Fenofibrate Increases Radiosensitivity in Head and Neck Squamous Cell Carcinoma via Inducing G2/M Arrest and Apoptosis

Liu, Jia,Ge, Yang-Yang,Zhu, Hong-Cheng,Yang, Xi,Cai, Jing,Zhang, Chi,Lu, Jing,Zhan, Liang-Liang,Qin, Qin,Yang, Yan,Yang, Yue-Hua,Zhang, Hao,Chen, Xiao-Chen,Liu, Zhe-Ming,Ma, Jian-Xin,Cheng, Hong-Yan,S Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

Radiation therapy is an important treatment for head and neck squamous cell carcinoma (HNSCC). However, how to promote radiation sensitivity in HNSCC remains a challenge. This study aimed to investigate the radiosensitizing effects of fenofibrate on HNSCC and explore the underlying mechanisms. HNSCC cell lines CNE-2 and KB were subjected to ionizing radiation (IR), in the presence or absence of fenofibrate treatment. Cell growth and survival, apoptosis and cell cycle were evaluated. In addition, CNE-2 cells were xenografted into nude mice and subjected to IR and/or fenofibrate treatment. The expression of cyclinB and CDK1 was detected by Western blotting. Our results showed that fenofibrate efficiently radiosensitized HNSCC cells and xenografts in mice, and induced apoptosis and G2/M arrest via reducing the activity of the CDK1/cyclinB1 kinase complex. These data suggest that fenofibrate could be a promising radiosensitizer for HNSCC radiotherapy.

Ultraviolet-assisted synthesis of encapsulating adhesives and their application for lifetime improvement of organic light emitting diodes

Chen-Ming Chen,Ming-Hua Chung,Tsung-Eong Hsieh,Bohr-Ran Huang,Huai-En Hsieh,Fuh-Shyang Juang,Yu-Sheng Tsai,Mark O. Liu,Jen-Lien Lin 한국물리학회 2009 Current Applied Physics Vol.9 No.4

The lifetimes of organic light emitting diodes (OLEDs) have been successfully enhanced with the modulation of LiF thickness and the utilization of encapsulating adhesives, which have been successfully and quickly synthesized with UV irradiation. Experimental results demonstrate that LiF and lab-made encapsulating adhesives can block the invasion of moisture as well as oxygen in the atmosphere into the OLEDs so that the lifetimes of devices with their encapsulation are 18-folds longer than those without encapsulation. The lifetimes of organic light emitting diodes (OLEDs) have been successfully enhanced with the modulation of LiF thickness and the utilization of encapsulating adhesives, which have been successfully and quickly synthesized with UV irradiation. Experimental results demonstrate that LiF and lab-made encapsulating adhesives can block the invasion of moisture as well as oxygen in the atmosphere into the OLEDs so that the lifetimes of devices with their encapsulation are 18-folds longer than those without encapsulation.

Absence of EZH2 Gene Mutation in Chronic Myeloid Leukemia Patients in Blast Crisis

Chen, Hao-Yue,Yao, Hong,Wu, Ling-Yu,Liu, Can-Jun,Zhu, Jian-Qin,Liu, Chun-Hua,Wang, Wei,Dong, Sha-Sha,Ping, Na-Na,Chen, Su-Ning,Sun, Miao Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5

Acute hepatitis C virus infection: clinical update and remaining challenges

Chen-Hua Liu,Jia-Horng Kao 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.3

