Potential regulatory mechanism and clinical significance of synaptotagmin binding cytoplasmic RNA interacting protein in colorectal cancer

BACKGROUND Colorectal cancer(CRC)causes many deaths worldwide.Synaptotagmin binding cytoplasmic RNA interacting protein(SYNCRIP)is an RNA-binding protein that plays an important role in multiple cancers by epigenetically targeting some genes.Our study will examine the expression,potential effect,biological function and clinical value of SYNCRIP in CRC.AIM To examine the expression,potential effect,biological function and clinical value METHODS The expression of SYNCRIP was examined by immunohistochemistry arrays and high-throughput data.The effect of SYNCRIP gene in CRC cell growth was evaluated by CRISPR-Cas9 technology.The target genes of SYNCRIP were calculated using various algorithms,and the molecular mechanism of SYNCRIP in CRC was explored by mutation analysis and pathway analysis.The clinical value of SYNCRIP in prognosis and radiotherapy was revealed via evidence-based medicine methods.RESULTS The protein and mRNA levels of SYNCRIP were both highly expressed in CRC samples compared to nontumorous tissue based on 330 immunohistochemistry arrays and 3640 CRC samples.Cells grew more slowly in eleven CRC cell lines after knocking out the SYNCRIP gene.SYNCRIP could epigenetically target genes to promote the occurrence and development of CRC by boosting the cell cycle and affecting the tumor microenvironment.In addition,CRC patients with high SYNCRIP expression are more sensitive to radiotherapy.CONCLUSION SYNCRIP is upregulated in CRC,and highly expressed SYNCRIP can accelerate CRC cell division by exerting its epigenetic regulatory effects.In addition,SYNCRIP is expected to become a potential biomarker to predict the effect of radiotherapy.

Changes of nitric oxide and endothelin, thromboxane A2 and prostaglandin in cirrhotic patients undergoing liver transplantation

AIM： To investigate the perioperative changes of nitric oxide （NO） and endothelin （ET）, thromboxane A2 （TXA2） and prostaglandin （PGI2） during liver transplantation in end-stage liver disease patients. METHODS： Twenty-seven patients with end-stage cirrhosis undergoing liver transplantation were enrolled in this prospective study. Blood samples were obtained from superior vena at five different surgical stages. Plasma concentrations of nitrate and nitrite were determined to reflect plasma NO levels. Plasma levels of ET-1, 6-keto-PGF1 alpha and thromboxane B2 （TXB2）, the latter two being stable metabolites of PGI2 and TXA2 respectively, were measured.RESULTS： The NO level decreased significantly after vascular cross-clamping and increased significantly at 30 rain after reperfusion. While the ET levels at 30 rain after clamping and after reperfusion were significantly elevated. The ratio of NO/ET decreased significantly at 30 rain after vascular cross-clamping and at the end of surgery. The PGI2 level and the TXA2 during liver transplantation were significantly higher than the baseline level, but the ratio of TXA2/PGI2 decreased significantly at 30 rain after clamping. CONCLUSION： NO/ET and TXA2/PGI2 change during liver transplantation. Although the precise mechanism remains unknown, they may play a role in the pathobiology of a variety of liver transplant-relevant processes.

Protective effect of Astragalus membranaceus on intestinal mucosa reperfusion injury after hemorrhagic shock in rats

AIM： To study the protective effect of Astragalus rnernbranaceus on intestinal mucosa reperfusion injury and its mechanism after hemorrhagic shock in rats. METHODS： A total of 32 SD rats were randomly divided into four groups （n = 8, each group）： normal group, model group, low dosage group （treated with 10 g/kg Astragalus membranaceus） and high dosage group （treated with 20 g/kg Astragalus membranaceus）. The model of hemorrhagic shock for 60 min and reperfusion for 90 min was established. Therapeutic solution （3 mL） was administrated before reperfusion. At the end of the study, the observed intestinal pathology was analyzed. The blood concentrations of lactic acid （LD）, nitric oxide （NO）, endothelin-1 （ET-1）, malondialdehyde （MDA） and the activity of superoxide dismutase （SOD）, glutathione peroxidase （GSH-PX） in intestinal mucosa were determined. RESULTS： The intestinal mucosa pathology showed severe damage in model group and low dosage group, slight damage in high dosage group and no obvious damage in normal group. The Chiu＇s score in low dose group and high dose group was significantly lower than that in model group. The content of MDA in model group was higher than that in low and high dose groups, while that in high dose group was almost the same as in normal group. The activity of SOD and GSH-PX was the lowest in model group and significantly higher in high dose group than in normal and low dose groups. The concentrations of LD and ET-1 in model group were the highest. The concentrations of NO in model group and low dose group were significantly lower than those in high dose group and normal group. CONCLUSION： High dose Astraga/us membranaeus has much better protective effect on hemorrhagic shockreperfusion injury of intestinal mucosa than low dose Astragalus membranaceus. The mechanism may be that Astragalus membranaceus can improve antioxidative effect and regulate NO/ET level during hemorrhagic reperfusion.

