Pre-Pandemic Factors Associated with Pandemic Impact and Psychosocial Distress Among Mothers of Young Children.

OBJECTIVE: To describe COVID-19 pandemic impact among mothers of young children (0-8 yrs.) and assess pre-pandemic factors associated with greater pandemic impact and psychosocial distress. METHODS: Mothers from three US birth cohorts (n=301, mean child age 2.4 years) reported on demographics and psychosocial distress (anxiety, perceived stress, financial stress) before the pandemic (2/2015-2/2020). During the pandemic (7/2020-6/2021), they completed a supplemental survey about the impact of the pandemic on their families (Coronavirus Impact Scale) and psychosocial distress. Multivariable linear and ordinal logistic regression were used to evaluate pre-pandemic factors associated with pandemic impact overall and by domain. RESULTS: Compared to pre-pandemic reports, maternal anxiety symptoms increased by 9.4%, perceived stress increased by 13.3%, and financial stress increased by 41.7%, of which all were statistically significant changes. Participants reported the most severe pandemic impact in family routines (72.4%), experiences of stress (40.2%), and social support (38.6%). Mothers with some college or a 4-year degree experienced higher overall pandemic impact compared to mothers with the least and highest education. Pre-pandemic distress was not associated with pandemic impact however, mid-pandemic, all three distress measures were significantly positively associated with overall CIS, with the largest effect size noted for perceived stress (B=1.36, 95% CI: 0.90,1.82). CONCLUSIONS: While, on average, mothers of young children experienced worsening psychosocial stress during the COVID-19 pandemic, pre-pandemic psychosocial stress alone was not prospectively associated with greater pandemic impact, suggesting that the COVID-19 pandemic may have both elaborated existing systemic social inequalities and created new burdens. WHAT'S NEW: While mothers of young children experienced worsening psychosocial distress during the pandemic, pre-pandemic psychosocial distress alone was not associated with greater family pandemic impact. The pandemic may have both exacerbated existing systemic social inequalities and created new burdens.

Association of Time in Bed, Social Jetlag, and Sleep Disturbances With Cognitive Performance in Children With ADHD.

OBJECTIVES: Children with ADHD commonly exhibit sleep disturbances, but there is limited knowledge about how sleep and sleep timing are associated with cognitive dysfunction in children with ADHD. METHODS: Participants were 350 children aged 5 to 12 years diagnosed with ADHD. Three sleep-related constructs-time in bed, social jetlag (i.e., discrepancy in sleep timing pattern between school nights and weekend nights), and sleep disturbances were measured using a caregiver-report questionnaire. Linear regression models assessed the associations between sleep-related constructs and cognitive performance. RESULTS: After adjustment for sociodemographic variables, there were few associations between time in bed or sleep disturbances and cognitive performance, however, greater social jetlag was negatively associated with processing speed (ß = -.20, 95% CI [-0.35, -0.06]), visually-based reasoning (ß = -.13, 95% CI [-0.27, 0.00]), and language-based reasoning (ß = -.22, 95% CI [-0.36, -0.08]); all p < .05). CONCLUSION: Social jetlag, but not time in bed or disturbances, was associated with lower cognitive performance among children with ADHD.

Early Changes in Transcriptomic Profiles in Synaptodendrosomes Reveal Aberrant Synaptic Functions in Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders characterized by the progressive decline of cognitive functions, and is closely associated with the dysfunction of synapses, which comprise the basic structure that mediates the communication between neurons. Although the protein architecture and machinery for protein translation at synapses are extensively studied, the impact that local changes in the mRNA reservoir have on AD progression is largely unknown. Here, we investigated the changes in transcriptomic profiles in the synaptodendrosomes purified from the cortices of AD mice at ages 3 and 6 months, a stage when early signatures of synaptic dysfunction are revealed. The transcriptomic profiles of synaptodendrosomes showed a greater number of localized differentially expressed genes (DEGs) in 6-month-old AD mice compared with mice 3 months of age. Gene Ontology (GO) analysis showed that these DEGs are majorly enriched in mitochondrial biogenesis and metabolic activity. More specifically, we further identified three representative DEGs in mitochondrial and metabolic pathways-Prnp, Cst3, and Cox6c-that regulate the dendritic spine density and morphology in neurons. Taken together, this study provides insights into the transcriptomic changes in synaptodendrosomes during AD progression, which may facilitate the development of intervention strategies targeting local translation to ameliorate the pathological progression of AD.