Acute hepatitis C virus (HCV) infection is a global health concern with substantial geographical variation in the incidence rate. People who have received unsafe medical procedures, used injection drugs, and lived with human immunodeficiency virus are reported to be most susceptible to acute HCV infection. The diagnosis of acute HCV infection is particularly challenging in immunocompromised, reinfected, and superinfected patients due to difficulty in detecting anti-HCV antibody seroconversion and HCV ribonucleic acid from a previously negative antibody response. With an excellent treatment effect on chronic HCV infection, recently, clinical trials investigating the benefit of direct-acting antivirals (DAAs) treatment for acute HCV infection have been conducted. Based on the results of cost-effectiveness analysis, DAAs should be initiated early in acute HCV infection prior to spontaneous viral clearance. Compared to the standard 8–12 week-course of DAAs for chronic HCV infection, DAAs treatment duration may be shortened to 6–8 weeks in acute HCV infection without compromising the efficacy. Standard DAA regimens provide comparable efficacy in treating HCV-reinfected patients and DAA-naïve ones. For cases contracting acute HCV infection from HCV-viremic liver transplant, a 12-week course of pangenotypic DAAs is suggested. While for cases contracting acute HCV infection from HCV-viremic non-liver solid organ transplants, a short course of prophylactic or pre-emptive DAAs is suggested. Currently, prophylactic HCV vaccines are unavailable. In addition to treatment scale-up for acute HCV infection, practice of universal precaution, harm reduction, safe sex, and vigilant surveillance after viral clearance remain critical in reducing HCV transmission.

Multiple Sexual Partners as a Potential Independent Risk Factor for Cervical Cancer: a Meta-analysis of Epidemiological Studies

Liu, Zhi-Chang,Liu, Wei-Dong,Liu, Yan-Hui,Ye, Xiao-Hua,Chen, Si-Dong Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

It's known that having multiple sexual partners is one of the risk factors of human papillomavirus (HPV) infection which is a major cause of cervical cancer. However, it is not clear whether the number of sexual partners is an independent risk factor for cervical cancer. We identified relevant studies by searching the databases of MEDLINE, PubMed and ScienceDirect published in English from January 1980 to January 2014. We analyzed those studies by combining the study-specific odds ratios (ORs) using random-effects models. Forty-one studies were included in this meta-analysis. We observed that the number of sexual partners was associated with the occurrence of non-malignant cervical disease (OR=1.82, 95%CI 1.63-2.00) and invasive cervical carcinoma (OR=1.77, 95%CI 1.50-2.05). Subgroup analyses revealed that the association remained significant after controlling for HPV infection (OR=1.52, 95%CI 1.21-1.83 for non-malignant disease; OR=1.53, 95%CI 1.30-1.76 for invasive cervical carcinoma). We found that there was a non-linear relation of the number of sexual partners with both non-malignant cervical disease and invasive cervical carcinoma. The risk of both malignant and non-malignant disease is relatively stable in women with more than 4-7 sexual partners. Furthermore, the frequency-risk of disease remained significant after controlling for HPV infection.The study suggested that h aving multiple sexual partners, with or without HPV infection, is a potential risk factor of cervical cancer.

Sputum Metabolomic Profiling Reveals Metabolic Pathways and Signatures Associated With Inflammatory Phenotypes in Patients With Asthma

Liu Ying,Zhang Xin,Zhang Li,Oliver Brian G,Wang Hong Guang,Liu Zhi Peng,Chen Zhi Hong,Wood Lisa,Hsu Alan Chen-Yu,Xie Min,McDonald Vanessa,Wan Hua Jing,Luo Feng Ming,Liu Dan,Li Wei Min,Wang Gang 대한천식알레르기학회 2022 Allergy, Asthma & Immunology Research Vol.14 No.4

