Inhibition of acetylation of histones 3 and 4 attenuates aortic valve calcification

Jia Gu,Yan Lu,Menqing Deng,Ming Qiu,Yunfan Tian,Yue Ji,Pengyu Zong,Yongfeng Shao,Rui Zheng,Bin Zhou,Xiangqing Kong,Wei Sun 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Aortic valve calcification develops in patients with chronic kidney disease who have calcium and phosphate metabolic disorders and poor prognoses. There is no effective treatment except valve replacement. However, metabolic disorders put patients at high risk for surgery. Increased acetylation of histones 3 and 4 is present in interstitial cells from human calcific aortic valves, but whether it is involved in aortic valve calcification has not been studied. In this study, we found that treating cultured porcine aortic valve interstitial cells with a high-calcium/high-phosphate medium induced calcium deposition, apoptosis, and expression of osteogenic marker genes, producing a phenotype resembling valve calcification in vivo. These phenotypic changes were attenuated by the histone acetyltransferase inhibitor C646. C646 treatment increased the levels of class I histone deacetylase members and decreased the acetylation of histones 3 and 4 induced by the high-calcium/high-phosphate treatment. Conversely, the histone deacetylase inhibitor suberoylanilide hydroxamic acid promoted valve interstitial cell calcification. In a mouse model of aortic valve calcification induced by adenine and vitamin D treatment, the levels of acetylated histones 3 and 4 were increased in the calcified aortic valves. Treatment of the models with C646 attenuated aortic valve calcification by restoring the levels of acetylated histones 3 and 4. These observations suggest that increased acetylation of histones 3 and 4 is part of the pathogenesis of aortic valve calcification associated with calcium and phosphate metabolic disorders. Targeting acetylated histones 3 and 4 may be a potential therapy for inoperable aortic valve calcification in chronic kidney disease patients.

Sensing Characteristics of Uncoated Double Cladding Long-period Fiber Grating Based on Mode Transition and Dual-peak Resonance

Yuan Zhou,Zheng Tian Gu,Qiang Ling 한국광학회 2021 Current Optics and Photonics Vol.5 No.3

In this paper, the sensing characteristics of a double cladding fiber (DCF) long-period fiber grating (LPFG) to the surrounding refractive index (SRI) are studied. The outer cladding of the DCF plays the role of the overlay, thus, the mode transition (MT) phenomenon of DCF can be induced by etching the outer cladding radius instead of coating overlays. The response characteristics of the effective refractive index (ERI) of the cladding mode to the outer cladding radius are analyzed. It is found that in the MT range, the change rate of ERIs of cladding modes is relatively larger than that for other ranges. Further, based on the features of the mode transition region (MTR), the phase-matching curve of the 11 th cladding mode is investigated, and the response of the DCF-LPFG to the SRI is characterized by the change of wavelength intervals between the dual peaks under different outer cladding radii. The numerical simulation results show that the SRI sensitivity is greatly improved, which is available to 3484.0 nm/RIU with the fitting degree 0.998 in the SRI range of 1.33–1.37. The proposed DCF-LPFG can provide new theoretical support for designing the DCF-LPFG refractive index sensor with excellent performances of sensitivity, linearity and structure.

Deuterium Clusters Fusion Induced by the Intense Femtosecond Laser Pulse

Hong-Jie, Liu,Zhi-Jian, Zheng,Yu-Qiu, Gu,Bao-Han, Zhang,Yong-Joo, Rhee,Sung-Mo, Nam,Jae-Min, Han,Yong-Woo, Rhee,Kwon-Hae, Yea,Jia-Bin, Chen,Hong-Bin, Wang,Chun-Ye, Jiao,Ying-Ling, He,Tian-Shu, Wen,Xia ALLERTON PRESS INC 2007 CHINESE PHYSICS LETTERS Vol.24 No.2

<P>Neutrons (2.45 MeV) from deuterium cluster fusion induced by the intense femtosecond (30 fs) laser pulse are experimentally demonstrated. The average neutron yield 10<SUP>3</SUP> per shot is obtained. It is found that the yield slightly increases with the increasing laser spot size. No neutron can be observed when the laser intensity I < 4.3×10<SUP>15</SUP> W/cm<SUP>2</SUP>.</P>

Comparison of Liver Transplantation and Liver Resection for Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus Type I and Type II

Jia-Yu Lv,Ning-Ning Zhang,Ya-Wei Du,Ying Wu,Tian-Qiang Song,Ya-Min Zhang,Yan Qu,Yu-Xin Liu,Jie Gu,Ze-Yu Wang,Yi-Bo Qiu,Bing Yang,Da-Zhi Tian,Qing-Jun Guo,Li Zhang,Ji-San Sun,Yan Xie,Zheng-Lu Wang,Xin 연세대학교의과대학 2021 Yonsei medical journal Vol.62 No.1

Purpose: The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellularcarcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. Materials and Methods: A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involvedand divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were comparedbefore and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. Results: Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR(p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longermedian RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335,respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase(AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. Conclusion: LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels>200 ng/mL.

