Activity Characteristics and Tyrosinase Inhibition Mechanism of a Silk Fibroin Oligopeptide and Cordyceps Polysaccharide Composite

International Journal of Peptide Research and Therapeutics - Silk fibroin is an excellent raw material for medical products as it shows remarkable biocompatibility, water-based processing, and...     

Formononetin,J1 and J2 have different effects on endothelial cells via EWSAT1‐TRAF6 and its downstream pathway

Formononetin is a natural isoflavone compound found mainly in Chinese herbal medicines such as astragalus and red clover. It is considered to be a typical phytooestrogen. In our previous experiments, it was found that formononetin has a two‐way regulatory effect on endothelial cells (ECs): low concentrations promote the proliferation of ECs and high concentrations have an inhibitory effect. To find a specific mechanism of action and provide a better clinical effect, we performed a structural transformation of formononetin and selected better medicinal properties for formononetin modifier J1 and J2 from a variety of modified constructs. The MTT assay measured the effects of drugs on human umbilical vein endothelial cell (HUVEC) activity. Scratch and transwell experiments validated the effects of the drugs on HUVEC migration and invasion. An in vivo assessment effect of the drugs on ovariectomized rats. Long‐chain non‐coding RNA for EWSAT1, which is abnormally highly expressed in HUVEC, was screened by gene chip, and the effect of the drug on its expression was detected by PCR after the drug was applied. The downstream factors and their pathways were analysed, and the changes in the protein levels after drug treatment were evaluated by Western blot. In conclusion, the mechanism of action of formononetin, J1 and J2 on ECs may be through EWSAT1‐TRAF6 and its downstream pathways.     

Identification of novel susceptibility loci for non‐syndromic cleft lip with or without cleft palate

Although several genome‐wide association studies (GWAS) of non‐syndromic cleft lip with or without cleft palate (NSCL/P) have been reported, more novel association signals are remained to be exploited. Here, we performed an in‐depth analysis of our previously published Chinese GWAS cohort study with replication in an extra dbGaP case‐parent trios and another in‐house Nanjing cohort, and finally identified five novel significant association signals (rs11119445: 3’ of SERTAD4, P = 6.44 × 10⁻¹⁴; rs227227 and rs12561877: intron of SYT14, P = 5.02 × 10⁻¹³ and 2.80 × 10⁻¹¹, respectively; rs643118: intron of TRAF3IP3, P = 4.45 × 10⁻⁶; rs2095293: intron of NR6A1, P = 2.98 × 10⁻⁵). The mean (standard deviation) of the weighted genetic risk score (wGRS) from these SNPs was 1.83 (0.65) for NSCL/P cases and 1.58 (0.68) for controls, respectively (P = 2.67 × 10⁻¹⁶). Rs643118 was identified as a shared susceptible factor of NSCL/P among Asians and Europeans, while rs227227 may contribute to the risk of NSCL/P as well as NSCPO. In addition, sertad4 knockdown zebrafish models resulted in down‐regulation of sox2 and caused oedema around the heart and mandibular deficiency, compared with control embryos. Taken together, this study has improved our understanding of the genetic susceptibility to NSCL/P and provided further clues to its aetiology in the Chinese population.     

Reduction of SOST gene promotes bone formation through the Wnt/β-catenin signalling pathway and compensates particle-induced osteolysis

The increase in bone resorption and/or the inhibition of bone regeneration caused by wear particles are the main causes of periprosthetic osteolysis. The SOST gene and Sclerostin, a protein synthesized by the SOST gene, are the characteristic marker of osteocytes and regulate bone formation and resorption. We aimed to verify whether the SOST gene was involved in osteolysis induced by titanium (Ti) particles and to investigate the effects of SOST reduction on osteolysis. The results showed osteolysis on the skull surface with an increase of sclerostin levels after treated with Ti particles. Similarly, sclerostin expression in MLO-Y4 osteocytes increased when treated with Ti particles in vitro. After reduction of SOST, local bone mineral density and bone volume increased, while number of lytic pores on the skull surface decreased and the erodibility of the skull surface was compensated. Histological analyses revealed that SOST reduction increased significantly alkaline phosphatase- (ALP) and osterix-positive expression on the skull surface which promoted bone formation. ALP activity and mineralization of MC3T3-E1 cells also increased in vitro when SOST was silenced, even if treated with Ti particles. In addition, Ti particles decreased β-catenin expression with an increase in sclerostin levels, in vivo and in vitro. Inversely, reduction of SOST expression increased β-catenin expression. In summary, our results suggested that reduction of SOST gene can activate the Wnt/β-catenin signalling pathway, promoting bone formation and compensated for bone loss induced by Ti particles. Thus, this study provided new perspectives in understanding the mechanisms of periprosthetic osteolysis.     

