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Background: Long non-coding RNAs (lncRNAs) are a distinct class of RNAs with longer than 200 base pairs that are not translated into proteins. Small Nucleolar RNA Host Gene 3 (SNHG3) is a lncRNA and frequently dysregulated in various human cancers., Objective: This review provides a comprehensive analysis of current research on lncRNA SNHG3, focusing on its role within the competitive endogenous RNA (ceRNA) network and its implications in cancer., Methods: A systematic literature review was conducted using PubMed up to October 2023. The search strategy included keywords such as "lncRNA SNHG3", "competitive endogenous RNA", "cancer", and related terms. Studies were selected based on relevance to SNHG3's involvement in cancer pathogenesis and progression., Results: Disruptions in the ceRNA network involving lncRNA SNHG3 can impair normal cell growth and differentiation, significantly contributing to disease pathogenesis, particularly cancer. This review highlights SNHG3's substantial impact on various cancer processes and its potential as a diagnostic and therapeutic tool for aggressive cancers., Conclusion: The findings underscore SNHG3's pivotal role in cancer prevention, diagnosis, and treatment, laying a foundation for future research in cancer management. Insights from this review emphasize the necessity for further exploration and development of SNHG3-based diagnostic and therapeutic strategies., (© 2024. The Author(s).)

Background: The dysregulation of tissue inhibitor of metalloproteinase-3 (TIMP3) was positively correlated with the progression of hepatocellular carcinoma (HCC). However, it is not clear whether TIMP3 expression is associated with the clinicopathological features and prognosis of aflatoxin B1 (AFB1)-related HCC (AHCC)., Aim: To assess the effects of TIMP3 expression on the clinicopathological features and prognosis of AHCC., Methods: A retrospective study, including 182 patients with AHCC, was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinicopathological characteristics and prognosis of AHCC. TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis. Odds ratio, hazard ratio (HR), median overall survival time (MST), median tumor recurrence-free survival time (MRT), and corresponding 95% confidential interval (CI) was calculated to evaluate the potential of TIMP3 expression in predicting AHCC prognosis., Results: Kaplan-Meier survival analysis showed that compared with high TIMP3 expression, low TIMP3 expression in tumor tissues significantly decreased the MST (36.00 mo vs 18.00 mo) and MRT (32.00 mo vs 16 mo) of patients with AHCC. Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death (HR = 2.85, 95%CI: 2.04-4.00) and tumor recurrence (HR = 2.26, 95%CI: 1.57-3.26). Furthermore, decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopathological features, such as tumor size, tumor grade and stage, tumor microvessel density, and tumor blood invasion. Additionally, TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues., Conclusion: These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome, suggesting that TIMP3 may act as a prognostic biomarker for AHCC., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aging is a complex biological process that involves multi-level structural and physiological changes. Aging is a major risk factor for many chronic diseases. The accumulation of senescent cells changes the tissue microenvironment and is closely associated with the occurrence and development of tissue and organ fibrosis. Fibrosis is the result of dysregulated tissue repair response in the development of chronic inflammatory diseases. Recent studies have clearly indicated that SIRT2 is involved in regulating the progression of fibrosis, making it a potential target for anti-fibrotic drugs. SIRT2 is a NAD + dependent histone deacetylase, shuttling between nucleus and cytoplasm, and is highly expressed in liver, kidney and heart, playing an important role in the occurrence and development of aging and fibrosis. Therefore, we summarized the role of SIRT2 in liver, kidney and cardiac fibrosis during aging.

Background : Our previous studies have reported that polycomb chromobox 4 ( CBX4 ) has a potential promoting hepatocellular carcinoma (HCC) angiogenesis and tumor progression. However, it is unclear whether genetic single-nucleotide polymorphisms (SNPs) in this gene are associated with HCC prognosis. Methods : We conducted a hospital-based two-phase study, including 598 patients with pathologically diagnosed HCC for the SNPs screening phase and 328 HCC patients for clinic significance validating phase, to elucidate the association between SNPs of CBX4 and the survival of HCC. The genotypes of CBX4 were tested using the SNaPshot method and the effects of CBX4 SNPs on HCC prognosis were analyzed using Kaplan-Meier survival model and Cox regression model. Results : A total of 33 SNPs were selected and genotyped in this study. We found the rs77447679 SNP was significantly related to survival in individuals with HCC. Specifically, survival was noticeably decreased in HCC patients who have mutant homozygote AA of this SNP (rs77447679-AA) compared with these with wild type (rs77447679-CC). An additive effect of rs77447679 polymorphism and aflatoxin B1 exposure level was also observed in the survival analyses of HCC cases. Furthermore, this SNP was positively correlated not only with tumor size, grade, stage, and microvessel density (correlation coefficient r = 0.17, 0.23, 0.23, and 0.42, respectively), but also with increasing CBX4 expression ( r = 0.57). Interestingly, the mutant genotypes of rs77447679 can significantly improve the therapeutic response of HCC cases on post-operative adjuvant transarterial chemoembolization (pa-TACE), but wild type not. Conclusions : These data suggest that genetic polymorphisms in the CBX4 may be a prognostic biomarker for HCC, and the rs77447679 SNP is such a potential candidate., (© 2021 The Author(s). Published by BRI.)

Previous studies have shown that single-nucleotide polymorphisms (SNPs) of a disintegrin and metalloproteinase with thrombospondin type 1 motif 4 (ADAMTS4) may involve in the pathogenesis of some diseases. However, it is not clear whether they are associated with hepatocellular carcinoma (HCC). A hospital-based case-control study, including 862 cases with HCC and 1120 controls, was conducted to assess the effects of 258 SNPs in the coding regions of ADAMTS4 on HCC risk and prognosis. We found that six SNPs in ADAMTS4 were differential distribution between cases and controls via the primary screening analyses; however, only rs538321148 and rs1014509103 polymorphisms were further identified to modify the risk of HCC (odds ratio: 2.73 and 2.95; 95% confidence interval, 2.28-3.29 and 2.43-3.58; P-value, 5.73 × 10 -27 and 1.36 × 10 -27 , respectively). Significant interaction between these two SNPs and two known causes of hepatitis B virus and aflatoxin B1 were also observed. Furthermore, rs538321148 and rs1014509103 polymorphisms were associated not only with clinicopathological features of tumor such as tumor stage and grade, microvessel density, and vessel metastasis, but with poor overall survival. Additionally, these SNPs significantly downregulated ADATMS4 expression in tumor tissues. These data suggest that SNPs in the coding region of ADAMTS4, such as rs538321148 and rs1014509103, may be potential biomarkers for predicting HCC risk and prognosis., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Our previous reports have shown that microRNA-4651 is a potential early diagnostic and prognostic marker for hepatocellular carcinoma. We aimed to investigate whether microRNA-4651 modified postoperative adjuvant transarterial chemoembolization (pa-TACE) to improve the prognosis of hepatocellular carcinoma. A hospital-based retrospective study, including 302 patients with advanced-stage hepatocellular carcinoma who received tumor resection or tumor resection plus pa-TACE as an initial therapy, was conducted to assess the effects of microRNA-4651 on pa-TACE treatment. MicroRNA-4651 expression in tumor tissues was tested using the TaqMan-PCR technique. The sensitivity of tumor cells to doxorubicin (an anticancer drug used in pa-TACE procedure) was analyzed by the half-maximal inhibitory concentration (IC50). Upregulated microRNA-4651 expression in tumor tissues can improve the therapeutic response of patients with hepatocellular carcinoma on pa-TACE (hazard ratios [95% confidence intervals] = 0.32 [0.22-0.46] for death risk and 0.39 [0.28-0.56] for tumor-recurrence risk, respectively), but downregulated expression cannot. Functional analyses-displayed microRNA-4651 mimics decreased while its inhibitor increased the IC50 of tumor cells to doxorubicin (0.65 [0.61-0.69] versus 2.17 [1.98-2.37] µM). Cytochrome P450 2W1 was shown as a possible target of microRNA-4651. Additionally, dysregulation of microRNA-4651 also affected the clinical pathological features of hepatocellular carcinoma and was an independent prognostic factor for this cancer. Conclusion: These results indicate that increasing microRNA-4651 expression may be beneficial for pa-TACE in improving hepatocellular carcinoma prognosis.

