Resveratrol reduces lactate production and modifies the ovarian cancer immune microenvironment.

Tumor cells show deregulated metabolism leading to an enrichment of lactate in the tumor microenvironment (TME). This lactate-rich environment has been reported to impair effector T cells. However, T-regulatory cells (Tregs) show metabolic advantages in lactate-rich TME that maintain a strong suppression of effector T cells, which leads to tumor immune evasion. Therefore, the glycolytic process of tumors could represent a therapeutic target, and agents that modify the energy metabolism of tumor cells have therapeutic potential. Resveratrol is a naturally occurring polyphenol that has been confirmed to suppress tumor cells' glycolytic metabolism. In this study, we show that resveratrol induces metabolic reprogramming in ovarian cancer cells. Resveratrol increases oxidative and decreases glycolysis, in association with decreased lactate production both in vitro and in vivo. Lactate reduction in TME weakens the suppressive function of Tregs, and subsequently restores anti-tumor immunity. Significantly, combined resveratrol and PD-1 blockade promote anti-tumor efficacy. These data suggest that resveratrol's anti-tumor actions in ovarian cancer could be explained, in part, through modification of the anti-tumor immunity, and indicate a novel treatment strategy for improving immune checkpoint blockade therapy using resveratrol.

Family with sequence similarity 46 member a confers chemo-resistance to ovarian carcinoma via TGF-ß/Smad2 signaling.

Ovarian cancer is the most lethal malignancy with depressive 5-year survival rate, mainly due to patients with advanced stages experience tumor recurrence and resistance to the current chemotherapeutic agents. Thus, exploring the underlying molecular mechanisms involved in chemo-resistance is crucial for management of treatment to improve therapeutic outcomes. In the current study, we found overexpression of FAM46A in ovarian cancer patients demonstrated an aggressive phenotype and poor outcome. Furthermore, FAM46A overexpression in ovarian cancer cells induces higher CDDP resistance. However, inhibition of FAM46A sensitized ovarian cancer cell lines to CDDP cytotoxicity both in vitro and in vivo. Mechanically, upregulation of FAM46A activated transforming growth factor-ß (TGF-ß)/Smad signaling and upregulated the levels of nuclear Smad2. Taken together, our results highlight the important oncogenic role of FAM46A in ovarian cancer progression and might provide a potential clinical target for patients with chemo resistant ovarian cancer.

CD34 and Bcl-2 as predictors for the efficacy of neoadjuvant chemotherapy in cervical cancer.

BACKGROUND: Successful neoadjuvant chemotherapy (NACT) could improve the surgical resection rate and radical curability of patients with cervical cancer, but only a subset of patients benefits. Therefore, identifying predictive biomarkers are urgently needed. The aim of this study was to evaluate the predictive value of CD34 and Bcl-2 in the NACT effectiveness of cervical cancer. METHODS: Sixty-seven patients with locally advanced cervical cancer (FIGO stages IB3, IIA2 or IIB) were classified into two groups based on effective (n = 48) and ineffective (n = 19) response to NACT. Immunohistochemistry was employed to identify CD34 and Bcl-2 expression before and after NACT. We analyzed the associations between the pre-NACT expression of these two biomarkers and the response of NACT. The expression of these two biomarkers before and after NACT was also assessed and compared. RESULTS: More patients were CD34 positive expression before NACT in effective group compared to ineffective group (p = 0.005). However, no statistically significant difference in Bcl-2 expression before NACT were found between two groups (p = 0.084). In NACT effective group, the expression of both CD34 and Bcl-2 after NACT are down-regulated (p < 0.001 and p < 0.001, respectively), while there are no statistical differences between the pre- and post-NACT expression of CD34 and Bcl-2 in NACT ineffective group (p = 0.453 and p = 0.317, respectively). CONCLUSION: The positive CD34 expression before NACT may serve as a predictive biomarker for NACT of cervical cancer, but the pre-NACT expression of Bcl-2 is not an independent predictor. The down-regulated expression of these two indicators after NACT may indicate effective NACT.

