DNA polymerase θ (POLQ) is important for repair of DNA double-strand breaks caused by fork collapse.

DNA polymerase θ (POLQ) plays an important role in alternative nonhomologous end joining or microhomology-mediated end joining (alt-NHEJ/MMEJ). Here, we show that POLQ is not only required for MMEJ to repair DNA double-strand breaks (DSBs) generated by endonucleases such as I-SceI or Cas9, but is also needed for repair of DSBs derived from DNA nicks generated by Cas9 nickase. Consistently, we found that POLQ deficiency leads to sensitivity to topoisomerase inhibitors that cause DNA single-strand break (SSB) accumulation at replication forks and to ATR inhibitors that induce replication fork collapse. These studies support the function of POLQ in coping with replication stress and repairing DSBs upon fork collapse. POLQ overexpression is present in many cancer types and is associated with poor prognosis, including breast cancer regardless of BRCA1 status. We provide proof-of-concept evidence to support a novel cancer treatment strategy that combines POLQ inhibition with administration of topoisomerase or ATR inhibitors, which induces replication stress and fork collapse. Given the prevalence of POLQ overexpression in tumors, such strategy may have a significant impact on developing targeted cancer treatment.

Glutathione S-Transferase T1 (GSTT1) Null Polymorphism, Smoking, and Their Interaction in Coronary Heart Disease: A Comprehensive Meta-Analysis.

BACKGROUND: The association between glutathione S-transferase T1 (GSTT1) null polymorphism and coronary heart disease (CHD) is inconsistent among studies, and data on the GSTT1 null genotype-smoking interplay in CHD is lacking. We conducted this meta-analysis to investigate the relationship between GSTT1 null polymorphism and CHD and to assess the potential interaction between GSTT1 null genotype and smoking. METHODS: PubMed and EMBASE databases were searched up to 27 January 2016 using the appropriate terms. Odds ratios were pooled using either fixed-effects or random-effects models. RESULTS: Twenty-nine articles including 31 studies with 15,004 cases and 35,597 controls were eligible. The random-effects model showed that the GSTT1 null genotype was associated with increased CHD risk (OR=1.213, 95%CI: 1.004-1.467; I2=90.4%). After excluding 10 studies detected by Galbraith plot, the fixed effects summary estimate also showed an increased risk of CHD (OR=1.14, 95% CI: 1.06-1.22; I2=27.7%). A case-only analysis including eight studies showed a statistically significant positive interaction between GSTT1 null polymorphism and smoking status on CHD (OR=1.34, 95% CI: 1.09-1.64; I2=0%). Sensitivity analyses further supported the associations. No publication bias was observed. CONCLUSIONS: This meta-analysis suggests that GSTT1 null polymorphism is associated with the risk of CHD. To our knowledge, this is the first meta-analysis to prove a positive effect of the interaction between GSTT1 null genotype and smoking status on the risk of CHD. Future studies with detailed individual information are needed to confirm our findings.

The dopamine ß-hydroxylase gene in Chinese goose (Anas cygnoides): cloning, characterization, and expression during the reproductive cycle.

BACKGROUND: Dopamine ß-hydroxylase (DBH) is a critical enzyme in the biosynthesis of catecholamines. This enzyme's role in neuroendocrine regulation is well known, but there are some indications that it may also modulate reproduction and endocrine in mammals and birds. We selected goose (Anas cygnoides) as an ideal model species for investigating the role of DBH in avian reproduction. RESULTS: Full-length cDNA encoding DBH was cloned from Zhedong goose using reverse transcription PCR and rapid amplification of cDNA ends. The cDNA consisted of a 126-base pair (bp) 5'-untranslated region (UTR), a 379-bp 3'-UTR, and an 1896-bp open reading frame encoding a polypeptide of 631 amino acids. The deduced amino acid sequence of gDBH shared high homology with an analogue from other birds and contained three conserved domains from a mono-oxygenase family including a DOMON domain and two Cu2_mono-oxygen domains. Real-time quantitative PCR analysis showed that gDBH mRNA was expressed in both reproductive and endocrine tissues of Zhedong goose, specifically in the hypothalamus, pituitary, ovary, and oviduct. More DBH mRNA of reproductive and endocrine tissues was detected at ovulation than at oviposition in Zhedong goose. Evidence of opposite trend of gDBH expression was found between the hypothalamus-pituitary and oviduct during the ovulation phase and the broody phase. In addition, we assessed DBH mRNA expression during ovulation in two breeds of geese that differ in egg production. The reproductive and endocrine tissues of Yangzhou geese with higher egg production had more gDBH expression than Zhedong geese. Finally, the five non-synonymous SNP(c.1739 C > T, c.1760G > T, c.1765A > G, c.1792 T > C and c.1861G > C) were identified in the coding region of DBH gene between Zhedong goose and Yangzhou goose. CONCLUSIONS: We conclude that goose DBH mRNA show obvious periodically variation in reproductive and endocrine tissues during the reproductive cycle in geese.