Methylation-mediated miR-214 regulates proliferation and drug sensitivity of renal cell carcinoma cells through targeting LIVIN

LIVIN, a member of the inhibitor of apoptosis proteins (IAPs), is reported playing important roles in the development and progression of multiple human cancers. However, its underlined mechanisms in human renal cell carcinoma (RCC) are still needed to be clarified. In the present study, we reported that inhibition of miR-214 promoted the expression of LIVIN, then facilitated RCC cells growth and reduced the sensitivity of RCC cells to chemotherapeutic drugs. In constant, overexpression of miR-214 had contradictory effects. Further investigation showed that miR-214 was down-regulated in RCC because of abnormal methylation. In addition, DNA methyltransferase DNMT1, miR-214 and LIVIN are directly correlated in RCC patients. In conclusion, these results suggest that abnormal miR-214 methylation negatively regulates LIVIN, which may promote RCC cells growth and reduced the sensitivity of RCC cells to chemotherapeutic drugs.     

海南岛海岸带木麻黄和厚藤叶片碳、氮、磷含量及其化学计量特征

海岸带植物叶片的化学计量学特征及其影响因素可以为改善海岸带的生态环境提供理论依据。选取海南岛沿岸12个市（县）海岸带木麻黄防护林的木麻黄和周边沙滩上的藤本植物厚藤为研究对象,通过测定木麻黄与厚藤叶片中的碳（C）、氮（N）和磷（P）含量,分析两种植物叶片C、N和P的化学计量学特征及其差异,探究不同环境因子对两种植物叶片C、N、P含量、C：N、C：P和N：P的影响,以期寻找影响海岸带植被生长的主要限制因素。结果表明：海南岛木麻黄叶片C、N和P的平均含量分别是399.06±20.29、12.56±1.04、1.04±0.35 g·kg^-1,C：N、C：P和N：P分别为32.04±2.82、420.65±121.27和12.92±3.21;厚藤叶片C、N和P的平均含量分别是364.31±30.20、12.84±1.96和2.06±0.64 g·kg^-1,C：N、C：P和N：P分别为29.13±4.95、185.85±63.14和6.47±2.12。相关性分析结果表明：木麻黄叶片的N含量与年平均气温和年平均降水量呈显著正相关关系,P含量与年平均降水量呈极显著正相关关系,C：P和N：P与年平均降水量呈显著负相关关系;厚藤叶片C含量与年平均气温呈显著正相关,C：N与年平均降水量呈显著负相关。木麻黄叶片的N含量与10~20 cm土层的SOC呈显著负相关关系,C：N与10~20 cm土层的SOC呈显著正相关,C：P与0~10 cm土层的C：N呈显著正相关关系;厚藤叶片的C含量与10~20 cm土层的SOC呈显著负相关关系,P含量与0~10 cm土层的TN含量,N：P和10~20 cm的SOC含量呈正相关关系,C：N与0~10 cm土层的C：N呈显著正相关关系,C：P与0~10 cm的TN含量呈显著负相关关系而与0~10 cm土层的C：N呈极显著正相关关系,N：P与0~10 cm土层的TN含量呈显著负相关关系。研究结果表明海南岛海岸带植被叶片的碳氮含量较低,N可能是影响该区域植物生长的主要因子,同时,植被生长受到年平均气温、年平均降水量的共同影响,受土壤养分含量影响低,环境因子对不同类型的植物的影响并不相同。     

阻断趋化因子CXCL10对脑缺血再灌注损伤及神经炎症的影响

目的:探讨趋化因子CXCL10在脑缺血再灌注损伤中对神经炎症的影响。方法:(1)线栓法建立脑缺血再灌注损伤大鼠模型,TTC染色检测梗死面积,Western blot检测CXCL10的表达;(2)建立小鼠神经瘤母细胞N2a氧糖剥夺/复氧(oxygen-glucose deprivation/reoxygenation,OGD/R)模型,通过CXCR3拮抗剂-NBI 74330阻断趋化因子CXCL10表达,Western blot检测CXCL10和CXCR3蛋白的表达;Real-time PCR检测CXCL10、CXCR3以及神经炎症因子TNF-α、IL-1β、IL-2 m RNA的表达。结果:(1)脑缺血再灌注(cerebral ischemia reperfusion injury,CIRI)模型大鼠脑梗死侧CXCR10的表达量显著高于其对侧和假手术组(P<0.05);(2)阻断CXCL10使得小鼠神经瘤母细胞N2a中CXCL10、CXCR3以及炎症因子TNF-α、IL-1β、IL-2的表达量均显著降低(P<0.05);(3)阻断CXCL10使得小鼠神经瘤母细胞细胞凋亡率降低(P<0.05)。结论:抑制CXCL10降低了氧糖剥夺模型细胞炎症因子的表达,表明阻断CXCL10可能通过减轻神经炎症在脑缺血再灌注损伤中发挥保护作用。     

