Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis

BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.

关于ICΦ-子群和p-超可解超中心的结果

设H是群G的子群。如果H∩[H,G]≤Φ(H),则称H是G的ICΦ-子群,这里ΦH是H的Frattini子群。围绕此概念,首先,对于奇素数,基于Kaspczyk的p-幂零结果,分析了给定阶子群的ICΦ性质对p-超可解超中心结构的影响;其次,对于5次对称群S_(5),确定了ICΦ-子群的所有类型。这些结果为子群的ICΦ-性质的研究提供了具体的例子,也为丰富该课题的研究做出了积极的尝试。

The new K_V3.4 inhibitor BDS-I[1–8] as a potential pharmacological opportunity in Alzheimer’s disease therapy

Alzheimer's disease(AD)is the most common neurodegenerative disorder and the first cause of dementia in the elderly,with no treatment able to prevent or to block disease progression.AD is characterized by memory impairment and cognitive dysfunction,followed in the late phases of the disease by severe neurodegeneration and neuronal death.The amyloid-β(Aβ)peptide,generated upon the processing of the amyloid precursor protein,is considered the main initiator of AD pathology.Indeed,Aβpeptides,which aggregate and accumulate to form extracellular plaques and intraneuronal deposits.

IEC 62368-1标准关于集成电路(IC)限流器的要求及应用

本文介绍了IC限流器用在PS3与PS2/PS1功率源隔离中起限制电流的要求及其应用。首先,比较不同IEC 62368-1版本对IC限流器可靠性试验的差异,总结IC限流器在最新标准中的应用。阐述满足标准所要求可靠性试验程序的IC限流器可以豁免单一故障测试,默认为受限制电源并划分到PS2功率源,降低防火防护要求,为测试领域提供技术参考。

Effect of protease inhibitor from Agaricus bisporus on glucose uptake and oxidative stress in 3T3-L1 adipocytes

Objective:To explore the effect of the protease inhibitor from Agaricus bisporus(J.E.Lange)Imbach(AbPI)on glucose uptake and oxidative stress in 3 T3-L1 adipocytes.Methods:Adipocytes were differentiated and stained with OilRed-O staining to confirm adipogenesis.The toxic/protective effect of AbPI on the adipocytes was determined by MTT assay,intracellular reactive oxygen species generation through flow cytometry,and morphologically through confocal microscopy using propidium iodide,4,6-diamino-2-phenylindol dihydrochloride,and 2’,7’-dichlorofluorescein diacetate dyes.The uptake of fluorescent glucose analog,2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose by adipocytes was also studied through confocal microscopy.Results:MTT assay showed that the cell survival rate was(28.00±3.00)%,(92.33±2.60)%,and(71.34±2.10)%in the presence of 2 mM H2O2,AbPI alone,and AbPI and H2O2 both,respectively,in comparison to the control.Oil-Red-O staining indicated that Ab PI enhanced adipogenesis.AbPI stimulated the glucose uptake by adipocytes similar to the drug rosiglitazone,and showed insulinsensitizing effect in the presence of insulin,but failed to stimulate the uptake in the absence of insulin.Intracellular reactive oxygen species generation was reduced in differentiating adipocytes upon Ab PI treatment.Confocal microscopy showed that the damaged cell population rose to 3.50%,117.84%,and 261.50%in the presence of Ab PI alone,AbPI with H2O2,and H2O2 alone,respectively.Conclusions:The protease inhibitor enhances glucose uptake by adipocytes and exhibits a cytoprotective effect on them.