Purpose: The molecular links between metabolism and inflammation that drive different inflammatory phenotypes in asthma are poorly understood. We aimed to identify the metabolic signatures and underlying molecular pathways of different inflammatory asthma phenotypes. Methods: In the discovery set (n = 119), untargeted ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to characterize the induced sputum metabolic profiles of asthmatic patients with different inflammatory phenotypes using orthogonal partial least-squares discriminant analysis (OPLS-DA), and pathway topology enrichment analysis. In the validation set (n = 114), differential metabolites were selected to perform targeted quantification. Correlations between targeted metabolites and clinical indices in asthmatic patients were analyzed. Logistic and negative binomial regression models were established to assess the association between metabolites and severe asthma exacerbations. Results: Seventy-seven differential metabolites were identified in the discovery set. Pathway topology analysis uncovered that histidine metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, linoleic acid metabolism as well as phenylalanine, tyrosine and tryptophan biosynthesis were involved in the pathogenesis of different asthma phenotypes. In the validation set, 24 targeted quantification metabolites were significantly expressed between asthma inflammatory phenotypes. Finally, adenosine 5′-monophosphate (adjusted relative risk [adj RR] = 1.000; 95% confidence interval [CI] = 1.000–1.000; P = 0.050), allantoin (adj RR = 1.000; 95% CI = 1.000–1.000; P = 0.043) and nicotinamide (adj RR = 1.001; 95% CI = 1.000–1.002; P = 0.021) were demonstrated to predict severe asthma exacerbation rates. Conclusions: Different inflammatory asthma phenotypes have specific metabolic profiles in induced sputum. The potential metabolic signatures may identify therapeutic targets in different inflammatory asthma phenotypes.

Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis

( Chen-hua Liu ),( Chi-yi Chen ),( Wei-wen Su ),( Chun-jen Liu ),( Ching-chu Lo ),( Ke-jhang Huang ),( Jyh-jou Chen ),( Kuo-chih Tseng ),( Chi-yang Chang ),( Cheng-yuan Peng ),( Yu-lueng Shih ),( Chia 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.4

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR₁₂) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. The safety profiles were reported. Results: The SVR₁₂ rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5-94.2%), 94.1% (95% CI, 87.8-97.3%), and 100% (95% CI, 96.2-100%). Number of patients who failed to achieve SVR₁₂ were attributed to virologic failures. The SVR₁₂ rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR₁₂, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16-14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 ㎡/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 ㎡/month; P<0.001). Conclusions: SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis. (Clin Mol Hepatol 2021;27:575-588)

Grem1 accelerates nucleus pulposus cell apoptosis and intervertebral disc degeneration by inhibiting TGF-β-mediated Smad2/3 phosphorylation

Chen Shunlun,Lei Linchuan,Li Zemin,Chen Fan,Huang Yuming,Jiang Guowei,Guo Xingyu,Zhao Zhuoyang,Liu Hui,Wang Hua,Liu Caijun,Zheng Zhaomin,Wang Jianru 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Intervertebral disc degeneration (IVDD) is a main cause of low back pain, and inflammatory factors play key roles in its pathogenesis. Gremlin-1 (Grem1) was reported to induce an inflammatory response in other fields. This study aimed to investigate the mechanisms of Grem1 in the degenerative process of intervertebral discs. Dysregulated genes were determined by analyzing microarray profiles. The expression of Grem1 in 17 human disc samples (male:female = 9:8) and rat models (n = 5 each group) was measured by western blotting (WB), real-time quantitative PCR (RT-qPCR), and immunohistochemistry (IHC). The regulatory effects of Grem1 on apoptosis were examined using siRNAs, flow cytometry, immunofluorescence (IF), and WB. The therapeutic effect was evaluated by locally injecting specific Grem1 siRNA into IVDD rats. The expression of Grem1 was significantly increased in human degenerative intervertebral discs; furthermore, the expression of Grem1 positively correlated with the level of intervertebral disc degeneration. Grem1 was significantly overexpressed in tumor necrosis factor (TNF)-α-induced degenerative NP cells. Apoptosis in degenerative NP cells transfected with siRNA targeting Grem1 was significantly lower than that in the control group. Specific Grem1 siRNA markedly repressed the development of IVDD in surgery-induced IVDD rats. These results indicated that the expression of Grem1 was positively correlated with the severity of intervertebral disc degeneration, and Grem1 siRNA could inhibit Grem1-induced apoptosis and extracellular matrix alterations by mediating the TGF-β/Smad signaling pathway. This study may provide a therapeutic strategy for alleviating inflammation-induced apoptosis associated with intervertebral disc degeneration.

