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Background: Colorectal cancer (CRC) is recognized as one of the most common cancer globally. The association between CRC and apurinic endonuclease 1 (APE1) Asp148Glu polymorphism remains unclear; thus, this meta-analysis aimed to explore whether APE1 Asp148Glu polymorphism is related to CRC risk.Methods: Embase, PubMed, Cochrane library, CNKI and Wanfang databases were subject to a systematic search until April, 17, 2020 to evaluate the effect of APE1 Asp148Glu polymorphism on CRC risk. The associated strength was used to evaluate with odds ratios (ORs) with 95% confidence intervals (CIs) between Asp148Glu polymorphism and CRC risk. Subgroup analyses were also performed.Results: In total, 11 articles including 8,136 subjects (3,836 cases and 4,300 controls) were included. Five genetic models were analyzed, including the additive model (G vs. T), the heterozygote comparison (TG vs. TT), the homozygote comparison (GG vs. TT), the dominant model (TG+GG vs. TT), and the recessive model (GG vs. TG+TT). In these models, T refers to thymine and G refers to guanine. The APE1 Asp148Glu polymorphism in heterozygote comparison [OR (95%CI) = 1.36 (1.05, 1.75), P=0.019] and dominant model [OR (95%CI) =1.31 (1.07, 1.61), P=0.010] significantly increased CRC risk. No significant association was seen for the additive model [OR (95%CI) = 1.14 (1.00, 1.31), P=0.057], recessive model [OR (95%CI) = 0.97 (0.71, 1.31), P=0.826] or in homozygote comparison [OR (95%CI) = 1.15 (0.88, 1.52), P=0.309]. Moreover, CRC risk indicated a remarkable association with APE1 Asp148Glu polymorphism in the PCR-RFLP additive model, homozygote comparison and recessive model (PG) may be a potential risk factor for CRC. [ABSTRACT FROM AUTHOR]

The multifactorial pathogenesis of Alzheimer's disease (AD) implicates that multi-target-directed ligands (MTDLs) intervention may represent a promising therapy for AD. Amyloid-β (Aβ) aggregation and oxidative stress, two prominent neuropathological hallmarks in patients, play crucial roles in the neurotoxic cascade of this disease. In the present study, a series of novel (-)-meptazinol-melatonin hybrids were designed, synthesized and biologically characterized as potential MTDLs against AD. Among them, hybrids 7-7c displayed higher dual inhibitory potency toward cholinesterases (ChEs) and better oxygen radical absorbance capacity (ORAC) than the parental drugs. Furthermore, compound 7c could effectively inhibit Aβ self-aggregation, showed favorable safety and the blood-brain barrier (BBB) permeability. Therefore, 7c may serve as a valuable candidate that is worthy of further investigations in the treatment of AD., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The incidence and mortality rate of biliary tract cancer have been increasing worldwide; however, its diagnosis and prognosis have not improved in recent years. A novel approach, termed 'metabolomics', may have the potential to be developed as an effective diagnostic tool. The present study prospectively obtained bile samples from 115 individuals, including 32 patients with biliary tract cancer, 61 patients with benign biliary tract diseases and 22 normal controls. A liquid chromatography/mass spectrometry (LC/MS)‑based approach was used to investigate the differences in bile samples between the three groups, followed by multivariate statistical analysis, which included partial least squares projection to latent structures with discriminant analysis (PLS‑DA) and orthogonal projection to latent structures with discriminant analysis (OPLS‑DA). The metabolomic 2D score plot and 3D plot revealed clear separation between the cancer, benign and normal control groups by PLS‑DA. To further address the significant difficulties in clinically differentiating between biliary tract cancer and benign biliary tract diseases, OPLS‑DA was performed to distinguish between the two disease groups and to select potential biomarkers. The cancer and benign groups were well differentiated. The metabolic analysis revealed significantly lower levels of lysophosphatidylcholine, phenylalanine, 2‑octenoylcarnitine, tryptophan and significantly higher levels of taurine‑ and glycine‑conjugated bile acids in the bile from patients with biliary tract cancer compared with those in the bile from patients with benign biliary tract disease. The present study suggested that an LC/MS‑based metabolomic investigation provides a potent and promising approach for discriminating biliary tract cancer from benign biliary tract diseases and the identified specific metabolites may offer potential as novel biomarkers for the early detection of biliary tract cancer.