Analysis of global gene expression profiles suggests a role of acute inflammation in type 3C diabetes mellitus caused by pancreatic ductal adenocarcinoma.

AIMS/HYPOTHESIS: Pancreatic ductal adenocarcinoma (PDAC) can cause type 3C diabetes, known as PDAC-associated diabetes mellitus (PDAC-DM), but the mechanism is unknown. This study aimed to reveal the mechanism. METHODS: PDAC lesions from patients with or without PDAC-DM (n = 4 in each group) were individually profiled for 23,512 mRNAs with microarrays. Bioinformatic analysis and in vivo and in vitro assays were then conducted. RESULTS: We determined that 2,778 genes were differentially expressed; over-representation of ten genes was validated with quantitative RT-PCR. The analysis of gene ontology showed that the differentially expressed secretory genes were related mainly to inflammation. High levels of a marker of inflammation (C-reactive protein [CRP]) and an inflammatory mediator (TNF super-family member 13 [TNFSF13]) were found in the serum of patients with PDAC-DM. After surgical resection of PDAC lesions, CRP and TNFSF13 levels significantly decreased (p < 0.01). Furthermore, we found that the levels of TNFSF13 in PDAC lesions and TNFSF13 and CRP in serum were significantly correlated with the diabetic status of patients with PDAC-DM (p < 0.01). Assays in vivo showed that after exposure to an inhibitor of inflammation (celecoxib), the fasting blood glucose level in the mouse model of PDAC-DM dramatically decreased from 6.9 ± 0.1 to 5.6 ± 0.1 mmol/l in 2-4 days (p < 0.01). CONCLUSIONS/INTERPRETATION: We found that acute inflammation was involved in the pathogenesis of PDAC-DM. We contend that acute inflammation is a potential target for the diagnosis and treatment of PDAC-DM.

The long non-coding RNA HOTTIP promotes progression and gemcitabine resistance by regulating HOXA13 in pancreatic cancer.

BACKGROUND: The human genome encodes many long non-coding RNAs (lncRNAs). However, their biological functions, molecular mechanisms, and the prognostic value associated with pancreatic ductal adenocarcinoma (PDAC) remain to be elucidated. Here, we identify a fundamental role for the lncRNA HOXA transcript at the distal tip (HOTTIP) in the progression and chemoresistance of PDAC. METHODS: High-throughput microarrays were performed to detect the expression profiles of lncRNAs and messenger RNAs in eight human PDAC tissues and four pancreatic tissues. Quantitative real-time PCR was used to determine the levels of HOTTIP and HOXA13 transcripts in PDAC cell lines and 90 PDAC samples from patients. HPDE6 cells (immortalized human pancreatic ductal epithelial cells) and corresponding adjacent non-neoplastic tissues were used as controls, respectively. The functions of HOTTIP and HOXA13 in cell proliferation, invasion, and epithelial-mesenchymal transition were evaluated by targeted knockdown in vitro. CCK-8 assays, colony formation assays, and xenografts in nude mice were used to investigate whether targeted silencing of HOTTIP could sensitize pancreatic cancer cells to gemcitabine. Immunohistochemistry was performed to investigate the relationship between HOXA13 expression and patient outcome. RESULTS: Microarray analyses revealed that HOTTIP was one of the most significantly upregulated lncRNAs in PDAC tissues compared with pancreatic tissues. Quantitative PCR further verified that HOTTIP levels were increased in PDAC cell lines and patient samples compared with controls. Functionally, HOTTIP silencing resulted in proliferation arrest by altering cell-cycle progression, and impaired cell invasion by inhibiting epithelial-mesenchymal transition in pancreatic cancer. Additionally, inhibition of HOTTIP potentiated the antitumor effects of gemcitabine in vitro and in vivo. Furthermore, knockdown of HOXA13 by RNA interference (siHOXA13) revealed that HOTTIP promoted PDAC cell proliferation, invasion, and chemoresistance, at least partly through regulating HOXA13. Immunohistochemistry results revealed that higher HOXA13 expression was correlated with lymph node metastasis, poor histological differentiation, and decreased overall survival in PDAC patients. CONCLUSIONS: As a crucial tumor promoter, HOTTIP promotes cell proliferation, invasion, and chemoresistance by modulating HOXA13. Therefore, the HOTTIP/HOXA13 axis is a potential therapeutic target and molecular biomarker for PDAC.