甲状腺结节良恶性的彩色多普勒超声特征及其诊断价值分析

目的:研究甲状腺结节良恶性的彩色多普勒超声特征及其诊断价值。方法:选取从2016年3月~2019年2月于我院接受手术治疗的甲状腺疾病患者300例作为研究对象,均予以彩超检查,比较甲状腺良恶性结节的超声特征(主要包括直径、钙化情况、边界、回声、血流状况)。以病理活检结果为金标准,分析彩超诊断甲状腺结节良恶性的敏感性、特异性以及准确度。对比甲状腺良恶性结节的血流分型情况以及各项血流动力学参数。结果:恶性结节超声特征直径≥2 cm、有钙化、边界模糊、无回声/低回声、血流丰富人数占比均高于良性结节(均P<0.05)。以手术病理组织活检结果作为金标准,彩色多普勒超声诊断甲状腺结节的敏感性、特异性以及准确度分别为97.73%、86.11%、96.33%。甲状腺良性结节血流分型为Ⅰ型、Ⅱ型人数占比高于恶性结节,而Ⅲ型、Ⅳ型人数占比低于恶性结节(均P<0.05)。甲状腺良性结节的收缩期峰值血流速度(PSV)、阻力指数(RI)均低于恶性结节,而舒张末期血流速度(EDV)高于恶性结节(均P<0.05)。结论:彩色多普勒超声对甲状腺结节良恶性的鉴别价值较高,且具有较高的敏感性、特异性以及准确度,可为甲状腺良恶性结节的早期诊断、临床治疗提供重要的参考依据。     

乳腺癌患者改良根治术后生活质量调查及复发转移的影响因素分析

目的:调查乳腺癌患者改良根治术后生活质量,并对其复发转移的影响因素进行分析。方法:选取2012年6月～2014年6月期间于我院行改良根治术的乳腺癌患者197例,于术后3个月、术后6个月、术后12个月采用乳腺癌患者生命质量测定量表(FACT-B)评价患者生活质量。采用我院自制的调查问卷统计患者基本治疗情况,分析乳腺癌改良根治术后复发转移的影响因素。结果:本研究中,共发放197份问卷调查,回收195份,回收率为98.98%(195/197)。其中195例患者中有73例发生复发转移(复发转移组),122例未发生复发转移(未复发转移组)。195例乳腺癌患者术后3个月、术后6个月、术后12个月社会/家庭状况、生理状况、功能状况、情感状况、附加关注条目、总体生活质量等项目评分呈递增趋势(P0.05)。多因素Logistic回归分析显示,病理类型为浸润性非特殊性癌、肿瘤大小≥2 cm、临床分期为Ⅲ期、激素受体为ER及PR均阴性均是乳腺癌改良根治术后复发转移的独立危险因素(P0.05),而采用放化疗、联合化疗方案、内分泌治疗以及p53蛋白阳性表达是乳腺癌改良根治术后复发转移的独立保护因素(P0.05)。结论:乳腺癌患者行改良根治术后生活质量呈动态变化,其术后复发转移影响因素为病理类型、临床分期、肿瘤大小、激素受体、化疗方案、p53蛋白、内分泌治疗及放化疗。     

沐舒坦联合布地奈德雾化治疗新生儿胎粪吸入综合征的临床应用分析

目的:探讨沐舒坦联合布地奈德雾化治疗新生儿胎粪吸入综合征的临床效果及安全性。方法:选择2017年1月～2018年2月我院新生儿科收治的76例新生儿胎粪吸入综合征患儿,按照随机数字表法将其分成两组,每组38例。对照组患者采用布地奈德雾化治疗,观察组在对照组的治疗基础上加用沐舒坦治疗,分析和比较两组的治疗效果,患儿治疗前后动脉血气分析指标变化以及预后情况。结果:治疗后,观察组临床总有效率明显高于对照组,观察组呼吸困难缓解时间、肺部湿罗音消失时间、发绀消失时间、血氧饱和度恢复时间均显著较对照组短(P0.05)。两组患儿治疗后PaCO_2、FIO_2、OI均较治疗前降低,PaO_2均较治疗前上升,其中观察组PaCO_2、FIO_2、OI明显低于对照组,PaO_2高于对照组,上述差异均具有统计学意义(P0.05)。观察组总并发症发生率显著低于对照组(P0.05),患儿治愈率显著高于对照组(P0.05),两组死亡率比较差异无统计学意义(P0.05)。结论:与布地奈德雾化治疗相比,沐舒坦联合布地奈德雾化治疗新生儿胎粪吸入综合征患儿可以更有效缩短临床症状改善时间,改善患儿肺功能及预后,且安全性更高。