7%, NNRTI‐based 25.0% integrase‐inhibitors 16.3%); diabetes, dyslipidaemia, and metabolic syndrome were common. Fatty liver disease was detected in 28.7%. There was significantly higher degree of liver stiffness 4.9 (IQR 4.1–6.2) kPa vs. 4.2 (IQR 3.6–5.0) kPa, P < 0.001, and greater proportions developed significant fibrosis (7.0 kPa, 14.3% vs. 3.1%, P = 0.001) and cirrhosis (10.3 kPa, 5.2% vs. 0.6%, P = 0.040) compared with controls. HIV infection was an independent risk factor for significant fibrosis (adjusted OR 4.00, 95% CI 1.29–12.41, P = 0.016). HIV‐infected individuals with fatty liver had excessive liver stiffness and fibrosis. Two cases of asymptomatic hepatocellular carcinoma were detected.
Conclusions
HIV‐monoinfected patients are at risk for liver fibrosis and cirrhosis. HIV‐related mechanisms and fatty liver disease may play important roles. Screening and intervention to prevent severe outcomes should be considered.
Summary
Background
The diagnosis of non‐alcoholic fatty liver disease (NAFLD), non‐alcoholic steatohepatitis (NASH) and fibrosis relies on liver biopsy. Non‐invasive assessments are urgently needed.
...Aim
To evaluate cell apoptotic marker cytokeratin‐18 M30 and total cell death markers cytokeratin‐18 M65/M65ED for the assessment and monitoring of NAFLD.
Methods
A cohort of 147 patients with biopsy‐proven NAFLD and 73 controls were enroled, including 51 patients who received paired liver biopsies 36 months apart. Biomarkers were determined by enzyme‐linked immunosorbent assay.
Results
M30, M65 and M65ED increased in a stepwise fashion in control subjects, patients with non‐NASH, NAFLD and NASH (all P < 0.001). All biomarkers had similarly high accuracy over 0.9 in predicting NAFLD and moderate accuracy around 0.7 in predicting NASH. Among patients with paired liver biopsies, changes in M30, M65 and M65ED positively correlated with disease progression (rho = 0.42, 0.32 and 0.39; P = 0.002, 0.023 and 0.005 respectively), and only changes in M65 and M65ED correlated with fibrosis progression (rho = 0.29, 0.34; P = 0.038, 0.015 respectively). Both M30 and M65 had area under receiver‐operating characteristics curve above 0.8 in predicting disease progression. At cut‐off of 236 U/L, changes of M65ED had 88% NPV and 59% PPV to exclude and predict fibrosis progression.
Conclusions
Cytokeratin‐18 M30 and M65/M65ED have moderate accuracy in detecting non‐alcoholic steatohepatitis. Changes in the biomarkers also correlate with histological progression. However, development of new biomarkers is still required to improve the diagnostic accuracy.
Summary
Middle East respiratory syndrome coronavirus (MERS‐CoV) is an existential threat to global public health. The virus has been repeatedly detected in dromedary camels (Camelus dromedarius). ...Adult animals in many countries in the Middle East as well as in North and East Africa showed high (>90%) seroprevalence to the virus. Middle East respiratory syndrome coronavirus isolated from dromedaries is genetically and phenotypically similar to viruses from humans. We summarize current understanding of the ecology of MERS‐CoV in animals and transmission at the animal–human interface. We review aspects of husbandry, animal movements and trade and the use and consumption of camel dairy and meat products in the Middle East that may be relevant to the epidemiology of MERS. We also highlight the gaps in understanding the transmission of this virus in animals and from animals to humans.
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