Hepatocellular carcinoma (HCC) is the fifth most common cancer with high mortality, due to late diagnosis and limited treatment options. Blood miRNAs, which circulate in a highly stable, cell-free ...form, show promise as novel potential biomarkers for early detection of HCC. Whole miRNome profiling was performed to identify deregulated miRNAs between HCC and normal healthy (NH) volunteers. These deregulated miRNAs were validated in an independent cohort of HCC, NH and chronic Hepatitis B (CHB) volunteers and finally in a 3
cohort comprising NH, CHB, cirrhotic and HCC volunteers to evaluate miRNA changes during disease progression. The associations between circulating miRNAs and liver-damage markers, clinicopathological characteristics and survival outcomes were analysed to identify prognostic markers. Twelve miRNAs are differentially expressed between HCC and NH individuals in all three cohorts. Five upregulated miRNAs (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p and miR-148a-3p) in CHB, cirrhosis and HCC patients are potential biomarkers for CHB infection, while miR-34a-5p can be a biomarker for cirrhosis. Notably, four miRNAs (miR-1972, miR-193a-5p, miR-214-3p and miR-365a-3p) can distinguish HCC from other non-HCC individuals. Six miRNAs are potential prognostic markers for overall survival.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Summary
Background Null mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris (IV) and predispose to atopic dermatitis (AD). Cohort studies in Europe and Japan have reported an FLG ...mutation carrier frequency of between 14% and 56%, but the prevalent European FLG mutations are rare or absent in Chinese patients with IV and AD.
Objectives To investigate further the spectrum of FLG‐null mutations in Chinese patients and to compare it with that in other populations.
Methods We conducted comprehensive FLG genetic analysis in a discovery cohort of 92 Singaporean Chinese individuals with IV and/or moderate‐to‐severe AD. All detected FLG mutations were then screened in a cohort of 425 patients with AD and 440 normal controls.
Results In total, 22 FLG‐null mutations, of which 14 are novel, were identified in this study; the combined null FLG genotype of 17 mutations detected in cases and controls showed strong association with AD Fisher’s exact test; P = 5·3 × 10−9; odds ratio (OR) 3·3, palmar hyperlinearity (Fisher’s exact test; P = 9·0 × 10−15; OR 5·8), keratosis pilaris (Fisher’s exact test; P = 0·001; OR 4·7) and with increased severity of AD (permutation test; P = 0·0063).
Conclusions This study emphasizes the wider genetic landscape of FLG‐null mutations in Asia that is slowly emerging.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
All homeotherms use thermogenesis to maintain their core body temperature, ensuring that cellular functions and physiological processes can continue in cold environments. In the prevailing model of ...thermogenesis, when the hypothalamus senses cold temperatures it triggers sympathetic discharge, resulting in the release of noradrenaline in brown adipose tissue and white adipose tissue. Acting via the β(3)-adrenergic receptors, noradrenaline induces lipolysis in white adipocytes, whereas it stimulates the expression of thermogenic genes, such as PPAR-γ coactivator 1a (Ppargc1a), uncoupling protein 1 (Ucp1) and acyl-CoA synthetase long-chain family member 1 (Acsl1), in brown adipocytes. However, the precise nature of all the cell types involved in this efferent loop is not well established. Here we report in mice an unexpected requirement for the interleukin-4 (IL-4)-stimulated program of alternative macrophage activation in adaptive thermogenesis. Exposure to cold temperature rapidly promoted alternative activation of adipose tissue macrophages, which secrete catecholamines to induce thermogenic gene expression in brown adipose tissue and lipolysis in white adipose tissue. Absence of alternatively activated macrophages impaired metabolic adaptations to cold, whereas administration of IL-4 increased thermogenic gene expression, fatty acid mobilization and energy expenditure, all in a macrophage-dependent manner. Thus, we have discovered a role for alternatively activated macrophages in the orchestration of an important mammalian stress response, the response to cold.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metabolism and immunity are two fundamental systems of metazoans. The presence of immune cells, such as macrophages, in metabolic tissues suggests dynamic, ongoing crosstalk between these two ...regulatory systems. Here, we discuss how changes in the recruitment and activation of macrophages contribute to metabolic homeostasis. In particular, we focus our discussion on the pathogenic and protective functions of classically and alternatively activated macrophages, respectively, in experimental models of obesity and metabolic disease.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary
