Clinical significance of BRD-containing protein members in hepatocellular carcinoma progression / 中国肿瘤生物治疗杂志

@#目的：通过检索挖掘多个肿瘤公共数据库中肝细胞癌（hepatocellular carcinoma，HCC）的相关数据，从转录本、蛋白质、基因突变、蛋白相互作用及相应的信号通路和功能富集等不同层面，揭示BRD（bromodomain）蛋白家族与HCC的相关性，探索BRD蛋白家族作为HCC的肿瘤进展及预后判断的潜在生物标志物价值。方法：从UALCAN数据库中获取BRD蛋白家族所有成员在HCC患者组织样本中的mRNA表达数据和患者临床信息并进行相关性分析。从TCGA数据库中获取BRD蛋白家族mRNA表达水平与HCC患者预后的数据并进行相关性分析。从The Human Protein Atlas数据库中获取BRD蛋白家族在HCC组织和正常肝组织中的免疫组化结果并进行对比分析。使用STRING数据库获取BRD蛋白家族的相互作用蛋白网络，并利用CYTOSCAPE软件对获取的相互作用蛋白进行KEGG和GO分析。结果：BRD家族7个成员均在HCC组织中高表达（P<0.01），并且与HCC患者肿瘤分级和临床分期正相关（P<0.01）,同时BRD8和BRD9的低表达提示HCC患者预后较好（P<0.05）。BRD相互作用蛋白主要参与组蛋白乙酰化修饰，并高度富集于HCC相关的信号通路。TP53基因突变HCC患者的BRD1、BRD3、BRD4、BRD7、BRD8和BRD9表达水平显著高于非突变患者（P<0.05）。结论：BRD蛋白家族分子能够作为HCC患者肿瘤分级、临床分期和预后判断的潜在靶标。

CARD10 promotes apoptosis inhibition of hepatocellular carcinoma cells by activating NF-κB pathway / 中国肿瘤生物治疗杂志

@# Objective: To investigate the expression of CARD10 in hepatocellular carcinoma (HCC) tissues, and the roles of CARD10 in HCC progression especially apoptosis inhibition. Methods: The expression of CARD10 was examined in pared non-tumor liver tissues and HCC tissues using qRT-PCR, and their correlation with HCC TNM stage was analyzed using Spearman’s rank correlation assay in SPSS 17.0. In HCC cells with CARD10 overexpression or knockdown, cytometry using Annexin-V/PI labeling was used to measure apoptosis, and Western blotting was used to determine the activation of NF-κB pathway. Results: CARD10 expression was significantly increased in HCC tissues as compared to that in pared non-tumor liver tissues (P<0.01), and the increased CARD10 in HCC was positively correlated with TNM staging (P<0.01). The apoptosis of HCC cell lines SMMC-7721 and BEL-7402 was inhibited by CARD10 overexpression while promoted by CARD10 knockdown, and the pro-survival NF-κB pathway was also enhanced by CARD 10 over-expression while suppressed by CARD10 knockdown. Conclusion: CARD10 expression is increased in HCC tissues and positively correlated with HCC progression. CARD10 inhibits HCC apoptosis by promoting the activation of NF-κB pathway. [Key words] hepatocellular carcinoma (HCC); caspase recruitment domain family member 10 (CARD10); apoptosis; NF-κB

Research progress on the regulatory mechanism of hepatic inflammation-induced carcinogenesis / 中国肿瘤生物治疗杂志

@#Uncontrolled chronic inflammation plays key roles in the carcinogenesis of hepatocellular carcinoma (HCC). Among the risk factors of HCC, such as chronic viral hepatitis, alcoholic hepatitis, non-alcoholic steatohepatitis and so on, the occurrence and development of uncontrolled chronic inflammation are the core factors of HCC. The damaged or dead hepatocytes generated during the process of chronic inflammation may lead to the activation of immune cells in the liver, resulting in hepatic inflammation. Chronic and prolonged liver inflammation promotes the occurrence of cancer. During this process, different injuries or death patterns of hepatocytes and progression of inflammation caused by activation of different immune cells play different roles in hepatic carcinogenesis, involving multiple pathological or pathophysiological processes such as liver injury, inflammation, and compensatory proliferation, as well as function alteration of various cells, signaling pathways, and regulatory molecules. Further studies on the regulatory mechanisms of hepatic inflammation-induced carcinogenesis are helpful to provide theoretical basis for the intervention of occurrence of HCC. This review focused on the research progress of regulatory mechanisms involved in the hepatic inflammation-induced carcinogenesis.