Players' strategy selection in co-governance and supervision of internet platforms' monopolistic behaviors: A study on new media participation.

Incidents of monopolies among Internet platforms have seriously endangered the development of the market economy, public interest, and social fairness, making it a highly discussed topic of broad public concern. Preventing such incidents requires not only a comprehensive supervision system by governments, but also contributions from other relevant parties. The new media environment has provided a new platform to support such joint supervision from multiple parties. As such, this study constructed an evolutionary game model involving the government, Internet platforms, new media, and the public to explore the stable equilibrium point of players' strategy selections. The stability of the strategy combinations was tested using Lyapunov's first stability method, and MATLAB 2021b was used to conduct simulation analysis of the impact of each decision variable on players' strategy selection. The results showed that (1) new media participation in co-governance and public complaints/reports facilitated government supervision; (2) government's application of co-governance and supervision and public complaints/reports promotes compliance by Internet platforms; (3) new media plays a supplementary role when government supervision is lacking; the greater the impact of new media, the greater its supervisory effect on Internet platforms; and (4) effective reduction of costs stimulates the enthusiasm of the government and new media, and increases the success of the anti-monopoly co-governance and supervision system. Measures and suggestions to improve supervision of monopolistic behaviors among Internet platforms are proposed.

Controllable release of self-assembled reduction-sensitive paclitaxel dimer prodrug and tetrandrine nanoparticles promotes synergistic therapy against multidrug-resistant cancer.

BACKGROUND: Multidrug resistance (MDR) is the main reason for chemotherapy failure. Nanocarriers combined delivery of anti-cancer drugs and MDR inhibitors is an effective strategy to avoid MDR and improve the anti-cancer activity of drugs. METHODS: Two paclitaxel (PTX) molecules are linked by disulfide bonds into PTX2. Then, the PTX2 and tetrandrine (TET) are coated together by mPEG-PLGA self-assembled NPs for combinational treatment. Microstructure, physiological stability, and cytotoxicity are characterized for the co-loaded NPs. RESULTS: The NPs exhibit excellent suitability and blood safety for intravenous injection, specifically responsive to pH 6-7, and promptly initiate chemical degradation. Ex vivo fluorescence microscopy image studies indicate that co-loaded NPs increase drug penetration into cancer cells compared with free drugs. MTT assay demonstrates that co-loaded NPs have higher cytotoxicity against HeLa and the flow cytometric analysis shows that co-loaded NPs trigger more apoptosis than the free drugs. Reactive oxygen species (ROS) assay indicates that the drug-loaded NPs generated higher levels of ROS to accelerate apoptosis in HeLa cells. CONCLUSIONS: TET can get desirable effects of inhibiting the MDR in advance by binding with the active site on P-gp, then the disulfide bond of PTX2 is broken by glutathione (GSH) in cancer cells and decomposed into PTX to inhibit cancer cell proliferation. GENERAL SIGNIFICANCE: Our studies indicate that the co-loaded NPs can potentially overcome the MDR of conventional chemotherapeutic agents.

Dosimetric parameters and safety analysis of 3D-printing non-coplanar template-assisted interstitial brachytherapy for non-centrally recurrent cervical cancer.

