Long term outcome of antiviral therapy in patients with hepatitis B associated decompensated cirrhosis

AIM To investigate survival rate and incidence of hepatocellular carcinoma(HCC) in patients with decompensated cirrhosis in the antiviral era.METHODS We used the Korean Health Insurance Review and Assessment. Korea's health insurance system is a public single-payer system. The study population consisted of 286871 patients who were prescribed hepatitis B antiviral therapy for the first time between 2007 and 2014 in accordance with the insurance guidelines.Overall, 48365 antiviral treatment-na?ve patients treated between 2008 and 2009 were included, and each had a follow-up period ≥ 5 years. Data were analyzed for the 1 st decompensated chronic hepatitis B(CHB) and treatment-na?ve patients(n = 7166). RESULTS The mean patient age was 43.5 years. The annual mortality rates were 2.4%-19.1%, and 5-year cumulative mortality rate was 32.6% in 1^(st) decompensated CHB treatment-na?ve subjects. But the annual mortality rates sharply decreased to 3.4%(2.4%-4.9%, 2-5 year) after one year of antiviral treatment. Incidence of HCC at first year was 14.3%, the annual incidence of HCC decreased to 2.5%(1.8%-3.7%, 2-5 year) after one year. 5-year cumulative incidence of HCC was 24.1%. Recurrence rate of decompensated event was 46.9% at first year, but the annual incidence of second decompensation events in decompensated CHB treatment-na?ve patients was 3.4%(2.1%-5.4%, 2-5 year) after one year antiviral treatment. 5-year cumulative recurrence rate of decompensated events was 60.6%. Meanwhile, 5-year cumulative mortality rate was 3.1%, and 5-year cumulative incidence of HCC was 11.5% in compensated CHB treatment-na?ve patients.CONCLUSION Long term outcome of decompensated cirrhosis treated with antiviral agent improved much, and incidence of hepatocellular carcinoma and mortality sharply decreased after one year treatment.

Bacteroides fragilis enterotoxin upregulates heme oxygenase-1 in dendritic cells via reactive oxygen species-,mitogen-activated protein kinase-,and Nrf2-dependent pathway

BACKGROUND Enterotoxigenic Bacteroides fragilis(ETBF)causes colitis and diarrhea,and is considered a candidate pathogen in inflammatory bowel diseases as well as colorectal cancers.These diseases are dependent on ETBF-secreted toxin(BFT).Dendritic cells(DCs)play an important role in directing the nature of adaptive immune responses to bacterial infection and heme oxygenase-1(HO-1)is involved in the regulation of DC function.AIM To investigate the role of BFT in HO-1 expression in DCs.METHODS Murine DCs were generated from specific pathogen-free C57BL/6 and Nrf2−/−knockout mice.DCs were exposed to BFT,after which HO-1 expression and the related signaling factor activation were measured by quantitative RT-PCR,EMSA,fluorescent microscopy,immunoblot,and ELISA.RESULTS HO-1 expression was upregulated in DCs stimulated with BFT.Although BFT activated transcription factors such as NF-κB,AP-1,and Nrf2,activation of NF-κB and AP-1 was not involved in the induction of HO-1 expression in BFT-exposed DCs.Instead,upregulation of HO-1 expression was dependent on Nrf2 activation in DCs.Moreover,HO-1 expression via Nrf2 in DCs was regulated by mitogenactivated protein kinases such as ERK and p38.Furthermore,BFT enhanced the production of reactive oxygen species(ROS)and inhibition of ROS production resulted in a significant decrease of phospho-ERK,phospho-p38,Nrf2,and HO-1 CONCLUSION These results suggest that signaling pathways involving ROS-mediated ERK and p38 mitogen-activated protein kinases-Nrf2 activation in DCs are required for HO-1 induction during exposure to ETBF-produced BFT.

Osthol attenuates hepatic steatosis via decreased triglyceride synthesis not by insulin resistance

AIM: To evaluate the effects of osthol on intrahepatic fat synthesis, β-oxidation, inflammation, and insulin resistance by multifaceted analysis.METHODS: Sprague-Dawley rats(n = 30) were randomly divided into control, non-alcoholic fatty liver disease(NAFLD), and osthol groups. NAFLD and osthol groups were fed with a high-fat diet for 14 wk. After 8 wk of the high-fat diet, the osthol group also received osthol 20 mg/kg orally 5 times/wk. To assess the insulin resistance, oral glucose tolerance was performed at the end of 14 wk. Immunohistochemical(4-HNE, F4/80) and hematoxylin and eosin(HE) staining wereperformed on liver tissue extracts after animal sacrifice at 14 wk. SREBP1 c, FAS, SCD-1, PPAR-α, CROT, MCP-1, IRS-1, and IRS-2 mRNA expressions were assessed with reverse transcription-polymerase chain reaction.RESULTS: HE staining revealed that, compared with the NAFLD group, the osthol group showed significantly decreased intrahepatic fat content(39.4% vs 21.0%; P = 0.021). SREBP1 c expression in the NAFLD group increased compared to controls(P = 0.0001), while osthol treatment decreased SREBP1 c expression compared with the NAFLD group(P = 0.0059). In the osthol group, intrahepatic FAS and SCD-1, which act downstream of SREBP1 c, decreased significantly compared with the NAFLD group. Moreover, PPAR-α expression in the osthol group was also significantly higher than in the NAFLD group(P = 0.0147).CONCLUSION: Osthol treatment attenuated liver steatosis by decreasing de novo liver triglyceride synthesis and had nominal effects on insulin resistance and liver inflammation.

