Impact of fatty liver on long-term outcomes in chronic hepatitis B: a systematic review and matched analysis of individual patient data meta-analysis

Yu Jun Wong,Vy H. Nguyen,Hwai-I Yang,Jie Li,Michael Huan Le,Wan-Jung Wu,Nicole Xinrong Han,Khi Yung Fong,Elizabeth Chen,Connie Wong,Fajuan Rui,Xiaoming Xu,Qi Xue,Xin Yu Hu,Wei Qiang Leow,George Boon-B 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.3

Background/Aims: Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients. Methods: We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment. Results: We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all P≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, P<0.0001). Conclusions: IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.

Effect of Producing Different Phenazines on Bacterial Fitness and Biological Control in Pseudomonas chlororaphis 30-84

Yu, Jun Myoung,Wang, Dongping,Pierson, Leland S. III,Pierson, Elizabeth A. The Korean Society of Plant Pathology 2018 Plant Pathology Journal Vol.34 No.1

Pseudomonas chlororaphis 30-84 is a biological control agent selected for its ability to suppress diseases caused by fungal pathogens. P. chlororaphis 30-84 produces three phenazines: phenazine-1-carboxylic acid (PCA), 2-hydroxy-phenazine-1-carboxylic acid (2OHPCA) and a small amount of 2-hydroxy-phenazine (2OHPHZ), and these are required for fungal pathogen inhibition and wheat rhizosphere competence. The two, 2-hydroxy derivatives are produced from PCA via the activity of a phenazine-modifying enzyme encoded by phzO. In addition to the seven biosynthetic genes responsible for the production of PCA, many other Pseudomonas strains possess one or more modifying genes, which encode enzymes that act independently or together to convert PCA into other phenazine derivatives. In order to understand the fitness effects of producing different phenazines, we constructed isogenic derivatives of P. chlororaphis 30-84 that differed only in the type of phenazines produced. Altering the type of phenazines produced by P. chlororaphis 30-84 enhanced the spectrum of fungal pathogens inhibited and altered the degree of take-all disease suppression. These strains also differed in their ability to promote extracellular DNA release, which may contribute to the observed differences in the amount of biofilm produced. All derivatives were equally important for survival over repeated plant/harvest cycles, indicating that the type of phenazines produced is less important for persistence in the wheat rhizosphere than whether or not cells produce phenazines. These findings provide a better understanding of the effects of different phenazines on functions important for biological control activity with implications for applications that rely on introduced or native phenazine producing populations.

Development and validation of a sunlight exposure questionnaire for urban adult Filipinos

Marc Gregory Yu,Nina Castillo-Carandang,Maria Elinor Grace Sison,Angelique Bea Uy,Katrina Lenora Villarante,Patricia Maningat,Elizabeth Paz-Pacheco,Eileen Abesamis-Cubillan 한국역학회 2018 Epidemiology and Health Vol.40 No.-

OBJECTIVES: To develop and validate a self-reported sunlight exposure questionnaire (SEQ) for urban adult Filipinos. METHODS: The study included adults (19-76 years old) in Metro Manila, Philippines, well-versed in the Filipino (Tagalog) language and had resided in Metro Manila for at least 1 year. Exclusion criteria included pregnancy, active skin disorders, and immunocompromised states. An expert panel created a questionnaire in Likert-scale format based on a conceptual framework and 4 existing instruments. The study proceeded in 4 phases: questionnaire item development, translation and back-translation, pretesting, and construct validity and reliability testing using factor analysis, the Cronbach alpha coefficient, and the paired t-test. RESULTS: A 25-item, self-administered, Filipino (Tagalog) SEQ answerable using a 4-point Likert scale was created. The questionnaire was administered to 260 adult participants twice at a 2-week interval, with all participants completing both the first and second rounds of testing. All questionnaire items possessed adequate content validity indices of at least 0.86. After factor analysis, 3 questionnaire domains were identified: intensity of sunlight exposure, factors affecting sunlight exposure, and sun protection practices. Internal consistency was satisfactory for both the overall questionnaire (Cronbach alpha, 0.80) and for each of the domains (Cronbach alpha, 0.74, 0.71, and 0.72, respectively). No statistically significant differences were observed in the responses between the first and second rounds of testing, indicating good test-retest reliability. CONCLUSIONS: We developed a culturally-appropriate SEQ with sufficient content validity, construct validity, and reliability to assess sunlight exposure among urban adult Filipinos in Metro Manila, Philippines.