正规IC^(*)-密码超富足半群

给出了正规IC* 密码超富足半群的若干等价刻划 ,并通过完全 J*

左炔诺孕酮联合miRNA-21-5p抑制剂对子宫内膜癌细胞增殖、转移的作用及机制

目的利用左炔诺孕酮(LNG)和miRNA-21-5p抑制剂(inhibitor)联合靶向多发性肿瘤抑制基因磷酸酶基因(PTEN)评估对子宫内膜癌细胞增殖、转移的作用。方法将实验用人子宫内膜癌细胞分为Control组、LNG处理组、LNG处理+miR-21 NC组和LNG处理+miR-21 inhibitor组;免疫组化检测LNG治疗前后子宫内膜癌患者内膜组织中PTEN表达;CCK8和流式细胞仪筛选LNG最佳作用浓度和时间;实时荧光定量(qRT)-聚合酶链反应(PCR)法检测miR-21-5p inhibitor处理后miR-21-5p mRNA表达水平;LNG联合miR-21-5p inhibitor处理后CCK8检测增殖,流式检测凋亡,Transwell检测侵袭,划线检测迁移,Western印迹检测细胞中PTEN、磷脂酰肌醇3-激酶(PI3K)、p-PI3K、丝氨酸/苏氨酸激酶(AKT)和p-AKT蛋白表达水平。结果与治疗前比,LNG治疗后子宫内膜组织中PTEN表达水平显著升高(P=0.000)。筛选出LNG最佳浓度为100μmol/L,时间为24 h。miR-21-5p inhibitor处理后miR-21-5p表达显著降低(P<0.05)。与Control组相比,LNG组处理后细胞凋亡及PTEN表达显著升高,细胞迁移、侵袭能力及细胞活力显著下降(P<0.05),miR-21-5p、p-AKT/AKT、p-PI3K/PI3K表达也明显下降(P<0.05);与LNG组相比,LNG+miR-21-5p inhibitor组细胞活力、细胞凋亡、迁移、侵袭能力、miR-21-5p表达、p-AKT/AKT、p-PI3K/PI3K明显下降,PTEN表达则明显升高(P<0.05)。结论LNG联合miR-21-5p inhibitor具有协同抑制子宫内膜癌细胞增殖、转移的作用,此过程与靶向上调PTEN并抑制PI3K/AKT通路活化相关。

Role of non-steroidal anti-inflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease

The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of nonalcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.

ICS法压力-流率测定在诊治BPH中的应用

目的 :介绍采用国际尿控协会 ( ICS)推荐的压力 -流率检测方法诊断前列腺增生症 ( BPH)的临床体会。方法 :45例患者接受了使用国产的 Nidoc- 970尿动力学分析仪所进行的压力 -流率检测和 B超检查 ,并采用 ICS推荐的标准方法分类。结果 :41例 TURP证实 ,在梗阻组中诊断完全符合 ,在非梗阻组和可疑组中有假阴性( 11.1% )存在。结论 :该方法简单、重复性好 ,虽然反映尿道阻力尚不准确 ,但仍适于对

A novel thioredoxin reductase inhibitor inhibits cell growth and induces apoptosis in HL-60 and K562 cells

Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone)ethane (BBSKE),a novel TrxR inhibitor,were investigated on human leu-kemia cell lines HL-60 and K562. BBSKE treatment induced cell growth inhibition and apoptosis in both cell lines. Apoptosis induced by BBSKE is through Bcl-2/Bax and caspase-3 pathways. Ehrlich's ascites carcinoma-bearing mice were used to inves-tigate the anti-tumor effect of BBSKE in vivo. Tumor-bearing mice treated with BBSKE showed an increase of life span with a comparable effect to cyclophosphamide (CTX). These results suggest a potential usage of BBSKE as a therapeutic agent against non-solid tumors.

Synthesis and Crystal Structure of a Novel Ethyl 5-(4-(2-Phenylacetamido)phenyl)-1H-pyrazole-3-carboxylate as an Acrosin Inhibitor

The title compound （ethyl5-（4-（2-phenylacetamido）phenyl）-lH-pyrazole-3-carboxylate, C20H19N3O3） was synthesized by the reaction of Claisen condensation, cyclization, reduction and acylation. The structure was characterized by X-ray diffraction, MS, NMR and IR. It belongs to the monoclinic system, space group C2/c with a = 22.723（9）, b = 9.324（4）, c = 18.890（8） A, β = 114.259（6）°, V = 3649（3） A^3, Dc = 1.272 Mg·m^3, Z = 8, Mr = 349.38, p = 0.087 mm^-1, F（000） = 1472, the final R = 0.0615 and wR = 0.1643. The biological test shows that the title compound has a moderate acrosin inhibition activity.

