Integrated analysis of the lncRNA-associated competing endogenous RNA network in salt sensitivity of blood pressure.

Accumulating evidence showed that competing endogenous RNA (ceRNA) mechanism plays a pivotal role in salt sensitivity of blood pressure (SSBP). We constructed a ceRNA network based on SSBP-related differently expressed lncRNAs (2), mRNAs (73) and miRNAs (18). Bioinformatic analyses were utilized to analyze network and found network genes participate in biological pathways related to SSBP pathogenesis such as regulation of nitric oxide biosynthetic process (GO:0045,428) and cellular response to cytokine stimulus (GO:0071,345). Fourteen candidate ceRNA pathways were selected from network to perform qRT-PCR validation and found nine RNAs (KCNQ1OT1, SLC8A1-AS1, IL1B, BCL2L11, KCNJ15, CX3CR1, KLF2, hsa-miR-362-5p and hsa-miR-423-5p) differently expressed between salt-sensitive (SS) and salt-resistant (SR) groups (P < 0.05). Four ceRNA pathways were further validated by luciferase reporter assay and found KCNQ1OT1→hsa-miR-362-5p/hsa-miR-423-5p→IL1B pathways may influence the pathogenic mechanism of SS. Our findings suggested the ceRNA pathway and network may affect SS occurrence mainly through endothelial dysfunction and inflammatory activation.

The prevalence of disability and associated factors among community adults in the baseline of CHCN-BTH Cohort Study.

BACKGROUND: Disability was a major public health problem in China. However, the prevalence of disabilities in community-dwelling adults and their relationships to chronic physical conditions were unclear. We aimed to estimate the prevalence of disabilities and associated factors among a large community-based cohort in China. METHODS: Participants who were local permanent residents aged 18 years or above and completed the disability assessments were selected from the Cohort study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei (CHCN-BTH) from 2017 to 2019. Disability was assessed using five questions about impairments and activity limitations based on the International Classification of Functioning (ICF), Disability and Health. Univariate, multivariate and multilevel logistic regressions were conducted to estimate the associations between disabilities and associated factors. RESULTS: Totally, 12,871 community-dwelling adults completed the survey. Among of them, 12.9% (95% CI: 12.3%-13.5%) reported having any disability. The prevalence of any disability was significantly higher in participants who were older age, widowed, retired and smokers, had higher BMI, average monthly income < 5000 RMB, lower education level, lower physical exercise frequency and heavy physical labor. Multilevel logistic regressions showed that there were significant associations between disabilities with chronic physical conditions, especially in the vision impairment with lower back pain, and hearing impairment as well as difficulty walking without special equipment with injuries. CONCLUSIONS: Many Chinese adults suffered from disabilities. Sustained efforts should be made to develop specific population-based health promotion and prevention programs for disabilities in China. TRAIL REGISTRATION: ChiCTR1900024725 (25/07/2019).

The mediation effect of lipids, blood pressure and BMI between air pollutant mixture and atherosclerotic cardiovascular disease: The CHCN-BTH cohort study.

BACKGROUND: The combine effect of air pollutant mixture on atherosclerotic cardiovascular disease (ASCVD) remain undefined. This study aims to explore the association between long-term exposure of air pollutants and ASCVD, focusing on the mediating role of lipids, blood pressure and BMI. METHODS: This study was based on the CHCN-BTH cohort study. The annual concentrations of air pollutants and PM2.5 constituents were sourced from in the Tracking Air Pollution in China (TAP) and ChinaHighAirPollutants (CHAP) datasets from 2014 to 2019. A Cox mixed-effects model was used to investigate the associations between long-term exposure of air pollutants and ASCVD. The combined impact of the air pollutant mixture was assessed using Quantile g-Computation. Stratified, sensitivity, and mediation analyses were conducted. RESULTS: A total of 27,134 participants aged 18-80 were recruited in the present study. We found that each IQR increase of PM2.5, PM1, NO2, O3, BC, SO42-, and OM were significantly associated with the incidence of ASCVD, the hazard ratios (HRs) and 95 % confidence interval (CI) were 1.55 (1.35, 1.78), 1.46 (1.27, 1.67), 1.30 (1.21, 1.39), 1.66 (1.41,1.95), 2.14 (1.63, 2.83), 1.65 (1.25, 2.17) and 1.92(1.52, 2.45), respectively. The combined effect of air pollutant mixture on ASCVD was 1.79 (1.46, 2.20), PM2.5 contributed 83.3 % to this combined effect. Mediation effect models suggested that air pollutants and ASCVD might be mediated through SBP, DBP, HDL-C, LDL-C, hsCRP and BMI (mediation proportion range from 1.3 % to 26.1 %), Notably, HDL-C played mediation roles of 11.3 % (7.0 %, 18.4), 26.1 % (17.7 %, 38.1 %) and 25.4 % (15.4, 47.7 %) in the effects of long-term exposure to PM2.5, PM1 and OM on ASCVD, respectively. CONCLUSIONS: Long-term, high-level air pollutant exposure was significantly associated with an elevated risk of ASCVD, particularly for PM2.5. Blood pressure, lipids and BMI, especially HDL-C, may mediate the effects of air pollutants exposure on ASCVD.

