Expressions of Peptidoglycan Recognition Protein 1, Neuron Towards Axon Guidance Factor-1 and miR-142-3p and Their Correlations in Patients with Rheumatoid Arthritis.

Purpose: We aimed to explore the expressions of peptidoglycan recognition protein 1 (PGLYRP-1), neuron towards axon guidance factor-1 (Netrin-1) and miR-142-3p and their correlations in patients with rheumatoid arthritis. Patients and Methods: Sixty patients with rheumatoid arthritis treated from January 2022 to January 2023 were enrolled as a rheumatoid group, 30 patients with osteoarthritis were selected as an osteoarthritis group, and 30 healthy volunteers were recruited as a control group. The enzyme-linked immunosorbent assay, Western blotting and reverse transcriptase-polymerase chain reaction were employed to measure the expressions of PGLYRP-1, Netrin-1 and miR-142-3p, respectively. The correlations among PGLYRP-1, Netrin-1 and miR-142-3p expressions in patients with rheumatoid arthritis were analyzed. Results: In patients with rheumatoid arthritis, PGLYRP-1 expression was negatively correlated with Netrin-1 expression (r=-0.570, P=0.001) but positively correlated with miR-142-3p expression (r=0.599, P=0.001), and a negative correlation was found between Netrin-1 and miR-142-3p expressions (r=-0.468, P=0.001). The combined detection of PGLYRP-1, Netrin-1 and miR-142-3p was more sensitive and less specific for predicting the prognosis of patients with rheumatoid arthritis than the measurement of a single marker (P<0.05). Conclusion: The combined measurement of PGLYRP-1, Netrin-1 and miR-142-3p has a predictive value for the prognosis of patients with rheumatoid arthritis.

[IL-6 Regulates the Chemosensitivity of Drug-Resistant Multiple Myeloma Cell Lines to Bortezomib through STAT3/Notch Signaling Pathway].

OBJECTIVE: To investigate the effect of interleukin-6 (IL-6) on the chemosensitivity of drug-resistant multiple myeloma (MM) cell lines to bortezomib (BTZ) and its mechanism. METHODS: Peripheral blood samples were collected from patients with BTZ-resistant MM before and after treatment. Human MM cell lines KM3 and KM3/BTZ were cultured in vitro. ELISA was used to detect the content of IL-6 in peripheral blood of MM patients, KM3 and KM3/BTZ cells. CCK-8 assay was used to detect the drug sensitivity of KM3 and KM3 / BTZ cells to BTZ. KM3 / BTZ cells were divided into KM3/BTZ control group (normal culture for 48 h), IL-6 neutralizing antibody Anti-IL-6 group (500 ng/ml Anti-IL-6 treated for 48 h), BTZ group (300 ng/ml BTZ treated for 48 h), BTZ + Anti-IL-6 group (300 ng/ml BTZ and 500 ng/ml Anti-IL-6 treated for 48 h). The proliferation activity of KM3 / BTZ cells was detected by CCK-8 assay. The cell cycle distribution of KM3/BTZ cells was detected by flow cytometry. The apoptosis of KM3/BTZ cells was detected by Annexin V-FITC/PI double staining. The mRNA expression levels of IL-6, Notch1, signal transducer and activator of transcription 3 (STAT3) in KM3/BTZ cells were detected by real-time fluorescent quantitative PCR (qRT-PCR), and the protein expression levels of IL-6, Notch1, STAT3 in KM3/BTZ cells were detected by Western blot. RESULTS: The level of IL-6 in peripheral blood of patients with BTZ-resistant MM after treatment was significantly higher than that before treatment (P<0.05). The level of IL-6 in KM3/BTZ cells was significantly higher than that in KM3 cells (P<0.05). The sensitivity of KM3/BTZ cells to BTZ was significantly lower than that of KM3 cells (P<0.05), and the resistance index (RI) was 19.62. Anti-IL-6 and BTZ could inhibit the proliferation of KM3 / BTZ cells, block cell cycle, and induce apoptosis (P<0.05). Compared with single drug treatment, the combined effect of Anti-IL-6 and BTZ was more obvious on KM3/BTZ cells (P<0.05), and significantly down regulated the mRNA and protein expression of IL-6, Notch1 and STAT3 in KM3/BTZ cells (P<0.05). CONCLUSION: Antagonizing IL-6 can increase the chemosensitivity of MM cells to BTZ, and IL-6 may reduce the sensitivity of MM cells to BTZ through STAT3/Notch signaling pathway.