Identification of infectious spleen and kidney necrosis virus (ISKNV)-encoded microRNAs.

MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression by complementary binding to target mRNAs. Virus-encoded miRNAs play important roles in virus life cycle and virus-host interactions. Viruses from the Megalocytivirus genus, family Iridoviridae, infect a wide range of fishes, bringing great challenges to aquaculture. Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the Megalocytivirus genus. In this study, using Illumina sequencing coupled with miRNA precursor prediction and stem-loop real-time PCR, 14 putative ISKNV-encoded miRNAs were preliminarily identified from ISKNV-infected mandarin fish MFF-1 cells. To initially study their functions, inhibitors of the 14 viral miRNAs were synthesized and transfected into MFF-1 cells, which were further infected with ISKNV. The results showed that these viral miRNAs could affect the virus titers in the supernatant of ISKNV-infected cells and the expression of major capsid protein (MCP). Moreover, we observed that inhibition of several ISKNV miRNAs had different effects on MCP expression and on titer of released virus, suggesting complex roles of viral miRNAs in ISKNV infection. The current study may provide a fundamental information for further identification and functional studies on miRNAs encoded by Megalocytivirus.

Elevated MYO10 Predicts Poor Prognosis and its Deletion Hampers Proliferation and Migration Potentials of Cells Through Rewiring PI3K/Akt Signaling in Cervical Cancer.

MYO10, recognized as an important regulator of cytoskeleton remodeling, has been reported to be associated with tumorigenesis. However, its functional implication in cervical cancer and potential mechanism still remain to be undetermined currently. MYO10 level in cervical cancer tissues was analyzed by using data retrieved from The Cancer Genome Atlas and ONCOMINE databases. Messenger RNA and protein expression levels were determined by quantitative real-time polymerase chain reaction and Western blotting. Small-interfering RNA and overexpressing plasmid were used for MYO10 silencing and overexpression, and cell proliferation was analyzed by CCK-8. Transwell assays were performed to investigate the ability of cell migration and invasion. MYO10 was upregulated in cervical cancer tissues and cells when compared to normal controls, and survival analysis showed patients with high MYO10 expression had worse overall survival. Moreover, knockdown/overexpression of MYO10 significantly inhibited/enhanced the proliferation, invasion, and migration capabilities of cervical cells transfected with siRNAs/overexpressing plasmid. Additionally, MYO10 silencing inhibited PI3K/Akt signaling pathway by decreasing the phosphorylation status of PI3K and AKT. Data from the present study indicated that MYO10 were overexpressed in patients with cervical cancer and positively linked with poor prognosis. Experimental results suggested that MYO10 induced a significant encouraging effect in cervical cancer cell proliferation, invasion, and migration, linked with involvement of PI3K/Akt signaling. Collectively, these results emphasize a novel role for MYO10 overexpression in cervical cancer and provide a potent therapeutic strategy against cervical cancer.

Laparoendoscopic single-site surgery compared with conventional laparoscopic surgery for benign ovarian masses: a systematic review and meta-analysis.