Associations between depressive, anxiety, stress symptoms and elevated blood pressure: Findings from the CHCN-BTH cohort study and a two-sample Mendelian randomization analysis.

BACKGROUND: We aimed to determine whether depressive, anxiety, stress symptoms were associated with the risk of elevated blood pressure by performing longitudinal cohort and Mendelian Randomization (MR) analyses. METHODS: We used data from the Cohort Study on Chronic Disease of Community Natural Population in the Beijing-Tianjin-Hebei region (CHCN-BTH) from 2017 to 2021. The Depression-Anxiety-Stress Scale was used to evaluate the depressive, anxiety, stress symptoms. The longitudinal associations between depressive, anxiety, stress symptoms and elevated blood pressure were estimated using Cox proportional regression models. Two-sample MR analysis was performed using the Inverse-variance weighted (IVW), weighted median, and MR-Egger to explore the causal relationships between depressive, anxiety, stress symptoms and elevated blood pressure. RESULTS: In total, 5624 participants were included. The risk of SBP ≥ 140 mmHg or DBP ≥ 90 mmHg was significantly higher in participants with baseline anxiety symptoms (HR = 1.48, 95 % CI: 1.03 to 2.12, P = 0.033; HR = 1.56, 95 % CI: 1.05 to 2.32, P = 0.028), especially in men and individuals with higher educational levels, independent of baseline depression and anxiety at the two-year follow-up. The two-sample MR analysis showed positive associations between depressive, anxiety, stress symptoms and elevated blood pressure. LIMITATION: Self-reported mental health symptoms, relatively shorter follow-up duration and the European-derived genome-wide association study data for MR analysis. CONCLUSIONS: Anxiety symptoms were positively associated with elevated blood pressures in the longitudinal analysis independent of depression, stress, and other confounders. The results were verified in MR analysis, providing evidence for causal effects of anxiety symptoms on the risk of elevated blood pressure.

Sequences analysis and pituitary actions of tachykinins in Chinese sturgeon (Acipenser sinensis).

Tachykinins belong to a large, evolutionarily conserved family of brain/gut peptides that are involved in a variety of physiological functions in mammals, such as reproductive regulation. However, little information was available about tachykinins in ancient fish lineage. In the present study, we firstly identified three tachykinin genes (named tac1, tac3 and tac4) and three neurokinin receptors (named nk1r, nk2r and nk3r) from Chinese sturgeon brain and pituitary. Sequence analysis showed that tac1 encoded substance P (SP) and neurokinin A (NKA), tac3 encoded neurokinin B (NKB) and NKB-related peptide (NKBRP), and tac4 encoded hemokin 1 (HK-1) and hemokin 2 (HK-2), respectively. The luciferase reporter assay results showed that NK1R preferentially selected asSP, NK2R preferentially selected asNKA, and NK3R preferentially selected asNKB. Tissue expression analysis showed that the three tac genes were highly detected in the telencephalon and hypothalamus, whereas nkr genes were widely expressed in peripheral tissues. Spatio-temporal expression analysis showed that all three tac genes were highly expressed in unknown sex individuals. Intraperitoneal injection experiments showed that both asSP and asNKB could stimulate luteinizing hormone (LH) release in Chinese sturgeon serum. At the transcriptional level, asSP and asNKB could significantly reduce pituitary follicle-stimulating hormone beta (fshß) mRNA expression, but induce pituitary growth hormone (gh) mRNA expression. In addition, estradiol (E2) could stimulate tac3 mRNA expression in hypothalamus. Taken together, this study provided information on the tachykinin family in Chinese sturgeon and demonstrates that asNKB and asSP could be involved in reproductive and growth regulation in pituitary.

