Urinary Concentrations of Bisphenol Mixtures during Pregnancy and Birth Outcomes: The MAKE Study.

Bisphenols are endocrine disruptors that may be associated with altered fetal growth in humans, and they have similar biological functions to mimic hormones. In addition, aggregated chemicals showed an adverse effect although individual concentration was at a low level. However, most studies between bisphenols and birth outcomes have focused on the effect of individual bisphenol. Thus, we explored the associations of urinary bisphenol mixtures with birth outcomes. We conducted a prospective birth cohort study in South Korea. One hundred eighty mother-infant pairs were recruited from 2017 to 2019. Bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS) in one spot urine were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry. We used two statistical approaches to examine potential associations of BPA, BPF, and BPS with birth weight and gestational age: (1) multivariable linear regression; (2) Bayesian kernel machine regression (BKMR). The geometric means of BPA, BPF, and BPS were 2.1, 0.2, and 0.1 µg/L, respectively. In stratified linear analyses by each median value, a higher BPF was positively associated with birth weight (g) (ß = 125.5; 95% CI: 45.0 to 205.9). Mixture analyses using BKMR suggested an inverse association between bisphenol mixtures and birth weight. Our findings suggest that in utero bisphenol exposure may influence birth weight and that such relationships may differ considering non-linearity and the combined effect.

Urinary bisphenol A and its analogues and haemato-biochemical alterations of pregnant women in Korea.

INTRODUCTION: Bisphenol F (BPF) and bisphenol S (BPS) are chemical substitutes for, and may have similar physiological effects to, bisphenol A (BPA). Bisphenols provoke endocrine disorders and are cytotoxic, oxidize hemoglobin, and induce morphological changes in human red blood cells (RBC). It is more sensitive to changes in the RBC number and hemoglobin (Hb) level during pregnancy. Therefore, we investigated the effects of bisphenols (BPs) and their substitute compounds on hemopoiesis and the serum biochemical parameters of pregnant women. METHODS: The study population comprised 196 pregnant women from the MAKE cohort study, recruitment for which occurred from 2017 to 2019. We measured the levels of BPA, BPF and BPS in urine samples and collected data on socioeconomic, lifestyle, and environmental factors at visits to the hospital. The associations between the levels of the three BPs and biochemical parameters were analyzed by multiple linear regression. RESULTS: The geometric mean urinary concentrations of specific gravity adjusted BPA, BPF, and BPS were 2.1, 0.2, and 0.1 µg/L, respectively. There was a significant negative association between the urinary concentration of BPA and the Hb level (ß = -0.5, p = 0.02). After stratifying by the median concentrations of the three BPs, the maternal urinary BPA level had a significantly negative effect on the RBC count, HB level, and hematocrit in the high BPA concentration group (RBC, ß = - 0.5, p = 0.001; Hb, ß = -1.4, p = 0.002; Hct, ß = -5.0, p = 0.001). CONCLUSIONS: BPA has a harmful effect on hemato-biochemical changes that occur during pregnancy. Further studies should investigate the relation between widespread exposure to bisphenols and effects on human health.

A novel canine influenza H3N2 virus isolated from cats in an animal shelter.

The interspecies transmission of avian-origin H3N2 canine influenza virus (CIV) to dogs was first reported in 2007. The present study characterized a novel CIV H3N2 isolated from cats in an animal shelter. A comparative analysis of the deduced amino acid sequences of the A/Canine/Korea/CY009/2010(H3N2) (CY009) and A/Feline/Korea/FY028/2010 (H3N2) (FY028) strains isolated from dogs and cats, respectively, in the animal shelter identified point mutations in 18 amino acid positions within eight viral genes. Interestingly, CY009 and FY028 replicated well in specific pathogen-free embryonated chicken eggs and in mice, respectively. Mice infected with the FY028 strain exhibited significant over expression of IL-10, TNF-α, and IFN-γ (p<0.001) at 3 days postinfection. Thus, an emergency monitoring system should be developed to identify influenza mutations that occur during interspecies transmission in companion animals and for continuous public health surveillance.

C-terminal substitution of HBV core proteins with those from DHBV reveals that arginine-rich 167RRRSQSPRR175 domain is critical for HBV replication.

