hOGG1 Ser326Cys Polymorphism and Risk of Hepatocellular Carcinoma among East Asians: A Meta-Analysis

Background

The hOGG1 gene encodes a DNA glycosylase enzyme responsible for DNA repair. The Ser326Cys polymorphism in this gene may influence its repair ability and thus plays a role in carcinogenesis. Several case-control studies have been conducted on this polymorphism and its relationship with the risk of hepatocellular carcinoma (HCC) among East Asians. However, their results are inconsistent.

Methods

We performed a meta-analysis of published case-control studies assessing the association of the hOGG1 Ser326Cys polymorphism with HCC risk among East Asians. PubMed, EMBASE, SCI, BIOSIS, CNKI and WanFang databases were searched. A random-effect model was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Analyses were conducted for additive, dominant and recessive genetic models.

Results

Eight studies were identified involving 2369 cases and 2442 controls assessing the association of the hOGG1 Ser326Cys polymorphism with HCC risk among East Asians. Applying a dominant genetic model, only in the Chinese population, the Cys allele was significantly associated with increased risk of HCC (OR 1.56, 95% CI 1.12–2.17). However, two studies influenced this finding according to sensitivity analysis. Furthermore, considerable heterogeneity and bias existed among Chinese studies.

Conclusion

There is limited evidence to support that the hOGG1 Ser326Cys polymorphism is associated with HCC risk among East Asians. Well-designed and large-sized studies are required to determine this relationship.     

Tolerance to Copper and to Salinity in Daphnia longispina: Implications within a Climate Change Scenario

Considering IPPC climate change scenarios, it is pertinent to predict situations where coastal ecosystems already impacted with chemical contamination became exposed to an additional stressor under a future scenario of seawater intrusion. Accordingly, the present study aimed at evaluating if a negative association between tolerance to a metal and to saltwater exists among genotypes of a freshwater organism. For this, five clonal lineages of the cladoceran Daphnia longispina O.F. Müller, exhibiting a differential tolerance to lethal levels of copper, were selected. Each clonal lineage was exposed to lethal and sublethal concentrations of sodium chloride (assumed as a protective surrogate to evaluate the toxicity of increased salinity to freshwater organisms). Mortality, time to release the first brood and total number of neonates per female were monitored and the somatic growth rate and intrinsic rate of natural increase were computed for each clonal lineage. Data here obtained were compared with their lethal responses to copper and significant negative correlations were found. These results suggest that genetically eroded populations of D. longispina, due to copper or salinity, may be particularly susceptible to a later exposure to the other contaminant supporting the multiple stressors differential tolerance.     

Alcohol Consumption,Types of Alcohol,and Parkinson’s Disease

Background

The epidemiologic evidence on alcohol consumption and Parkinson’s disease (PD) is equivocal. We prospectively examined total alcohol consumption and consumption of specific types of alcoholic beverage in relation to future risk of PD.

Methods

The study comprised 306,895 participants (180,235 male and 126,660 female) ages 50–71 years in 1995–1996 from the NIH-AARP Diet and Health Study. Consumption of alcoholic beverages in the past 12 months was assessed in 1995–1996. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were obtained from logistic regression models.

Results

A total of 1,113 PD cases diagnosed between 2000 and 2006 were included in the analysis. Total alcohol consumption was not associated with PD. However, the association differed by types of alcoholic beverages. Compared with non-beer drinkers, the multivariate ORs for beer drinkers were 0.79 (95% CI: 0.68, 0.92) for <1 drink/day, 0.73 (95% CI: 0.50, 1.07) for 1–1.99 drinks/day, and 0.86 (95% CI: 0.60, 1.21) for ≥2 drinks/day. For liquor consumption, a monotonic increase in PD risk was suggested: ORs (95% CI) were 1.06 (0.91, 1.23), 1.22 (0.94, 1.58), and 1.35 (1.02, 1.80) for <1, 1–1.99, and ≥2 drinks/day, respectively (P for trend <0.03). Additional analyses among exclusive drinkers of one specific type of alcoholic beverage supported the robustness of these findings. The results for wine consumption were less clear, although a borderline lower PD risk was observed when comparing wine drinkers of 1–1.99 drinks/day with none drinkers (OR = 0.74, 95% CI: 0.53, 1.02).

Conclusions

Our results suggest that beer and liquor consumption may have opposite associations with PD: low to moderate beer consumption with lower PD risk and greater liquor consumption with higher risk. These findings and potential underlying mechanisms warrant further investigations.     

