Quantitative assessment of the association between MTHFR rs1801131 polymorphism and risk of liver cancer.

Methylenetetrahydrofolate reductase (MTHFR) is one of the most important enzymes for folate metabolism which plays a key role in cell metabolism. MTHFR rs1801131 (A1298C) polymorphism can decrease in vitro MTHFR enzyme activity and has been hypothesized to be associated with liver cancer risk. This study aimed to quantify the strength of the association between MTHFR rs1801131 polymorphism and liver cancer risk by performing a meta-analysis. We searched the PubMed and Wanfang databases for studies relating on the association between MTHFR rs1801131 polymorphism and risk of liver cancer. Seven studies with 2,030 cases of liver cancer and 3,096 controls were finally included into the meta-analysis. Meta-analysis of a total of seven studies showed that the homozygote genotype CC of MTHFR rs1801131 polymorphism was significantly associated with decreased risk of liver cancer (for CC versus AA: odds ratio (OR) = 0.65, 95% confidence interval (CI) 0.47-0.89, P = 0.007; for CC versus AA + AC: OR = 0.65, 95% CI 0.48-0.89, P = 0.006). Subgroup by race showed that the homozygote genotype CC of MTHFR rs1801131 polymorphism was significantly associated with decreased risk of liver cancer in Asians (CC versus AA: OR = 0.64, 95% CI 0.46-0.90, P = 0.010; for CC versus AA + AC: OR = 0.63, 95% CI 0.45-0.88, P = 0.007). However, the association in Caucasians was still unclear owing to the limited data available now. Thus, Asian individuals with the homozygote genotype CC of MTHFR rs1801131 polymorphism are significantly associated with decreased risk of liver cancer. The association in Caucasians needs further studies.

Perioperative Administration of Pregabalin and Esketamine to Prevent Chronic Pain After Breast Cancer Surgery: A Randomized Controlled Trial.

Background: Perioperative multimodal analgesia can prevent chronic pain after breast cancer surgery. This study aimed to investigate the efficacy of combined perioperative oral pregabalin and postoperative esketamine in preventing chronic pain after breast cancer surgery. Methods: Ninety patients undergoing elective breast cancer surgery were randomized into the combined pregabalin and esketamine group (EP group) and the general anesthesia alone group (Control group). The EP group received 150 mg of oral pregabalin 1 h before surgery and twice daily for seven days postoperatively, and a patient-controlled analgesia pump after surgery that delivered 100 µg sufentanil + 1.25 mg/kg esketamine + 4 mg tropisetron in 100 mL saline solution intravenously. The Control group received placebo capsules before and after the surgery and routine postoperative analgesia (100 µg sufentanil + 4 mg tropisetron in 100 mL saline solution). The primary outcome was the incidence of chronic pain three and six months after surgery. Secondary outcomes included acute postoperative pain, postoperative opioid consumption, and incidence of adverse events. Results: The incidence of chronic pain in the EP group was significantly lower than in the Control group three (14.3% vs 46.3%, P = 0.005) and six (7.1% vs 31.7%, P = 0.009) months postoperatively. The rest numerical rating scale (NRS) pain scores 1-3 days postoperatively and coughing NRS pain scores 1-7 days postoperatively in the EP group were significantly lower than in the Control group (all P ˂ 0.05). The cumulative sufentanil consumption in the EP group during postoperative 0-12, 12-24, and 24-48, 0-24, and 0-48 hours were significantly lower than in the Control group (all P ˂ 0.05). Conclusion: Combined perioperative oral pregabalin and postoperative esketamine effectively prevented chronic pain after breast cancer surgery, improved acute postoperative pain, and reduced postoperative opioid consumption.

Regional scalable priorities for national biodiversity and carbon conservation planning in Asia.

To achieve the goals of the post-2020 global biodiversity framework, we must identify representative targets that effectively protect biodiversity and can be implemented at a national level. We developed a framework to identify synergies between biodiversity and carbon across the Asian region and proposed a stepwise approach based on scalable priorities at regional, biome, and national levels that can complement potential Convention on Biological Diversity targets of protecting 30% land in the post-2020 global biodiversity framework. Our targets show that 30% of Asian land could effectively protect over 70% of all assessed species relative to only 11% now (based on analysis of 8932 terrestrial vertebrates), in addition to 2.3 to 3.6 hundred billion metric tons of carbon. Funding mechanisms are needed to ensure such targets to support biodiversity-carbon mutually beneficial solutions at the national level while reflecting broader priorities, especially in hyperdiverse countries where priorities exceed 30% of land.