Association between atopic diseases and neurodevelopmental disabilities in a longitudinal birth cohort.

Reports on the association between the prevalence of atopic diseases and neurodevelopmental disabilities (NDs) have been inconsistent in the literature. We investigated whether autism spectrum disorder (ASD), attention deficit-hyperactivity disorders (ADHD), and other NDs are more prevalent in children with asthma, atopic dermatitis (AD) and allergic rhinitis (AR) compared to those without specific atopic conditions. A total of 2580 children enrolled at birth were followed prospectively, of which 119 have ASD, 423 have ADHD, 765 have other NDs, and 1273 have no NDs. Atopic diseases and NDs were defined based on physician diagnoses in electronic medical records. Logistic regressions adjusting for maternal and child characteristics estimated the associations between NDs (i.e., ASD, ADHD, and other NDs) and asthma, AD and AR, respectively. Children with asthma, AD or AR had a greater likelihood of having ADHD or other NDs compared with children without specific atopic conditions. The association between ASD and asthma diminished after adjusting for maternal and child factors. Either mothers or children having atopic conditions and both mothers and children with atopic conditions were associated with a higher prevalence of ADHD in children, compared with neither mothers nor children having atopic conditions. Children diagnosed with multiple atopic diseases were more likely to have NDs compared with those without or with only one type of atopic disease. In conclusion, in this U.S. urban birth cohort, children with atopic diseases had a higher co-morbidity of NDs. The findings have implications for etiologic research that searches for common early life antecedents of NDs and atopic conditions. Findings from this study also should raise awareness among health care providers and parents about the possible co-occurrence of both NDs and atopic conditions, which calls for coordinated efforts to screen, prevent and manage NDs and atopic conditions.

Relationship between moderate to late preterm, diet types and developmental delay in less-developed rural China.

Aim: To measure the development of moderate to late preterm children by Ages and Stages Questionnaires (ASQ) and explore the relationship between moderate to late preterm, diet types and development delay in less-developed rural China.Methods: Data were collected from a cross-sectional community-based survey, which recruited 1748 children aged 1-59 months in eight counties of China. Caregivers of these children completed the Chinese version of ASQ-3 (ASQ-C) while physical examination and questionnaires on socio-demographic characteristics were conducted. Multivariate logistic regressions were used to analyze the association between moderate to late preterm and suspected developmental delay, as well as the association between diet types and suspected developmental delay. Consumption of certain food types was compared between moderate to late preterm and full-term children.Results: The prevalence of suspected overall developmental delay was 31.3% in the moderate to the late preterm group, compared with 21.6% in the full-term group. Moderate to late preterm birth was not associated with total suspected developmental delay and developmental delay in all the domains of ASQ, except for fine motor (OR = 2.43 95% C.I.: 1.04-5.56). The intake of vegetables and fruits had a protective influence on developmental delay in fine motor function, and moderate to late preterm children had lower relative consumption of fruits and vegetables than full-term children.Conclusion: Moderate to late preterm children in rural China showed an increased likelihood of developmental delay in fine motor function. Future interventions to improve the intake of vegetables and fruits in moderate to late preterm children are recommended.

Epigenetic Modulation of TLR4 Expression by Sulforaphane Increases Anti-Inflammatory Capacity in Porcine Monocyte-Derived Dendritic Cells.