Long non-coding RNA LINC01793 as a potential diagnostic biomarker of hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: There is growing evidence that long non-coding RNAs (lncRNAs) play important roles in the progression of hepatocellular carcinoma (HCC) and may serve as diagnostic markers. This study investigates the diagnostic efficiency of the long intergenic non-protein-coding RNA 1793 (LINC01793) in hepatitis B virus (HBV)-related HCC. METHODS: Bioinformatics methods were used to screen the aberrantly expressed lncRNAs in HCC tissues based on The Cancer Genome Atlas (TCGA). Quantitative reverse transcription polymerase chain reaction was performed to assess the expression of the candidate lncRNAs in tissues, cells and whole blood samples of patients with HBV-related HCC, liver cirrhosis (LC), chronic hepatitis (CHB), and healthy controls. Then, the correlations between LINC01793 and clinical characteristics were analyzed. Finally, the diagnostic value of LINC01793 was explored based on the receiver operating characteristic curve. RESULTS: LINC01793 was remarkably upregulated in the HCC tissues and cells. It was highly expressed in the whole blood of the HBV-related HCC patients, unlike in that of the healthy controls and of the CHB and LC patients. Subsequent analysis revealed that high LINC01793 was related to the Barcelona Clinic Liver Cancer (P = 0.007), tumor invasion (P = 0.042), the number of tumors (P = 0.031) and serum level of alanine aminotransferase(p = 0.022). The areas under the curve of LINC01793, for distinguishing HCC from healthy controls, CHB and LC patients, were 0.824, 0.767 and 0.756, respectively. In addition, the combination of LINC01793 with alpha fetoprotein (AFP) had a stronger diagnostic value than LINC01793 or AFP alone in AFP-negative HCC patients. CONCLUSION: High expression of LINC01793 is correlated with adverse clinical characteristics and can serve as a non-invasive biomarker of HCC.

MiR-197-3p reduces bortezomib resistance in multiple myeloma by inhibiting IL-6 expression in a MEAF6-dependent manner.

OBJECTIVE: This study investigated the mechanism by which miR-197-3p regulated IL-6 expression and reduced bortezomib (BTZ) resistance in multiple myeloma (MM). METHODS: The expression of miR-197-3p, MEAF6 and IL-6 in BTZ-resistant MM cells was measured. The effects of miR-197-3p/IL-6 axis on drug resistance and cell apoptosis were evaluated in BTZ-resistant MM cells. The expression of JAK/STAT3 proteins was detected by Western blotting. The binding of miR-197-3p to MEAF6 mRNA was verified using molecular biology techniques. Chromatin immunoprecipitation was used to assess histone acetylation in IL-6 promoter. The effect of miR-197-3p on MM growth was investigated in a mouse model. RESULTS: MiR-197-3p was lowly expressed, and MEAF6 and IL-6 were highly expressed in BTZ-resistant MM cells. Overexpression of miR-197-3p increased drug sensitivity in BTZ-resistant MM cells, which was counteracted by overexpression of IL-6. Overexpression of miR-197-3p also inhibited MM growth in vivo. Mechanistically, miR-197-3p suppressed the expression of IL-6 by inhibiting MEAF6-mediated histone H3 acetylation in IL-6 promoter. The miR-197-3p/IL-6 axis also inhibited the activation of JAK/STAT3 signaling pathway. CONCLUSION: miR-197-3p reduces BTZ resistance in MM by inhibiting acetylation-mediated expression of IL-6 and by inactivating JAK/STAT3 signaling pathway.

The Significance of Blood Index and Biochemistry Index in Patients with Rheumatoid Arthritis.

BACKGROUND: The aim of this study is to demonstrate the clinical significance of the platelet-to-lymphocyte ratio (PLR) and the ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) in patients with rheumatoid arthritis (RA). METHODS: A total of 215 patients with RA, 115 patients with osteoarthritis (OA), and 303 healthy controls (HCs) were included in this study. Data on the AST and ALT levels were collected from liver function test reports, and data on the number of platelets and lymphocytes were obtained from a routine blood analysis. Moreover, all the laboratory parameters of patients with RA, patients with OA, and HCs were retrospectively analyzed. RESULTS: The results obtained in this study showed that patients with RA had the highest PLR and AST/ALT ratio, whereas HCs had the lowest ratios (p < 0.05). Receiver operating characteristic (ROC) analysis showed that PLR + AST/ALT can produce high sensitivity and moderate specificity, distinguishing patients with RA from HCs, with a sensitivity of 91.1%, specificity of 75.3%, and area under the ROC curve (AUC) of 0.907. Spearman's analysis showed the PLR is negatively correlated with the erythrocyte sedimentation rate and C-reactive protein levels (p < 0.005). CONCLUSIONS: Combined detection of PLR and AST/ALT is better than each indicator individually and can improve the diagnostic efficiency of RA.