Introduction: The prognosis of patients with non-central recurrent cervical cancer (NRCC) remains poor, and treatment options are limited. We aimed to explore the accuracy and safety of the 3D-printed non-coplanar template (3D-PNCT)-assisted 192Ir interstitial brachytherapy (ISBT) in the treatment of NRCC. Material and methods: A total of 36 patients with NRCC who received 3D-PNCT-guided 192Ir ISBT in the First Affiliated Hospital of Zhengzhou University from January 2021 to July 2022 were included in this study. There were 36 3D-PNCTs that were designed and printed. The prescribed dose was 30-36 Gy, divided into five to six times, once a week. To evaluate whether the actual parameters were consistent with the preoperative design, the dosimetric parameters of pre- and postoperative treatment plans were compared, including dose of 90% high-risk clinical target volume (HR-CTV D90), volume percentage of 100% and 150% prescribed dose V100% and V150%, homogeneity index (HI), conformal index (CI), external index (EI), and dose received by 2 cm3 (D2cm3) of the rectum, colon, bladder, and ileum. The safety parameters including occurrence of bleeding, infection, pain, radiation enteritis, and radiation cystitis within 3 months after operation were recorded. Results: All patients successfully completed the treatment and achieved the goals of the preoperative plan. There was no significant difference in the accuracy (HRCTVD90, V100%, EI, CI, and HI) and safety (D2cm3 of rectum, colon, bladder, and ileum) parameters of the postoperative plan compared with the preoperative plan (all p>0.05). Major side effects included bleeding at the puncture site (13.9%), postoperative pain (8.3%), acute radiation cystitis (13.9%), and radiation enteritis (19.4%). There were no serious perioperative complications and no grade 3-4 acute radiotherapy side effects. Conclusion: 3D-PNCT-assisted 192Ir ISBT can be accurately and safely applied in the treatment of patients with NRCC.

To identify the association between dietary vitamin D intake and serum levels and risk or prognostic factors for melanoma-systematic review and meta-analysis.

OBJECTIVE: To evaluate the association of serum vitamin D levels and dietary intake with melanoma risk and prognostic factors. METHODS: Two independent investigators systematically searched PubMed, Embase and ISI Web of Knowledge (Thomson Scientific Technical Support, New York) databases for eligible studies published between January 1992 and September 2020 using the following combinations of search terms: (vitamin D, or 25-hydroxyvitamin D) AND (melanoma, malignant melanoma, cutaneous melanoma, or cutaneous malignant melanoma). Articles not written in English but with English titles and abstracts were also checked. We obtained the full text of all potentially eligible articles, and reference lists of all studies retrieved at the first stage were also checked to identify other eligible papers. Review articles not reporting original data were excluded, but their reference lists were inspected. RESULTS: Six studies including 212 723 cases reported the association between dietary intake of 25(OH) D serum levels and melanoma risk. The total relative risk for the comparison between the highest and lowest quantiles of the distribution of vitamin D intake was 1.10 (95% CI 0.96 to 1.26) with I 2=56%. Another six studies including 12 297 cases evaluated the association between serum vitamin D levels and melanoma risk. The total relative risk for the comparison of serum vitamin D levels between the highest and lowest quantiles was 1.12 (95% CI 0.53 to 2.35) with I 2=91%. Four studies with 2105 cases investigated the association between serum 25(OH)D (nmol/L) and Breslow thickness, three of which found an inverse association between serum 25(OH)D (nmol/L) and melanoma thickness. CONCLUSIONS: Vitamin D intake and serum 25(OH)D levels were not closely related with melanoma risk, but an inverse association between serum 25(OH)D levels with melanoma thickness was discovered. As the positive correlation between melanoma thickness and melanoma mortality has been recognised, hence it is concluded that a moderate dietary vitamin D supplement to avoid the serum 25(OH)D deficient might be beneficial to the long-term survival of patients with melanoma.

An updated meta-analysis showed smoking modify the association of GSTM1 null genotype on the risk of coronary heart disease.