白藜芦醇及其衍生物在TNF-α诱导的人脐静脉内皮细胞中的抗炎作用

二苯乙烯类化合物，自1940年首次从毛藜芦根中分离出白藜芦醇以来就对此进行了广泛研究。这类化合物存在于许多植物中并具有广泛的生理活性，主要有抗氧化、抗肿瘤、抗淤血综合征（如脑炎、动脉粥样硬化、慢性炎症）等。白藜芦醇（trans-3，5，4’-trihydroxystiibene），是从中药虎杖中提取出来的一种二苯乙烯类化合物，同时也是一种非常重要的植物内毒素，在近年来的实验研究中已充分证明其具有很多有益的药理作用，如抗癌、心血管保护、神经保护、抗衰老和抗炎等等。大量研究证实其在抗动脉粥样硬化中起着非常重要的作用。近年来随着白藜芦醇的类似物的不断出现，研究者们发现其中一些二苯乙烯类化合物同样具有许多与白藜芦醇相似的药理活性且某些化合物的活性、选择性及稳定性均要强于白藜芦醇，故成为目前研究的热点。为了探讨白藜芦醇类似物中甲基化白藜芦醇和自藜芦醇苷的抗炎效应并阐明其作用机制，同时与白藜芦醇进行比较，我们首先用细胞黏附实验测定其是否具有抗细胞黏附的能力，然后对其相关的黏附分子的表达及NF—κB进行考察。

Initiation and evolution of coarse-grained deposits in the Late Quaternary Lake Chenghai source-to-sink system:From subaqueous colluvial apron(subaqueous fans)to Gilbert-type delta

Investigating the formation and evolution of coarse-grained deposits in modern lakes and the relevant controlling conditions is indispensable to the prediction of reservoir sandbodies, disaster prediction,and limnological research. The source-to-sink system of coarse-grained deposits in Lake Chenghai, a deep,scarped Late Quaternary lake, was investigated in this study based on 62 outcrops, Advanced Land Observing Satellite(ALOS) digital elevation model(DEM) data, and regional geological survey data. The findings include the following:(1) the source areas of coarse-grained deposits in Lake Chenghai were lithologically classified into carbonate source areas, basaltic source areas and siliciclastic source areas, and were geomorphically categorized as scarp type or confluence type. Subaqueous colluvial aprons have formed downstream of the carbonate source areas and scarp-type basaltic source areas, while Gilbert-type deltas have formed downstream of siliciclastic source areas and confluence-type basaltic source areas.(2) The formation and evolution of coarse-grained deposits are controlled by the sediment flux that evolves in synchrony with the geomorphic evolution of the source areas and the sink regimes. Scarps represent the initial landform of the source areas.Source material rolls off or slides down scarps or forms small-scale debris flows before entering the lake. The source material initially formed subaqueous colluvial apron(synonymous with subaqueous fans) where sufficient space was present to accommodate sediments and the basement angle exceeded than the natural angle of repose. As weathering and denudation have progressed, the initial scarps have transformed into confluencetype slopes, and the source material has formed medium-and large-scale debris flows that have entered the lake, resulting in an increase in sediment flux. Consequently, the subaqueous colluvial aprons have rapidly grown and developed subaerial deposits, which have evolved into larger-scale Gilbert-type deltas that overlie the initial aprons.(3) The morphology and distribution of coarse-grained deposits vary in response to differences in quantity and composition of materials from different source areas, which resulting from different rates of weathering and denudation and different sediment input regimes. Firstly, the size and surface slope angle of a subaqueous colluvial apron from a carbonate source are smaller than those of a subaqueous colluvial apron of basaltic origin. Secondly, a Gilbert-type delta from a basaltic source features a greater slope angle and a thicker topset than does a Gilbert-type delta of siliciclastic origin, and the latter exhibits a longer foreset and a thicker bottomset than in the former. Thirdly, the sizes of subaqueous colluvial aprons are not strongly correlated with the sizes of the source areas, while the sizes of Gilbert-type deltas are.