Benchmarking all-atom simulations using hydrogen exchange

Skinner, John J.,Yu, Wookyung,Gichana, Elizabeth K.,Baxa, Michael C.,Hinshaw, James R.,Freed, Karl F.,Sosnick, Tobin R. National Academy of Sciences 2014 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.111 No.45

<P><B>Significance</B></P><P>Molecular dynamics simulations have recently become capable of observing multiple protein unfolding and refolding events in a single-millisecond–long trajectory. This major advance produces atomic-level information with nanosecond resolution, a feat unmatched by experimental methods. Such simulations are being extensively analyzed to assess their description of protein folding, yet the results remain difficult to validate experimentally. We apply a combination of hydrogen exchange, NMR, and other techniques to test the simulations with a resolution of single H-bonds. Several significant discrepancies between the simulations and experimental data were uncovered for regions of the energy surface outside of the native basin. This comparison yields suggestions for improving the force fields and provides a general method for experimentally validating folding simulations.</P><P>Long-time molecular dynamics (MD) simulations are now able to fold small proteins reversibly to their native structures [Lindorff-Larsen K, Piana S, Dror RO, Shaw DE (2011) <I>Science</I> 334(6055):517–520]. These results indicate that modern force fields can reproduce the energy surface near the native structure. To test how well the force fields recapitulate the other regions of the energy surface, MD trajectories for a variant of protein G are compared with data from site-resolved hydrogen exchange (HX) and other biophysical measurements. Because HX monitors the breaking of individual H-bonds, this experimental technique identifies the stability and H-bond content of excited states, thus enabling quantitative comparison with the simulations. Contrary to experimental findings of a cooperative, all-or-none unfolding process, the simulated denatured state ensemble, on average, is highly collapsed with some transient or persistent native 2° structure. The MD trajectories of this protein G variant and other small proteins exhibit excessive intramolecular H-bonding even for the most expanded conformations, suggesting that the force fields require improvements in describing H-bonding and backbone hydration. Moreover, these comparisons provide a general protocol for validating the ability of simulations to accurately capture rare structural fluctuations.</P>

Maintenance of pegylated liposomal doxorubicin/carboplatin in patients with advanced ovarian cancer: randomized study of an Asian Gynecologic Oncology Group

Chyong-Huey Lai,Elizabeth Vallikad,Hao Lin,Lan-Yan Yang,Shih-Ming Jung,Hsueh-Erh Liu,Yu-Che Ou,Hung-Hsueh Chou,Cheng-Tao Lin,Huei-Jean Huang,Kuan-Gen Huang,Jiantai Qiu,Yao-Ching Hung,Tzu-I Wu,Wei-Yang 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.1

Objectives: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. Methods: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m2, n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. Results: Enrollment was slow, accrual was closed when 7+ years had passed. With a median follow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19–0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCA/non-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11–1.18; p=0.091). Conclusions: Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.

AUF1 promotes let-7b loading on Argonaute 2

Yoon, Je-Hyun,Jo, Myung Hyun,White, Elizabeth J.F.,De, Supriyo,Hafner, Markus,Zucconi, Beth E.,Abdelmohsen, Kotb,Martindale, Jennifer L.,Yang, Xiaoling,Wood III, William H.,Shin, Yu Mi,Song, Ji-Joon,T Cold Spring Harbor Laboratory Press 2015 Genes & development Vol.29 No.15

<P>Yoon et al. discovered that RBP AU-rich-binding factor 1 (AUF1) promotes let-7b loading onto Argonaute 2 (AGO2), the catalytic component of the RNA-induced silencing complex (RISC). In turn, AGO2–let-7 triggered target mRNA decay.</P><P>Eukaryotic gene expression is tightly regulated post-transcriptionally by RNA-binding proteins (RBPs) and microRNAs. The RBP AU-rich-binding factor 1 (AUF1) isoform p37 was found to have high affinity for the microRNA let-7b in vitro (<I>K</I><SUB>d</SUB> = ∼6 nM) in cells. Ribonucleoprotein immunoprecipitation, in vitro association, and single-molecule-binding analyses revealed that AUF1 promoted let-7b loading onto Argonaute 2 (AGO2), the catalytic component of the RNA-induced silencing complex (RISC). In turn, AGO2–let-7 triggered target mRNA decay. Our findings uncover a novel mechanism by which AUF1 binding and transfer of microRNA let-7 to AGO2 facilitates let-7-elicited gene silencing.</P>

Potential Molecular and Cellular Mechanism of Psychotropic Drugs

Myoung Suk Seo,Brian Dean,Elizabeth Scarr,Chi-Yu Lai 대한정신약물학회 2014 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.12 No.2

Psychiatric disorders are among the most debilitating of all medical illnesses. Whilst there are drugs that can be used to treatthese disorders, they give sub-optimal recovery in many people and a significant number of individuals do not respond to anytreatments and remain treatment resistant. Surprisingly, the mechanism by which psychotropic drugs cause their therapeuticbenefits remain unknown but likely involves the underlying molecular pathways affected by the drugs. Hence, in this review,we have focused on recent findings on the molecular mechanism affected by antipsychotic, mood stabilizing and antidepressantdrugs at the levels of epigenetics, intracellular signalling cascades and microRNAs. We posit that understanding these importantinteractions will result in a better understanding of how these drugs act which in turn may aid in considering how to developdrugs with better efficacy or increased therapeutic reach.