PIN1 genetic polymorphisms and the susceptibility of HBV-related hepatocellular carcinoma in a Guangxi population.

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) plays a critical role in different signaling pathways, cell cycle progression and proliferation, and gene expression, and it has been found to overexpress in many tumor tissues. Recently, researchers have found that PIN1 gene polymorphisms may alter the function of protein and be associated with the risk of cancer. The present study analyzed three common polymorphisms in promoter regions (rs2233678 and rs2233679) and in exon2 (rs2233682) of the PIN1 gene in 254 patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and 235 healthy controls in a Guangxi study population to determine whether any relationship exists between the polymorphisms and the risk of HBV-related HCC. The results revealed that the rs2233679 TT genotype was associated with increased risk of HCC with HBV infection [odds ratio (OR) = 2.04, 95 % confidence interval (95 % CI) = 1.13-3.69, p = 0.019]. This association was stronger in men than in women (OR = 2.17, 95 % CI = 1.09-4.34, p = 0.028) as well as in men 50 years of age and older (OR = 3.91, 95 % CI = 1.29-11.80, p = 0.016); moreover, for alcohol drinkers, being a carrier of the PIN1 rs2233679 CT genotype had a moderately increased risk of HCC (OR = 3.98, 95 % CI = 1.02-15.57, p = 0.047). In contrast, people carrying the rs2233682 GA genotype and A alleles were 0.23 times more likely to develop HCC (OR = 0.23, 95 % CI = 0.06-0.87, p = 0.031 and OR = 0.23, 95 % CI = 0.06-0.87, p = 0.030). No such associations were found in the PIN1 rs2233678 polymorphisms between the HBV-related HCC cases and the controls. In addition, the haplotype GCA was found to be a high protection factor for HCC with HBV infection (OR = 0.14, 95 % CI = 0.03-0.62, p = 0.003). In conclusion, this study's findings suggest that the PIN1 rs2233679 TT genotype, the rs2233682GA genotype, and A alleles might be associated with the HBV-related HCC in a Guangxi study population.

Association between hypoxia-inducible factor-1α gene polymorphisms and risk of chronic hepatitis B and hepatitis B virus-related liver cirrhosis in a Chinese population: a retrospective case-control study.

BACKGROUND: Our recent study demonstrated a significant association between HIF-1α polymorphisms and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Since chronic hepatitis B (CHB), liver cirrhosis (LC), and HCC are progressive stages of chronic HBV infection, the aim of this study is to further determine if HIF-1α polymorphisms are associated with CHB and HBV-related LC. METHODS: Two HIF-1α polymorphisms (rs11549465 and rs115494657) were examined in 173 healthy controls, 153 patients with CHB, and 132 patients with HBV-related LC, using the polymerase chain reaction-restriction fragment length polymorphism method. DNA sequencing was also used to validate the genotype results. RESULTS: There were no significant differences regarding the HIF-1α rs11549465 and rs115494657 polymorphisms between the patient groups and the healthy controls, no matter the genotypes, alleles, or haplotypes. To exclude the potential influence of HBV infection in the association between HIF-1a and HBV-related LC, a comparison between the LC patients and HBV infected patients was also conducted, but a similar insignificant result was found. CONCLUSIONS: Our data suggest that the HIF-1α gene polymorphisms might not contribute to the development of CHB and HBV-related LC in a Chinese population.

Genetic polymorphisms in hypoxia-inducible factor-1a gene and its association with HBV-related hepatocellular carcinoma in a Chinese population.