Background: Altered expression of ataxin-3 (AT3) can modify DNA repair capacity and is observed in human diseases. The genetic polymorphisms of this gene in aflatoxin B1 (AFB1)-related liver cirrhosis (LC) have not yet been elucidated., Materials and Methods: We conducted a hospital-based case-control study, including 384 patients with LC and 851 controls without any liver diseases, to assess the association between 264 polymorphisms in AT3 and AFB1-related LC risk. Genotype were tested using TaqMan-PCR or sequencing technique., Results: We found three differentially distributed SNPs (rs8021276, rs7158733, and rs10146249) via the screening analysis; however, only rs8021276 polymorphism was further identified to modify the risk of LC. Compared with the homozygote of rs8021276 A alleles (rs8021276-AA), the genotypes of rs8021276 G alleles (rs8021276-AG or -GG) increased LC risk (OR: 2.48 and 6.98; 95% CI: 1.84-3.33 and 4.35-11.22, respectively). Significant interactive effects between risk genotypes and AFB1 exposure status were also observed in the joint effects analysis. Additionally, rs8021276 polymorphism was also associated with down-regulation of AT3 mRNA expression and increasing AFB1-DNA adducts in liver tissues with cirrhosis., Conclusions: These results suggest AT3 polymorphisms may be risk biomarkers of AFB1-related LC, and rs8021276 is a potential candidate., Competing Interests: CONFLICTS OF INTEREST The authors declare no competing financial interests.

Background: Our previous investigations have shown that the variants of X-ray repair complementing 4 (XRCC4) may be involved in hepatocellular carcinoma (hepatocarcinoma) tumorigenesis. This study aimed to investigate the possible prognostic significance of XRCC4 expression for hepatocarcinoma patients and possible value for the selection of transarterial chemoembolization (TACE) treatment., Materials and Methods: We conducted a hospital-based retrospective analysis (including 421 hepatocarcinoma cases) to analyze the effects of XRCC4 on hepatocarcinoma prognosis and TACE. The levels of XRCC4 expression were tested using immunohistochemistry. The sensitivity of cancer cells to anti-cancer drug doxorubicin was evaluated using the half-maximal inhibitory concentration (IC50)., Results: XRCC4 expression was significantly correlated with pathological features including tumor stage, liver cirrhosis, and micro-vessel density. XRCC4 expression was an independent prognostic factor of hepatocarcinoma, and TACE treatments had no effects on prognosis of hepatocarcinoma patients with high XRCC4 expression. More intriguingly, TACE improved the prognosis of hepatocarcinoma patients with low XRCC4 expression. Functionally, XRCC4 overexpression increased while XRCC4 knockdown reduced the IC50 of cancer cells to doxorubicin., Conclusions: These results suggest that XRCC4 may be an independent prognostic factor for hepatocarcinoma patients, and that decreasing XRCC4 expression may be beneficial for post-operative adjuvant TACE treatment in hepatocarcinoma., Competing Interests: CONFLICTS OF INTEREST The authors declare no competing financial interests.

Background: The serum microRNAs have been reported as potential biomarkers for hepatitis virus-related hepatocellular carcinoma (HCC); however, their role in aflatoxin B1 (AFB1)-related HCC to has not yet been evaluated., Materials and Methods: We conducted a case-control study, including 366 HCC cases and 662 controls without any evidence of tumors, to identify and assess diagnostic and prognostic potential of serum microRNAs for AFB1-related HCC. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were used to elucidate diagnostic performance, and to compare the microRNAs with α-fetoprotein (AFP) at a cutoff of 20 ng/mL (AFP20) and 400 ng/mL (AFP400)., Results: We found 8 differentially expressed microRNAs via the microRNA array analysis; however, only microRNA-4651 was further identified to detect AFB1-positive HCC but not AFB1-negative HCC. For AFB1-positive HCC, microRNA-4651 showed higher accuracy and sensitivity than AFP400 (AUC, 0.85 vs . 0.72; Sensitivity, 78.1% vs. 43.0%). Compared to AFP20, microRNA-4651 exhibited higher potential in identifying small-size (0.68 vs. 0.84 for AUC and 36.7% vs . 75.5% for sensitivity, respectively) and early-stage HCC (0.69 vs . 0.84 for AUC and 38.7% vs . 75.7% for sensitivity, respectively). Additionally, miR-4651 was also associated with HCC prognosis (hazard risk value, 2.67 for overall survival and 3.62 for tumor recurrence analysis)., Conclusions: These data suggest that serum microRNA-4651 may be a useful marker for HCC diagnosis and prognosis, especially AFB1-positive cases., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Our recent investigation has shown that the variables of microRNA-1268a may involve in hepatocellular carcinoma (HCC) tumorigenesis. Here, we attempted to identify the prognostic significance of microRNA-1268a expression in tumor tissues by a retrospective analysis in 411 patients with HCC, and analyze its effects on post-operative adjuvant transarterial chemoembolization (TACE) improving HCC prognosis. All cases received tumor resection or tumor resection plus post-operative adjuvant TACE as an initial treatment. Logistical regression analysis exhibited that microRNA-1268a expression was significantly correlated with tumor stage, tumor grade, tumor size, and microvessel density. Cox regression analysis showed that microRNA-1268a expression was an independent prognostic factor for HCC, and TACE treatment had no effects on prognosis of HCC patients with high microRNA-1268a expression. More intriguingly, TACE improved the prognosis of HCC patients with low microRNA-1268a expression. Functionally, overexpression of microRNA-1268a inhibited while its inhibitor enhanced doxorubicin-induced the death of cancer cells. These results suggest that microRNA-1268a may be an independent prognostic factor for HCC patients, and that decreasing microRNA-1268a expression may be beneficial for post-operative adjuvant TACE treatment in HCC.

Acute pancreatitis is characterized by zymogen pre-activation. Severe inflammation caused by zymogen activation can eventually lead to multiple organ dysfunctions, which contributes to the high mortality rate of severe acute pancreatitis. However, there is no specific treatment available for acute pancreatitis therapy. Here, we show that spautin-1, which effectively inhibits autophagy flux, ameliorated the pathogenesis of acute pancreatitis induced by cerulein or L-Arginine. CaMKII phosphorylation due to cytosolic calcium oeverload was revealed in this paper. It was also demonstrated that autophagic protein aggregates degradation blockade accompanying with impaired autophagy correlated positively to intra acinar cells digestive aymogen activation sitimulated by cerulein or L-Arginine. The role of spautin-1 in ameliorating acute pancreatitis was shown here to be associated with impaired autophagy inhibition and Ca 2+ overload alleviation. We provided a promising therapy for acute pancreatitis here through targeting both impaired autophagy and increased cytosolic calcium.