Hepatocellular carcinoma (HCC) is one of the most deadly cancers. Using mRNA microarray analysis, we found that H2AX decreased under hypoxic conditions. Hypoxia is an important physiological and pathological stress that induces H2AX phosphorylation (γ-H2AX), but the regulatory mechanism of γ-H2AX remains elusive in the progress of HCC. We report here that increased γ-H2AX expression in HCC is associated with tumor size, vascular invasion, TNM stage and reduced survival rate after liver transplantation (LT). γ-H2AX knockdown was able to effectively inhibit VEGF expression in vitro and tumorigenicity and angiogenesis of HCC in vivo. The mechanism of γ-H2AX on the angiogenic activity of HCC might go through EGFR/HIF-1α/VEGF pathways under hypoxic conditions. Combined γ-H2AX, HIF-1α and EGFR has better prognostic value for HCC after LT. This study suggests that γ-H2AX is associated with angiogenesis of HCC and γ-H2AX or a combination of γ-H2AX/EGFR/HIF-1α is a novel marker in the prognosis of HCC after LT and a potential therapeutic target.

PVT1, which maps to chromosome 8q24, is a copy number amplification-associated long non-coding RNA. Overexpression of PVT1 is a powerful predictor of tumor progression and patient survival in a diverse range of cancer types. However, the association between PVT1 and hepatocellular carcinoma (HCC) remains unclear. The aim of the present study was to examine the expression pattern of PVT1, and its clinical significance in HCC. Between 2003 and 2012, reverse transcription-quantitative polymerase chain reaction was used to determine the expression levels of PVT1 in two independent cohorts: Cohort one, 58 HCC resection samples; and cohort 2, 214 HCC transplant samples. Additionally, the correlation between PVT1 expression levels and clinical parameters and outcomes was analyzed. The relative expression levels of PVT1 were significantly higher in cancerous tissues compared with the corresponding non-cancerous tissues (cohort one, P=0.0016; cohort two, P=0.0274). Furthermore, overexpression of PVT1 was associated with a higher serum α-fetoprotein expression level (P=0.011) and a higher recurrence rate (P=0.004). Kaplan-Meier analysis indicated that the patients with high PVT1 expression exhibited poor recurrence-free survival (P=0.021), and multivariate analysis demonstrated that high levels of PVT1 expression are an independent predictor for HCC recurrence (P=0.042; hazard ratio, 1.653). Thus, the high expression levels of PVT1 in HCC may serve as a novel biomarker for predicting tumor recurrence in HCC patients, and as a potential therapeutic target.

Objective: The objective is to determine the effects of BAG3 and HIF-1 α expression on the prognosis of HCC patients after liver transplantation., Methods: Samples from 31 patients with HCC receiving liver transplantation were collected for this study. The immunohistochemistry was used to detect the expression of BAG3 and HIF-1 α of HCC samples., Results: According to the immunohistochemistry results, BAG3 and HIF-1 α staining were significantly associated with tumor TNM stage (P = 0.004, P = 0.012). A significant association between high BAG3/HIF-1 α levels and a shorter overall survival was detected, so as the combined BAG3 and HIF-1 α analysis., Conclusion: The results suggested that the expression level of BAG3 and HIF-1 α is efficient prognostic parameters in patients with HCC after liver transplantation.

Background: Traditional Chinese Medicine (TCM), has over thousands-of-years history of use. Chaihu-Shugan-San (CSS), and Shen-ling-bai-zhu-San (SLBZS), are famous traditional Chinese herbal medicine formulas, which have been used in China, for the treatment of many chronic diseases., Materials and Methods: This study investigated the anti-inflammatory effects of CSS and SLBZS on signaling molecules involved in p38 mitogen-activated protein kinase (p38 MAPK), pathway on hepatocytes of non-alcoholic steatohepatitis (NASH), rats induced by high fat diet. SD male rats were randomly divided into 8 groups: negative control group, model control group, high (9.6g/kg/day)/low (3.2g/kg/day)-dose CSS group, high (30g/kg/day)/low (10g/kg/day)-dose SLBZS group, high (39.6g/kg/day)/low (13.2g/kg/day)-dose integrated group. The rats of NASH model were induced by feeding a high-fat diet. After 16, wks, Hepatocytes were isolated from 6, rats in each group by collagenase perfusion. The liver histopathological changes and serum inflammatory cytokines TNF-α, IL-6 were determined. The proteins of TLR4, phosphor-p38 MAPK and p38 MAPK involved in p38 MAPK signal pathway were assayed., Results: The statistical data indicated the NASH model rats reproduced typical histopathological features of NASH in human. CSS and SLBZS ameliorated lipid metabolic disturbance, attenuated NASH progression, decreased the levels of TNF-α and IL-6 in serum, as well as inhibited TLR4 protein expression, p38 MAPK phosphorylation, and activation of p38 MAPK. In conclusion, CSS and SLBZS might work as a significant anti-inflammatory effect on hepatocyte of NASH by inhibiting the activation of TLR4, p-p38 MAPK and p38 MAPK involved in p38 MAPK signal pathway., Conclusion: To some extent, CSS and SLBZS may be a potential alternative and complementary medicine to protect against liver injury, alleviate the inflammation reaction, moderate NASH progression.