To investigate the contributions of carboxyl-terminal nucleic acid binding domain of HBV core (C) protein for hepatitis B virus (HBV) replication, chimeric HBV C proteins were generated by substituting varying lengths of the carboxyl-terminus of duck hepatitis B virus (DHBV) C protein for the corresponding regions of HBV C protein. All chimeric C proteins formed core particles. A chimeric C protein with 221-262 amino acids of DHBV C protein, in place of 146-185 amino acids of the HBV C protein, supported HBV pregenomic RNA (pgRNA) encapsidation and DNA synthesis: 40% amino acid sequence identity or 45% homology in the nucleic-acid binding domain of HBV C protein was sufficient for pgRNA encapsidation and DNA synthesis, although we predominantly detected spliced DNA. A chimeric C protein with 221-241 and 251-262 amino acids of DHBV C, in place of HBV C 146-166 and 176-185 amino acids, respectively, could rescue full-length DNA synthesis. However, a reciprocal C chimera with 242-250 of DHBV C ((242)RAGSPLPRS(250)) introduced in place of 167-175 of HBV C ((167)RRRSQSPRR(175)) significantly decreased pgRNA encapsidation and DNA synthesis, and full-length DNA was not detected, demonstrating that the arginine-rich (167)RRRSQSPRR(175) domain may be critical for efficient viral replication. Five amino acids differing between viral species (underlined above) were tested for replication rescue; R169 and R175 were found to be important.

Seroprevalence of subtype H3 influenza A virus in South Korean cats.

To investigate the potential transmission of subtype H3 influenza virus to cats, a serological survey was carried out in South Korea. Serum samples (n=1027) were obtained from 809 pet cats and 218 domesticated cats living in urban colonies (D-cats) from 2008 to 2010, and tested using an influenza anti-nucleoprotein (NP)-specific enzyme-linked immunosorbent assay (ELISA) and the haemagglutination inhibition (HI) test, which was recommended by the World Organization for Animal Health. Anti-influenza virus antibodies were detected in 3.12% and 2.43% of cat sera tested using the NP-specific ELISA and HI test, respectively. Anti-H3 antibodies were also identified when the HI assay was used for influenza virus serotyping. These data may indicate the sporadic transmission of subtype H3 influenza virus from other infected species to cats in South Korea.

A novel vaccine combined with an alum adjuvant for porcine encephalomyocarditis virus (EMCV)-induced reproductive failure in pregnant sows.

To evaluate a novel vaccine for porcine encephalomyocarditis virus (EMCV), which causes reproductive failure in pregnant sows, virus like particles (VLPs) were generated and immunized twice in 2 week intervals before sow mating. Sows were divided into 4 groups (n=4, per group). Group 1 was immunized with the alum adjuvant alone, Group 2 with VLPs alone, Group 3 with VLPs mixed alum adjuvant, and Group 4 with a commercial killed vaccine. In Group 2, seroconversion was observed at very low levels, while in Group 3, neutralizing antibodies were maintained at a high level until 30 days after farrowing. Similar levels neutralizing antibodies were observed in Group 4. The gestation period of the pregnant sows was on average 115 days, and no injection site reaction or side effects were observed. The mean temperature of the sows after immunization increased temporarily to 38.7-39.1 °C for 1 day. The numbers and weights of surviving piglets were similar among the groups. These data describe a novel EMCV vaccine composed of VLPs mixed with an alum adjuvant that is safe to use during sow gestation and induces and maintains high levels of seroconversion. This vaccine could thus be a candidate for protecting against EMCV induced reproductive failure in pig farms.

Immunogenicity and safety of virus-like particle of the porcine encephalomyocarditis virus in pig.

BACKGROUND: In this study, porcine encephalomyocarditis virus (EMCV) virus-like particles (VLPs) were generated using a baculovirus expression system and were tested for immunogenicity and protective efficacy in vivo. RESULTS: VLPs were successfully generated from Sf9 cells infected with recombinant baculovirus and were confirmed to be approximately 30-40 nm by transmission electron microscopy (TEM). Immunization of mice with 0.5 µg crude protein containing the VLPs resulted in significant protection from EMCV infection (90%). In swine, increased neutralizing antibody titers were observed following twice immunization with 2.0 µg crude protein containing VLPs. In addition, high levels of neutralizing antibodies (from 64 to 512 fold) were maintained during a test period following the second immunization. No severe injection site reactions were observed after immunization and all swine were healthy during the immunization period. CONCLUSION: Recombinant EMCV VLPs could represent a new vaccine candidate to protect against EMCV infection in pig farms.