The altered expression of some microRNAs (miRNAs) is observed in hepatocellular carcinoma (HCC); however, the genetic polymorphisms in the precursor miRNAs (pre-miRNAs) in aflatoxin B1 (AFB1)-related HCC have not yet been investigated. A hospital-based case-control study, including 1,706 HCC cases and 2,270 controls without any liver diseases or tumors, was conducted in a high AFB1 exposure area of China to assess the relationship between 48 polymorphisms in the pre-miRNAs and AFB1-related HCC risk and prognosis. Among 48 polymorphisms, only rs28599926 (in the miRNA 1268a) affected HCC risk. Compared with the homozygote of rs28599926C alleles (rs28599926-CC), the genotypes of rs28599926 T alleles (namely rs28599926-CT or -TT) increased HCC risk (odds ratio [OR]: 1.63 and 5.52, 95% confidence interval [CI]: 1.40-1.90 and 4.27-7.14, respectively). Significant interactive effects between risk genotypes and AFB1 exposure status were also observed in the joint effects analysis. This polymorphism was associated not only with larger tumor size, higher portal vein tumor risk, and tumor dedifferentiation, but also with higher AFB1 adducts levels and increasing the mutation risk of TP53 gene. Furthermore, rs28599926 modified the tumor recurrence-free survival (hazard ratio [HR]: 2.86, 95% CI: 2.36-3.43) and overall survival (HR: 2.12, 95% CI: 1.86-2.41) of cases. Additionally, one target of miR-1268a was show to be the ADAMTS4 mRNA and rs28599926 polymorphism might modify ADAMTS4 expression. These findings indicate that polymorphisms in the pre-miRNAs may be risk and prognostic biomarkers of AFB1-related HCC, and rs28599926 in miR-1268a is such a potential candidate. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Background: Altered expression of a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) is observed in hepatocellular carcinoma. The genetic polymorphisms of this gene in aflatoxin B1 (AFB1)-related hepatocellular carcinoma have not yet been elucidated., Methods: We conducted a hospital-based case-control study, including 1,706 hepatocellular carcinoma cases and 2,270 controls without any liver diseases or tumors, to assess the association between 74 polymorphisms in ADAMTS5 and AFB1-related hepatocellular carcinoma risk and prognosis. Genotype, mRNA levels, and TP53 gene mutation (TP53M) related to AFB1 exposure were tested using TaqMan-PCR or sequencing technique. ADAMTS5 protein level and microvessel density were analyzed by IHC., Results: Among these 74 polymorphisms, only rs2830581 affected hepatocellular carcinoma risk. Compared with the homozygote of rs2830581 G alleles (rs2830581-GG), the genotypes of rs2830581 A alleles (rs2830581-GA or -AA) increased hepatocellular carcinoma risk (OR: 1.85 and 4.40; 95% CI: 1.57-2.19 and 3.43-5.64, respectively). Significant interactive effects between risk genotypes and AFB1 exposure status were also observed in the joint effects analysis. Furthermore, the rs2830581 polymorphism modified the tumor recurrence-free survival and overall survival of patients. This polymorphism not only affected pathologic features of hepatocellular carcinoma such as tumor dedifferentiation and microvessel density, but also modified ADAMTS5 expression and the effects of transarterial chemoembolization treatment on hepatocellular carcinoma., Conclusions: These results suggest ADAMTS5 polymorphisms may be risk and prognostic biomarkers of AFB1-related hepatocellular carcinoma, and rs2830581 is a potential candidate., Impact: Our findings support the hypothesis that ADAMTS5 rs2830581 polymorphism modifies AFB1-related hepatocellular carcinoma risk and prognosis., (©2015 American Association for Cancer Research.)

CD4(+)CD25(+) cells are critical regulators in almost all of the animal models of human organ-specific autoimmune diseases, transplant rejection and allergic diseases. We aimed to explore the role of CD4(+)CD25(+) cells in the pathogenesis of multiple myeloma (MM) related renal impairment (RI). Thirty patients with MM related RI and 30 healthy volunteers were studied. The number of CD4(+)CD25(+) cells was examined by flow cytometry. Clinical and laboratory data were collected from each subject. Glomerular injury was assessed by histopathology. Serum IL-2, IL-4 and IL-6 were analyzed by ELISA. CD4(+)CD25(+) cells significantly decreased in MM related RI patients compared to the controls (P<0.05). CD4(+)CD25(+) cell number was negatively associated with blood urea nitrogen (BUN), supernatant IL-4, serum IL-6, monoclonal immunoglobulin and β2-microglobulin, as well as bone marrow plasma cell percentage and proteinuria; whereas positively associated with estimated glomerular filtration rate (eGFR) (all P < 0.05). CD4(+)CD25(+) cells gradually decreased as the Clinic Stage increased. The number of CD4(+)CD25(+) cells reduced in MM related RI patients, and was correlated with disease severity. CD4(+)CD25(+) cells may play an important role in the pathogenesis of MM related RI.

Unlabelled: Hepatitis B virus affects more than 2 billion people worldwide, 350 million of which have developed chronic hepatitis B (CHB). The genetic factors that confer CHB risk are still largely unknown. We sought to identify genetic variants for CHB susceptibility in the Chinese population. We undertook a genome-wide association study (GWAS) in 2,514 CHB cases and 1,130 normal controls from eastern China. We replicated 33 of the most promising signals and eight previously reported CHB risk loci through a two-stage validation totaling 6,600 CHB cases and 8,127 controls in four independent populations, of which two populations were recruited from eastern China, one from northern China and one from southern China. The joint analyses of 9,114 CHB cases and 9,257 controls revealed significant association of CHB risk with five novel loci. Four loci are located in the human leukocyte antigen (HLA) region at 6p21.3, including two nonsynonymous variants (rs12614 [R32W] in complement factor B [CFB], Pmeta =1.28 × 10(-34) ; and rs422951 [T320A] in NOTCH4, Pmeta  = 5.33 × 10(-16) ); one synonymous variant (rs378352 in HLA-DOA corresponding to HLA-DOA*010101, Pmeta  = 1.04 × 10(-23) ); and one noncoding variant (rs2853953 near HLA-C, Pmeta  = 5.06 × 10(-20) ). Another locus is located at 20q13.1 (rs1883832 in the Kozak sequence of CD40, Pmeta  = 2.95 × 10(-15) ). Additionally, we validated seven of eight previously reported CHB susceptibility loci (rs3130542 at HLA-C, rs1419881 at TCF19, rs652888 at EHMT2, rs2856718 at HLA-DQB1, rs7453920 at HLA-DQB2, rs3077 at HLA-DPA1, and rs9277535 at HLA-DPA2, which are all located in the HLA region, 9.84 × 10(-71)  ≤ Pmeta  ≤ 9.92 × 10(-7) )., Conclusion: Our GWAS identified five novel susceptibility loci for CHB. These findings improve the understanding of CHB etiology and may provide new targets for prevention and treatment of this disease., (© 2015 by the American Association for the Study of Liver Diseases.)

Epidemiological, preclinical and cellular studies in the last 5 years have shown that metformin exerts anti-tumoral properties, but its mode of action in cancer remains unclear. Here, we investigated the effects of metformin on a mouse hepatocellular carcinoma (HCC) model and tumor-associated T cell immune responses. Oral metformin administration led to a significant reduction of tumor growth, which was accompanied by decreased interleukin-22 (IL-22). Meanwhile, IL-22-induced STAT3 phosphorylation and upregulation of downstream genes Bcl-2 and cyclin D1 were inhibited by metformin. At the cellular level, metformin attenuated Th1- and Th17-derived IL-22 production. Furthermore, metformin inhibited de novo generation of Th1 and Th17 cells from naive CD4(+) cells. These observations were further supported by the fact that metformin treatment inhibited CD3/CD28-induced IFN-γ and IL-17A expression along with the transcription factors that drive their expression (T-bet [Th1] and ROR-γt [Th17], respectively). The effects of metformin on T cell differentiation were mediated by downregulated STAT3 and STAT4 phosphorylation via the AMP-activated kinase-mammalian target of rapamycin complex 1 pathway. Notably, metformin led to a reduction in glucose transporter Glut1 expression, resulting in less glucose uptake, which is critical to regulate CD4(+) T cell fate. Taken together, these findings provide evidence for the growth-inhibitory and immune-modulatory effects of metformin in HCC and thus, broaden our understanding about the action of metformin in liver cancer treatment., (© 2014 UICC.)

Aflatoxin B1 (AFB1), resulting in the formation of AFB1-DNA adducts, is a known human carcinogen. AFB1-exposure individuals with inherited susceptible carcinogen-repairing genotypes may experience an increased risk of genotoxicity. This study was aimed to investigate whether DNA repair gene xerodermapigmentosum complementation group C codon 939 polymorphism (rs2228001) affected the levels of AFB1-DNA adducts in Guangxi Population (n = 2558), from an AFB1-exposure area. AFB1-DNA adducts were measured by ELISA, and XPC codon 939 genotypes were identified by TaqMan-PCR. We found that longer AFB1-exposure years significantly increased XPC genotypes with codon 939 Gln alleles (namely, XPC-LG and -GG, odds ratios [95% confidence intervals] were 1.37 (1.15-1.63) and 1.99 (1.55-2.55), respectively) was significantly associated with higher levels of AFB1-DNA adducts. Furthermore, there was a positive joint effect between XPC genotypes and long-year AFB1 exposure in the formation of AFB1-DNA adducts. These results suggest that individuals with susceptible genotypes XPC-LG and -GG may experience an increased risk of DNA damage elicited by AFB1 exposure.