Inflammation is regulated by epigenetic modifications, including DNA methylation and histone acetylation. Sulforaphane (SFN), a histone deacetylase (HDAC) inhibitor, is also a potent immunomodulatory agent, but its anti-inflammatory functions through epigenetic modifications remain unclear. Therefore, this study aimed to investigate the epigenetic effects of SFN in maintaining the immunomodulatory homeostasis of innate immunity during acute inflammation. For this purpose, SFN-induced epigenetic changes and expression levels of immune-related genes in response to lipopolysaccharide (LPS) stimulation of monocyte-derived dendritic cells (moDCs) were analyzed. These results demonstrated that SFN inhibited HDAC activity and caused histone H3 and H4 acetylation. SFN treatment also induced DNA demethylation in the promoter region of the MHC-SLA1 gene, resulting in the upregulation of Toll-like receptor 4 (TLR4), MHC-SLA1, and inflammatory cytokines' expression at 6 h of LPS stimulation. Moreover, the protein levels of cytokines in the cell culture supernatants were significantly inhibited by SFN pre-treatment followed by LPS stimulation in a time-dependent manner, suggesting that inhibition of HDAC activity and DNA methylation by SFN may restrict the excessive inflammatory cytokine availability in the extracellular environment. We postulate that SFN may exert a protective and anti-inflammatory function by epigenetically influencing signaling pathways in experimental conditions employing porcine moDCs.

The socioeconomic and lifestyle determinants of contraceptive use among Chinese college students: a cross-sectional study.

BACKGROUND: Chinese youth have become more sexually active over the years, yet their behaviours of contraceptive use are influenced by socioeconomic and lifestyle factors. This study aimed to investigate the socioeconomic and lifestyle determinants of contraceptive use among Chinese college students, and to investigate quantitatively their reasons for choosing different contraceptive methods. METHODS: The study used the data from a cross-sectional survey, which was conducted in 2015 among 17,517 students from 130 colleges and professional schools in mainland China. Chi-square tests were performed to test the differences in the awareness and uses of contraceptives between male and female students. Multivariable logistic regression models were used to analyse the associations between socioeconomic and lifestyle factors and contraceptive uses. RESULTS: Condoms (95%), oral contraceptives (91%) and emergency contraceptives (71%) were the most commonly known contraceptive methods among the sample of Chinese youth that were surveyed. Among male participants, high monthly expenditure (OR = 1.37, 95%CI: 1.07-1.75), light alcohol consumption (OR = 1.47, 95%CI: 1.03-2.11), and high sexual knowledge (OR = 1.96, 95%CI: 1.57-2.45) were positively associated with contraceptive uses, while tobacco use (OR = 0.47, 95%CI: 0.23-0.95) showed a negative association with contraceptive uses. Among female students, suburban residency (OR = 1.38, 95%CI: 1.03-1.83), high level of parental education (OR = 1.96, 95%CI: 1.19-3.22), moderate alcohol consumption (OR = 2.66, 95%CI: 1.05-6.77), and high sexual knowledge (OR = 1.50, 95%CI: 1.18-1.91) were positively associated with contraceptive uses, while tobacco use (OR = 0.60, 95%CI: 0.36-0.99) showed a negative association. CONCLUSIONS: A series of socioeconomic and lifestyle factors were associated with contraceptive choices among Chinese college students. Targeted sexual education programs are in demand to improve the awareness and the use of contraceptives in this population.

Socio-emotional challenges and development of children left behind by migrant mothers.