Klotho enhances bone regenerative function of hPDLSCs via modulating immunoregulatory function and cell autophagy.

BACKGROUND: Human periodontal ligament stem cells (hPDLSCs) have a superior ability to promote the formation of new bones and achieve tissue regeneration. However, mesenchymal stem cells (MSCs) are placed in harsh environments after transplantation, and the hostile microenvironment reduces their stemness and hinders their therapeutic effects. Klotho is an antiaging protein that participates in the regulation of stress resistance. In our previous study, we demonstrated the protective ability of Klotho in hPDLSCs. METHODS: A cranial bone defect model of rats was constructed, and the hPDLSCs with or without Klotho pretreatment were transplanted into the defects. Histochemical staining and micro-computed tomography were used to detect cell survival, osteogenesis, and immunoregulatory effects of hPDLSCs after transplantation. The in vitro capacity of hPDLSCs was measured by a macrophage polarization test and the inflammatory level of macrophages. Furthermore, we explored autophagy activity in hPDLSCs, which may be affected by Klotho to regulate cell homeostasis. RESULTS: Pretreatment with the recombinant human Klotho protein improved cell survival after hPDLSC transplantation and enhanced their ability to promote bone regeneration. Furthermore, Klotho pretreatment can promote stem cell immunomodulatory effects in macrophages and modulate cell autophagy activity, in vivo and in vitro. CONCLUSION: These findings suggest that the Klotho protein protects hPDLSCs from stress after transplantation to maintain stem cell function via enhancing the immunomodulatory ability of hPDLSCs and inhibiting cell autophagy.

Combined effects of ambient air pollution and PM2.5 components on renal function and the potential mediation effects of metabolic risk factors in China.

Growing evidence links long-term air pollution exposure with renal function. However, little research has been conducted on the combined effects of air pollutant mixture on renal function and multiple mediation effects of metabolic risk factors. This study enrolled 8996 adults without chronic kidney disease (CKD) at baseline from the CHCN-BTH cohort study. Three-year exposure to air pollutants [particulate matter ≤ 2.5 µm (PM2.5), PM10, PM1, ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO)] and PM2.5 components [black carbon (BC), ammonium (NH4+), nitrate (NO3-), sulfate (SO42-) and organic matter (OM)] were assessed using well-validated machine learning methods. Linear mixed models were applied to investigate the associations between air pollutants and estimated glomerular filtration rate (eGFR). Quantile G-computation was used to assess the combined effects of pollutant mixtures. Causal mediation analysis and Bayesian mediation analysis were employed to estimate the mediation effects of metabolic risk factors. An interquartile range increases in BC (-0.256, 95 %CI: -0.331, -0.180) and OM (-0.603, 95 %CI: -0.810, -0.397) were significantly associated with eGFR decline; while O3 (1.151, 95 %CI: 0.813, 1.489), PM10 (0.721, 95 %CI: 0.309, 1.133), NH4+ (0.990, 95 %CI: 0.638, 1.342), and NO3- (0.610, 95 %CI: 0.405, 0.815) were associated with higher eGFR. The combined effect of the PM2.5 component mixture was found to be associated with lower eGFR (-1.147, 95 % CI: -1.456, -0.839), with OM contributing 72.4 % of the negative effect. Univariate mediation analyses showed that high-density lipoprotein (HDL) mediated 7.1 %, 6.9 %, and 6.1 % effects of O3, BC, and OM, respectively. However, these mediation effects were not significant in Bayesian mediation analysis. These findings suggest the effect of the PM2.5 component mixture on eGFR decline and the strong contribution of OM. Metabolic risk factors may not mediate the effects of air pollutants. Further study is warranted to clarify the potential mechanisms involved.