Previous studies have demonstrated that hypoxia-inducible factor-1a (HIF-1a) may play a vital role in the pathogenesis of hepatocellular carcinoma (HCC). However, the relationship between HIF-1a polymorphisms and HCC has not been thoroughly investigated. The aim of this study is to determine whether HIF-1a polymorphisms are associated with HCC through a case-control study. Two polymorphisms in the HIF-1a gene (rs11549465 and rs115494657) were examined in 157 hepatitis B virus (HBV)-related HCC patients and 173 healthy controls using the polymerase chain reaction-restriction fragment length polymorphism method. DNA sequencing was used to validate genotype results. There were no significant differences in the genotype and allele frequencies of HIF-1a rs11549465 and rs115494657 polymorphisms between the HBV-related HCC patients and healthy controls. However, the data revealed that subjects with the CG haplotype have a higher susceptibility to HBV-related HCC [odds ratio (OR)=2.327, 95% confidence interval (CI)=1.578-4.721, P=0.008]. In contrast, the CA haplotype was associated with a significantly decreased risk of HBV-related HCC (OR=0.416, 95% CI=0.172-0.910, P=0.025). HIF-1a rs11549465 and rs115494657 polymorphisms appeared to be irrelevant to HBV-related HCC. However, the HIF-1a CG and CA haplotypes might be a risk factor and a protective marker, respectively, for HBV-related HCC in a Chinese population. Further investigations with a larger sample size may be required to validate the genetic effects of HIF-1a polymorphisms on HBV-related HCC.

Establishing reference values for blood urea nitrogen and serum creatinine in Chinese Han ethnic adult men.

BACKGROUND: The aim was to calculate the two-sided 95th percentile reference values for blood urea nitrogen (BUN) and serum creatinine (SCr) in Chinese Han ethnic adult men. METHODS: Serum samples were collected from Chinese Han ethnic adult men aged 20 - 69 years. After screening based on the inclusion and exclusion criteria, a total of 1575 individuals were enrolled in our study. BUN and SCr values were measured on an automatic analyzer (Dade Behring, USA). The data was analyzed and calculated using nonparametric statistical methods. RESULTS: BUN and SCr values were not normally distributed. The reference values were in the range 3.3 - 7.5 mmol/L for BUN and 64 - 113 micromol/L for SCr. BUN levels were significantly lower in the smoking group than the non-smoking group (Z = -4.52, p < 10(-5)). An increase with age was observed in BUN levels (r(s) = 0.172, p < 0(-5)) and lower SCr levels were weakly associated with the older subjects (r(s) = -0.071, p = 0.005). Moreover, it was found that higher Body Mass Index (BMI) tended toward higher levels of SCr (r(s) = 0.118, p < 10(-5)). CONCLUSIONS: The reference values established for BUN and SCr exhibit a slight deviation compared to those developed in previous studies. We propose reference values of BUN for smokers and non-smokers be constructed, and age- and BMI-specific reference values be applied in clinical laboratories.

Association of PvuII and XbaI polymorphisms in estrogen receptor alpha gene with the risk of hepatitis B virus infection in the Guangxi Zhuang population.

BACKGROUND AND OBJECTIVE: Available evidence has suggested that estrogen receptor alpha (ESR1) is implicated in the pathogenic process of hepatitis B infection. Therefore, we evaluated the association of PvuII (rs2234693) and XbaI (rs9340799) in ESR1 and HBV infection in Guangxi Zhuang populations. METHODS: A total of 389 subjects were divided into four groups: 112 patients with chronic hepatitis B (CHB), 65 patients with hepatitis B virus (HBV)-related liver cirrhosis (LC), 107 patients with HBV-related hepatocellular carcinoma (HCC), and 105 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect ESR1 gene PvuII and XbaI polymorphisms. RESULTS: Compared with healthy controls, binary logistic regression analyses show that the CC genotype of PvuII was associated with a significantly increased susceptibility to CHB compared with the TT genotype (OR=1.760, 95% CI 1.316-2.831; p=0.044). The PvuII CC genotype was also associated with significantly increased risk of HBV-related LC (OR=1.921, 95% CI 1.342-2.478; p=0.043). Similarly, the subjects bearing the homozygous CC genotype of PvuII polymorphism also had more than a 1.7-fold increased risk for development of HCC (OR=1.748, 95% CI 1.313-2.787; p=0.010) compared with those bearing the TT genotype. Furthermore, the AC haplotype was associated with a significantly increased risk of HCC with an OR of 1.456 (p=0.003). In contrast, there were no significant differences in the genotype and allele of XbaI polymorphisms in the ESR1 gene between the groups of patients and healthy controls. In addition, ESR1 polymorphisms were not significantly associated with susceptibility to HBV-related HCC when using CHB and LC patients as references. CONCLUSION: We conclude that the CC genotype of PvuII in ESR1 is associated with an increased risk of CHB, HBV-related LC and HCC in Guangxi Zhuang populations.