Background Oxidative stress is considered to be involved in the pathogenesis of coronary heart disease (CHD). Glutathione-S-transferase (GST) enzymes play important roles in antioxidant defenses and may influence CHD risk. The present meta-analysis was performed to investigate the link between glutathione S-transferase M1 (GSTM1) null genotype and CHD and to get a precise evaluation of interaction between GSTM1 null genotype and smoking by the case-only design. Methods PubMed and EMBASE databases were searched through 15 December 2020 to retrieve articles. Odds ratios (ORs) were pooled using either fixed-effects or random-effects models. Results Thirty-seven studies showed that GSTM1 null genotype was associated with risk of CHD in total population, Caucasians and Asians (for total population, OR = 1.38, 95% confidence interval (CI): 1.15, 1.65; for Caucasians, OR = 1.34, 95% CI: 1.04, 1.72; for Asians, OR = 1.40, 95% CI: 1.11, 1.77). After adjustment for heterogeneity, these relationships were still significant. After adjustment for heterogeneity, case-only analysis of 11 studies showed a positive multiplicative interaction between GSTM1 null genotype and smoking (ever smoking vs. never smoking) (OR = 1.27, 95% CI: 1.08, 1.50; I2 = 0%, P=0.553). Conclusions The overall results indicated that GSTM1 null genotype was associated with a higher risk of CHD, and the association may be affected by smoking status. This is the first meta-analysis to prove a positive effect of the interaction between GSTM1 null genotype and smoking status on the risk of CHD. Well-designed studies are needed to investigate the possible gene-gene or gene-environment interactions.

Development of a loop-mediated isothermal amplification assay combined with a nanoparticle-based lateral flow biosensor for rapid detection of plasmid-mediated colistin resistance gene mcr-1.

A loop-mediated isothermal amplification assay combined with a nanoparticle-based lateral flow biosensor (LAMP-LFB) was established for the rapid and accurate detection of the mobilized colistin resistance gene (mcr-1), which causes the loss of colistin antibacterial efficacy in clinical treatments. The amplification stage of the assay was completed in 60 min at 63°C, and the reaction products could be visually detected by employing the LFB, which provided a fast (within 2 min) and objective method to evaluate the amplification results. The LAMP assay amplified the target sequences of mcr-1 with high specificity. In pure strains, the detection limit of the LAMP-LFB assay was 360 fg plasmid DNA/reaction, and in spiked feces samples the value was approximately 6.3×103 CFU/mL (~6.3 CFU/reaction), which was tenfold more sensitive than the PCR assay. The results show that the developed LAMP-LFB assay will be a worthy tool for the simple, rapid, specific, and sensitive detection of mcr-1 gene in clinical settings and resource-limited areas.

Association of GSTP1 Ile105Val polymorphism with the risk of coronary heart disease: An updated meta-analysis.

BACKGROUND: Numerous case-control studies have investigated the association between GSTP1 Ile105Val polymorphism and CHD risk, but the results from published studies were inconclusive. The present meta-analysis was performed to derive a more precise estimation. METHODS: PubMed, EMBASE, and Web of Science database searches were conducted to retrieve relevant articles. RESULTS: Ultimately, 5,451 CHD cases and 5,561 controls from 15 studies were included. Pooled analysis did not yield any statistically significant association between GSTP1 Ile105Val polymorphism and CHD risk for the overall population (Val vs. Ile: OR, 1.05; 95% CI, 0.93 to 1.18; Val/Val vs. Ile/Ile: OR, 1.09; 95% CI, 0.83 to 1.42; Val/Ile vs. Ile/Ile: OR, 1.09; 95% CI, 0.93 to 1.28; Val/Val vs. Val/Ile+Ile/Ile: OR, 1.04; 95% CI, 0.83 to 1.30; Val/Val+Val/Ile vs. Ile/Ile: OR, 1.14; 95% CI, 0.97 to 1.33). Subgroup analyses and sensitivity analyses indicated that GSTP1 Ile105Val polymorphism was still not associated with an increased risk of CHD. After excluding studies detected by Galbraith plots as major sources of heterogeneity, these relationships were still not significant. CONCLUSIONS: The overall results did not reveal a major role of the GSTP1 Ile105Val polymorphism in modulating CHD risk. Well-designed studies with large sample sizes are needed to validate our findings and explore the possible gene-gene or gene-environment interactions.

Targeting Angiogenesis by Blocking the ATM-SerRS-VEGFA Pathway for UV-Induced Skin Photodamage and Melanoma Growth.