Association of long-term exposure to air pollutant mixture and incident cardiovascular disease in a highly polluted region of China.

Despite growing evidence that links long-term air pollution exposure to cardiovascular disease (CVD), the combined effects of air pollutants and particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) components are still limited. A prospective cohort study was performed based on the Cohort Study on Chronic Disease of the Community Natural Population in the Beijing-Tianjin-Hebei Region (CHCN-BTH) to assess the association of long-term air pollutants with incident CVD and the combined effect of the air pollutants mixture among 26,851 adults. Three-year residential exposure to air pollutants (PM2.5, O3, PM10, PM1, NO2, SO2 and CO) and PM2.5 components [black carbon (BC), NH4+, SO42-, NO3- and organic matter (OM)] were calculated based on well-validated models. Proportional hazard models were applied to assess the association of air pollutants with incident CVD. Quantile g-Computation was used to examine the combined effect of the pollutant mixture. During the 56,090 person-years follow-up, 629 participants reported incident CVD. Adjusted hazard ratios with 95% confidence intervals (CIs) of CVD per interquartile range increase in O3, PM2.5, PM1, NO2, BC, and OM concentrations were 4.52 (95%CI: 2.61, 7.83), 2.39 (95%CI: 1.83, 3.13), 2.37 (95%CI: 1.20, 4.70), 1.36 (95%CI: 1.19, 1.56), 3.84 (95%CI: 2.38, 6.18), and 3.07 (95%CI: 2.01, 4.69), respectively. In multi-pollutant models, the combined effect of air pollutant mixture on incident CVD was 2.37 (95%CI: 2.30, 2.44). PM2.5 and O3 contributed 54.3% and 44.5% of the combined effect of the air pollutant mixture, respectively. After using PM2.5 components instead of PM2.5 as part of the mixture, OM drove 55.2% of the combined effect. The findings indicated associations of air pollutant mixtures with CVD incidence. PM2.5 (especially OM) and O3 might strongly contribute to air pollutant mixtures that lead to incident CVD.

Association of Serum Metabolites and Salt Sensitivity of Blood Pressure in Chinese Population: The EpiSS Study.

BACKGROUND: To identify novel metabolites associated with salt sensitivity of blood pressure (SSBP) in Chinese Han population. METHODS: A case-control study was conducted with 25 salt sensitive (SS) and 26 salt resistant (SR) participants, which was selected from the Systems Epidemiology Study on Salt Sensitivity of Blood Pressure (EpiSS) study. The modified Sullivan's acute oral saline load and diuresis shrinkage test (MSAOSL-DST) was conducted to identify SS. Untargeted, ultra-high performance liquid chromatograph-high resolution mass spectrometer (UPLC-HRMS) was conducted and orthogonal partial least squares-discriminate analysis (OPLS-DA) and multivariable logistic regression model were used to screen the metabolites related to SS, mixed linear regressions models were used to examined the association of SSBP with metabolites during saline load period and diuresis shrinkage period. Receiver operating characteristic (ROC) curve analysis was performed. The area under the curve's (AUC) sensitivity and specificity were calculated to identified metabolites biomarkers for SS. RESULTS: There were 39 differentially expressed metabolites (DE-metabolites) between SS and SR. Thirty-five and four of DE-metabolites were inversely or positively associated with SS, respectively. Four biochemical pathways demonstrated significant enrichment for identified metabolites. In single-metabolite analyses, L-Glutamine displayed the best diagnostic performance (AUC = 0.88, 95% CI: 0.78-0.97). In multi-metabolites analyses, L-Glutamine + Cholesterol ester 22:5n6 combination showed the best diagnostic performance (AUC = 0.96, 95% CI: 0.91-1.00). Adjusted for traditional risk factors, L-Glutamine and Cholesterol ester 22:5n6 explained an additional 38.3% of SS susceptibility. CONCLUSIONS: This study provide potential evidence for clarifying the mechanism of SS and provide novel biological insights into salt sensitive hypertension.