OBJECTIVE: We aimed to evaluate the safety, efficiency and preferred indication for laparoendoscopic single-site surgery (LESS) compared with conventional laparoscopic (CL) surgery for benign ovarian masses. DESIGN: A systemic review and cumulative meta-analysis were performed in line with the criteria of Grading of Recommendations Assessment, Development and Evaluation: levels of evidence and grades of recommendation. DATA SOURCES: We comprehensively searched the electronic databases including PubMed, Medline, Embase and the Cochrane Library in November 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included all randomised controlled trials (RCTs) and retrospective studies published in recent 10 years, which investigated the performance of LESS versus CL in patients at all ages with benign ovarian masses. RESULTS: Four RCTs and nine retrospective studies published in recent decade including 1542 cases (744 cases for LESS and 798 cases for CL) were identified. Perioperative complication was consisted of intraoperative and postoperative complications, including ileus, wound infection or dehiscence and incisional hernia. Although LESS has less postoperative analgesic consumption (46.78% and 79.25%; OR: 0.49; 95% CI: 0.33 to 0.74, p<0.001) and shorter hospital stay (weighted mean difference (WMD): -0.24 days; 95% CI: -0.35 to -0.14; p<0.001), CL has less perioperative complications (6.59% and 2.85%; OR: 2.08; 95% CI: 1.05 to 4.11, p=0.04) and shorter operative time (WMD: 3.43 min; 95% CI: -0.03 to 6.88; p=0.05). Body mass index, history of previous abdominal surgery, size of adnexal mass, estimated blood loss and postoperative pain scores did not differ significantly between two techniques. CONCLUSIONS: The indications of LESS for benign ovarian masses are similar to CL and it has better postoperative recovery. However, with less perioperative complications, CL surgery is safer than LESS.

Association of socioeconomic and lifestyle factors with chronic non-communicable diseases and multimorbidity among the elderly in rural southwest China.

BACKGROUND: This study estimates the prevalence of five chronic non-communicable disease (NCDs) (hypertension, diabetes, CHD, COPD and stroke) and its multimorbidity, and examines the relationship between SES and lifestyle factors and multimorbidity among older adults in rural southwest China. METHODS: A cross-sectional survey of 4833 consenting adults aged ≥60 years was conducted in 2017. Data on the demographics, smoking, drinking, height, weight, blood pressure and fasting blood glucose were collected. RESULTS: Among the participants, the overall prevalence of hypertension, diabetes, stroke, COPD and CHD was 50.6, 10.2, 6.4, 5.4 and 5.5%, respectively, and of multimorbidity was 16.1%. Females had a higher prevalence of hypertension, diabetes and multimorbidity of chronic NCDs, but a lower prevalence of COPD than males (P < 0.05). Older adults with good household assets and access to medical services were less likely to experience multimorbidity, whereas obese and centrally obese participants, current smokers, current drinkers and those with a family history of chronic NCDs had a greater probability of multimorbidity. CONCLUSIONS: The findings suggest that effective strategies for prevention and control of chronic NCDs and its multimorbidity are urgently needed, especially for low-income, elderly, ethnic minority adults with poor access to medical services.

High reduced/oxidized glutathione ratio in infectious spleen and kidney necrosis virus-infected cells contributes to degradation of VP08R multimers.

Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus, family Iridoviridae. The ISKNV-infected cells in fish tissues are attached by lymphatic endothelial cells (LECs), which is a unique pathological phenomenon of ISKNV infection. The viral proteins VP23R and VP08R and the host protein nidogen-1 constitute the virus-mock basement membrane (VMBM) on the membrane of infected cells to provide attaching sites for LECs. VP08R can form cross-linked multimers via intermolecular disulfide bonds to make VMBM a compact and strong structure. A question is that when the virions mature, how do they penetrate VMBMs to be released from the cells? In this study, the redox state in ISKNV-infected cells was investigated. We demonstrated that the ratio of reduced/oxidized glutathione (GSH/GSSG) was significantly elevated in ISKNV-infected cells, suggesting the increasing of reducing power. Remarkable changes were also observed in activities of many GSH metabolic enzymes and in the ratio of NADPH/NADP. We further exhibited that the high ratio of GSH/GSSG could lead to degradation of the VP08R multimer in vitro. These may suggest that the high GSH/GSSG ratio in infected cells could act on the VP08R multimer to facilitate the disassembly of VMBMs after virus maturation.

A microRNA from infectious spleen and kidney necrosis virus modulates expression of the virus-mock basement membrane component VP08R.

Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus, family Iridoviridae. Infection of ISKNV is characterized by a unique pathological phenomenon in that the infected cells are attached by lymphatic endothelial cells (LECs). ISKNV mediates the formation of a virus-mock basement membrane (VMBM) structure on the surface of infected cells to provide attaching sites for LECs. The viral protein VP08R is an important component of VMBM. In this study, a novel ISKNV-encoded microRNA, temporarily named ISKNV-miR-1, was identified. ISKNV-miR-1 is complementary to the VP08R-coding sequence and can modulate VP08R expression through reducing its mRNA level. This suggests that formation of VMBM may be under fine regulation by ISKNV.

A mitochondrial outer membrane-localized protein encoded by White spot syndrome virus.

White spot syndrome virus (WSSV) is a devastating pathogen of crustaceans that causes huge losses to global shrimp farming. In this study, a mitochondrial outer membrane protein encoded by WSSV, termed as wsv152, was identified. Bioinformatics analysis showed that wsv152 shared no similarity with any known proteins. Real-time RT-PCR revealed that wsv152 was initially transcribed at 6 h post WSSV infection. Fluorescent microscopy demonstrated that the wsv152-GFP fusion protein was present in the mitochondrion. Western blot further suggested that wsv152 was specifically localized on the outer membrane of mitochondria. To our knowledge, this is the first report of a mitochondrion-localized protein encoded by WSSV.

Socioeconomic variations in nicotine dependence in rural southwest China.

BACKGROUND: This study examines how nicotine dependence is distributed across socioeconomic gradients in rural Yunnan province, which has the most ethnic minorities in one province in southwest China. METHODS: A cross-sectional survey was conducted in four rural areas of Yunnan province among 17,158 consenting individuals aged ≥18 years in 2011. Information on demographic characteristics and smoking habits was obtained using a standard questionnaire. The Fagerstrom Test for Nicotine Dependence (FTND) was applied to assess nicotine dependence. Multilevel logistic regression was used to model the variation in prevalence of nicotine dependence. RESULTS: In the study population, the overall prevalence of current smokers and nicotine dependence was 32.4 % and 31.6 %, respectively. Females were much less likely to have nicotine addiction than males: odds ratio (OR) of 0.01 (95 % CI: 0.008 - 0.012). Higher annual household income was associated with a greater risk of nicotine dependence (OR 1.09, 95 % CI: 1.01 - 1.17). Adults who grew tobacco were more likely to have nicotine addiction (OR 1.22, 95 % CI 1.07 - 1.41). Individual educational level was inversely associated with the probability of nicotine dependence (OR 0.63, 95 % CI 0.55 - 0.72), lower community educational level was also associated with an increased risk of nicotine dependence (OR 0.94, 95 % CI 0.92 - 0.98). CONCLUSIONS: Nicotine dependence showed significant variations across different indicators of both contextual and individual socioeconomic status in rural southwest China. Future interventions on tobacco cessation should give increased attention to men, tobacco farmers, less educated or poorer persons, and lower educational level communities.

The economic burden of smoking and secondhand smoke exposure in rural South-West China.

OBJECTIVE: To estimate the direct and indirect costs of chronic diseases attributed to smoking and exposure to secondhand smoke (SHS) in a given year (2011) in rural southwest China. METHODS: A prevalence-based, disease-specific attributable-risk approach was used to estimate the economic burden of chronic diseases attributable to both smoking and exposure to secondhand smoke (SHS). A cross-sectional questionnaire survey of 17 158 consenting adults aged ≥18 years was used to derive prevalence of smoking and exposure to SHS, as well as direct and indirect costs of chronic diseases. RESULTS: In the study population, the prevalence rates of smoking and exposure to SHS are 73.1 and 38.2% for males and 1.4 and 43.4% for females, respectively. The total costs of illness are $25.85 million for COPD, $18.80 million for asthma, $37.25 million for CHD, $17.91 million for stroke, $264.35 million for hypertension and $17.11 million for peptic ulcer. The estimated costs attributable to smoking and exposure to SHS are $95.51 million and $79.35 million, accounting for 7.15 and 5.94% of local healthcare costs, respectively. Of the total costs of tobacco, direct costs and indirect costs are $94.66 million and $0.85 million for smoking, and $78.22 million and $1.36 million for exposure to SHS. Smoking contributes more cost of illness than exposure to SHS in men, whereas exposure to SHS contributes more cost of illness than smoking in women. CONCLUSIONS: Smoking and exposure to SHS produce substantial economic burden as well as have a considerable public health impact in rural southwest China.