Retinoic acid (RA) has been widely used to protect skin from photo damage and skin carcinomas caused by solar ultraviolet (UV) irradiation, yet the mechanism remains elusive. Here, we report that all-trans retinoic acid (tRA) can directly induce the expression of a newly identified potent anti-angiogenic factor, seryl tRNA synthetase (SerRS), whose angiostatic role can, however, be inhibited by UV-activated ataxia telangiectasia mutated (ATM) kinase. In both a human epidermal cell line, HaCaT, and a mouse melanoma B16F10 cell line, we found that tRA could activate SerRS transcription through binding with the SerRS promoter. However, UV irradiation induced activation of ATM-phosphorylated SerRS, leading to the inactivation of SerRS as a transcriptional repressor of vascular endothelial growth factor A (VEGFA), which dampened the effect of tRA. When combined with ATM inhibitor KU-55933, tRA showed a greatly enhanced efficiency in inhibiting VEGFA expression and a much better protection of mouse skin from photo damage. Also, we found the combination greatly inhibited tumor angiogenesis and growth in mouse melanoma xenograft in vivo. Taken together, tRA combined with an ATM inhibitor can greatly enhance the anti-angiogenic activity of SerRS under UV irradiation and could be a better strategy in protecting skin from angiogenesis-associated skin damage and melanoma caused by UV radiation.

Solvothermal fabrication and construction of highly photoelectrocatalytic TiO2 NTs/Bi2MoO6 heterojunction based on titanium mesh.

The fabrication of TiO2 NTs/Bi2MoO6 type-II heterojunction photocatalyst was carried out by a simple solvothermal method. Bi2MoO6 nanoparticles with nanosheet microstructures were successfully loaded on TiO2 NTs surface through the adjustment of reaction intervals. The heterojunction photocatalyst showed excellent organic dye and heavy metal ion removal performances, and nearly 100%, 75%, 100% and 100% of MO, RhB, MB and Cr (VI) were removed by simulative sunlight irradiation for 3 or 2 h, respectively. The outstanding photocatalyic performance was mainly due to the formation of type-II heterojunction between TiO2 and Bi2MoO6. The type-II heterojunction not only enhanced visible light response but also accelerated photogenerated charge carrier transfer and restrained the recombination of photogenerated electron-hole pairs with the assistance of internal electric field.

Comparative characterization of bacterial communities in geese fed all-grass or high-grain diets.

BACKGROUND: Gut microbial composition is dependent on diet. Geese are herbivores and can digest crude fibre, but the relationship between composition of the microbiota and a fibre-rich diet in geese is not well understood. RESULTS: Here, caecal and faecal samples were collected simultaneously from all-grass-fed geese and high-grain-fed geese and the hypervariable V3-V4 regions of the bacterial 16S rRNA gene were sequenced. The results was identified that high-grass-fed geese possessed significantly higher alpha diversity both in caecum and faeces compared with that in all-grain-fed geese. In addition, the composition of dominant bacterium occurred remarkable shifting due to different diet patterns, Firmicutes were more abundant in all-grass-fed geese, whereas Bacteroidetes were abundant in high-grain-fed geese. Fusobacteria and Deferribacteres were obviously present in high-grain-fed geese and few in all-grass-fed geese. Most importantly, some specific microorgnisms such as Ruminococcaceae, Lachnospiraceae and Bacteroidaceae which may associated with cellulose-degrading that were characterized to show distinctly diverse between the two diet patterns. PICRUSt analysis revealed the metabolic pathways such as carbohydrate and amino acid metabolism were overrepresented in all-grass-fed geese. CONCLUSIONS: In conclusion, Firmicutes and Bacteroidetes were identified abundantly when the geese was fed with all-grass feed and high-grain feed, respectively. And Ruminococcaceae, Lachnospiraceae and Bacteroidaceae were recognized as main cellulose-degrading bacteria in the geese. The functional profiles of gut microbiota revealed the dominant microbiota communities were involved mainly in the carbohydrate metabolism in all-grass-fed geese.

Embryotoxicity Caused by DON-Induced Oxidative Stress Mediated by Nrf2/HO-1 Pathway.