Living-donor liver transplantation (LDLT) has increasingly performed all around the world. However, LDLT donors achieve no medical benefits and are exposed to the risk of complications, and even death. The potential effects of LDLT on donor safety, donor recovery, and post-donation psychological impairment are essential to be better understood. We searched the MEDLINE database to identify articles about the quality of life (QOL) in adults after LDLT donation. Twenty-eight studies with a total of 1944 donors were included in the review. 14 of the 28 studies (50%) had a cross-sectional design, and the remaining half had a prospective design. The Physical Component Score (PCS) decreased immediately after the donation, then returned to the baseline within 6 to 12 months while the Mental Component Score (MCS) remains comparable to that of normative population throughout the procedure. Compared with the left graft (LG) donors, right graft (RG) donors were significantly older, had longer hospital stays and higher rates of postoperative complications, and a higher recipient mortality rate, while there were no difference in the PCS and MCS between the two groups. Our review clearly indicates that the LDLT donors can endure the donation procedure and return to their normal daily life without major problem in the short term. However, to improve the donor selection criteria and ensure the QOL in donors throughout donation procedure, more studies with longer follow up and larger samples are essential and predictors of poor QOL should be identified in study with sufficient response rate and ideal control groups.

Background: The relationship between tonsillar autoimmune response and the pathogenesis of IgA nephropathy (IgAN) has been previously demonstrated. However, the role of CD4 (+)CD25 (+)Treg cells, which play critical roles in maintaining peripheral tolerance and preventing autoimmunity, has not yet been defined in IgAN., Methods: Thirty-five patients with IgAN and 35 patients without renal disease were studied. The CD4 (+)CD25 (+)Treg cells were examined by flow cytometry. Clinical and laboratory data, such as serum creatinine and urinary samples, were obtained from each patient. Glomerular injury was assessed by histopathology. Serum IgA, C3, IL-2, IL-4 and IL-6 were analyzed by ELISA., Results: CD4 (+)CD25 (+)Treg cells significantly decreased in IgAN patients compared with the controls before tonsillectomy (p < 0.05). CD4 (+)CD25 (+)Treg cells were negatively correlated with blood urea nitrogen, supernatant IL-4 and proteinuria in IgAN patients, and positively with estimated glomerular filtration rate. CD4 (+)CD25 (+)Treg cells gradually decreased as the severity of renal histology increased. In addition, serum IgA, IL-2, IL-6 and supernatant IL-4 elevated while CD4 (+)CD25 (+)Treg cells decreased in IgAN patients. CD4 (+)CD25 (+)Treg cells were significantly increased when serum IgA, IL-2, IL-6 and supernatant IL-4, urine protein and urine erythrocytes were decreased after tonsillectomy in patients with IgAN, but were still lower than those of the controls (p < 0.05)., Conclusions: CD4 (+)CD25 (+)Treg cells were associated with IgAN, and tonsillectomy may increase CD4 (+)CD25 (+)Treg cells in IgAN patients, leading to clinical improvement.

Aim: CD(+)(4)CD(+)(25) Treg cells are of critical importance for maintenance of tolerance. The purpose of the this study was to observe the number of CD(+)(4)CD(+)(25) Treg cells in the patients with thrombotic thrombocytopenic purpura (TTP) associated with systemic lupus erythematosus (SLE), and to study pathogenesis of TTP with SLE., Methods: Seven patients with TTP associated with SLE and seven healthy volunteers were studied. The CD(+)(4)CD(+)(25) Treg cells were examined by flow cytometry. Clinical and laboratory data, such as urinary protein, serum creatinine, endothelial markers and immunologic serologics, were obtained from each patient and healthy volunteer. Glomerular injury was assessed by histopathology. Serum IL-2, IL-4, IL-6 and anti-endothelial cell antibody were analyzed by ELISA and anti-ADAMTS13 antibody were detected by Western blotting., Results: CD(+)(4)CD(+)(25) Treg cells significantly decreased in TTP with SLE patients compared with controls (p < 0.05). CD(+)(4)CD(+)(25) Treg cells are negatively correlated with blood urea nitrogen, serum uric acid, supernatant IL-4, and proteinuria, and positively with estimated glomerular filtration rate (eGFR) in TTP with SLE patients. [Formula: see text] Treg cells gradually decreased as the severity of renal histology increased. Serum IL-2, IL-6, supernatant IL-4, anti-endothelial cell antibody, and anti-ADAMTS13 antibody significantly increased in TTP with SLE patients compared to those of the control groups (all p < 0.05). In contrast, serum levels of C3 were significantly decreased in TTP with SLE patients compared to those of the control groups (p < 0.05)., Conclusions: CD(+)(4)CD(+)(25) Treg cells are not only lower in TTP with SLE patients, but also are correlated with disease severity in TTP with SLE patients.CD(+)(4)CD(+)(25)Treg cells may play an important role in the pathogenesis of TTP with SLE.

Aflatoxin B1 (AFB1) is an important environmental carcinogen and can induce DNA damage and involve in the carcinogenesis of hepatocellular carcinoma (HCC). The deficiency of DNA repair capacity related to the polymorphisms of DNA repair genes might play a central role in the process of HCC tumorigenesis. However, the interaction of DNA repair gene polymorphisms and AFB1 in the risk of hepatocellular carcinoma has not been elucidated. In this study, we investigated whether six polymorphisms (including rs25487, rs861539, rs7003908, rs28383151, rs13181, and rs2228001) in DNA repair genes (XPC, XRCC4, XRCC1, XRCC4, XPD, XRCC7, and XRCC3) interacted with AFB1, and the gene-environmental interactive role in the risk of HCC using hospital-based case-control study (including 1486 HCC cases and 1996 controls). Genotypes of DNA repair genes were tested using TaqMan-PCR technique. Higher AFB1 exposure was observed among HCC patients versus the control group [odds ratio (OR) = 2.08 for medium AFB1 exposure level and OR = 6.52 for high AFB1 exposure level]. Increasing risk of HCC was also observed in these with the mutants of DNA repair genes (risk values were from 1.57 to 5.86). Furthermore, these risk roles would be more noticeable under the conditions of two variables, and positive interactive effects were proved in the followed multiplicative interaction analysis. These results suggested that DNA repair risk genotypes might interact with AFB1 in the risk of HCC.

Cbx4 is a polycomb group protein that is also a SUMO E3 ligase, but its potential roles in tumorigenesis remain to be explored. Here, we report that Cbx4, but not other members of the Cbx family, enhances hypoxia-induced vascular endothelial growth factor (VEGF) expression and angiogenesis in hepatocellular carcinoma (HCC) cells through enhancing HIF-1α sumoylations at K391 and K477 in its two SUMO-interacting motifs-dependent mechanisms and increasing transcriptional activity of HIF-1. The Cbx4 expression is significantly correlated with VEGF expression, angiogenesis, and the overall survival of HCC patients and also in subcutaneously and orthotopically transplanted mice HCC models. Collectively, our findings demonstrate that Cbx4 plays a critical role in tumor angiogenesis by governing HIF-1α protein., (Copyright © 2014 Elsevier Inc. All rights reserved.)

MicroRNA-24 (miR-24) may be involved in neoplastic process; however, the role of this microRNA in the hepatocellular carcinoma (HCC) related to aflatoxin B1 (AFB1) has not been well elaborated. Here, we tested miR-24 expression in 207 pathology-diagnosed HCC cases from high AFB1 exposure areas and HCC cells. We found that miR-24 was upregulated in HCC tumor tissues relative to adjacent noncancerous tissue samples, and that the high expression of miR-24 was significantly correlated with larger tumor size, higher microvessel density, and tumor dedifferentiation. Additionally, this microRNA overexpression modified the recurrence-free survival (relative hazard ratio [HR], 4.75; 95% confidence interval [CI], 2.66-8.47) and overall survival (HR = 3.58, 95% CI = 2.34-5.46) of HCC patients. Furthermore, we observed some evidence of joint effects between miR-24 and AFB1 exposure on HCC prognosis. Functionally, miR-24 overexpression progressed tumor cells proliferation, inhibited cell apoptosis, and developed the formation of AFB1-DNA adducts. These results indicate for the first time that miR-24 may modify AFB1-related HCC prognosis and tumorigenesis.