Synthesis of Thermoresponsive Hyperbranched Polyamidoamine and the Molecular Weight, pH, and Anion Sensitive Thermoresponsive Properties Thereof

Yi Liu,Yu Chen,Xun-Yong Liu,Hua-Ji Liu,Fa Cheng 한국고분자학회 2012 Macromolecular Research Vol.20 No.6

Hyperbranched polyamidoamine (HPAMAM) polymers, chemically analogous to the commercially available PAMAM dendrimer, were modified with isobutyric anhydride to result in isobutyramide (IBAm) terminated HPAMAMs (HPAMAM-IBAm). The aqueous solutions of HPAMAM-IBAm polymers had the lower critical solution temperature (LCST). The lower molecular-weight HPAMAM-IBAm exhibited higher LCST and the LCST difference was around 18 oC for one pseudo-generation variation. Further, the hyperbranched thermoresponsive polymers exhibited much lower LCSTs than the corresponding dendrimers with similar molecular weight. The LCST of HPAMAM-IBAm was pH sensitive. At pH below 10, the LCST increased significantly upon decreasing the pH,whereas, at pH above 10, the LCST decreased slowly with an increasing pH value. Nine sodium salts were used to measure the anion effect on the LCST of HPAMAM-IBAm. It was found that the LCST could also be modulated up or down in a broad range by simply adding a small amount of different kinds of inorganic anions. The specific ranking of inorganic anions in salting-out HPAMAM4-IBAm polymer was in accordance with the well-known Hofmeister series.

Unilateral ureteral obstruction causes gut microbial dysbiosis and metabolome disorders contributing to tubulointerstitial fibrosis

Lin Chen,Dan-Qian Chen,Jing-Ru Liu,Jun Zhang,Nosratola D. Vaziri,Shougang Zhuang,Hua Chen,Ya-Long Feng,Yan Guo,Ying-Yong Zhao 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Chronic kidney disease (CKD) increases the risk and prevalence of cardiovascular disease (CVD) morbidity and mortality. Recent studies have revealed marked changes in the composition of the microbiome and the metabolome and their potential influence in renal disease and CVD via the accumulation of microbial-derived uremic toxins. However, the effect of unilateral ureteral obstruction (UUO) on the gut microbiome and circulating metabolites is unknown. Male Sprague-Dawley rats were randomized to UUO and sham-operated control groups. Renal histology, colonic microbiota, and plasma metabolites were examined two weeks later. We employed 16S rRNA sequence and untargeted metabolomic analyses to explore the changes in colonic microbiota and plasma metabolites and their relationship with tubulointerstitial fibrosis (TIF). The UUO rats exhibited tubular atrophy and dilatation, interstitial fibrosis and inflammatory cell infiltration in the obstructed kidney. UUO rats showed significant colonic enrichment and depletion of genera. Significant differences were identified in 219 plasma metabolites involved in lipid, amino acid, and bile acid metabolism, which were consistent with gut microbiota-related metabolism. Interestingly, tryptophan and its metabolites kynurenine, 5-hydroxytryptophan and 5-hydroxytryptamine levels, which were linked with TIF, correlated with nine specific genera. Plasma tryptophan level was positively correlated with Clostridium IV, Turicibacter, Pseudomonas and Lactobacillales, and negatively correlated with Oscillibacter, Blautia, and Intestinimonas, which possess the genes encoding tryptophan synthase (K16187), indoleamine 2,3-dioxygenase (K00463) and tryptophan 2,3-dioxygenase (K00453) and their corresponding enzymes (EC:1.13.11.52 and EC:1.13.11.11) that exacerbate TIF. In conclusion, UUO results in profound changes in the gut microbiome and circulating metabolites, events that contribute to the pathogenesis of inflammation and TIF.