The NQO1 Pro187Ser polymorphism and breast cancer susceptibility: evidence from an updated meta-analysis.

BACKGROUND NAD(P)H: quinone oxidoreductase 1 (NQO1) plays a central role in catalyzing the two-electron reduction of quinoid compounds into hydroquinones. The NQO1 Pro187Ser polymorphism was found to correlate with a lower enzymatic activity, which may result in increased incidence of carcinomas including breast cancer. Previous studies investigating the association between NQO1 Pro187Ser polymorphism and breast cancer risk showed inconsistent results. We performed a meta-analysis to summarize the possible association. METHODS: All studies published from January 1966 to February 2014 on the association between NQO1 Pro187Ser polymorphism and breast cancer risk were identified by searching electronic databases PubMed, EMBASE, Cochrane library, and Chinese Biomedical Literature database (CBM). The association between NQO1 Pro187Ser polymorphism and breast cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). RESULTS: Ten studies with 2,773 cases and 4,076 controls were finally included in the meta-analysis. We did not observe a significant association between NQO1 Pro187Ser polymorphism and breast cancer risk when all studies were pooled into the meta-analysis. In subgroup analysis by ethnicity, significant increased breast cancer risk was found in Caucasians (Ser/Pro vs. Pro/Pro: OR=1.145, 95% CI=1.008-1.301, P=0.038; Ser/Ser+Ser/Pro vs. Pro/Pro: OR=1.177, 95% CI=1.041-1.331, P=0.009). When stratified by source of control, significant increased breast cancer risk was found in population-based studies (Ser/Pro vs. Pro/Pro: OR=1.180, 95% CI=1.035-1.344, P=0.013; Ser/Ser+Ser/Pro vs. Pro/Pro: OR=1.191, 95% CI=1.050-1.350, P=0.007). However, in subgroup analyses according to menopausal status, quality score, and HWE in controls, no any significant association was detected. CONCLUSIONS: Our meta-analysis provides the evidence that the NQO1 Pro187Ser polymorphism contributed to the breast cancer susceptibility among Caucasians. Further large and well-designed studies are needed to confirm this association. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1248639991252504.

Association between OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and breast cancer risk: a meta-analysis.

BACKGROUND: The base excision repair (BER) pathway removes DNA damage caused by ionizing radiation, reactive oxidative species and methylating agents. OGG1 and APE1 are two important genes in the BER pathway. Many epidemiological studies have evaluated the association between polymorphisms in the two BER genes (OGG1 Ser326Cys and APE1 Asp148Glu) and breast cancer risk. However, the results are inconsistent. METHODS: We searched the electronic databases including PubMed, Embase and Cochrane library for all eligible studies for the period up to February 2014. Data were extracted by two independent authors and pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the strength of the association. RESULTS: A total of 17 studies including 9,040 cases and 10,042 controls were available for OGG1 Ser326Cys polymorphism and 7 studies containing 2,979 cases and 3,111 controls were included for APE1 Asp148Glu polymorphism. With respect to OGG1 Ser326Cys polymorphism, we did not find a significant association with breast cancer risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and menopausal status, statistical significant increased breast cancer risk was found in Asian populations (Cys/Cys vs. Ser/Ser: OR=1.157, 95% CI 1.013-1.321, P=0.011; Cys/Cys vs. Ser/Cys+Ser/Ser: OR=1.113, 95% CI 1.009-1.227, P=0.014) and postmenopausal patients (Cys/Cys vs. Ser/Cys+Ser/Ser: OR=1.162, 95% CI 1.003-1.346, P=0.024). In subgroup analysis according to quality score, source of control, and HWE in controls, no any significant association was detected. With respect to APE1 Asp148Glu polymorphism, no significant association with breast cancer risk was demonstrated in the overall and stratified analyses. CONCLUSIONS: The present meta-analysis suggests that the OGG1 Ser326Cys polymorphism may be a risk factor for breast cancer in Asians and postmenopausal patients. Further large and well-designed studies are needed to confirm this association. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1156934297124915.

Determination of reference intervals for serum complement C3 and C4 levels in Chinese Han ethnic males.