BACKGROUND: With great economic development and rapid urbanization in China, left-behind children whose parents migrate to big cities for job has become a large special population which requires more attention. The present study aims to explore the specific influence of migrant mothers on early child development, especially on social-emotional problems. METHODS: The data of this study was obtained from a cross-sectional study in 8 counties of central and western rural China. Development status of 1880 children aged <60 months were assessed by Ages & Stages Questionnaire-Chinese Edition (ASQ) and the Ages and Stages Questionnaire: Social Emotional-Chinese Edition (ASQ: SE). Multivariate logistic regressions were used to analyze the association between being left behand by migrant mothers and developmental problems in various domains, while adjusting socio-demographic, socio-economic and perinatal co-variates, and effect modification analysis were conducted to explore the effect of age, gender and birth order. RESULTS: Children left behind by migrant mothers were more likely to have overall suspected developmental delay (odds ratio (OR) = 1.24, 95% confidence interval (CI) = 1.13-1.35), developmental delay in personal social domain (OR = 1.55, 95% CI = 1.17-2.04) and socio-emotional delay compared with those living with their own mothers (OR = 1.49, 95% CI = 1.11-2.00) after adjusting for potential confounders. Additionally, girls increased the odds of social-emotional problems among children being left behind by migrating mother (P for interaction = 0.037). CONCLUSIONS: The study concluded that children left behind by migrant mothers were more likely to have suspected developmental delay compared with their peers living with mothers, especially on social emotional development. Future intervention is needed for this special population and should pay more attention to girls.

Association between age at first childbirth and type 2 diabetes in Chinese women.

AIMS/INTRODUCTION: The present study aims to explore the relationship between age at first childbirth and developing type 2 diabetes, and analyze potential modifiers of its relationship. MATERIALS AND METHODS: The data were obtained from the baseline survey of a large-scale cohort study in 10 diverse areas of China. Multivariate logistic regressions were used to analyze the association between developing type 2 diabetes and the age at first childbirth. Adjustments were made in each model on sociodemographic, socioeconomic and reproductive covariates. Subgroup analyses were further carried out to investigate the effects of reproductive factors, body mass index at 25 years of age and hypertension on the above-mentioned association. RESULTS: Women who have their first child at age <20 years (odds ratio [OR] 1.33, 95% confidence interval [CI] 1.22-1.44) and between the ages of 20 and 24 years (OR 1.16, 95% CI 1.10-1.23) were more likely to be diagnosed with type 2 diabetes compared with those who have their first child between the ages of 25 and 29 years; equal to or more than three parities (OR 1.44, 95% CI 1.30-1.60), premenopausal status (OR 1.58, 95% CI 0.99-2.54), overweight at age 25 years (OR 1.62, 95% CI 1.37-1.93) and hypertension (OR 1.37, 95% CI 1.22-1.53) are all conditions found to increase the odds of developing type 2 diabetes in those who have their their first child at an early age (<20 years). CONCLUSIONS: The study concluded that having the first child at an early age is associated with an increased likelihood of developing type 2 diabetes later in life; reproductive factors, overweight at age 25 years and status of hypotension could modify such an association.

The role of education in maternal depressive symptoms among different ethnic groups: A cross-sectional study in rural western China.

OBJECTIVE: To estimate the maternal depressive symptoms (MDS) rates in different ethnic groups, and to explore possible reasons especially the role of education for its ethnic differences. METHODS: A community-based cross-sectional survey was conducted in 20 rural counties of 8 provinces in western China. The possible influencing factors of MDS were collected. The Edinburgh Postpartum Depression Scale (EPDS) was used to assess MDS. Univariate and multivariate logistic regression models were used to analyze the risk factors of MDS. Two multivariate logistic regression models that separately containing and not containing the factor of educational level were used to explore the role of education in the ethnic differences of MDS. RESULTS: A total of 3,163 mothers were included in the analysis, and the MDS rate was 15.6%. In multivariate analysis, educational level of primary school and below (adjOR1: 1.47, 95%CI: 1.07-2.03), delivery at home (adjOR1: 1.66, 95%CI: 1.11-2.47) and diarrhea of youngest child in the past two weeks (adjOR1: 1.31, 95%CI: 1.03-1.67) remained as independent predictors of MDS after adjusting all the factors significant in univariate analysis. If educational level was not adjusted in above multivariate model, women from Yi ethnic group (adjOR2: 1.39, 95%CI: 1.03-1.89) would additionally become significant. LIMITATIONS: EPDS is a screening tool and some possible risk factors for MDS were not included. CONCLUSION: The ethnic differences in MDS were largely due to the ethnic differences in educational level. To reduce the high risk of MDS among Yi mothers, further popularizing nine-year compulsory education could be effective.