Milk yield variation partially attributed to blood oxygen-mediated neutrophil activation in lactating dairy goats.

Blood oxygen is an essential component for numerous biological processes of mammalian animals. Milk production of ruminants largely relies on the supply of nutrients, such as glucose, amino acids and fatty acids. To define the regulatory role of blood oxygen availability in regard to milk production, seventy-five healthy Guanzhong dairy goats with similar body weight, days in milk and parities were selected. For each animal, milk yield was recorded and milk sample was collected to determine compositions. Milk vein blood was collected to determine parameters including blood gas, physio-biochemistry and haematology. Another blood sample was prepared for transcriptome and RT-qPCR. Results showed that both pressure of oxygen (pO2) in the milk vein (positively) and numbers of neutrophils in mammary vein (negatively) were associated with milk yield of the animals. To learn the role of pO2 in blood cell functionality, twelve animals (six with higher yield (H-group) and six with lower yield (L-group)) from seventy-five goats were selected. Compared with animals in L-group, goats in H-group were higher in pO2 but lower in pCO2, lactate, lactate dehydrogenase activity and neutrophil abundance in milk vein, compared with L-group. The blood transcriptome analysis suggested that compared with L-group, animals in H-group were depressed in functionality including neutrophil activation and metabolic pathways including glycolysis, NF-κB and HIF-1. Our result revealed that lower milk production could be associated with neutrophil activation responding to low pO2 in the mammary vein. In the meantime, we highlighted the potential importance of blood oxygen as a milk yield regulator.

Neuropeptides and hormones in hypothalamus-pituitary axis of Chinese sturgeon (Acipenser sinensis).

The hypothalamus and pituitary serve as important neuroendocrine center, which is able to secrete a variety of neuropeptides and hormones to participate in the regulation of reproduction, growth, stress and feeding in fish. Chinese sturgeon is a basal vertebrate lineage fish with a special evolutionary status, but the information on its neuroendocrine system is relatively scarce. Using the transcriptome data on the hypothalamus-pituitary axis of Chinese sturgeon as reference, we found out 46 hypothalamus neuropeptide genes, which were involved in regulation of reproduction, growth, stress and feeding. The results of sequence alignment showed that the neuroendocrine system of Chinese sturgeon evolves slowly, which confirms that Chinese sturgeon is a species with a slow phenotypic evolution rate. In addition, we also isolated six pituitary hormones genes from Chinese sturgeon, including reproductive hormones: follicle-stimulating homone (FSH) and luteinizing hormone (LH), growth-related hormones: growth hormone (GH)/prolactin (PRL)/somatolactin (SL), and stress-related hormone gene: proopiomelanocortin (POMC). Similar to teleost, immunostaining localization analysis in Chinese sturgeon pituitary showed that LH and FSH were located in the pituitary proximal pars distalis, SL was located in the pituitary rostral pars distalis, and POMC was located in the pituitary pars intermedia and pituitary rostral pars distalis. This study will give a contribution to enrich our information on the neuroendocrine system in Chinese sturgeon.

Serum lipoprotein (a) associates with the risk of renal function damage in the CHCN-BTH Study: Cross-sectional and Mendelian randomization analyses.

Background: Evidence regarding the effects of lipoprotein (a) [lp(a)] and renal function remains unclear. The present study aimed to explore the causal association of serum lp(a) with renal function damage in Chinese general adults. Methods: A total of 25343 individuals with available lp(a) data were selected from the baseline survey of the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin, and Hebei (CHCN-BTH). Five renal function indexes [estimated glomerular filtration rate (eGFR), serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), high-sensitivity C-reactive protein(CRPHS)] were analyzed. The restricted cubic spline (RCS) method, logistic regression, and linear regression were used to test the dose-response association between lp(a) and renal function. Stratified analyses related to demographic characteristics and disease status were performed. Two-sample Mendelian randomization (MR) analysis was used to obtain the causal association of lp(a) and renal function indexes. Genotyping was accomplished by MassARRAY System. Results: Lp(a) levels were independently associated with four renal function indexes (eGFR, Scr, BUN, CRPHS). Individuals with a higher lp(a) level had a lower eGFR level, and the association with Scr estimated GFR was stronger in individuals with a lower lp(a) level (under 14 mg/dL). . The association was similar in individuals regardless of diabetes or hypertension. MR analysis confirmed the causal association of two renal function indexes (Scr and BUN). For MR analysis, each one unit higher lp(a) was associated with 7.4% higher Scr (P=0.031) in the inverse-variance weighted method. But a causal effect of genetically increased lp(a) level with increased eGFR level which contrasted with our observational results was observed. Conclusion: The observational and causal effect of lp(a) on Scr and BUN were founded, suggesting the role of lp(a) on the risk of renal function damage in general Chinese adults.