Multilevel analysis of the determinants of smoking and second-hand smoke exposure in a tobacco-cultivating rural area of southwest China.

OBJECTIVES: To examine contextual and individual demographical predictors of smoking and exposure to second-hand smoke (SHS) in a tobacco-cultivating rural area of southwest China. METHODS: A cross-sectional survey of 4070 consenting individuals aged 18 years or more was conducted in 2010. Information on demographical characteristics, tobacco smoking status and SHS exposure were obtained by a standard questionnaire. Multilevel logistic regression was used to model the variation in prevalence of smoking and SHS exposure. RESULTS: In the study population, the prevalence rates of smoking and exposure to SHS were 63.5% and 74.7% for men, and 0.6% and 71.2% for women, respectively. Men were more likely to use tobacco than women: OR 8.27, 95% CI (4.83 to 10.97). Age was inversely associated with the probability of tobacco use (OR 0.98, 95% CI 0.97 to 0.99), and exposure to SHS (OR 0.97, 95% CI 0.96 to 0.99). Individual educational level was inversely associated with smoking, but showed no association with exposure to SHS. Adults who did not grow tobacco were less likely to consume tobacco (OR 0.75, 95% CI 0.57 to 0.99) and to be exposed to SHS (OR 0.76, 95% CI 0.58 to 0.99). Living in a high-income community was associated with a low rate of current smoking (OR 0.66, 95% CI 0.57 to 0.77) and SHS exposure (OR 0.58, 95% CI 0.52 to 0.65). CONCLUSIONS: Future interventions to reduce smoking and exposure to SHS in China should focus more on tobacco farmers, less-educated individuals and on poor rural communities.

Mutations in POFUT1, encoding protein O-fucosyltransferase 1, cause generalized Dowling-Degos disease.

Dowling-Degos disease (DDD), or reticular pigmented anomaly of the flexures, is a type of rare autosomal-dominant genodermatosis characterized by reticular hyperpigmentation and hypopigmentation of the flexures, such as the neck, axilla, and areas below the breasts and groin, and shows considerable heterogeneity. Loss-of-function mutations of keratin 5 (KRT5) have been identified in DDD individuals. In this study, we collected DNA samples from a large Chinese family affected by generalized DDD and found no mutation of KRT5. We performed a genome-wide linkage analysis of this family and mapped generalized DDD to a region between rs1293713 and rs244123 on chromosome 20 [corrected]. By exome sequencing, we identified nonsense mutation c.430G>T (p.Glu144(∗)) in POFUT1, which encodes protein O-fucosyltransferase 1, in the family. Study of an additional generalized DDD individual revealed the heterozygous deletion mutation c.482delA (p.Lys161Serfs(∗)42) in POFUT1. Knockdown of POFUT1 reduces the expression of NOTCH1, NOTCH2, HES1, and KRT5 in HaCaT cells. Using zebrafish, we showed that pofut1 is expressed in the skin and other organs. Morpholino knockdown of pofut1 in zebrafish produced a phenotype characteristic of hypopigmentation at 48 hr postfertilization (hpf) and abnormal melanin distribution at 72 hpf, replicating the clinical phenotype observed in our DDD individuals. At 48 and 72 hpf, tyrosinase activities decreased by 33% and 45%, respectively, and melanin protein contents decreased by 20% and 25%, respectively. Our findings demonstrate that POFUT1 mutations cause generalized DDD. These results strongly suggest that the protein product of POFUT1 plays a significant and conserved role in melanin synthesis and transport.