Vaccination coverage and its determinants of live attenuated hepatitis A vaccine among children aged 24-59 months in 20 rural counties of 10 provinces of China in 2016.

OBJECTIVE: To understand one single dose coverage of live attenuated hepatitis A vaccine and its determinants among children aged 24-59 months in 20 rural counties of 10 provinces of China in 2016. METHODS: In 20 counties, using three-stage probability proportion to size sampling, 1979 children aged 24-59 months with a vaccination card were selected from 20 rural counties in 2016. Socio-demographic and socio-economic characteristics of children and their caregivers were acquired from face-to-face questionnaire survey and copies of the vaccination cards. We used multivariate logistic regression models to identify the determinants of one single dose coverage of live attenuated hepatitis A vaccine. RESULTS: In 2016, the overall one single dose coverage of live attenuated hepatitis A vaccine among children aged 24-59 months in rural areas of China was 77.1%. The adjusted analysis showed that being in second birth order (adjusted OR: 1.40; 95%CI: 1.03-1.90), being in third birth order or more (adjusted OR: 2.10; 95%CI: 1.26-3.51), being born at home (adjusted OR: 2.01; 95%CI: 1.04-3.88) and having the lowest per capita income of household (adjusted OR: 2.36; 95%CI: 1.11-4.99) were significantly related to being unvaccinated one single dose coverage of live attenuated hepatitis A vaccine against hepatitis A virus. CONCLUSION: one single dose coverage of live attenuated hepatitis A vaccine was still at a low level in 20 rural counties of 10 provinces in China. To improve the coverage of live attenuated hepatitis A vaccine, the government should pay more attention to the disadvantaged groups, especially the children who were in second birth order or higher, or delivered at home, or who have the lowest per capita income of household.

Effects on developmental outcomes after cesarean birth versus vaginal birth in Chinese children aged 1-59 months: a cross-sectional community-based survey.

OBJECTIVE: It is controversial whether the mode of delivery is associated with developmental outcome, and little was known about growth and development of cesarean children in poor rural areas in China. We aim to measure the development of both cesarean and vaginal-delivered children by Ages and Stages Questionnaires (ASQ) and explore the association between mode of delivery and developmental outcome in poor rural areas in China. METHODS: Data were collected from a cross-sectional community-based survey, which recruited 1,755 vaginal delivered and cesarean children ages 1 to 59 months in eight counties of China. Caregivers of those children completed the Chinese version of ASQ-3 (ASQ-C) while physical examination andquestionnaires on socio-demographic and neonatal characteristics were conducted. Multivariate logistic regressions were used to measure the association between developmental delay and mode of delivery as well as each socio-demographic factor, respectively, after adjusting other socio-demographic characteristics. RESULTS: The prevalence of suspected overall developmental delay was 23.4% in the cesarean group, compared with 21.3% in the vaginal delivered group, yet without statistical difference (p < 0.05). Developmental delay was also not significantly different between cesarean and vaginal delivered group in five ASQ domains of communication (7.7% vs. 7.8%, p = 0.949), fine motor (7.0% vs. 6.1%, p = 0.538), gross motor (8.5% vs. 6.4%, p = 0.154), problem solving (7.2% vs. 6.7%, p = 0.722) and personal social (8.0% vs. 7.9%, p = 0.960). CONCLUSIONS: Our findings suggest that cesarean delivery does not increase or decrease the risk of suspected developmental in children delay as compared with vaginal delivery.

Association between maternal education and breast feeding practices in China: a population-based cross-sectional study.