Psychiatric Symptoms and Frequency of Eating out among Commuters in Beijing: A Bidirectional Association?

BACKGROUND: Mental illness places as a distant first in global burdens, exceeding both cardiovascular and circulatory diseases, in terms of the years lived with the disability. The emergence of the new and burgeoning area of "Nutrition Psychiatry" offers promise in improving mental health with diet. Mental health and well-being are critical to commuters but rarely recieve the attention they need. This study aimed to examine the bidirectional relationship between the frequency of eating out and depression, anxiety, and stress symptoms in a sample of Beijing commuters. METHODS: A total of 3337 commuters (mean (SD) age, 38.78 (10.41); 74.74% males) from the cohort study CHCN-BTH were included. The psychiatric symptoms were evaluated using a 21-item self-reported depression-anxiety-stress scale (DASS-21). A Cochran-Armitage trend chi-square test, restricted cubic spline, multiple logistic regression, multinomial logit models, and E-values were performed to estimate the associations between eating out and psychiatric symptoms in both directions. RESULTS: A daily rate of eating out more than 50% had a higher risk for depression (OR, 95% CI: 1.68, 1.184-2.393), anxiety (1.73, 1.259-2.369), and stress (1.99, 1.191-3.329) than the individuals eating at home. A higher frequency of eating out for lunch was significantly associated with an increased risk of depression (1.78, 1.28-2.46), anxiety (1.67, 1.26-2.23), and stress (2.05, 1.31-3.22). Similar results were found when eating out for dinner with increased risks for depression 2.20 (1.59, 3.06), anxiety 1.91 (1.42, 2.59), and stress 2.61 (1.68, 4.05). There is limited evidence supporting the effects of psychiatric symptoms on the frequency of eating out in the reverse analyses. CONCLUSIONS: The frequency of eating out is positively associated with an increased risk of psychiatric symptoms, especially when eating out for lunch and dinner. People eating at home have the lowest risk of suffering psychiatric symptoms, followed by those eating in the workplace canteen. Eating at home should be considered for future recommendations for the prevention of psychiatric symptoms.

Higher Potassium Intake and Lower Sodium Intake May Help in Reducing CVD Risk by Lowering Salt Sensitivity of Blood Pressure in the Han Chinese Population.

Sodium (Na) reduction with a parallel supplemental potassium (K) intake can prevent cardiovascular diseases (CVDs). The relationship of the urinary Na/K ratio and salt sensitivity of blood pressure (SSBP) with CVDs is not clearly explained. We assumed that the SSBP mediates the relationship between the Na/K ratio and CVDs. In total, 2055 subjects who had 24 h urine collected and SSBP determined were included in this study. CVD risk was estimated using the China-PAR equation. MediationMultivariate logistic regression was used to explore the associations between the Na/K ratio or SSBP with CVD risk. Mediation analysis using a logistic regression model was performed. Both the urinary Na/K ratio and SSBP were related to the estimated CVD risk (p < 0.05). The mediation analysis found that SSBP mediated approximately 12% of the association between Na/K ratio and CVD risk. Our findings indicate that higher K intake and lower Na intake may help in preventing CVD risk by reducing SSBP risk in individuals with normotension or stage-one hypertension.

Novel pituitary actions of GnRH in teleost: The link between reproduction and feeding regulation.