The DNA repair gene X-ray cross-complementary group 4 (XRCC4), an important caretaker of the overall genome stability, is thought to play a major role in human tumorigenesis. We investigated the association between an important polymorphic variant of this gene at codon 247 (rs373409) and diffusely infiltrating astrocytoma (DIA) risk and prognosis. This hospital-based case-control study investigated this association in the Guangxi population. In total, 242 cases with DIA and 358 age-, sex-, and race-matched healthy controls were genotyped using TaqMan-PCR technique. We found a significant difference in the frequency of XRCC4 genotypes between cases and controls. Compared with the homozygote of XRCC4 codon 247 Ala alleles (XRCC4-AA), the genotypes of XRCC4 codon 247 Ser alleles (namely XRCC4-AS or -SS) increased DIA risk (odds ratios [OR], 1.82 and 2.89, respectively). Furthermore, XRCC4 polymorphism was correlated with tumor dedifferentiation of DIA (r = 0.261, p < 0.01). Additionally, this polymorphism modified the overall survival of DIA patients (the median survival times were 26, 14, and 8 months for patients with XRCC4-AA, -AS, and -SS, respectively). Like tumor grade, XRCC4 codon 247 polymorphism was an independent prognostic factor influencing the survival of DIA. These results suggest that XRCC4 codon 247 polymorphism may be associated with DIA risk and prognosis among the Guangxi population.

Background: Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity and may play an important role in carcinogenesis. We investigated the role of genetic polymorphisms at XRCC4 codon 247 (rs3734091, XRCC4P) and XRCC5 codon 180 (rs80309960, XRCC5P) in liver cancer (hepatocellular carcinoma) caused by aflatoxin B1 (AFB1)., Methods: A hospital-based case-control study, including 1499 liver cancer cases and 2045 controls without any liver disease, was conducted in a high aflatoxin exposure area in the Guangxi region of China to assess the relationship between these two polymorphisms and aflatoxin-related liver cancer risk and prognosis. Genotypes, mRNA levels, and the hot-spot mutation of TP53 gene (TP53M) related to AFB1 exposure was tested using TaqMan-PCR technique. XRCC4 protein level was analyzed by immunohistochemistry., Results: For XRCC4P and XRCC5P, only XRCC4P modified liver cancer risk. Compared with the homozygote of XRCC4 codon 247 Ala alleles (XRCC4-AA), the genotypes of XRCC4 codon 247 Ser alleles (namely XRCC4-AS or -SS) increased liver cancer risk (odds ratio [OR] = 1.35 and 2.02, respectively). Significant interactive effects between risk genotypes (OR > 1) and aflatoxin exposure status were also observed in the joint effects analysis. Moreover, this polymorphism was associated not only with lower XRCC4 expression levels but also with higher AFB1-DNA adduct levels and increasing TP53M and portal vein tumor risk. Additionally, XRCC4P modified the recurrence-free survival and overall survival of cases, especially under conditions of high aflatoxin exposure., Conclusion: XRCC4P may be a genetic modifier for the risk and outcome of hepatocellular carcinoma induced by AFB1 exposure.

Unlabelled: X-ray repair complementing group 4 (XRCC4) is very important in maintaining overall genome stability and may play an important role in carcinogenesis. We aimed to investigate the role of polymorphisms in the coding region of this gene in hepatocellular carcinoma (HCC) caused by aflatoxin B1 (AFB1). A hospital-based case-control study, including 1,499 HCC cases and 2,045 controls without any liver diseases or tumors, was conducted in a high AFB1 exposure area (the Guangxi region) to assess the relationship between 21 polymorphisms in the coding region of XRCC4 and AFB1-related HCC risk and prognosis. Among these 21 polymorphisms, only rs28383151 modified HCC risk. These individuals with the genotypes of rs28383151 A alleles (rs28383151-GA/AA), compared with the homozygote of rs28383151 G alleles (rs28383151-GG), faced increasing risk of HCC (odds ratio [OR]: 2.17; 95% confidence interval: 1.77-2.67). Significant interactive effects between risk genotypes (OR, >1) and AFB1 exposure status were also observed in the joint-effects analysis. Furthermore, this polymorphism was correlated not only with lower XRCC4-expressing levels, but also with higher AFB1-DNA adducts levels and increasing TP53M and portal vein tumor risk. The rs28383151 polymorphism modified the recurrence-free survival and overall survival of HCC patients, especially under high AFB1 exposure conditions. Additionally, this polymorphism multiplicatively interacted with the glutathione S-transferase M1 polymorphism with respect to HCC risk (ORinteraction = 2.13)., Conclusion: Genetic polymorphisms in the coding region of XRCC4 may be risk and prognostic biomarkers of AFB1-related HCC, and rs28383151 is such a potential candidate., (Copyright © 2013 American Association for the Study of Liver Diseases.)

Aim: The purpose of the present study was to detect bacterial strains and antibiotic susceptibility in chronic tonsillitis patients with IgA nephropathy (IgAN) and without nephritis, in order to provide evidence for clinical therapy and pathogenesis of IgAN., Methods: A total of 53 patients with IgAN (group A) and 53 chronic tonsillitis patients without nephritis (group B) underwent tonsillectomy. The tonsil tissues of patients were collected under sterile condition. The bacteria in the tonsil crypt of patients in both groups were isolated and identified for antibiotic susceptibility test by the manual routine of the laboratory and also with the autoScan/Microscan system., Results: There were bacteria in each specimen in both groups. The bacteria detection rate was 100%, but there was no significant difference between two groups (p > 0.05). The 522 strains of bacteria in group A and 494 strains of bacteria in group B were isolated. Streptococcus. Neisseria, Hemophilus parainfluenzae. Staphylococcus. Bacillus proteus and Streptococcus pneumoniae were detected in both groups, but there was no significant difference in the types of bacteria between the two groups (all p > 0.05). Alpha streptococcus was the most common in both groups. The antibiotic susceptibility test showed that there was no significant difference in the susceptibility to penicillin, chloramphenicol, macrolides, cephalosporin, gentamicin, amikacin sulphate, norfloxacin, ciprofloxacin, rifampicin and vancomycin between two groups (all p > 0.05)., Conclusions: Alpha streptococcus in both two groups can be detected and is the most common. There was no significant difference in bacterial strains and antibiotic susceptibility between two groups.

The X-ray repair cross-complementing group 7 (XRCC7) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. To determine whether XRCC7 rs#7003908 polymorphism (XRCC7P) is associated with Helicobacter pylori (H. pylori) infection-related gastric antrum adenocarcinoma (GAA) risk, we conducted a hospital-based case-control study, including 642 patients with pathologically confirmed GAA and 927 individually matched controls without any evidence of tumours or precancerous lesions, among Guangxi population. Increased risks of GAA were observed for individuals with cagA positive (odds ratio (OR) 6.38; 95% confidence interval (CI) 5.03-8.09). We also found that these individuals with the genotypes of XRCC7 rs#7003908 G alleles (XRCC7-TG or -GG) featured increasing risk of GAA (ORs 2.80 and 5.13, resp.), compared with the homozygote of XRCC7 rs#7003908 T alleles (XRCC7-TT). GAA risk, moreover, did appear to differ more significantly among individuals featuring cagA-positive status, whose adjusted ORs (95% CIs) were 15.74 (10.89-22.77) for XRCC7-TG and 38.49 (22.82-64.93) for XRCC7-GG, respectively. Additionally, this polymorphism multiplicatively interacted with XRCC3 codon 241 polymorphism with respect to HCC risk (ORinteraction = 1.49). These results suggest that XRCC7P may be associated with the risk of Guangxiese GAA related to cagA.