A new angiotensin-converting enzyme inhibitor from Peperomia pellucida(L.) Kunth

Objective:To isolate,identify,and evaluate a new angiotensin-converting enzyme inhibitor from Peperomia pellucida(L.)Kunth herbs.Methods:A dried sample of Peperomia pellucida herb was successively macerated with n-hexane and ethyl acetate.The ethyl acetate extract solution was evaporated to obtain the crude extract.Vacuum liquid column chromatography and thin layer chromatography were performed to obtain two pure compounds.Then,both compounds were elucidated and identified using the spectroscopic method.Angiotensin-converting enzyme inhibitory activity studies of both compounds were determined using angiotensin-converting enzyme kit WST-1 with spectrophotometer microplate reader 96-well at 450 nm wavelength.Results:Two bioactive compounds were successfully isolated from Peperomia pellucida herb,including a new compound of 2,3,5-trimethoxy-9-(12,14,15-trimethoxybenzyl)-1 H-indene and pellucidin A.Both compounds demonstrated angiotensin-converting enzyme inhibitory activity,with IC50 values of 72 μM(27.95 μg/mL)and 1 1μM(4.4 μg/mL),respectively.Conclusions:In the present study,two active angiotensin-converting enzyme inhibitors were successfully isolated and purified from Peperomia pellucida which is used as an antihypertensive in traditional medicine,and support its use as an angiotensin-converting enzyme-inhibiting drug.

Cloning and characterization of human IC53-2,a novel CDK5 activator binding protein

We have identified IC53-2, a human homologue of the rat C53 gene from a human placenta cDNA library (GeneBank Accession No. AF217982). IC53-2 can bind to the CDK5 activator p35 by in vitro association assay. IC53-2 is mapped to human chromosome 17q21.31. The IC53-2 transcript is highly expressed in kidney, liver, skeletal muscle and placenta. It is abundantly expressed in SMMC-7721, C-33A, 3AO, A431and MCF-7 cancer cell lines by RT-PCR assay. Stable transfection of IC53-2 cDNA into the hepatocellularcarcinoma SMMC-7721 cell remarkably stimulates its growth in vitro. The above results indicate thatIC53-2 is a novel human gene, which may be involved in the regulation of cell proliferation.

应用HPLC-ICP-MS与离子色谱测定包装饮用水中溴酸盐的对比研究

建立了高效液相色谱-电感耦合等离子体质谱(HPLC-ICP-MS)测定包装饮用水中溴酸盐的方法。比较了HPLC-ICP-MS法与离子色谱法测定溴酸盐的检出限、准确度和精密度,并用这两种方法同时分析了20份实际水样品中溴酸盐的浓度。结果表明:HPLC-ICP-MS法在1.0~50.0μg/L范围内线性关系良好,相关系数R为0.999 9,检出限为0.048μg/L,回收率为96.8%~104.9%;离子色谱法在10.0~200.0μg/L范围内线性关系良好,相关系数R为0.999 2,检出限为2.0μg/L,回收率为85.6%~101.3%。两种方法测定结果的一致性较好,且准确度和精密度均符合方法学要求。但比较而言,HPLC-ICP-MS法的检出限更低、灵敏度更高、准确度和精密度更好、分析速度更快,更适用于包装饮用水中低浓度溴酸盐的常规检测。

Combined Effects of Capsaicin and HA14-1 in Inducing Apoptosis in Melanoma Cells

Abnormal regulation of apoptosis is an important aspect of tumour development. Capsaicin, an extract of red chilli peppers, has been shown to inhibit growth of melanoma and other malignant cell lines and HA14-1 is an organic compound that directly induces apoptosis by binding to Bcl-2 protein. The aim of this work was to investigate whether combination therapy with capsaicin and HA14-1 might hold any promise for the treatment of melanoma. Three melanoma cell lines of a range of aggressive potential, melanocytes and fibroblasts were examined, looking at the effects of both drugs singly and in combination on cell viability and induction of apoptosis. This comparative study showed that melanoma cells and melanocytes have a similar sensitivity to capsaicin while fibroblasts are more resistant to it. HA14-1, as expected, induced apoptosis in all cells at relatively low concentrations. A combination of the two agents produced the expected results of an additive effect for 2 (HBL and A375SM) out of 3 melanoma cell lines in inducing apoptosis, but encouragingly for the most metastatically aggressive cancer cell line (C8161), a combination of the two showed a synergistic induction of apoptosis.