Gonadotropin-releasing hormone (GnRH), as a vital hypothalamic neuropeptide, was a key regulator for pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the vertebrate. However, little is known about the other pituitary actions of GnRH in teleost. In the present study, two GnRH variants (namely, GnRH2 and GnRH3) and four GnRH receptors (namely, GnRHR1, GnRHR2, GnRHR3, and GnRHR4) had been isolated from grass carp. Tissue distribution displayed that GnRHR4 was more highly detected in the pituitary than the other three GnRHRs. Interestingly, ligand-receptor selectivity showed that GnRHR4 displayed a similar and high binding affinity for grass carp GnRH2 and GnRH3. Using primary culture grass carp pituitary cells as model, we found that both GnRH2 and GnRH3 could not only significantly induce pituitary reproductive hormone gene (GtHα, LHß, FSHß, INHBa, secretogranin-2) mRNA expression mediated by AC/PKA, PLC/IP3/PKC, and Ca2+/CaM/CaMK-II pathways but also reduce dopamine receptor 2 (DRD2) mRNA expression via the Ca2+/CaM/CaMK-II pathway. Interestingly, GnRH2 and GnRH3 could also stimulate anorexigenic peptide (POMCb, CART2, UTS1, NMBa, and NMBb) mRNA expression via AC/PKA, PLC/IP3/PKC, and Ca2+/CaM/CaMK-II pathways in grass carp pituitary cells. In addition, food intake could significantly induce brain GnRH2 mRNA expression. These results indicated that GnRH should be the coupling factor to integrate the feeding metabolism and reproduction in teleost.

SNPs in lncRNA KCNQ1OT1 Modulate Its Expression and Confer Susceptibility to Salt Sensitivity of Blood Pressure in a Chinese Han Population.

Long noncoding RNA (lncRNA) plays an important role in cardiovascular diseases, but the involvement of lncRNA in salt sensitivity of blood pressure (SSBP) is not well-known. We aimed to explore the association of sixteen single-nucleotide polymorphisms (SNPs) in five lncRNA genes (KCNQOT1, lnc-AGAP1-8:1, lnc-IGSF3-1:1, etc.) with their expression and susceptibility to SSBP. A two-stage association study was conducted among 2057 individuals. Quantified expression of the lncRNA was detected using real-time PCR. Genotyping was accomplished using the MassARRAY System. The expression quantitative tra2it loci test and the generalized linear model were utilized to explore the function of SNPs. One-sample Mendelian randomization was used to study the causal relationship between KCNQOT1 and SSBP. Significant effects were observed in KCNQ1OT1 expressions on the SSBP phenotype (p < 0.05). Rs10832417 and rs3782064 in KCNQ1OT1 may influence the secondary structure, miRNA binding, and expression of KCNQ1OT1. Rs10832417 and rs3782064 in KCNQ1OT1 were identified to be associated with one SSBP phenotype after multiple testing corrections and may be mediated by KCNQ1OT1. One-sample Mendelian randomization analyses showed a causal association between KCNQ1OT1 and SSBP. Our findings suggest that rs10832417 and rs3782064 might be associated with a lower risk of SSBP through influencing the KCNQ1OT1 secondary structure and miRNA binding, resulting in changes in KCNQ1OT1 expression.

SHED-derived exosomes promote LPS-induced wound healing with less itching by stimulating macrophage autophagy.

High-quality cutaneous wound healing is associated with rapid wound closure and a comfortable healing process. Currently, exosomes derived from mesenchymal stem cells displayed a prominent therapeutic effect on skin wound closure. But the therapeutic approaches for wound itching are very limited in clinical. Stem cells from human exfoliated deciduous teeth (SHED) may offer a unique exosome resource for cell-free therapeutics in potential clinical applications. Here, we investigated the common mechanisms underlying wound closure and unpleasant sensation of itching, focusing on the contribution of the SHED-derived exosome to immune response and wound itching during healing. The effects of SHED-derived exosomes on inflammatory wound healing were examined using lipopolysaccharide (LPS)-induced wounds in a mouse model. We found prolonged inflammation and distinct itch responses in skin wound tissue during LPS-induced wound healing. SHED-derived exosomes facilitated LPS-induced wound closure and relieved wound itching. Therefore, they are ideal for the treatment of wound healing. Macrophages in skin wound tissues are responsible for autophagy during wound healing. Macrophage autophagy also regulates cell proliferation, migration, and neuronal signal transduction in vitro. SHED-derived exosomes containing miR-1246 enhanced autophagy by regulating macrophage function through the AKT, ERK1/2, and STAT3 signaling pathways. Thus, SHED-derived exosomes promote wound healing with less itching in an LPS-induced wound model by stimulating macrophage autophagy, which has implications for the treatment of inflammatory wound healing.