Background/aim: CD4+CD25+ regulatory T (Treg) cells are of critical importance for maintenance of tolerance. We showed that the number of CD4+CD25+ Treg cells was significantly lower in tonsils of patients with IgA nephropathy (IgAN); however, the function of tonsillar CD4+CD25+ Treg cells in IgAN has not been reported. The aim of this study was to investigate the effect of tonsillar CD4+CD25+ Treg cells of IgAN patients on experimental IgAN in rats., Methods: Tonsillar CD4+CD25+ Treg cells were isolated by magnetic beads. A total of 2 × 10(6) CD4+CD25+ Treg cells were transferred into rats that were previously orally immunized over a period of 14 weeks and subsequently received an injection of BSA into the tail vein on 3 consecutive days. Urine protein and erythrocytes were measured. Glomerular injury was assessed by histopathology. Plasminogen activator inhibitor type 1 (PAI-1), interleukin (IL)-6 and transforming growth factor (TGF)-β1 in mesangial cells of rats were examined by reverse transcription PCR. Serum IgA and C3 and supernatants of IL-2, IL-4 and IL-6 in splenic cells were analysed by ELISA. Transferred tonsillar CD4+CD25+ Treg cells were tracked by reverse transcription PCR and flow cytometry., Results: IgA deposition in the mesangial region and the glomerular planar area and the number of cells, levels of serum IgA and supernatant IL-2, IL-4 and IL-6 in splenic cells and PAI-1, IL-6 and TGF-β1 expression in renal mesangial cells of rats that received CD4+CD25+ Treg cells from IgAN patients were significantly higher than in rats that received CD4+CD25+ Treg cells from the control group, although they were dramatically lower compared with rats treated without CD4+CD25+ Treg cells. Transferred tonsillar CD4+CD25+ Treg cells migrated predominantly to secondary lymphoid organs but not to the kidneys., Conclusion: Dysfunction of tonsillar CD4+CD25+ Treg cells may be an important cause of IgAN progression., (Copyright © 2013 S. Karger AG, Basel.)

MicroRNA-429 (miR-429) may modify the development and progression of cancers; however, the role of this microRNA in the hepatocellular carcinoma (HCC) has not been well elaborated. Here, we tested miR-429 expression in 138 pathology-diagnosed HCC cases and SMMC-7721 cells. We found that miR-429 was upregulated in HCC tumor tissues and that the high expression of miR-429 was significantly correlated with larger tumor size (odd ratio (OR), 2.70; 95% confidence interval (CI), 1.28-5.56) and higher aflatoxin B1-DNA adducts (OR = 3.13, 95% CI = 1.47-6.67). Furthermore, this microRNA overexpression modified the recurrence-free survival and overall survival of HCC patients. Functionally, miR-429 overexpression progressed tumor cells proliferation and inhibited cell apoptosis. These results indicate for the first time that miR-429 may modify HCC prognosis and tumorigenesis and may be a potential tumor therapeutic target.

To identify genetic susceptibility loci for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Chinese population, we carried out a genome-wide association study (GWAS) in 2,514 chronic HBV carriers (1,161 HCC cases and 1,353 controls) followed by a 2-stage validation among 6 independent populations of chronic HBV carriers (4,319 cases and 4,966 controls). The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 at STAT4, P(meta) = 2.48 × 10(-10), odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P(meta) = 2.72 × 10(-17), OR = 1.49. The risk allele G at rs7574865 was significantly associated with lower mRNA levels of STAT4 in both the HCC tissues and nontumor tissues of 155 individuals with HBV-related HCC (P(trend) = 0.0008 and 0.0002, respectively). We also found significantly lower mRNA expression of STAT4 in HCC tumor tissues compared with paired adjacent nontumor tissues (P = 2.33 × 10(-14)).

Background and Purpose: Anion exchanger 1 (AE1) is an integral membrane protein found in erythrocytes. Our previous studies have demonstrated that AE1 is expressed in human gastric cancer cells and may be involved in the carcinogenesis of cancer. In this study, we further investigated the role of AE1 in gastric carcinogenesis and the anti-tumour effects of AE1-targeted small interfering RNAs (siRNAs) in two experimental models of gastric cancer., Experimental Approach: Molecular and cellular experiments were performed to elucidate the role of AE1 in the malignant transformation of gastric epithelium and the effects of AE1-targeted siRNAs on gastric cancer cells. The anti-tumour effect of the siRNA was evaluated in vivo in two mouse models, nude mice implanted with human gastric cancer xenografts (Model I) and mice with gastric cancer induced by N-methyl-N-nitrosourea (MNU) and Helicobacter pylori (Model II)., Key Results: AE1 was found to increase gastric carcinogenesis by promoting cell proliferation. AE1-targeted siRNA significantly suppressed AE1 expression and hindered tumour growth. Furthermore, the siRNA markedly decreased the detection rate of gastric cancer, in parallel with an increase in atypical hyperplasia at the end of the experiment in Model II., Conclusions and Implications: Knockdown of AE1 expression in gastric mucosa by administration of synthetic siRNAs significantly inhibits the growth of gastric cancer and decreases the detection rate of this tumour in experimental mice. These results suggest that AE1 is potentially a key therapeutic target and the silencing of AE1 expression in gastric mucosa could provide a new therapeutic approach for treating gastric cancer., (© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.)

Background: The relationship between Helicobacter pylori infection and gastric antrum adenocarcinoma (GAA) has previously been demonstrated and supported with strong epidemiological evidence. However, the role of genetic polymorphism of X-ray cross-complementing group 3 (XRCC3) Thr241Met (rs#861539), which may be involved in the repair of DNA double-strand breaks caused by carcinogens such as CagA, a protein produced by H. pylori, has been less well elaborated., Methods: We conducted a hospital-based case-control study, including 721 patients with pathologically confirmed GAA and 989 individually matched controls without any evidence of tumors or precancerous lesions to evaluate the associations between this polymorphism and GAA risk in the Guangxi population. XRCC3 codon 241 genotypes and CagA status were determined using TaqMan-PCR and PCR, respectively., Results: Increased risks of GAA were found for cagA-positive individuals [odds ratio (OR), 7.31; 95% confidence interval (CI), 5.87-9.09]. We also found that individuals with the XRCC3 genotypes with codon 241 Met (namely XRCC3-TM or XRCC3-MM) had an increased risk of GAA compared with those with the homozygote of XRCC3 codon 241 Thr alleles (namely XRCC3-TT, adjusted ORs 1.76 and 3.73; 95% CIs 1.37-2.24 and 2.66-5.23, respectively). The risk of GAA, moreover, appeared to differ more significantly among individuals featuring cagA-positive status, whose adjusted ORs (95% CIs) were 11.31 (8.34-15.33) and 27.48 (15.17-49.78), respectively., Conclusion: These results suggest that XRCC3 Thr241Met polymorphism may be associated with the risk of GAA related to CagA., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

Aim:   The X-ray repair cross-complementing group 7 (XRCC7) plays an important role in the repair of DNA double-strand breaks by nonhomologous end-joining repair (NEJR) pathway. However, the role of XRCC7 polymorphisms (rs#7003908 and rs#10109984) possibly influencing NEJR capacity in hepatocellular carcinoma (HCC) induced by aflatoxin B1 (AFB1) has not been well elaborated., Methods:   This hospital-based case-control study, including 348 patients with newly diagnosed HCC and 597 controls without any evidence of liver diseases, was conducted to elucidate the association between these two polymorphisms and the risk of HCC related to AFB1 exposure among a Guangxi population from a high AFB1-exposure area by means of TaqMAN-polymerase chain reaction technique., Results:   We observed that HCC patients featured higher AFB1 exposure than control group (odds ratios [OR] = 6.49 and 6.75 for exposure years and exposure levels, respectively). Furthermore, these individuals with the genotypes of XRCC7 rs#7003908 G alleles (namely XRCC7-TG or -GG), compared the homozygote of XRCC7 rs#7003908 T alleles (XRCC7-TT), faced increasing risk of HCC (OR, 3.45 and 5.04; 95% confidence intervals [CIs], 2.40-4.94 and 3.28-7.76, respectively). We also found some evidence that this polymorphism interacted with AFB1-expousure years or levels in the process of HCC carcinogenesis. Additionally, XRCC7 rs#7003908 polymorphism was correlated with the levels of AFB1-DNA adducts (r = 0.142, P < 0.001). XRCC7 rs#10109984 polymorphism, however, did not modify the risk of HCC related to AFB1 exposure (P > 0.05)., Conclusion:   These data suggest that XRCC7 rs#7003908 polymorphism may be one of the genetic modifiers for AFB1-related HCC among Guangxi population., (© 2011 The Japan Society of Hepatology.)