Deoxynivalenol (DON) belongs to the type B group of trichothecenes family, which is composed of sesquiterpenoid metabolites produced by Fusarium and other fungi in grain. DON may cause various toxicities, such as cytotoxicity, immunotoxicity, genotoxicity as well as teratogenicity and carcinogenicity. In the present study, we focus on a hypothesis that DON alters the expressions of Nrf2/HO-1 pathway by inducing embryotoxicity in C57BL/6 mouse (5.0, 2.5, 1.0, and 0 mg/kg/day) and BeWo cell lines (0 and 50 nM; 3 h, 12 h and 24 h). Our results indicate that DON treatment in mice during pregnancy leads to ROS accumulation in the placenta, which results in embryotoxicity. At the same time Nrf2/HO-1 pathway is up-regulated by ROS to protect placenta cells from oxidative damage. In DON-treated BeWo cells, the level of ROS has time-effect and dose-effect relationships with HO-1 expression. Moderate increase in HO-1 protects the cell from oxidative damage, while excessive increase in HO-1 aggravates the oxidative damage, which is called in some studies the "threshold effect". Therefore, oxidative stress may be the critical molecular mechanism for DON-induced embryotoxicity. Besides, Nrf2/HO-1 pathway accompanied by the "threshold effect" also plays an important role against DON-induced oxidative damage in this process.

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) null polymorphisms and the risk of hypertension: a meta-analysis.

BACKGROUND: Some studies have recently focused on the association between glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms and hypertension; however, results have been inconsistent. OBJECTIVE: In order to drive a more precise estimation, the present systematic review and meta-analysis is performed to investigate the relationship between the GSTM1 and GSTT1 null polymorphisms and hypertension. METHODS: Eligible articles were identified by a search of several bibliographic databases for the period up to August 17, 2013. Odds ratios were pooled using either fixed-effects or random-effects models. RESULTS: Regarding the GSTM1 null/present genotype, 14 case-control studies were eligible (2773 hypertension cases and 3189 controls). The meta-analysis revealed that it might present a small increased risk for hypertension, although the effect was not statistically significant (odd ratio (OR) = 1.16, 95% confidence interval (CI): 0.96, 1.40; P = 0.002, I2 = 59.8%). Further subgroup analysis by ethnicity and control source suggested that the association was still not significant. Thirteen case-control studies were eligible for GSTT1 (2497 hypertension cases and 3078 controls). No statistically significant association was observed between the GSTT1 null genotype and hypertension risk (OR = 1.14, 95% CI: 0.85, 1.53; P = 0.000, I2 = 80.3%). Furthermore, stratification by ethnicity and control source indicated no association between the GSTT1 null genotype and hypertension risk. We further confirmed the association by sensitivity analysis. No publication bias was detected. CONCLUSION: This meta-analysis suggests that the GSTM1 and GSTT1 null polymorphisms are not associated with the risk of hypertension. Future large well-designed epidemiological studies with individual information, lifestyle factors, and environmental factors are warranted to validate the present findings.

Molecular cloning and expression patterns of the cholesterol side chain cleavage enzyme (CYP11A1) gene during the reproductive cycle in goose (Anas cygnoides).

BACKGROUND: CYP11A1, a gene belonging to the family 11 of cytochrome P450, encodes a crucial steroidogenic enzyme that catalyzes the initial step in the production of all classes of steroids. Many studies show that CYP11A1 plays a role in ovary function. However, the role of CYP11A1 in goose reproductive cycle remains largely unknown. RESULTS: In this study, full-length CYP11A1 cDNA of Zhedong goose was obtained using reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). The cDNA consisted of a 96-base pair (bp) 5'untranslated region (UTR), a 179-bp 3'UTR and a 1509-bp open reading frame. The open reading frame encodes a putative 503 amino acid protein that shares high homology with CYP11A1 of other birds. The amino acid sequence possesses conserved domains of the P450 superfamily, which include the steroid-binding domain and the heme-binding region. Real-time quantitative polymerase chain reaction (qPCR) analysis revealed CYP11A1 mRNA was expressed ubiquitously in every Zhedong goose tissue analyzed, including the heart, liver, glandular stomach, lung, spleen, kidney, intestinum tenue, intestinum crassum, cerebrum, cerebellum, muscle, oviduct, pituitary, hypothalamus and ovary.. The relatively low levels of CYP11A1 mRNA were detected in pituitary, ovary and oviduct tissues at ovulation when compared with levels at oviposition. Interestingly, higher expression was observed in ovary and oviduct tissues during brooding. Lastly, higher mRNA expression of Yangzhou geese was detected during the ovulation period than that of Zhedong geese. CONCLUSIONS: Our findings reveal the sequence characterization and expression patterns of the CYP11A1 gene during the goose reproductive cycle, which may provides correlative evidence that CYP11A1 expression is important in reproduction activity.