Development and Validation of Nomograms to Provide Individualized Predictions of Sur-vival Benefits from Surgery in Patients with Intermediate/Advanced Hepatocel-lular Carcinoma

( Wen-tao Yan ),( Jia-he Wang ),( Ming-da Wang ),( Zheng Wang ),( Bing Quan ),( Ya-hao Zhou ),( Wei-min Gu ),( Hong Wang ),( Ting-hao Chen ),( Tian Yang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: According to the BCLC treatment guidelines, surgery does not be recommended for intermediate/advanced hepatocellular carcinoma (HCC). In real world, however, liver resections are often performed in patients with intermediate/ advanced but resectable HCC, especially in the East. Methods: We retrospectively evaluated multicentric data of 1,325 patients newly diagnosed with intermediate/advanced HCC who underwent curative resection. We randomly divided the subjects into development (n = 875) and validation (n = 450) samples. Multivariate Cox proportional hazards models were developed and separately validated on the basis of patients’ clinicopathological variables assessed for associations with 1-year recurrence and 3-year mortality. The discriminatory accuracy of these models was compared with conventional tools by analyzing receiver operating characteristic (ROC) curves. Results: He statistical nomograms built based on performance status, Child-Pugh grade, portal hypertension, preoperative alpha-fetoprotein level, tumor rupture, largest tumor diameter, tumor number, macrovascular and microvascular invasion, and satellites had good calibration and discriminatory abilities, with c-indices of 0.70 (1-year recurrence) and 0.68 (3-year survival), respectively. These models showed satisfactory goodness-of-fit and discrimination abilities in the validation cohort (c-index, 0.68 for 1-year recurrence and 0.69 for 3-year survival). The areas under the ROC curve using these nomograms exceeded those of traditional staging systems, indicating superior discriminatory capability (c-indices, 0.60-0.63 and 0.56-0.62, respectively). Conclusions: Our proposed online nomograms, which present graphically postoperative prognostic models for recurrence and survival in patients with intermediate/advanced but resectable HCC, offer valuable guidance to surgeons and hepatologists for individually predicting survival benefits from surgery and planning recurrence surveillance and adjuvant therapy.

Novel blood-based hypomethylation of SH3BP5 is associated with very early-stage lung adenocarcinoma

Qiao Rong,Zhong Runbo,Liu Chunlan,Di Feifei,Zhang Zheng,Wang Ling,Xu Tian,Wang Yue,Dai Liping,Gu Wanjian,Han Baohui,Yang Rongxi 한국유전학회 2022 Genes & Genomics Vol.44 No.4

Background: Early detection is essential to improve the survival of lung cancer (LC). The quantitative measurement of specific DNA methylation changes in the peripheral blood could provide an efficient strategy for the detection of early cancer. Objective: We applied a candidate approach and assess the association between blood-based SH3BP5 methylation and the risk of lung adenocarcinoma (LUAD) in a case-control cohort. Methods: The methylation level of four CpG sites in the promoter of SH3BP5 gene was quantitatively determined by mass spectrometry in 171 very early-stage LUAD patients (93.6% LUAD at stage I) and 190 age and gender-matched controls. The logistic regression and non-parametric tests were used for the statistical analyses. Results: We observed a significant association between decreased methylation of SH3BP5_CpG_4 in the peripheral blood and increased risk of LUAD (odds ratio (OR) per-10% methylation = 1.51, P = 0.006, FDR = 0.024), and even for the LUAD at stage I (OR per-10% methylation = 1.53, P = 0.006, FDR = 0.024). Moreover, the lower quartile of SH3BP5_CpG_4 methylation was correlated with increased risk for LUAD with a P trend of 0.011. Further investigation disclosed that the hypomethylation of SH3BP5_CpG_4 was mostly associated with LUAD in younger subjects (OR per-10% methylation = 2.02, P = 0.010, age < 55 years old) and probably could be enhanced by advance stage. Conclusion: Our study revealed an association between blood-based SH3BP5 hypomethylation and very early-stage LUAD, which provides a novel support for the blood-based methylation signatures as a potential marker for the evaluation of cancer risk.