OBJECTIVE: To investigate the association between maternal education and breast feeding in the Chinese population, with a consideration of household income and health-seeking behaviours. DESIGN: A nationally representative population-based cross-sectional study. SETTING: 77 counties from 12 geographically distinct regions in China. PARTICIPANTS: 10 408 mothers with children from 0 to 12 months of age, aged 15-53 years old (mean: 29.15, SD: 5.11) were classified into primary school or below group (n=781), middle school group (n=3842), high school/vocational school group (n=1990), college or above group (n=3795), according to their highest completed education. OUTCOMES: Five breastfeeding outcomes, including early initiation of breast feeding (EIB), exclusive breast feeding (EBF) under 6 months, predominant breast feeding under 6 months, current breast feeding and children ever breast fed, were calculated based on the standardised questionnaire from the WHO and Wellstart International's toolkit for monitoring and evaluating breastfeeding activities. RESULTS: The absolute risk of EIB and EBF in the lowest maternal education level was 64.85% and 26.53%, respectively, whereas the absolute risk of EIB and EBF in the highest maternal education level was 77.21% and 14.06%, respectively. A higher level of maternal education was positively associated with EIB (risk ratio (RR): 1.22; 95% CI: 1.12 to 1.30) and was inversely associated with EBF (RR: 0.59; 95% CI: 0.38 to 0.88). Stratified by household income, a positive association with EIB was observed only in the group with the highest household income and an inverse association with EBF was found in both low household and high household income groups. CONCLUSIONS: Mothers with a higher education were more likely to initiate early breast feeding when they were also from a high-income household while also being less likely to exclusively breast feed their babies. Routine and successful nursing is crucial for the health of infants and is influenced by maternal education. Future public health interventions to promote breast feeding should consider the issues related to the educational level of mothers.

Childhood sexual abuse, risky sexual behaviors and adverse reproductive health outcomes among Chinese college students.

BACKGROUND: Childhood sexual abuse (CSA) is a serious public health problem worldwide. OBJECTIVES: We reported the prevalence of CSA and examined its association with risky sexual behaviors and adverse reproductive health outcomes among college students in China. PARTICIPANTS AND SETTING: Participants were 17,966 college students from 130 colleges in Eastern, Central, and Western China, who completed the online questionnaire in January-August 2015. METHODS: Data were obtained from a cluster-random Internet-based survey. Multivariate logistic regression analyses were employed: risky sexual behaviors and adverse reproductive health outcomes were outcome variables, and various types of CSA were predictor variables, while adjusting for socio-demographic and lifestyle characteristics. RESULTS: The overall prevalence of any type of CSA was 27.5%. Most perpetrators were friends/acquaintances (34.6%) or intimate partners (24.7%) of the victims. Respondents who reported penetrative CSA were strongly associated with regular unprotected sex (odds ratio (OR): 3.0, 95% confidence interval (CI): 2.2-4.0), early sexual debut (OR: 5.5, 95% CI: 3.3-9.1), having genital tract symptoms in the last 12 months (OR: 5.0, 95% CI: 4.1-6.0), unintended pregnancy (OR: 6.2, 95% CI: 4.2-9.0), and induced abortion (OR: 5.5, 95% CI: 3.7-8.2) (for boys, the survey asked about history of unintended pregnancy and induced abortion of their sexual partners). A dose-response relationship was found across non-contact, contact, and penetrative CSA. CONCLUSIONS: CSA experience may increase the likelihood of risky sexual behaviors and adverse reproductive health outcomes in victims' early adulthood.

Transcriptome profile of lung dendritic cells after in vitro porcine reproductive and respiratory syndrome virus (PRRSV) infection.

