The landscape of histone modification in organ fibrosis.

An increase in fibrous connective tissue and a decrease in parenchymal cells in organ tissues are the primary pathological alterations linked to organ fibrosis. If fibrosis is not treated, organ structure is destroyed, function can decline, or even fail, posing a serious risk to human life and health. Numerous organs develop fibrosis, and organ fibroproliferative illnesses account for almost 45% of patient deaths from various diseases in the industrialized world, as well as a major cause of disability and mortality in many other diseases. Recently, it has become evident that histone modification is an important way to regulate gene expression in organ fibrosis. Histone modifications alter the structure of chromatin, thereby affecting gene accessibility. Histone acetylation modifications relax chromatin, making it easier for gene transcription factors to access DNA, thereby promoting gene transcription. In addition, histone modifications recruit other proteins to interact with chromatin to form complexes that further regulate gene expression. Histone methylation modifications recruit methylation-reading proteins that recognize methylation marks and alter gene expression status. It not only affects the normal physiological function of cells, but also plays an important role in organ fibrosis. This article reviews the important role played by histone modifications in organ fibrosis and potential therapeutic approaches.

Properties and Microstructure of an Interfacial Transition Zone Enhanced by Silica Fume in Concrete Prepared with Coal Gangue as an Aggregate.

The wide application of concrete prepared with coal gangue (CG) as an aggregate (CPCGA) is limited because of the low mechanical strength and strong water absorption capacity of CG. This paper used silica fume (SF) to improve the performance of the interfacial transition zone (ITZ) in CPCGA and revealed the enhancement mechanism. The results showed that the compressive strength of CPCGA prepared with cement replaced by a suitable amount of SF at the age of 28 days increased by more than 30%, and the flexural strength increased by over 20%. The SF could effectively reduce the porosity and micropore size in the ITZ of CPCGA, and the porosity of the ITZ in CPCGA added with 7.50% SF decreased by 44.22, 46.16, and 24.46% at distances from the aggregate surface of 10, 50, and 100 µm, respectively, compared with CPCGA without SF. Further research showed that Ca(OH)2 (CH) generated in the cement hydration reaction reacted with a large amount of active SiO2 in SF to restrain the formation of coarse CH in the ITZ of CPCGA, and the calcium silicate hydrate (C-S-H) gel generated filled the ITZ micropores to reduce the ITZ porosity further. Moreover, the reaction of SF and CH helped to promote the hydration reaction of cement to proceed thoroughly in CPCGA, thus improving CPCGA performance.

New aspects of the epigenetic regulation of EMT related to pulmonary fibrosis.

Pulmonary fibrosis is a chronic and progressive fibrotic disease that results in impaired gas exchange, ventilation, and eventual death. The pro-fibrotic environment is instigated by various factors, leading to the transformation of epithelial cells into myofibroblasts and/or fibroblasts that trigger fibrosis. Epithelial mesenchymal transition (EMT) is a biological process that plays a critical role in the pathogenesis of pulmonary fibrosis. Epigenetic regulation of tissue-stromal crosstalk involving DNA methylation, histone modifications, non-coding RNA, and chromatin remodeling plays a key role in the control of EMT. The review investigates the epigenetic regulation of EMT and its significance in pulmonary fibrosis.

Epigenetic reader MeCP2 repressed WIF1 boosts lung fibroblast proliferation, migration and pulmonary fibrosis.

Epigenetic has been implicated in pulmonary fibrosis. However, there is limited information regarding the biological role of the epigenetic reader MeCP2 in pulmonary fibrosis. The aim of this study was to investigate the role of MeCP2 and its target WIF1 in pulmonary fibrosis. The pathological changes and collagen depositions was analyzed by H&E, Masson's Trichrome Staining and Sirius Red staining. MeCP2, WIF1, α-SMA, Wnt1, ß-catenin, and collagen I expression were analyzed by western blotting, RT-qPCR, immunohistochemistry, immunofluorescence, respectively. The effects of MeCP2 on pulmonary fibrosis involve epigenetic mechanisms, using cultured cells, animal models, and clinical samples. Herein, our results indicated that MeCP2 level was up-regulated, while WIF1 was decreased in Bleomycin (BLM)-induced mice pulmonary fibrosis tissues, patients pulmonary fibrosis tissues and TGF-ß1-induced lung fibroblast. Knockdown of MeCP2 by siRNA can rescue WIF1 downregulation in TGF-ß1-induced lung fibroblast, inhibited lung fibroblast activation. The DNA methylation inhibitor 5-azadC-treated lung fibroblasts have increased WIF1 expression with reduced MeCP2 association. In addition, we found that reduced expression of WIF1 caused by TGF-ß1 is associated with the promoter methylation status of WIF1. Moreover, in vivo studies revealed that knockdown of MeCP2 mice exhibited significantly ameliorated pulmonary fibrosis, decreased interstitial collagen deposition, and increased WIF1 expression. Taken together, our study showed that epigenetic reader MeCP2 repressed WIF1 facilitates lung fibroblast proliferation, migration and pulmonary fibrosis.

Z-score of some pulsed-wave Doppler indices of right pulmonary artery segments of normal fetuses in the second and third trimestries.