Antidepressant-Like Activity of YL-0919: A Novel Combined Selective Serotonin Reuptake Inhibitor and 5-HT1A Receptor Agonist

It has been suggested that drugs combining activities of selective serotonin reuptake inhibitor and 5-HT_1A receptor agonist may form a novel strategy for higher therapeutic efficacy of antidepressant. The present study aimed to examine the pharmacology of YL-0919, a novel synthetic compound with combined high affinity and selectivity for serotonin transporter and 5-HT_1A receptors. We performed in vitro binding and function assays and in vivo behavioral tests to assess the pharmacological properties and antidepressant-like efficacy of YL-0919. YL-0919 displayed high affinity in vitro to both 5-HT_1A receptor and 5-HT transporter prepared from rat cortical tissue. It exerted an inhibitory effect on forskolin-stimulated cAMP formation and potently inhibited 5-HT uptake in both rat cortical synaptosomes and recombinant cells. After acute p.o. administration, very low doses of YL-0919 reduced the immobility time in tail suspension test and forced swimming test in mice and rats, with no significant effect on locomotor activity in open field test. Furthermore, WAY-100635 (a selective 5-HT_1A receptor antagonist, 0.3 mg/kg) significantly blocked the effect of YL-0919 in tail suspension test and forced swimming test. In addition, chronic YL-0919 treatment significantly reversed the depressive-like behaviors in chronically stressed rats. These findings suggest that YL-0919, a novel structure compound, exerts dual effect on the serotonergic system, as both 5-HT_1A receptor agonist and 5-HT uptake blocker, showing remarkable antidepressant effects in animal models. Therefore, YL-0919 may be used as a new option for the treatment of major depressive disorder.     

Relative Amino Acid Composition Signatures of Organisms and Environments

Background

Identifying organism-environment interactions at the molecular level is crucial to understanding how organisms adapt to and change the chemical and molecular landscape of their habitats. In this work we investigated whether relative amino acid compositions could be used as a molecular signature of an environment and whether such a signature could also be observed at the level of the cellular amino acid composition of the microorganisms that inhabit that environment.

Methodologies/Principal Findings

To address these questions we collected and analyzed environmental amino acid determinations from the literature, and estimated from complete genomic sequences the global relative amino acid abundances of organisms that are cognate to the different types of environment. Environmental relative amino acid abundances clustered into broad groups (ocean waters, host-associated environments, grass land environments, sandy soils and sediments, and forest soils), indicating the presence of amino acid signatures specific for each environment. These signatures correlate to those found in organisms. Nevertheless, relative amino acid abundance of organisms was more influenced by GC content than habitat or phylogeny.

Conclusions

Our results suggest that relative amino acid composition can be used as a signature of an environment. In addition, we observed that the relative amino acid composition of organisms is not highly determined by environment, reinforcing previous studies that find GC content to be the major factor correlating to amino acid composition in living organisms.     

Differential Regulation of MAPK Phosphorylation in the Dorsal Hippocampus in Response to Prolonged Morphine Withdrawal-Induced Depressive-Like Symptoms in Mice

Depression is one of the most frequent neuropsychiatric comorbidities associated with opiate addiction. Mitogen activated protein kinase (MAPK) and MAPK phosphatase (MKP) are involved in drug addiction and depression. However, the potential role of MAPK and MKP in depression caused by morphine withdrawal remains unclear. We utilized a mouse model of repeated morphine administration to examine the molecular mechanisms that contribute to prolonged withdrawal induced depressive-like behaviors. Depressive-like behaviors were significant at 1 week after withdrawal and worsened over time. Phospho-ERK (extracellular signal-regulated protein kinase) was decreased and MKP-1 was elevated in the hippocampus, and JNK (c-Jun N-terminal protein kinase), p38 (p38 protein kinase) and MKP-3 were unaffected. A pharmacological blockade of MKP-1 by intra-hippocampal sanguinarine (SA) infusion prevented the development of depressive-like behaviors and resulted in relatively normal levels of MKP-1 and phospho-ERK after withdrawal. Our findings support the association between hippocampal MAPK phosphorylation and prolonged morphine withdrawal-induced depression, and emphasize the MKP-1 as an negative regulator of the ERK phosphorylation that contributes to depression.     