Thermochemical degradation of cotton fabric under mild conditions

Michael Cuiffo,정혜정,Asta Skocir,Theanne Schiros,Emily Evans,Elizabeth Orlando,Yu-Chung Lin,Yiwei Fang,Miriam Rafailovich,Taejin Kim,Gary Halada 한국의류학회 2021 Fashion and Textiles Vol.8 No.1

Textile waste presents a major burden on the environment, contributing to climate change and chemical pollution as toxic dyes and finishing chemicals enter the environment through landfill leachate. Moreover, the majority of textile waste reaching landfills is discarded clothing, which could be reused or recycled. Here we investigate environmentally benign morphology changing of cotton textiles as a precursor for reintegration into a circular materials economy. At 50 °C using low concentrations of acids and bases, the interfiber structures of woven cotton were successfully degraded when treated with the following sequence of chemical treatment: citric acid, urea, sodium hydroxide, ammonium hydroxide, and sodium nitrate. Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) reveal separation of the constituent fibers without depolymerization of the cellulose structure, and streaming potential measurements indicate that surface charge effects play a key role in facilitating degradation. The proposed reaction procedures show feasibility of effective waste-fabric recycling processes without chemically intensive processes, in which staple fibers are recovered and can be re-spun into new textiles.

Overall and cause-specific mortality in patients with dementia: a population-based cohort study in Taiwan

Chia-Lun Kuo,Pei-Chen Lee,Li-Jung Elizabeth Ku,Yu Sun,Tsung-Hsueh Lu,Muhammad Atoillah Isfandiari,Chung-Yi Li 한국역학회 2023 Epidemiology and Health Vol.45 No.-

OBJECTIVES: Information regarding the underlying causes of death (UCODs) and standardized mortality ratio (SMR) of dementia is instrumental in formulating medical strategies to prolong life in persons with dementia (PWD). We examined the leading UCODs among PWD and estimated the overall and cause-specific SMRs in relation to dementia in Taiwan. METHODS: Data were retrieved from 2 national datasets: the Taiwan Death Registry and the medical claim datasets of the National Health Insurance program. The observed person-years for each study participant were counted from the date of cohort enrollment to either the date of death or the final day of 2016. Sex-specific and age-specific SMRs were then calculated. RESULTS: The leading UCOD was circulatory disease, accounting for 26.0% of total deaths (n=3,505), followed by respiratory disease at 21.3% (n=2,875). PWD were at significantly increased risk of all-cause mortality (SMR, 2.01), with SMR decreasing with advancing age. A cause-specific analysis revealed that the highest SMRs were associated with nervous system diseases (SMR, 7.58) and mental, behavioral, and neurodevelopmental disorders (SMR, 4.80). Age appeared to modify SMR, suggesting that younger age at cohort enrollment was linked to higher SMRs for nearly all causes of mortality. CONCLUSIONS: Circulatory and respiratory diseases were the leading UCODs among PWD. The particularly elevated mortality due to nervous system diseases and mental disorders suggests that allocating more resources to neurological and psychiatric services is warranted. The elevated SMRs of various UCODs among younger PWD underscore the need for clinicians to pay particular attention to the medical care provided to these patients.

Short-term weight loss attenuates local tissue inflammation and improves insulin sensitivity without affecting adipose inflammation in obese mice

Jung, Dae Young,Ko, Hwi Jin,Lichtman, Eben I.,Lee, Eunjung,Lawton, Elizabeth,Ong, Helena,Yu, Kristine,Azuma, Yoshihiro,Friedline, Randall H.,Lee, Ki Won,Kim, Jason K. American Physiological Society 2013 AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND M Vol.304 No.9

<P>Obesity is a major cause of insulin resistance, and weight loss is shown to improve glucose homeostasis. But the underlying mechanism and the role of inflammation remain unclear. Male C57BL/6 mice were fed a high-fat diet (HFD) for 12 wk. After HFD, weight loss was induced by changing to a low-fat diet (LFD) or exercise with continuous HFD. The weight loss effects on energy balance and insulin sensitivity were determined using metabolic cages and hyperinsulinemic euglycemic clamps in awake mice. Diet and exercise intervention for 3 wk caused a modest weight loss and improved glucose homeostasis. Weight loss dramatically reduced local inflammation in skeletal muscle, liver, and heart but not in adipose tissue. Exercise-mediated weight loss increased muscle glucose metabolism without affecting Akt phosphorylation or lipid levels. LFD-mediated weight loss reduced lipid levels and improved insulin sensitivity selectively in liver. Both weight loss interventions improved cardiac glucose metabolism. These results demonstrate that a short-term weight loss with exercise or diet intervention attenuates obesity-induced local inflammation and selectively improves insulin sensitivity in skeletal muscle and liver. Our findings suggest that local factors, not adipose tissue inflammation, are involved in the beneficial effects of weight loss on glucose homeostasis.</P>