OBJECTIVE: To establish the Z-score equation of right pulmonary artery (RPA) segments for some valuable pulse-wave Doppler parameters (PWD) and estimate their reference ranges in normal fetuses. METHODS: Two hundred and seventy-three normal singleton fetuses at 18-38 weeks were enrolled in this fetal echocardiography of a prospective cross-sectional study. The proximal, middle, and distal segments of RPA of pulsed-wave Doppler parameters, such as peak systolic velocity (PSV) and pulsation index (PI) were obtained by using fetal Doppler echocardiography. The mean and standard deviation (SD) of each parameter and gestational age (GA) were analyzed by regression, and the optimal model of Z-score was established. RESULTS: There was a significant correlation between fetal pulmonary artery Doppler parameters and gestational age, during the whole pregnancy, PI showed a downward trend with the progress of gestational week, while PSV showed an upward trend. Whether it was the original data or the data converted for the normal distribution of Z-score, the model that best described the mean value of parameters was quadratic regression. The SDs for PSV of the middle segment was a linear equation, others were constants. From proximal to distal of RPA, PSV showed a decreasing trend while PI showed an increasing trend. CONCLUSION: Z-score models and reference values for some PWD parameters of three segments of RPA were proposed against GA, which may quantitatively assess the flow dynamics of fetal RPA and quantitatively assess fetal lung circulation development and hemodynamic changes.

Ultrasonic Cavitation Ameliorates Antitumor Efficacy of Residual Cancer After Incomplete Radiofrequency Ablation in Rabbit VX2 Liver Tumor Model.

Residual cancer after incomplete ablation remains a major problem for radiofrequency ablation (RFA). We aimed to investigate the synergetic treatment efficacy of RFA combined with ultrasonic cavitation for liver tumor. Sixty rabbits with VX2 liver tumor were randomly divided into three groups. Group A was control group without any treatment. Combined ultrasonic cavitation with RFA was performed for group B1. Group B2 underwent RFA alone. The histopathological results were compared at the 5th, 11th, and 18th day of experiment, and the survival time and metastasis were assessed. The tumor volume growth rate, percentage of necrosis area, microvessel density, and apoptosis index showed significant differences among these groups at the 5th day, 11th day, and 18th day of experiment (P < .05). In contrast, the difference of metastatic score was not significant at the 5th and 11th day (P > .05). At the 18th day, the metastatic score of group A was significant higher than that of group B1 (P < .05), whereas the differences between group A and group B2, or group B1 and group B2 were not significant (P > .05). The median/range interquartile of survival time in groups A, B1, and B2 were 25/8 days, 50/19 days, and 48/20 days, respectively, and there was significant difference between groups A and B1 or B2 (P < .05). The difference between groups B1 and B2 was not significant (P > .05). Ultrasonic cavitation after incomplete RFA for liver tumor improved the antitumor effect, which could be considered as a potentially useful combined therapeutic strategy for liver malignancy.

Double contrast-enhanced two-dimensional and three-dimensional ultrasonography for evaluation of gastric lesions.

AIM: To investigate the value of two-dimensional (2D) and three-dimensional (3D) double contrast-enhanced ultrasonography (DCUS) imaging for evaluation of gastric lesions. METHODS: 2D and 3D DCUS imaging with both oral and intravenous administrations of contrast agents was used to assess gastroscopiclly-confirmed gastric lesions in 46 patients with benign and malignant diseases. Initially, liquid-based ultrasound contrast agent (Xinzhang®) was given orally at dose of 500-600 mL for conventional ultrasound examination of the gastric lesions, and then a microbubble-based contrast agent (SonoVue) was injected intravenously at dose of 1.2-2.4 mL in bolus fashion to assess the perfusion pattern of the lesions using contrast imaging modes. The parameters derived from time-intensity curves including the arrival time (AT), time to peak (TTP), peak intensity (PI) and enhanced intensity (EI) were measured on the 2D DCUS imaging. 3D DCUS of the lesions was acquired to demonstrate the value of this imaging mode. RESULTS: There were 22 cases with benign lesions including chronic gastritis (n = 5), gastric ulcer (n = 9), gastric polyps (n = 3), gastric stromal tumors (n = 5), and 24 cases with malignant lesions including gastric cancer (n = 20), gastric cardia carcinoma (n = 3) and post-operative recurrent gastric cancer (n = 1) in the study. The oral contrast-enhanced ultrasonography (CEUS) imaging of the stomach clearly demonstrated the anatomy of the stomach and morphologic features of gastric lesions. With optimal scanning window and imaging display under oral CEUS, intravenous CEUS clearly showed the perfusion of gastric lesions with various characteristic manifestations. Both 2D and 3D DCUS images clearly demonstrated normal gastric wall as a three-layer structure, from the inside out, hyperechoic mucosa, hypoechoic muscularis and hyperechoic serosa, respectively. There were statistical significant differences of AT (8.68 ± 2.06 vs 10.43 ± 2.75, P = 0.017), PI (34.64 ± 6.63 vs 29.58 ± 8.22, P = 0.023) and EI (29.72 ± 6.69 vs 22.66 ± 7.01, P = 0.001) between malignant lesions and normal gastric wall. However, no differences of AT, PI and EI between benign lesions and normal gastric wall tissue were found. 3D DCUS could intuitively display morphological features and vascularities of the lesions with multiplanar and volume views. 3D DCUS imaging provided comprehensive information complementary to 2D imaging. The crater or wellhead appearances and feeding vessels as well as distorted nourishing vasculature of gastric carcinoma were better seen with 3D imaging than 2D imaging. CONCLUSION: DCUS imaging can simultaneously display the anatomic and perfusion features of gastric lesions. 3D DCUS can provide additional information to 2D DCUS for evaluation of gastric lesions.