Unlabelled: Genetic polymorphisms in DNA repair genes may influence individual variations in DNA repair capacity, and this may be associated with the risk and outcome of hepatocellular carcinoma (HCC) related to aflatoxin B1 (AFB1) exposure. In this study, we focused on the polymorphism of xeroderma pigmentosum complementation group C (XPC) codon 939 (rs#2228001), which is involved in nucleotide excision repair. We conducted a case-control study including 1156 HCC cases and 1402 controls without any evidence of hepatic disease to evaluate the associations between this polymorphism and HCC risk and prognosis in the Guangxi population. AFB1 DNA adduct levels, XPC genotypes, and XPC protein levels were tested with a comparative enzyme-linked immunosorbent assay, TaqMan polymerase chain reaction for XPC genotypes, and immunohistochemistry, respectively. Higher AFB1 exposure was observed among HCC patients versus the control group [odds ratio (OR) = 9.88 for AFB1 exposure years and OR = 6.58 for AFB1 exposure levels]. The XPC codon 939 Gln alleles significantly increased HCC risk [OR = 1.25 (95% confidence interval = 1.03-1.52) for heterozygotes of the XPC codon 939 Lys and Gln alleles (XPC-LG) and OR = 1.81 (95% confidence interval = 1.36-2.40) for homozygotes of the XPC codon 939 Gln alleles (XPC-GG)]. Significant interactive effects between genotypes and AFB1 exposure status were also observed in the joint-effects analysis. This polymorphism, moreover, was correlated with XPC expression levels in cancerous tissues (r = -0.369, P < 0.001) and with the overall survival of HCC patients (the median survival times were 30, 25, and 19 months for patients with homozygotes of the XPC codon 939 Lys alleles, XPC-LG, and XPC-GG, respectively), especially under high AFB1 exposure conditions. Like AFB1 exposure, the XPC codon 939 polymorphism was an independent prognostic factor influencing the survival of HCC. Additionally, this polymorphism multiplicatively interacted with the xeroderma pigmentosum complementation group D codon 751 polymorphism with respect to HCC risk (OR(interaction) = 1.71)., Conclusion: These results suggest that the XPC codon 939 polymorphism may be associated with the risk and outcome of AFB1-related HCC in the Guangxi population and may interact with AFB1 exposure in the process of HCC induction by AFB1.

Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of gastric antrum adenocarcinoma (GAA) related to Helicobacter pylori infection. This study, including 361 GAAs and 616 controls without any evidence of tumors, was designed to evaluate the association between the polymorphisms of DNA repair genes XPC Ala499Val (RS#2228000) and Lys939Gln (RS#2228001), XPD Lys751Gln (RS#13181), and XRCC4 Ala247Ser (RS#3734091) and Ser298Asn (RS#1805377), and GAA risk for Guangxi population by means of TaqMan-PCR analysis. Increased risks of GAA were found for individuals with H. pylori positive [odds ratio (OR), 2.48; 95% confidence interval (CI), 1.84-3.33] or cagA positive (OR, 7.34; 95% CI, 5.46-9.87). No differences were observed among the studied groups with regard to the genotype distribution of XPC codons 499 and 939 and of XRCC4 codon 247; but XPD codon 751 genotypes with Gln [ORs (95% CI) were 2.67 (1.98-3.58) and 3.97 (2.64-5.99) for Lys/Gln and Gln/Gln, respectively] and XRCC4 codon 298 genotypes with Asn [ORs (95% CI) were 3.01 (2.21-4.10) and 4.78 (3.24-7.05) for Ser/Asn and Asn/Asn, respectively] increased the risk of GAA. Interestingly, there was an interactive effect between the risk genotypes of these two genes and cagA-positive status in the GAA risk (OR(interact) = 2.05 and 2.08, respectively). However, we did not find the gene-H. pylori-status interaction effects on the risk of GAA (P(interact) > 0.05). The results suggested that the polymorphisms of XPD codon 751 and XRCC4 codon 298 are associated with an increased risk of developing H. pylori-related GAA among Guangxi population., ((c) 2010 Wiley-Liss, Inc.)

Background: Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of hepatocellular carcinoma (HCC) related to the exposure of aflatoxin B1 (AFB1). In this study, we have focused on the polymorphisms of xeroderma pigmentosum complementation group D (XPD) codon 312 and 751 (namely Asp312Asn and Lys751Gln), involved in nucleotide excision repair., Methods: We conducted a case-control study including 618 HCC cases and 712 controls to evaluate the associations between these two polymorphisms and HCC risk for Guangxi population by means of TaqMan-PCR and PCR-RFLP analysis., Results: We found that individuals featuring the XPD genotypes with codon 751 Gln alleles (namely XPD-LG or XPD-GG) were related to an elevated risk of HCC compared to those with the homozygote of XPD codon 751 Lys alleles [namely XPD-LL, adjusted odds ratios (ORs) were 1.75 and 2.47; 95% confidence interval (CIs) were 1.30-2.37 and 1.62-3.76, respectively]. A gender-specific role was evident that showed an higher risk for women (adjusted OR was 8.58 for XPD-GG) than for men (adjusted OR = 2.90 for XPD-GG). Interestingly, the interactive effects of this polymorphism and AFB1-exposure information showed the codon 751 Gln alleles increase the risk of HCC for individuals facing longer exposure years (Pinteraction = 0.011, OR = 0.85). For example, long-exposure-years (> 48 years) individuals who carried XDP-GG had an adjusted OR of 470.25, whereas long-exposure-years people with XDP-LL were at lower risk (adjusted OR = 149.12). However, we did not find that XPD codon 312 polymorphism was significantly associated with HCC risk., Conclusion: These findings suggest that XPD Lys751Gln polymorphism is an important modulator of AFB1 related-HCC development in Guangxi population.

Purpose: The relationship between aflatoxin B1 (AFB1) exposure and hepatocellular carcinoma (HCC) has been previously demonstrated and supported with strong epidemiological evidence. However, the role of genetic polymorphism of X-ray cross-complementing group 3 (XRCC3) codon 241 (namely: Thr241Met), which may be involved in the repair of DNA double-strand breaks caused by carcinogens such as AFB1, been less well elaborated., Methods: We conducted a case-control study including 491 cases and 862 controls to evaluate the associations between this polymorphism and HCC risk for Guangxi population by means of polymerase chain reaction-restriction fragment length polymorphism analysis., Results: We found that individuals with the XRCC3 genotypes with codon 241 Met (namely XRCC3-TM or XRCC3-MM) had an increased risk of HCC than those with the homozygote of XRCC3 codon 241 Thr alleles (namely XRCC3-TT, adjusted odds ratios 2.22 and 7.19; 95% confidence intervals 1.72-2.88 and 4.52-11.42, respectively). The risk of HCC, moreover, did appear to differ more significantly among individuals featuring high-level AFB1-DNA adducts, whose adjusted odds ratios (95% confidence intervals) were 11.59 (5.73-23.47) and 37.54 (16.32-86.32), respectively., Conclusions: These findings support the hypothesis that the XRCC3 Thr241Met polymorphism may be associated with the risk of AFB1-related HCC among the Guangxi population.

Objective: To explore the association of the Thr241Met polymorphism of X-ray cross-complementing group 3 (XRCC3) gene with genetic susceptibility to aflatoxin B1(AFB-1)-related hepatocellular carcinoma (HCC)in Guangxi population., Methods: We conducted a hospital-based case-control study, including 257 HCC cases and 711 controls without cancers or liver diseases. The XRCC3 Thr241Met polymorphism was analyzed by PCR., Results: The XRCC3 genotypes XRCC3-Thr/Met or XRCC3-Met/Met were related with an elevated risk of HCC. The risk of HCC was associated with the number of mutant Met copies (adjusted OR were 2.20 and 8.56 for XRCC3-Thr/Met and Met/Met, respectively); moreover, there seemed to be combined effects for HCC risk between the variant genotypes and AFB1-DNA adduct levels from peripheral blood leukocytes (adjusted OR was 2.34 to 20.44, P < 0.01)., Conclusion: These results suggested that XRCC3 polymorphism may be associated with the risk of AFB1- related HCC among the Guangxi population, and interacts with AFB1 exposure in the development of HCC induced by AFB1.