[Analysis of association of economic burden of hypertension with tobacco exposure in Luoping county of Yunnan province].

OBJECTIVE: To analyze the association between hypertension and tobacco exposure Luoping county of Yunnan province and estimate the direct cost attributable to hypertension . METHODS: Using Probability proportional to size (PPS) sampling method, 5000 rural residents aged over 18 years were selected from 12 townships in Luoping county, Yunnan province in April 2011, from which 4611 subjects completed the survey. Self-designed questionnaires were used to collect general information, smoking status, costs for outpatient consultation, inpatient, treatment, medication, travel, accommodation and extra-nutrition caused by hypertension as well as the information of health-related behavior. Their height, weight, waist circumference, hip circumference and blood pressure were measured. The direct economic burden of hypertension was calculated. Chi-square (χ(2)) test was used to compare gender differences of hypertension prevalence, smoking and passive smoking. And t test was used to compare the differences of direct economic burden of hypertension among different gender, smoking and passive smoking status. Multivariable logistic regression model was used to analyze the influence factors of hypertension. RESULTS: Among the 4611 subjects, the age was (46.90 ± 16.74) years old. Male accounted for 49.8% (2294/4611) and female 50.2% (2317/4611) . The smoking rate was higher in males (75.7% (1736/2294)) than in females(1.6% (38/2317)) (χ(2) = 2669.21, P < 0.01). The passive smoking rate was lower in males (10.0% (230/2294)) than in females (46.2% (1070/2317)) (χ(2) = 744.27, P < 0.05). Non-tobacco exposure rate in males (14.3% (328/1537)) was lower than in females (52.2% (1209/1537)) (χ(2) = 744.37, P < 0.05) . The risk of hypertension in smokers and passive smokers were higher than those without tobacco exposure, OR (95%CI) was 1.41 (1.15-1.71) (P < 0.05) and 1.31 (1.07-1.63) (P < 0.05) respectively. The per capita direct cost of hypertension was (3444.09 ± 3067.83) Yuan. Of this, tobacco exposure (4552.46 ± 3189.05) Yuan was higher than non-tobacco exposure (1907.71 ± 1383.94) Yuan (t = -3.81, P < 0.05) . Moreover, smokers were (6951.71 ± 3422.87) Yuan higher than passive smokers (3128.09 ± 2083.17) Yuan (t = 3.19, P < 0.05) and males (5827.39 ± 3240.50) Yuan were higher than females (2633.03 ± 2569.01) Yuan (t = 3.22, P < 0.05) . The total direct costs of hypertension attributable to smoking and SHS was 41 million and 38 million, respectively. CONCLUSION: Both smoking and SHS had significant impact on prevalence and economic burden of hypertension in Luoping county. Implementing effective strategies to control tobacco exposure is useful to reduce the economic burden of hypertension in the study region.

Patterns and socioeconomic influences of tobacco exposure in tobacco cultivating rural areas of Yunnan Province, China.

BACKGROUND: This study describes the patterns and socioeconomic influences of tobacco use among adults in tobacco-cultivating regions of rural southwest China. METHODS: A cross-sectional survey was conducted in 8681 adults aged ≥18 years in rural areas of Yunnan Province, China from 2010 to 2011. A standardized questionnaire was administered to obtain data about participants' demographic characteristics, individual socioeconomic status, ethnicity, self-reported smoking habits, and exposure to secondhand smoke (SHS). The socioeconomic predictors of current smoking, nicotine addiction, and SHS exposure were analyzed using multivariate logistic regression. RESULTS: The prevalence rates of tobacco use were much higher in men compared with women (current smoking 68.5% vs. 1.3%; and nicotine dependence 85.2% vs. 72.7%). However, the rate of SHS exposure was higher in women compared with men (76.6% vs. 70.5%). Tobacco farmers had higher prevalence rates of current smoking, nicotine dependence, and SHS exposure compared with participants not engaged in tobacco farming (P<0.01). Most tobacco users (84.5%) reported initiating smoking during adolescence. A total of 81.1% of smokers smoked in public places, and 77.6% smoked in workplaces. Individuals belonging to an ethnic minority had a lower probability of SHS exposure and nicotine dependence. Individual educational level was found to be inversely associated with the prevalence of current smoking, exposure to SHS, and nicotine dependence. Higher annual household income was associated with a greater risk of nicotine dependence. CONCLUSIONS: This study suggests that tobacco control efforts in rural southwest China must be tailored to address tobacco-cultivating status and socioeconomic factors.