Insulin-Producing Cells Derived from Human Embryonic Stem Cells: Comparison of Definitive Endoderm- and Nestin-Positive Progenitor-Based Differentiation Strategies

Human embryonic stem cells (hESCs) are pluripotent and capable of undergoing multilineage differentiation into highly specialized cells including pancreatic islet cells. Thus, they represent a novel alternative source for targeted therapies and regenerative medicine for diabetes. Significant progress has been made in differentiating hESCs toward pancreatic lineages. One approach is based on the similarities of pancreatic β cell and neuroepithelial development. Nestin-positive cells are selected as pancreatic β cell precursors and further differentiated to secrete insulin. The other approach is based on our knowledge of developmental biology in which the differentiation protocol sequentially reproduces the individual steps that are known in normal β cell ontogenesis during fetal pancreatic development. In the present study, the hESC cell line PKU1.1 was induced to differentiate into insulin-producing cells (IPCs) using both protocols. The differentiation process was dynamically investigated and the similarities and differences between both strategies were explored. Our results show that IPCs can be successfully induced with both differentiation strategies. The resulting IPCs from both protocols shared many similar features with pancreatic islet cells, but not mature, functional β cells. However, these differently-derived IPC cell types displayed specific morphologies and different expression levels of pancreatic islet development-related markers. These data not only broaden our outlook on hESC differentiation into IPCs, but also extend the full potential of these processes for regenerative medicine in diabetes.     

Design and Optimization of Planting Process Parameters for 2ZYX-2 Type Green Onion Ditching and Transplanting Machine

Considering the current low level of mechanization for domestic green onion planting and the high labor intensity of artificial planting, a 2ZYX-2 green onion ditching and transplanting machine, which can complete ditching, ridging, transplanting, repression, soil covering and other operations, is designed in this study. The Central Composite test design method was carried out with the speed of the transplanting machine, the depth of the opener and the horizontal position of the opener as the experimental factors and with the qualification ratio of perpendicularity, the variation coefficient of the plant spacing and the qualification ratio of the planting depth as the test index. Through the analysis of the model interaction and response surface, the change laws that the influence the machine’s forward speed, the depth of the opener and the horizontal position of the opener were studied. The regression model was optimized by Design-Expert 8.0.6 software, and the accuracy of the predicted results was verified by experiments. The optimal working parameters showed that the forward speed of the machine was 0.06 m/s, the depth of the opener was 102 mm, and the horizontal position of the opener was 29 mm. Under conditions of optimal working parameters, the qualification rate of the verticality was 86.83%, the coefficient of variation for the plant spacing was 2.77, and the pass rate of planting depth was 88.26%. The research related to the thesis can provide a reference for the mechanized planting of green onion, which is of great significance to the cost-effectiveness of the green onion industry.     

Protecting tobacco plants from O3 injury by Bacillus velezensis with production of acetoin

Plant growth-promoting rhizobacteria (PGPRs) confer benefits to crops by producing volatile organic compounds (VOCs) to trigger induced systemic tolerance (IST). Here we show that Bacillus velezensis GJ11, a kind of PGPRs, produce VOCs such as 2,3-butanediol and acetoin to trigger IST and cause stomatal closure against O₃ injury in tobacco plants. Compared to 2,3-butanediol, acetoin was more effective on triggering IST against O₃ injury. The bdh-knockout strain GJ11Δbdh with a blocked metabolic pathway from acetoin to 2,3-butanediol produced more acetoin triggering stronger IST against O₃ injury than GJ11. Both acetoin and GJ11Δbdh effectively enhance the antioxidant enzymes activity (e.g. superoxide dismutase and catalases) that is favorable for scavenging the reactive oxygen species like H₂O₂ in leaves after exposure to O₃. Consequently, less H₂O₂ accumulation was observed, and reasonably less chlorophylls and proteins were damaged by H₂O₂ in the tobacco leaves treated with acetoin or GJ11Δbdh. The field experiment also showed that both acetoin and GJ11Δbdh could protect tobacco plants from O₃ injury after application by root-drench. This study provides new insights into the role of rhizobacterial B. velezensis and its volatile component of acetoin in triggering defense responses against stresses such as O₃ in plants.     

Exogenous Spermidine Promotes Somatic Embryogenesis of <i>Cunninghamia lanceolata</i> by Altering the Endogenous Phytohormone Content

In order to study how exogenous hormones in C. lanceolata (gymnosperm) regulate somatic embryogenesis, we measured the endogenous phytohormones of two genotypes with different somatic embryogenesis efficiency and found that an increase in endogenous concentrations of IAA and ABA may be correlated to more efficient somatic embryogenesis. By applying exogenous spermidine, we found that exogenous hormones may affect somatic embryogenesis efficiency through affecting the endogenous phytohormone content. Based on these results, further studies can be conducted whereby the concentration of exogenous hormones or the levels of endogenous phytohormones by molecular methods are regulated to promote somatic embryogenesis. Our research may benefit the long-term economic output of the forestry industry and lays the foundation to studying the molecular mechanism that controls somatic embryogenesis efficiency.