LW6-110IC与PASS MO开关操作性能之比较

与LW6-110IC相比,PASS MO组合电器设备更符合现代化、科技化、智能化、快速化变电站的发展要求。

和-库高速公路IC卡管理及防范IC卡流失对策

随着和-库高速公路联网收费工作的不断推进，IC卡管理和IC卡流失的多样化与复杂性已成为和．库高速公路IC卡管理的难题。

A Prospective, Multicenter Study on Efficacy of Long-Acting Testosterone Undecanoate, If Desired in Combination with Vardenafil, in Late Onset Hypogonadal Patients with Erectile Dysfunction

Introduction: There is substantial evidence suggesting the additive effect on erectile function (ED) of testosterone and phosphodiesterase (PDE)-5 inhibitors. But the combination of long-acting testosterone undecanoate (TU), in combination with the PDE5-I vardenafil men with with late-onset hypogonadal patients (LOH) with (ED) has not yet been studied. Aims: To evaluate the effects of TU i.m., and if desired, the PDE5i vardenafil (PDE-5I) in LOH patients with ED measured with the International Index of Erectile Function (IIEF-5). Methods: A prospective study was performed following four administrations of TU in week 0, 6, 18, 30. If no improvement of ED assessed with IIEF-5 or the Global Assessment Questionnaire (GAQ) in week 12, the PDE5 inhibitor vardenafil was added. The final evaluation was in week 46. Main Outcome Measures: Aging Male Symptom (AMS) score, IIEF-5 score, and International Prostate Symptoms Score (IPSS) at each visit were summarized as mean with standard deviation;while GAQ was summarized using frequency and percentage. Scores at each visit were also categorized into different levels of symptom severity. Results: AMS score decreased significantly at week 12, 30 and 46. IIEF-5 score increased but a significant change was found only at week 30 and 46. The GAQ assessment indicated erection and sexual intercourse already improved at the first assessment continuing thereafter. IPSS score decreased from baseline at week 46. Levels of total, free and bioavailable testosterone had increased significantly from baseline at all visits. Hematocrit, hemoglobin and prostate specific antigen increased significantly from baseline. Adverse events were rare with pain at injection site found in one patient. The two events were non-serious in type, mild in their intensity and recovered. Conclusions: Therapy with TU and, and if desired, combined with the PDE5 inhibitor vardenafil improved sexual activity in LOH patients with ED.

Synthesis of 1-aryl-3-(3,4-dihydro-2H-chromen-5-yl) ureas as TNF-αinhibitors

A new series of compounds, 1-aryl-3-（3,4-dihydro-2H-chromen-5-yl） ureas, have been synthesized and their structures were confirmed by FAB-MS and IH NMR. The preliminary pharmacological screening showed that these compounds inhibited TNF-α production in lipopolysaccharide （LPS）-stimulated THP-1 cells.

The New Molecular Entity Evolocumab, One Kind of PCSK9 Inhibitor, Reduce Plasma Small Size LDL-Cholesterol Levels by Using a New Standardized Method of Measuring LDL Size

Aims: There has been no evidence on the effects of evolocumab, protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, on small size LDL. We observationally investigated the efficacy and side effects of evolocumab on the LDL subfraction particle diameter using PAGE system for lipoprotein analysis. Methods: We defined 30 patients with high-risk hyperlipidemia. As for analysis of LDL subfraction profile, we used polyacrylamide gel electrophoresis three methods: 1) 3% nondenatured poly-acrylamide gel electrophoresis method (3%PAGE), 2) 2% - 16% nondenatured poly-acrylamide gradient gel electro-phoresis method (2% - 16% GGE) and 3) 2.7% - 5% GGE. Evolocumab 140 mg/day administered together with statin significantly improved serum total cholesterol (TC), triglyceride (TG), high-dense lipoprotein-cholesterol (HDL-C), and LDL-C after four-week treatment. Results: TC, TG, HDL-C and LDL-C levels were improved by, respectively, 33%, 20%, 10%, and 54%. The mean LDL size significantly increased from 25.6 ± 0.4 nm to 26.4 ± 0.8 nm. The small dense LDL-cholesterol (sdLDL-C), large buoyant LDL-cholesterol (lbLDL-C), and mid-band lipoprotein-cholesterol were reduced, respectively. Therefore, the preliminary study on this paper can be the first step into a new insight on the world of lipid metabolism. Conclusion: Short-term administration of evolocumab addedons to statin therapy, significantly reduced small size LDL levels.