Past,present and future of indium phosphide quantum dots

Indium phosphide(InP)colloidal quantum dots(QDs)have been drawn significant attention as a potentially less toxic alternative to cadmium-based QDs over the past two decades.The advances in their colloidal synthesis methods have allowed for the synthesis of a wide variety of compositions,heterojunctions,dopants,and ligands that enabled spectral tunability from blue to near-infrared,narrow emission linewidths,and perfect quantum yields approaching unity.Furthermore,it has higher covalency compared to cadmium chalcogenides leading to improved optical stability.The state-of-the-art InP QDs with appealing optical and electronic properties have excelled in many applications such as light-emitting diodes,luminescent solar concentrators(LSCs),and solar cells with high potential for commercialization.This review focuses on the history,recent development,and future aspect of synthesis and application of colloidal InP QDs.

Dissecting microRNA-mediated regulation of stemness,reprogramming,and pluripotency

Increasing evidence indicates that microRNAs(miRNAs),endogenous short non-coding RNAs 19–24 nucleotides in length,play key regulatory roles in various biological events at the post-transcriptional level.Embryonic stem cells(ESCs)represent a valuable tool for disease modeling,drug discovery,developmental studies,and potential cell-based therapies in regenerative medicine due to their unlimited self-renewal and pluripotency.Therefore,remarkable progress has been made in recent decades toward understanding the expression and functions of specific miRNAs in the establishment and maintenance of pluripotency.Here,we summarize the recent knowledge regarding the regulatory roles of miRNAs in self-renewal of pluripotent ESCs and during cellular reprogramming,as well as the potential role of miRNAs in two distinct pluripotent states(naïve and primed).

Erratum to:Exciton recycling via InP quantum dot funnels for luminescent solar concentrators

The article“Exciton recycling via InP quantum dot funnels for luminescent solar concentrators”written by Houman Bahmani Jalali,Sadra Sadeghi,Isinsu Baylam,Mertcan Han,Cleva W.Ow-Yang,Alphan Sennaroglu,and Sedat Nizamoglu,was originally published Online First without Open Access.After publication online first,the author decided to opt for Open Choice and to make the article an Open Access publication.Therefore,the copyright of the article has been changed to©The Author(s)2020 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/),which permits use,duplication,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons license,and indicate if changes were made.The original article has been corrected.

Developmental thyroid hormone action on pro-opiomelanocortin-expressing cells programs hypothalamic BMPR1A depletion and brown fat activation

Thyroid hormone excess secondary to global type 3 deiodinase(DIO3)deficiency leads to increased locomotor activity and reduced adiposity,but also to concurrent alterations in parameters of the leptin-melanocortin system that would predict obesity.To distinguish the underlying contributions to the energy balance phenotype of Dlo3 deficiency,we generated mice with thyroid hormone excess targeted to pro-opiomelanocortin(POMC)-expressing cells via cell-specific DIO3 inactivation.These mice exhibit a male-specific phenotype of reduced hypothalamic Pomc expression,hyperphagia,and increased activity in brown adipose tissue,with adiposity and serum levels of leptin and thyroid hormones remained normal.These male mice also manifest a marked and widespread hypothalamic reduction in the expression of bone morphogenetic receptor 1a(BMPR1A),which has been shown to cause similar phenotypes when inactivated in PoMC-expressing cells.Our results indicate that developmental overexposure to thyroid hormone in PoMC-expressing cells programs energy balance mechanisms in a sexually dimorphic manner by suppressing adult hypothalamic BMPR1A expression.

Exciton recycling via InP quantum dot funnels for luminescent solar concentrators

Luminescent solar concentrators (LSC) absorb large-area solar radiation and guide down-converted emission to solar cells for electricity production. Quantum dots (QDs) have been widely engineered at device and quantum dot levels for LSCs. Here, we demonstrate cascaded energy transfer and exciton recycling at nanoassembly level for LSCs. The graded structure composed of different sized toxic-heavy-metal-free InP/ZnS core/shell QDs incorporated on copper doped InP QDs, facilitating exciton routing toward narrow band gap QDs at a high nonradiative energy transfer efficiency of 66%. At the final stage of non-radiative energy transfer, the photogenerated holes make ultrafast electronic transitions to copper-induced mid-gap states for radiative recombination in the near-infrared. The exciton recycling facilitates a photoluminescence quantum yield increase of 34% and 61% in comparison with semi-graded and ungraded energy profiles, respectively. Thanks to the suppressed reabsorption and enhanced photoluminescence quantum yield, the graded LSC achieved an optical quantum efficiency of 22.2%. Hence, engineering at nanoassembly level combined with nonradiative energy transfer and exciton funneling offer promise for efficient solar energy harvesting.