BACKGROUND: Clinical laboratory reference intervals (RIs) for serum complement C3 and C4 levels have been established in many countries but there is a lack of published data regarding normal RIs in Chinese population. We attempted to establish RIs for serum complement C3 and C4 levels in Chinese Han ethnic males. METHODS: A total of 1,234 healthy male subjects, aged 20 - 69 years, were collected from the Fangchenggang Area Male Health and Examination Survey (FAMHES). Serum complement C3 and C4 levels were measured by immunoturbidimetry. The two-sided 95-percentile RIs were calculated using parametric statistical methods. RESULTS: Serum C3 values showed normal distribution and C4 were log-normal distributed. The two-sided 95% RIs (mean +/- 2 SD) for serum C3 and C4 were 0.656 - 1.52 g/L and 0.181 - 0.561 g/L, respectively. Body Mass Index (BMI) had a significant positive association with C3 (r = 0.342) and C4 (r = 0.258), and age had a significant positive association with C4 (r = 0.117). No significant difference was found either between smoking groups or drinking groups. A significant increase with BMI was found both for C3 (p < 0.001) and C4 (p < 0.001). BMI-specific RIs were also calculated. CONCLUSIONS: The RIs for serum C3 and C4 show a slight deviation compared to previously reported reference levels. BMI-specific reference values should be implemented in clinical laboratories.

MiR-291b-3p induces apoptosis in liver cell line NCTC1469 by reducing the level of RNA-binding protein HuR.

BACKGROUND: There is increasing evidence that miRNAs are involved in cellular apoptosis. However, the specific role of miR-291b-3p in apoptosis has not been elucidated. In the present study, we investigated the effect of miR-291b-3p on NCTC1469 cell growth and apoptosis. METHODS: Cell viability and apoptosis were examined in NCTC1469 cells transfected with miR-291b-3p mimics, inhibitor miRNA or negative control. Using computational miRNA target prediction databases, HuR was predicted as a target of miR-291b-3p. Luciferase assay, immunofluorescence and western blot were used to further explore the effects of miR-291b-3p on HuR expression. In addition, the effect of HuR on cell apoptosis was evaluated using a HuR-specific siRNA. RESULTS: TNF-α-induced hepatocyte apoptosis was accompanied by enhanced expression of miR-291b-3p, suggesting that miR-291b-3p might contribute to the apoptotic process. Follow-up experiments showed that upregulation of miR-291b-3p decreased cell viability and induced NCTC1469 cell apoptosis. Additionally, similar to the activity of miR-519, which is another member of the same miRNA family, miR-291b-3p suppressed HuR translation through binding to the HuR coding region (CR). We further showed that the downregulation of HuR expression by miR-291b-3p was accompanied by reduced Bcl-2 expression. Moreover, knockdown of HuR also impaired Bcl-2 expression and increased the ratio of Bax/Bcl-2. More significantly, downregulation of miR-291b-3p failed to increase Bcl2 expression in NCTC1469 cells that were co-transfected with siRNA-HuR. Finally, inhibition of miR-291b-3p led to reduced apoptosis, while knockdown of HuR by siRNA promoted apoptosis, even in NCTC1469 cells that were co-transfected with the miR-291b-3p inhibitor. CONCLUSION: The current data suggested that miR-291b-3p contributed to NCTC1469 cell apoptosis by regulating the expression of HuR, which in turn increased Bcl-2 stability.

Meta-analysis of the association between COX-2 polymorphisms and risk of colorectal cancer based on case-control studies.

OBJECTIVE: Cyclooxygenase-2 (COX-2) is an inducible enzyme converting arachidonic acid to prostaglandins and playing important roles in inflammatory diseases as well as tumor development. Previous studies investigating the association between COX-2 polymorphisms and colorectal cancer (CRC) risk reported conflicting results. We performed a meta-analysis of all available studies to explore this association. METHODS: All studies published up to October 2013 on the association between COX-2 polymorphisms and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Cochrane library. The association between COX-2 polymorphisms and CRC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). RESULTS: Ten studies with 6,774 cases and 9,772 controls were included for -1195A>G polymorphism, 13 studies including 6,807 cases and 10,052 controls were available for -765G>C polymorphism, and 8 studies containing 5,121 cases and 7,487 controls were included for 8473T>C polymorphism. With respect to -765G>C polymorphism, we did not find a significant association with CRC risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and cancer location, with a Bonferroni corrected alpha of 0.05/2, statistical significant increased CRC risk was found in the Asian populations (dominant model CC+CG vs. GG: OR = 1.399, 95%CI: 1.113-1.760, P = 0.004) and rectum cancer patients (CC vs. GG: OR = 2.270, 95%CI: 1.295-3.980, P = 0.004; Recessive model CC vs. CG+GG: OR = 2.269, 95%CI: 1.297-3.970, P = 0.004). In subgroup analysis according to source of control, no significant association was detected. With respect to -1195A>G and 8473T>C polymorphisms, no significant association with CRC risk was demonstrated in the overall and subgroup analyses. CONCLUSIONS: The present meta-analysis suggests that the COX-2 -765G>C polymorphism may be a risk factor for CRC in Asians and rectum cancer patients. Further large and well-designed studies are needed to confirm this association.