Comparative analysis of eubacterial DNA polymerase III alpha subunits.

DNA polymerase III is one of the five eubacterial DNA polymerases that is responsible for the replication of DNA duplex. Among the ten subunits of the DNA polymerase III core enzyme, the alpha subunit catalyzes the reaction for polymerizing both DNA strands. In this study, we extracted genomic sequences of the alpha subunit from 159 sequenced eubacterial genomes, and carried out sequence-based phylogenetic and structural analyses. We found that all eubacterial genomes have one or more alpha subunits, which form either homodimers or heterodimers. Phylogenetic and domain structural analyses as well as copy number variations of the alpha subunit in each bacterium indicate the classification of alpha subunit into four basic groups: polC, dnaE1, dnaE2, and dnaE3. This classification is of essence in genome composition analysis. We also consolidated the naming convention to avoid further confusion in gene annotations.

KaKs_Calculator: calculating Ka and Ks through model selection and model averaging.

KaKs_Calculator is a software package that calculates nonsynonymous (Ka) and synonymous (Ks) substitution rates through model selection and model averaging. Since existing methods for this estimation adopt their specific mutation (substitution) models that consider different evolutionary features, leading to diverse estimates, KaKs_Calculator implements a set of candidate models in a maximum likelihood framework and adopts the Akaike information criterion to measure fitness between models and data, aiming to include as many features as needed for accurately capturing evolutionary information in protein-coding sequences. In addition, several existing methods for calculating Ka and Ks are also incorporated into this software.

Promoter demethylation of nuclear factor-erythroid 2-related factor 2 gene in drug-resistant colon cancer cells.

The mechanisms underlying drug resistance in colorectal cancer (CRC) treatment remain to be fully elucidated. Therefore, the present study aimed to investigate the underlying mechanism resistance to a widely used anticancer drug, 5-Fluorouracil (5-FU). Nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important transcription factor involved in cellular protection. In the present study, it was hypothesized that the epigenetic modification of Nrf2 may be a potential target for 5-FU resistance in CRC treatment. Protein and messenger RNA levels of Nrf2, heme oxygenase-1 (HO-1), DNA methylases and DNA methyltransferases were determined and DNA methylation analysis for the Nrf2 promoter was performed in a human CRC control (SNU-C5) and resistant (SNU-C5R) cell line. The results demonstrated that Nrf2 expression levels, nuclear translocation and promoter binding were significantly increased in SNU-C5R cells compared with SNU-C5 cells. Elevated levels of activated Nrf2 in SNU-C5R cells resulted in the increased protein expression and activity of HO-1. In addition, increased production of reactive oxygen species (ROS) and upregulation of ten-eleven translocation (TET)1 were observed in SNU-C5R cells compared with SNU-C5 cells. Furthermore, methylation analysis revealed Nrf2 promoter cytosine-phosphate-guanine island hypomethylation in 5-FU-treated cells. In conclusion, the results indicated that 5-FU-induced ROS production resulted in the upregulation of TET1 expression and function. In addition, these results indicated that TET-dependent demethylation of the Nrf2 promoter upregulated Nrf2 and HO-1 expression, which induced cellular protection mechanisms, ultimately leading to drug resistance.

Lack of association of MiR-34b/c polymorphism (rs4938723) with hepatocellular carcinoma: a meta-analysis.

BACKGROUND: Previous studies have focused on the association of miR-34 family members with carcinogenesis of many cancers, including hepatocellular carcinoma (HCC). It has been suggested that miR-34b/c polymorphism (rs4938723) is associated with susceptibility to HCC. In the present study, we performed a meta-analysis to systematically summarize the possible association between rs4938723 and the risk for HCC. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a search of case-control studies on the associations of rs4938723 with susceptibility to HCC in PubMed, EMBASE, ISI Web of Science, Cochrane Central Register of Controlled Trials, ScienceDirect, Wiley Online Library, Wangfang database in China, and Chinese National Knowledge Infrastructure databases. Data from eligible studies were extracted for meta-analysis. HCC risk associated with rs4938723 was estimated by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). 3 studies on rs4938723 were included in our meta-analysis. Our results showed that neither allele frequency nor genotype distribution of the rs4938723 was associated with risk for HCC in all genetic models. CONCLUSIONS/SIGNIFICANCE: This meta-analysis suggests that rs4938723 is not associated with the risk of HCC. Well-designed studies with larger sample size and more ethnic groups are required to further validate the results.