With their novel, insulin‐independent mechanism, sodium‐glucose cotransporter‐2 (SGLT2) inhibitors are a major turning point in the management of type 2 diabetes mellitus. At present, there ...are several SGLT2 inhibitors available or in development, and these oral anti‐hyperglycaemic agents lower plasma glucose through the inhibition of SGLT2‐mediated reuptake of filtered glucose in the kidney. This unique mechanism of action is also expected to result in other beneficial effects, such as weight loss and blood pressure reduction. In various studies, including randomized controlled trials and real‐world studies, patients treated with SGLT2 inhibitors have reported weight loss of around 1 to 3 kg. This review describes the characteristics of weight loss associated with SGLT2 inhibitor therapy, the clinical factors affecting SGLT2 inhibitor‐associated weight loss and the possible underlying mechanisms of SGLT2 inhibitor‐associated weight loss, including changes in metabolism and body composition, and the role of a reduction in insulin dose and compensatory hyperphagia. Understanding the weight loss effect of SGLT2 inhibitors, its related factors and underlying mechanisms can aid clinicians in optimal treatment decision‐making, provide valuable insight on both obesity and diabetes management and reveal areas of future research and new therapeutic options.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The sustainability of global clean and safe water supply is one of the grand challenges facing the world. Membrane technology based on polymeric membranes is one of the most important and widely ...recognized technologies for desalination and wastewater treatment. While polymeric membranes are known to be plagued with some bottlenecks, the technical progress and the accompanying knowledge in inorganic membrane development have grown inexorably to solve some of the underlying issues. Aside from the conventionally used ceramic membranes which based on metal oxides, nanostructures such as zeolites, metal organic frameworks and carbon based materials have sparked enormous interest in the preparation of inorganic membranes owing to their tunable nanoscaled structural properties that can render excellent rejection and/or ultrafast water transport. This review provides insights into the physico-chemical properties and fabrication approaches of different classes of inorganic membranes. The transport mechanisms that are associated to their unique structural features are also discussed. Furthermore, the performance evaluation of these inorganic membranes in a wide spectrum of desalination and wastewater treatment applications are also elaborated. Finally, the challenges in the development of inorganic membrane for practical commercial application are identified and the future perspectives are presented.
•Inorganic membranes for desalination and wastewater treatment are reviewed.•Properties and fabrication approaches of inorganic membranes are discussed.•Separation mechanisms and performance of various inorganic membranes are elaborated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic–pituitary–adrenal ...(HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
The purpose of the present study was to determine whether intrahepatic injection of
131
I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular ...carcinoma (HCC).
Methods
From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4–6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan–Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong.
Results
The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval 95 % CI 0.46–1.23;
p
= 0.25) and OS (HR = 0.88; 95 % CI 0.51–1.51;
p
= 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by
131
I-lipiodol and hepatic artery dissection during angiography.
Conclusions
The randomized trial provides insufficient evidence to recommend the routine use of
131
I-lipiodol in these patients.
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EMUNI, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, SBNM, UL, UM, UPUK
Continuous fiber-reinforced polymer (FRP) composites have been used for many applications to create strong yet lightweight products due to their high strength-to-weight and stiffness-to-weight ...ratios. Aerospace 1, automotive 2, and sport 3industries are three of the few industries that have been using FRP composites. The increasing need for prototyping and customization of fiber reinforced polymer composite parts is prompting innovations in new manufacturing processes to realize short manufacturing cycle time and low production cost, which is challenging to accomplish using conventional molding process. Fused filament fabrication (FFF) - a material extrusion additive manufacturing (AM) technique trademarked as fused deposition modelling (FDM) by Stratasys- holds promise to achieve low-cost production on continuous fiber-reinforced thermoplastic (FRTP) composites. In this paper, the FFF technique is employed to fabricate continuous carbon and glass FRTP composites and its microstructural characteristics and the resulting tensile, flexural, and quasi-static indentation characteristics of the printed composites are examined. Additionally, the fracture behavior of each test sample is evaluated and discussed in detail.
•A comparison of fracture behaviors between 3D-printed carbon and glass fiber reinforced composites is performed.•Difference in fracture behavior between glass and carbon fibers reinforced composites is observed in flexural test.•Similar fracture behavior is observed for tensile and quasi-static indentation tests.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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