Interactions between zinc transporter-8 gene (SLC30A8) and plasma zinc concentrations for impaired glucose regulation and type 2 diabetes.

Although both SLC30A8 rs13266634 single nucleotide polymorphism and plasma zinc concentrations have been associated with impaired glucose regulation (IGR) and type 2 diabetes (T2D), their interactions for IGR and T2D remain unclear. Therefore, to assess zinc-SLC30A8 interactions, we performed a case-control study in 1,796 participants: 218 newly diagnosed IGR patients, 785 newly diagnosed T2D patients, and 793 individuals with normal glucose tolerance. After adjustment for age, sex, BMI, family history of diabetes, and hypertension, the multivariable odds ratio (OR) of T2D associated with a 10 µg/dL higher plasma zinc level was 0.87 (95% CI 0.85-0.90). Meanwhile, the OR of SLC30A8 rs13266634 homozygous genotypes CC compared with TT was 1.53 (1.11-2.09) for T2D. Similar associations were found in IGR and IGR&T2D groups. Each 10 µg/dL increment of plasma zinc was associated with 22% (OR 0.78 [0.72-0.85]) lower odds of T2D in TT genotype carriers, 17% (0.83 [0.80-0.87]) lower odds in CT genotype carriers, and 7% (0.93 [0.90-0.97]) lower odds in CC genotype carriers (P for interaction = 0.01). Our study suggested that the C allele of rs13266634 was associated with higher odds of T2D, and higher plasma zinc was associated with lower odds. The inverse association of plasma zinc concentrations with T2D was modified by SLC30A8 rs13266634. Further studies are warranted to confirm our findings and clarify the mechanisms underlying the interaction between plasma zinc and the SLC30A8 gene in relation to T2D.

Egg consumption and risk of coronary heart disease and stroke: dose-response meta-analysis of prospective cohort studies.

OBJECTIVE: To investigate and quantify the potential dose-response association between egg consumption and risk of coronary heart disease and stroke. DESIGN: Dose-response meta-analysis of prospective cohort studies. DATA SOURCES: PubMed and Embase prior to June 2012 and references of relevant original papers and review articles. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective cohort studies with relative risks and 95% confidence intervals of coronary heart disease or stroke for three or more categories of egg consumption. RESULTS: Eight articles with 17 reports (nine for coronary heart disease, eight for stroke) were eligible for inclusion in the meta-analysis (3,081,269 person years and 5847 incident cases for coronary heart disease, and 4,148,095 person years and 7579 incident cases for stroke). No evidence of a curve linear association was seen between egg consumption and risk of coronary heart disease or stroke (P=0.67 and P=0.27 for non-linearity, respectively). The summary relative risk of coronary heart disease for an increase of one egg consumed per day was 0.99 (95% confidence interval 0.85 to 1.15; P=0.88 for linear trend) without heterogeneity among studies (P=0.97, I(2)=0%). For stroke, the combined relative risk for an increase of one egg consumed per day was 0.91 (0.81 to 1.02; P=0.10 for linear trend) without heterogeneity among studies (P=0.46, I(2)=0%). In a subgroup analysis of diabetic populations, the relative risk of coronary heart disease comparing the highest with the lowest egg consumption was 1.54 (1.14 to 2.09; P=0.01). In addition, people with higher egg consumption had a 25% (0.57 to 0.99; P=0.04) lower risk of developing hemorrhagic stroke. CONCLUSIONS: Higher consumption of eggs (up to one egg per day) is not associated with increased risk of coronary heart disease or stroke. The increased risk of coronary heart disease among diabetic patients and reduced risk of hemorrhagic stroke associated with higher egg consumption in subgroup analyses warrant further studies.