The porcine reproductive and respiratory syndrome (PRRS) is an infectious disease that leads to high financial and production losses in the global swine industry. The pathogenesis of this disease is dependent on a multitude of factors, and its control remains problematic. The immune system generally defends against infectious diseases, especially dendritic cells (DCs), which play a crucial role in the activation of the immune response after viral infections. However, the understanding of the immune response and the genetic impact on the immune response to PRRS virus (PRRSV) remains incomplete. In light of this, we investigated the regulation of the host immune response to PRRSV in porcine lung DCs using RNA-sequencing (RNA-Seq). Lung DCs from two different pig breeds (Pietrain and Duroc) were collected before (0 hours) and during various periods of infection (3, 6, 9, 12, and 24 hours post infection (hpi)). RNA-Seq analysis revealed a total of 20,396 predicted porcine genes, which included breed-specific differentially expressed immune genes. Pietrain and Duroc infected lung DCs showed opposite gene expression courses during the first time points post infection. Duroc lung DCs reacted more strongly and distinctly than Pietrain lung DCs during these periods (3, 6, 9, 12 hpi). Additionally, cluster analysis revealed time-dependent co-expressed groups of genes that were involved in immune-relevant pathways. Key clusters and pathways were identified, which help to explain the biological and functional background of lung DCs post PRRSV infection and suggest IL-1ß1 as an important candidate gene. RNA-Seq was also used to characterize the viral replication of PRRSV for each breed. PRRSV was able to infect and to replicate differently in lung DCs between the two mentioned breeds. These results could be useful in investigations on immunity traits in pig breeding and enhancing the health of pigs.

Sulforaphane epigenetically regulates innate immune responses of porcine monocyte-derived dendritic cells induced with lipopolysaccharide.

Histone acetylation, regulated by histone deacetylases (HDACs) is a key epigenetic mechanism controlling gene expressions. Although dendritic cells (DCs) are playing pivotal roles in host immune responses, the effect of epigenetic modulation of DCs immune responses remains unknown. Sulforaphane (SFN) as a HDAC inhibitor has anti-inflammatory properties, which is used to investigate the epigenetic regulation of LPS-induced immune gene and HDAC family gene expressions in porcine monocyte-derived dendritic cells (moDCs). SFN was found to inhibit the lipopolysaccharide LPS induced HDAC6, HDAC10 and DNA methyltransferase (DNMT3a) gene expression, whereas up-regulated the expression of DNMT1 gene. Additionally, SFN was observed to inhibit the global HDAC activity, and suppressed moDCs differentiation from immature to mature DCs through down-regulating the CD40, CD80 and CD86 expression and led further to enhanced phagocytosis of moDCs. The SFN pre-treated of moDCs directly altered the LPS-induced TLR4 and MD2 gene expression and dynamically regulated the TLR4-induced activity of transcription factor NF-κB and TBP. SFN showed a protective role in LPS induced cell apoptosis through suppressing the IRF6 and TGF-ß1 production. SFN impaired the pro-inflammatory cytokine TNF-α and IL-1ß secretion into the cell culture supernatants that were induced in moDCs by LPS stimulation, whereas SFN increased the cellular-resident TNF-α accumulation. This study demonstrates that through the epigenetic mechanism the HDAC inhibitor SFN could modulate the LPS induced innate immune responses of porcine moDCs.

Comparison of the innate immune responses of porcine monocyte-derived dendritic cells and splenic dendritic cells stimulated with LPS.

Dendritic cell (DC) subsets form a remarkable cellular network that regulate innate and adaptive immune responses. Although pigs are the most approximate model to humans, little is known about the regulation of monocyte-derived DCs (moDCs) and splenic DCs (SDCs) in the initiation of immune responses under inflammatory conditions. We investigated the activation and maturation of porcine moDC and SDC subpopulations following LPS stimulation. Porcine monocytes that would differentiate into moDCs were isolated. SDCs were isolated directly from the porcine spleen. Following LPS stimulation, phagocytosis activity, TLR4/MyD88-dependent gene expression, co-stimulatory molecule, and pro-inflammatory cytokine (TNF-α, IL-1ß) and chemokine (IL-8) expressions were increased in both cell subsets. Furthermore, moDCs showed higher levels of gene and protein expression compared with SDCs. Interestingly, moDCs were found to be more responsive via the TLR4/TRAF-dependent signalling pathway of activation. Only SDCs expressed higher level of IL-12p40 gene and protein, whereas, IFN-γ gene and protein expression were likely to be unchanged after LPS stimulation in both cell subtypes. These data demonstrate that porcine moDCs display a greater ability to initiate innate immune responses, and could be used as a model to investigate immune responses against Ags.