Roles of RIG-I in tumorigenesis and progression / 中国肿瘤生物治疗杂志

@#在天然免疫应答尤其是抗病毒天然免疫应答中，维甲酸诱导基因-I（retinoic acid inducible gene I,RIG-I）是重要的胞内 病毒RNA模式识别受体，其通过结合和识别病毒来源的RNA进而活化下游RIG-I信号通路，从而激发炎症因子和I型干扰素的 表达，实现抗病毒天然免疫应答的启动。然而，新近研究表明，在肿瘤发生发展的过程中，RIG-I亦可发挥重要的调控作用。在肿 瘤进展的不同病理阶段，RIG-I可发挥抑制或促进肿瘤进展的功能。本文就RIG-I在不同肿瘤及其发生发展不同阶段所发挥的抑 癌基因或促癌基因样作用的研究进展作一综述。

Incorporation of TV regularization in deconvolution for partial volume correction in PET imaging / 南方医科大学学报

We propose a method using total variation (TV) regularization in deconvolution for partial volume correction in PET imaging. In the degraded image model, we used TV regularization procedure in Van Cittert (VC) and Richardson-Lucy (RL) deconvolution algorithms. These methods were tested in simulated NCAT images and images of NEMA NU4-2008 IQ phantom and tumor-bearing mouse scanned by Simens Invoen microPET. The simulated experiment and tumor-bearing mouse experiment showed that the algorithms using TV regularization provided superior qualitative and quantitative appearance compared with traditional VC and RL algorithms. When the mean intensity of the tumor increased by (10±1.8)%, the SD increase percentage was decreased from 49.98% to 14.26% and from 42.76% to 4.70%, suggesting the efficiency of the proposed algorithms for reducing PVEs in PET.

Polymorphism of four microsatellites and their polymerisation effect on litter size in Boer goats

Background: Finding molecular markers linked to quantitative trait loci is the first step in marker-assisted selection (MAS). Microsatellites are excellent molecular markers because of their large numbers, even distribution in the genome, and high polymorphism. In this study, the polymerisation effect of four microsatellites (OarAE101, BM1329, BM143, and LSCV043) on litter size was analysed using microsatellite markers and pedigrees. Results: The results indicate that the polymerisation effect of four microsatellite loci significantly affected the litter size. E5E10F2F6G1G5H6H11 and E3E8F5F7G1G5H3H9 had the highest and lowest litter sizes in the F2 generation, respectively. The polymerisation effect value (v) of the E5E10 genotype was 3.18% higher than that of the E2E7 genotype. The v of genotype F2F6 was 14.47% higher than that of the F5F7 genotype. The v of genotype G1G5 was 58.99% higher than that of the G2G7 genotype. The v of the H6H11 genotype was 5.60% to 49.74% higher than those of the H4H10 and H1H7 genotypes. The v of the H3H9 genotype was 17.22% higher than that of the H1H7 genotype. Conclusions: The results of the present study are vital to improving the reproductive performance in goat breeds MAS.

Clinical analysis of primary hyperparathyroidism with kidney stones: 23 cases report / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the clinical characteristics of primary hyperparathyroidism (PHPT) with kidney stones.</p><p><b>METHODS</b>The clinical data of 23 cases undergoing diagnostic evaluation and surgery for PHPT combined with kidney stones between January 2004 and February 2012 was retrospectively analyzed. The 23 cases had undergone preoperative parathyroid neck color ultrasound, CT or (99)mTc-methoxy isobutyl isonitrile ((99)mTc-MIBI) diagnosis. The surgical treatment included parathyroid disease and kidney stones. The intravenous calcium, phosphorus and serum intact parathyroid hormone (iPTH) levels, 24 hours urinary calcium concentrations were measured 3 days before and 7 days after surgery.</p><p><b>RESULTS</b>There were 8 male and 15 female patients. The stone diameter were (3.2 ± 0.7) cm (range 2.1-4.0 cm). All patients did both parathyroid surgery and kidney surgery. The statistical discrepancy of serum calcium (there were (3.31 ± 0.39) mmol/L before surgery and (2.12 ± 0.18) mmol/L at 7 days after surgery, t = 11.26), serum phosphorus ((0.70 ± 0.09) and (1.21 ± 0.21) mmol/L in before and after surgery respectively, t = 10.53), iPTH (there were (28.8 ± 10.0) pmol/L before surgery and (3.6 ± 2.6) pmol/L after surgery, t = 12.83) and 24-hours urine calcium (there were (7.2 ± 3.1) mmol/d before surgery and (3.6 ± 2.5) mmol/d after surgery, t = 8.81) before and after the operation was significant (all P < 0.01). PTH concentration with serum calcium concentration correlation coefficient was r = 0.59 (P < 0.01). Eighteen patients (78.3%) had solitary parathyroid adenomas, two patients (8.7%) had multiple parathyroid adenomas, and three patients (13.0%) had multiglandular hyperplasia confirmed at surgery and histology. During follow-up, 8 patients had stone recurrence and 3 patients were did operation again to deal with renal stone within 2 years. Among them, 7 cases were normal, 1 case of parathyroid adenomas recurrence and reoperation.</p><p><b>CONCLUSIONS</b>The parathyroid operation may reduce the calculus recurrence remarkably. Early diagnosis and treatment of primary hyperparathyroidism is helpful to reduce the calculus recurrence and preserve the renal function.</p>