Lack of association between cathepsin D C224T polymorphism and Alzheimer's disease risk: an update meta-analysis.

BACKGROUND: Cathepsin D C224T polymorphism has been reported to associate with AD susceptibility. But the results were inconsistent. This study aimed to assess the relationship between C224T polymorphism and AD risk. METHODS: The relevant studies were identified by searching PubMed, Embase, Web of Science, Google Scholar and Wan fang electronic databases updated on July 2013. The relationship between Cathepsin D C224T polymorphism and AD risk was evaluated by ORs and 95% CIs. RESULTS: A total of 25 case-control studies including 5,602 cases and 11,049 controls were included in the meta-analysis. There was no association between C224T polymorphism and AD risk with all the studies were pooled in the meta-analysis (CT vs. CC: OR = 1.125, 95% CI = 0.974-1.299, P = 0.109; CT + TT vs. CC: OR = 1.136, 95% CI = 0.978-1.320, P = 0.094). Furthermore, when stratified by ethnicity, age of onset and APOEϵ4 status, significant association did not found in all subgroups. CONCLUSION: The present meta-analysis suggested that the Cathepsin D C224T polymorphism was not associated with AD susceptibility.

DNA repair gene XRCC3 polymorphisms and bladder cancer risk: a meta-analysis.

The X-ray repair cross-complementing group 3 (XRCC3) in homologous recombination repair (HRR) pathway plays a vital role in DNA double-strand break repair (DSBR). Variants in the XRCC3 gene might result in altered protein structure or function which may influence DSBR efficiency and lead to cancer. Numerous epidemiological studies have been conducted to evaluate the association between XRCC3 polymorphisms and bladder cancer risk. However, the results of these previous studies have been inconsistent. To derive a more precise estimation of the association, we performed a meta-analysis of all available studies relating XRCC3 polymorphisms and bladder cancer. All studies published up to April 2013 on the association between XRCC3 polymorphisms and bladder cancer risk were identified by searching electronic databases PubMed, EMBASE, and Chinese Biomedical Literature databases. The association between the XRCC3 polymorphisms and bladder cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). A total of 16 case-control studies met the inclusion criteria and were selected. With respect to C18067T polymorphism, significant increased bladder cancer risk was found when all eligible studies were pooled into the meta-analysis (TT vs. CC: OR = 1.174, 95%CI = 1.033-1.335, P = 0.014 and recessive model TT vs. TC + CC: OR = 1.147, 95%CI = 1.020-1.290, P = 0.022, respectively). The results were still significant after excluding the Hardy-Weinberg equilibrium violation studies (TT vs. CC: OR = 1.178, 95%CI = 1.036-1.339, P = 0.013 and recessive model TT vs. TC + CC: OR = 1.144, 95%CI = 1.017-1.287, P = 0.025, respectively). In subgroup analysis by ethnicity, significant elevated risk was found among Asians (dominant model TT + TC vs. CC: OR = 1.285, 95%CI = 1.012-1.631). In the subgroup analyses according to smoking status, no significant association was detected in all genetic comparison models. With respect to A17893G and A4541G polymorphisms, no significant association with bladder cancer risk was observed in the overall and subgroup analyses. This meta-analysis suggests that the XRCC3 C18067T polymorphism was associated with increased bladder cancer risk especially among Asians. However, the XRCC3 A17893G and A4541G polymorphisms may not play important roles in bladder carcinogenesis. Further studies with larger sample sizes are needed to validate our finds.

The association of interleukin-16 gene polymorphisms with IL-16 serum levels and risk of nasopharyngeal carcinoma in a Chinese population.