In hepatocellular carcinoma (HCC), hotspot mutation in codon 249 of the p53 gene has been associated with exposure to aflatoxin B1 (AFB1). While the polymorphism of DNA repair gene X-ray repair cross-complementary group 1 (XRCC1) Arg399Gln may be related with AFB1-DNA adducts and gene mutations. Five hundred one HCCs were included in this study to investigate the role of the XRCC1 codon 399 polymorphism on hotspot mutation in codon 249 of the p53 gene. The genotypes of XRCC1 codon 399 and p53 codon 249 were examined by PCR-RFLP. The HCC patients with XRCC1 genotypes with 399 Gln (namely: XRCC1-AG/GG) exhibited a significantly higher frequency of the p53 hotspot mutations in codon 249 than those with the wild-type homozygote of XRCC1 [namely: XRCC1-AA, adjusted odds ratio (OR) = 6.77, 95% confidence interval (CI) = 4.34-10.57]. Compared with those individuals who did express XRCC1-AA as reference (OR = 1), moreover, individuals featuring XRCC1-AG/GG and AFB1-DNA adducts did experience a significantly greater frequency of the hotspot mutation in codon 249 of the p53 gene (adjusted OR = 28.37, 95% CI = 13.19-61.02, P < 0.01). This study suggests that the XRCC1 Arg399Gln polymorphism and AFB1-DNA adducts are associated with the increased frequency of the p53 mutations in codon 249., ((c) 2007 Wiley-Liss, Inc.)

Many low density lipoprotein (LDL) apheresis systems have been applied to patients with hyperlipidemia, but these systems usually work on the basis of complicated equipment and the cost of treatment is expensive. In order to achieve effective treatment of hyperlipidemia at a lower cost, we developed a new LDL apheresis system with dextran sulfate (LAS-DS). In this study, 50 patients with hyperlipidemia were treated 120 times with the new LAS-DS. In each treatment, 600 +/- 100 mL of plasma (equal to approximately 25% of the total plasma of patients) was collected by apheresis, and DS solution and calcium chloride solution were added into the collected plasma as LDL absorber and catalyzer, respectively. DS selectively binds LDL cholesterol (LDL-C) under the catalysis of calcium ion and the LDL-C-DS complex is removed by centrifugation. The treated plasma was transfused back into the patients and the excessive calcium in the plasma was removed by the cation exchange column integrated in the transfusion set. After treatment with our new system, the acute mean LDL-C reduction was 97% in the apheresis plasma of hyperlipidemia patients. The corresponding reduction was 55.2% and 69.4% for total cholesterol and total triglyceride. There were insignificant reductions of high density lipoprotein cholesterol (HDL-C) and albumin. The new LDL apheresis system with DS that we developed is very simple to operate without relying on complicated equipment, and it can achieve significant clinical results at a much lower cost compared with existing systems. Based on this study we think the new system can provide a safe, effective and much cheaper means for the treatment of hyperlipidemia patients.

Aim: High incidence rates of hepatocellular carcinoma (HCC) in Guangxi, China, are primarily due to heavy aflatoxin B1 (AFB1) exposure via corn and groundnut consumption. This study was designed to examine the polymorphisms associated of three carcinogen-metabolizing genes (namely: GSTM1, GSTT1, and HYL1*2) and one DNA-repair gene (namely: XRCC1), and investigate their role as susceptibility markers for HCC., Methods: We conducted a case-control study including 257 cases of cancer and 649 hospital-based age, sex, ethnicity, and hepatitis B virus infection-matched controls to examine the role of genetic polymorphisms of four genes (GSTM1, GSTT1, HYL1*2, and XRCC1) in the context of HCC risk for the Guangxi population. Genomic DNA isolated from 2ml whole blood was used to genotype GSTM1, GSTT1, HYL1*2, and XRCC1 by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis., Results: GSTT1-null genotype was not significantly associated with the risk of HCC, but GSTM1-null genotype [adjusted odds ratio (OR)=2.29, 95% confidence interval (CI)=1.59-3.31], HYL1*2 genotypes with 113 His allele (namely: YH/HH, adjusted OR=2.55, CI=1.78-3.65), and XRCC1 genotypes with 399 Gln allele (namely: AG/GG, adjusted OR=2.47, CI=1.72-3.54) increased the HCC risk. Compared with those individuals who did not express any putative risk genotypes as reference (OR=1), individuals featuring all of the putative risk genotypes [GSTM1-null, HYL1*2-YH/HH, and XRCC1-AG/GG] did experience a significantly greater cancer risk (adjusted OR=10.83, CI=5.44-21.59, P(interaction)<0.01). Additionally, the risk of HCC did appear to differ more significantly among individuals featuring risk genotypes and high-level or long-term AFB1 exposure, whose adjusted ORs (CIs) were 52.44 (17.51-157.08) and 326.93 (38.58-2770.52), respectively., Conclusions: The results suggest that carcinogen metabolism and DNA-repair pathways may simultaneously modulate the risk of HCC for Guangxi population, and, particularly for these having high-level or long-term AFB1 exposure.

Objective: To study the association between susceptibility to aflatoxin B1 (AFB1)-related hepatocellular carcinoma(HCC) and the null genotypes of detoxication gene gstM1 and gstT1., Methods: Peripheral blood white blood cells DNA samples were obtained from all the subjects including 140 HCC cases and 536 controls from AFB1 high risk area Guangxi. gstM1 and gstT1 polymorphisms were detected by polymerase chain reaction technique., Results: (1) gstM1- and gstT1-present were associated with decreasing risk of HCC. gstM1- and gstT1-null were associated with the increasing risk of HCC [adjusted OR (95 % CI) = 2.07 (1.20-3.57) and 1.44 (0.85-2.45), respectively]; (2) The appearance of both gstM1- and gstT1-null genotypes were more susceptible to HCC than either one of them(adjusted OR and 95% CI are 2.43 and (1.19-4.97); (3) From low/median to high level of AFB1 exposure, both gstM1- and gstTl-null genotypes were associated with significantly conspicuous increasing risk of HCC [adjusted OR(95% CI) = 12.76(5.38-30.24) and 7.82(3.61-16.90) respectively]., Conclusion: It was suggested that: genetic polymorphisms of gstM1 and gstT1 were susceptible to HCC; individuals who were gstM1- or gstT1-null would have an increasing risk of developing HCC while individuals with both nulls were more susceptible. There was evidence of interaction between gstM1- and gstT1-null and the level of AFB1 exposure which was associated with the increasing risk of HCC.

Objectives: To investigate the association between susceptibility to aflatoxin B1(AFB1)-related hepatocellular carcinoma (HCC) and the polymorphism of detoxication gene GSTM1., Methods: The peripheral white blood cell DNA samples were obtained from all the subjects including 140 HCC cases and 536 controls from an AFB1 high risk area in Guangxi province. The GSTM1 polymorphism was detected using PCR technique., Results: (1) The GSTM1-present was associated with a decreased HCC risk. The GSTM1-null was associated with an increased HCC risk [adjusted OR (95% CI)= 2.07 (1.20-3.57)]. (2) In the cohorts of both low/median and high exposure levels of AFB1, GSTM1-null genotype was associated with a conspicuous significantly increased risk for HCC [adjusted OR (95% CI) = 1.92 (0.92-4.00) and 1.80 (0.77-4.17)]., Conclusion: The results suggest that genetic polymorphism of GSTM1 was susceptible to HCC and individuals who are GSTM1-null have an increased risk of developing HCC. There is evidence of interaction between GSTM1 polymorphism and AFB1 exposure, especially with low/median degrees of AFB1 exposure.