Application of GP5 protein to develop monoclonal antibody against porcine reproductive and respiratory syndrome virus.

In this study, a panel of monoclonal antibodies (mAbs) against Porcine reproductive and respiratory syndrome virus(PRRSV), named as 8C9 and4B4, were produced by fusing SP2/0 myeloma cells and spleen cells of BALB/c mice immunized with the PRRSV (TCID(50)=5.5), screened by the indirect ELISA and subjected to several limiting dilutions. mAbs were then identified by biological characterization. Among the two fusion cell strains, 8C9 belonged to the IgG1 subclass and 4B4 belonged to the IgG2a subclass. The titers in cell culture supernatant and abdomen liquor reached to 1:10(4)and 1:10(5), respectively. The specificity test indicated that the two cells had specific reactions for the PRRSV and GP5 protein respectively, and no reaction with Classical swine fever virus (CSFV) or Swine vesicular disease virus (SVDV). The molecular weights of the heavy chain and light chain were about 45.0 kDa and 25.0 kDa, respectively. In neutralization activity tests, the results showed that the prepared mAb 4B4 can protect 50% of cells with no CPE in dilution up to 1:512, but mAB 8C9 has no neutralization activities to PRRSV.

Chronic zebrafish low dose decabrominated diphenyl ether (BDE-209) exposure affected parental gonad development and locomotion in F1 offspring.

Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants around the world. Because of large production volumes, widespread usage and persistence, PBDEs are now ubiquitous environmental pollutants detected in a wide variety of environment media and human samples and therefore pose a significant public health concern. Deca-PBDE (BDE-209) is the only commercial PBDE mixture still allowed for use at present, and has been recently detected at high levels in human samples. However, few studies explore its effect on development, reproduction or neurobehavior with animal models. In particular, studies with long-term chronic exposure at relatively low doses are lacking. In this study, we utilize the zebrafish model to explore the developmental, reproductive, and behavioral toxicities associated with long-term chronic exposure to deca-PBDE (BDE-209). Our findings revealed that long-term chronic exposure to low dose of deca-BDE (ranging from 0.001 to 1 µM) affected overall fitness (measured by condition factor), gonad development, male gamete quantity and quality in F0 parental fish. For F1 offspring without continuous exposure to BDE-209, parental BDE treatment led to delayed hatch and motor neuron development, loose muscle fiber, slow locomotion behavior in normal conditions, and hyperactivity when subjected to light-dark photoperiod stimulation. In conclusion, parental chronic low dose BDE-209 exposure not only affects F0 growth and reproduction, but also elicits neurobehavior alternations in F1 offspring.

Indirect ELISA with recombinant GP5 for detecting antibodies to porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome is caused by the PRRS virus (PRRSV), which has six structural proteins (GP2, GP3, GP4, GP5, M and N). GP5 and N protein are important targets for serological detection by enzyme-linked immunosorbent assay (ELISA) and other methods. Toward this goal, we developed an indirect ELISA with recombinant GP5 antigens and this method was validated by comparison to the LSI PRRSV-Ab ELISA kit. The results indicated that the optimal concentration of coated recombinant antigen was 0.2 µg/well for a serum dilution of 1:40. The rate of agreement with the LSI PRRSV-Ab kit was 88.7% (266/300). These results support the potential use of recombinant GP5 as an antigen for indirect ELISA to detect PRRSV antibodies in pigs.