Interleukin (IL)-16 plays a fundamental role in inflammatory diseases, as well as in the development and progression of tumors. Genetic variation in DNA sequence of IL16 gene may lead to altered cytokine production and/or activity, and this variation may modulate an individual's susceptibility to nasopharyngeal carcinoma (NPC). To test this hypothesis, we investigated the association of IL16 gene polymorphisms and serum IL-16 levels with NPC risk in a Chinese population. We analyzed IL16 gene rs11556218 T/G, rs4778889 T/C, and rs4072111 C/T polymorphisms using PCR-RFLP and DNA sequencing, and serum IL-16 levels were measured by ELISA. The IL16 rs11556218 T/G polymorphism was significantly associated with the susceptibility to NPC patients. The TG genotype was associated with a significantly higher risk of NPC as compared with the TT genotype (OR = 2.05, 95% CI 1.04-4.01; p = 0.037). Patients carrying the G allele had a significantly higher risk for developing NPC compared with individuals carrying the T allele (OR = 1.79, 95% CI 1.07-3.01; p = 0.027). The serum IL-16 levels were increased in NPC patients compared with controls (p < 0.01); the genotypes carrying the IL16 rs11556218 G variant allele were associated with increased serum IL-16 levels compared with the homozygous wild-type genotype in NPC patients (all p values <0.01). Our data suggested that IL16 rs11556218 T/G polymorphism was associated with increased susceptibility to NPC through increasing the production of serum IL-16 levels.

Meta-analysis of randomized controlled trials on the efficacy of probiotics in Helicobacter pylori eradication therapy in children.

UNLABELLED: The efficacy of probiotics supplementation in children undergoing Helicobacter pylori (H. pylori) eradication therapy remains controversial. This study aimed to meta-analyze whether probiotics supplementation in triple therapy could improve H. pylori eradication rates and reduce therapy-related side effects in children. Electronic databases PubMed and Embase were searched to identify all randomized controlled trials in pediatric patients comparing probiotics supplementation with placebo or no extra intervention in H. pylori eradication therapy. Two authors independently extracted the data. Results were expressed as odds ratios (ORs) and accompanying 95 % confidence intervals (CIs). Stata version 12.0 was used to perform all statistical analyses. Seven studies consisting of 508 pediatric patients were included in our study. The pooled ORs (studies n = 7) of eradication rates by intention-to-treat and per-protocol analysis in the probiotics group versus the control group were 1.96 (95 % CI 1.28-3.02) and 2.25 (95 % CI 1.41-3.57), respectively. The pooled OR (studies n = 5) of incidence of total side effects was 0.32 (95 % CI 0.13-0.79), with significant heterogeneity observed (I (2) = 71.9 %). CONCLUSION: Probiotics supplementation in triple therapy for H. pylori infection may have beneficial effects on eradication and therapy-related side effects, particularly diarrhea, in children.

TP53 and MDM2 gene polymorphisms, gene-gene interaction, and hepatocellular carcinoma risk: evidence from an updated meta-analysis.

BACKGROUND: The association between TP53 R72P and/or MDM2 SNP309 polymorphisms and hepatocellular carcinoma (HCC) risk has been widely reported, but results were inconsistent. To clarify the effects of these polymorphisms on HCC risk, an updated meta-analysis of all available studies was conducted. METHODS: Eligible articles were identified by search of databases including PubMed, Cochrane Library, EMBASE and Chinese Biomedical Literature database (CBM) for the period up to July 2013. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Metaregression and subgroup analyses were performed to identify the source of heterogeneity. RESULTS: Finally, a total of 10 studies including 2,243 cases and 3,615 controls were available for MDM2 SNP309 polymorphism and 14 studies containing 4,855 cases and 6,630 controls were included for TP53 R72P polymorphism. With respect to MDM2 SNP309 polymorphism, significantly increased HCC risk was found in the overall population. In subgroup analysis by ethnicity and hepatitis virus infection status, significantly increased HCC risk was found in Asians, Caucasians, Africans, and HCV positive patients. With respect to TP53 R72P polymorphism, no significant association with HCC risk was observed in the overall and subgroup analyses. In the MDM2 SNP309-TP53 R72P interaction analysis, we found that subjects with MDM2 309TT and TP53 Pro/Pro genotype, MDM2 309 TG and TP53 Arg/Pro genotype, and MDM2 309 GG and TP53 Pro/Pro genotype were associated with significantly increased risk of developing HCC as compared with the reference MDM2 309TT and TP53 Arg/Arg genotype. CONCLUSIONS: We concluded that MDM2 SNP309 polymorphism may play an important role in the carcinogenesis of HCC. In addition, our findings further suggest that the combination of MDM2 SNP 309 and TP53 Arg72Pro genotypes confers higher risk to develop HCC. Further large and well-designed studies are needed to confirm this association.