Vitamin D Receptor Gene TaqI, BsmI and FokI Polymorphisms in Korean Patients with Tuberculosis

BACKGROUND: The active metabolite (1, 25-dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to activation of macrophages and deficiency of vitamin D seems to be involved in the risk of tuberculosis. The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and may be influenced by polymorphism in the VDR gene. In this study, variation in the VDR gene was investigated in Korean population with tuberculosis. METHODS: We typed three VDR polymorphisms of restriction endonuclease sites for TaqI, BsmI and FokI in 155 patients with tuberculosis and 105 healthy volunteers. RESULTS: The frequencies of FokI genotypes determined from TB patients were 29.13% for FF, 56.31% for Ff, and 14.56% for ff. We observed 1.4-fold increased prevalence of the Ff genotype in TB patients compared with normal healthy groups (p=0.0857). However, there was no significant association between the genotype groups, TB patient and normal control, for FokI polymorphism. There was also no significant association between VDR gene and tuberculosis in another polymorphism (BsmI and TaqI). CONCLUSION: Three polymorphisms (TaqI, BsmI and FokI) in the VDR gene do not appear to be responsible for host susceptibility to human tuberculosis in Korean population.

Vitamin D Receptor Gene TaqI, BsmI and FokI Polymorphisms in Korean Patients with Tuberculosis

BACKGROUND: The active metabolite (1, 25-dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to activation of macrophages and deficiency of vitamin D seems to be involved in the risk of tuberculosis. The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and may be influenced by polymorphism in the VDR gene. In this study, variation in the VDR gene was investigated in Korean population with tuberculosis. METHODS: We typed three VDR polymorphisms of restriction endonuclease sites for TaqI, BsmI and FokI in 155 patients with tuberculosis and 105 healthy volunteers. RESULTS: The frequencies of FokI genotypes determined from TB patients were 29.13% for FF, 56.31% for Ff, and 14.56% for ff. We observed 1.4-fold increased prevalence of the Ff genotype in TB patients compared with normal healthy groups (p=0.0857). However, there was no significant association between the genotype groups, TB patient and normal control, for FokI polymorphism. There was also no significant association between VDR gene and tuberculosis in another polymorphism (BsmI and TaqI). CONCLUSION: Three polymorphisms (TaqI, BsmI and FokI) in the VDR gene do not appear to be responsible for host susceptibility to human tuberculosis in Korean population.

A novel sesquiterpene Hirsutanol A induces autophagical cell death in human hepatocellular carcinoma cells by increasing reactive oxygen species / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Hirsutanol A is a novel sesquiterpene compound purified from fungus chondrostereum sp in Sarcophyton tortuosum. Its pharmacologic effect has not been reported yet. This study aimed to investigate cytotoxic effect of Hirsutanol A on hepatocellular carcinoma (HCC) cells and its mechanism.</p><p><b>METHODS</b>Hep3B cells were treated with different concentrations of Hirsutanol A. Cell proliferation was detected by MTT assay. The protein expression of LC3 was determined by Western blot. The generation of reactive oxygen species (ROS) was monitored by flow cytometry.</p><p><b>RESULTS</b>Hirsutanol A significantly inhibited proliferation of Hep3B cells with 50% inhibition concentrations (IC50) of 14.54, 6.71, and 3.59 micromol/L when exposed to Hirsutanol A for 24, 48, and 72 h, respectively. Incubation of Hep3B cells with Hirsutanol A markedly increased the level of ROS and the autophagy marker MAP-LC3 conversion from type I to type II. Pre-incubation with an antioxidant N-acetyl cystein (NAC) decreased the level of ROS, and reduced MAP-LC3 I-II conversion, and suppressed cell death. Blocking autophagy with a specific autophagy inhibitor 3-methyladenine (3-MA), the cytotoxic effect of this compound was attenuated.</p><p><b>CONCLUSION</b>Hirsutanol A has potent cytotoxic effect, and can induce autophagic cell death via increasing ROS production.</p>