Associations of long-term ambient air pollution and traffic-related pollution with blood pressure and hypertension defined by the different guidelines worldwide: the CHCN-BTH study.

The assessment of the generalization of the strict hypertension definition in the 2017 ACC/AHA Hypertension Guideline from environmental condition remains sparse. The aims of this study are to investigate and compare the associations of ambient air pollution and traffic-related pollution (TRP) with hypertension defined by the different criteria. A total of 32,135 participants were recruited from the baseline survey of the CHCN-BTH in 2017. We defined hypertension as SBP/DBP ≥ 140/90 mmHg according to the hypertension guidelines in China, Japan, Europe and ISH (traditional criteria) and defined as SBP/DBP ≥ 130/80 mmHg according to the 2017 ACC/AHA Hypertension Guideline (strict criteria). A two-level generalized linear mixed models were applied to investigate the associations of air pollutants (i.e. PM2.5, SO2, NO2) and TRP with blood pressure (BP) measures and hypertension. Stratified analyses and two-pollutant models were also performed. The stronger associations of air pollutants were found in the hypertension defined by the strict criteria than that defined by the traditional criteria. The ORs per an IQR increase in PM2.5 were 1.17 (95% CI: 1.09, 1.25) for the strict criteria and 1.14 (95% CI: 1.06, 1.23) for the traditional criteria. The similar conditions were also observed for TRP. The above results were robust in both stratified analyses and two-pollutant models. Our study assessed the significance of the hypertension defined by the strict criteria from environmental aspect and called attention to the more adverse effects of air pollution and TRP on the earlier stage of hypertension.

Polymorphisms and Gene-Gene Interaction in AGER/IL6 Pathway Might Be Associated with Diabetic Ischemic Heart Disease.

Background: Although the genetic susceptibility to diabetes and ischemic heart disease (IHD) has been well demonstrated, studies aimed at exploring gene variations associated with diabetic IHD are still limited; Methods: Our study included 204 IHD cases who had been diagnosed with diabetes before the diagnosis of IHD and 882 healthy controls. Logistic regression was used to find the association of candidate SNPs and polygenic risk score (PRS) with diabetic IHD. The diagnostic accuracy was represented with AUC. Generalized multifactor dimensionality reduction (GMDR) was used to illustrate gene-gene interactions; Results: For IL6R rs4845625, the CT and TT genotypes were associated with a lower risk of diabetic IHD than the CC genotype (OR = 0.619, p = 0.033; OR = 0.542, p = 0.025, respectively). Haplotypes in the AGER gene (rs184003-rs1035798-rs2070600-rs1800624) and IL6R gene (rs7529229-rs4845625-rs4129267-rs7514452-rs4072391) were both significantly associated with diabetic IHD. PRS was associated with the disease (OR = 1.100, p = 0.005) after adjusting for covariates, and the AUC were 0.763 (p < 0.001). The GMDR analysis suggested that rs184003 and rs4845625 were the best interaction model after permutation testing (p = 0.001) with a cross-validation consistency of 10/10; Conclusions: SNPs and haplotypes in the AGER and IL6R genes and the interaction of rs184003 and rs4845625 were significantly associated with diabetic IHD.

Metagenomics reveals differences in microbial composition and metabolic functions in the rumen of dairy cows with different residual feed intake.

BACKGROUND: Rumen microbial composition and functions have vital roles in feed digestion and fermentation and are linked to feed efficiency in cattle. This study selected Holstein cows, which are high in both milk protein content and milk yield, to analyse the relationship between the rumen microbiota and residual feed intake (RFI). Eighteen multiparous lactating cows were divided into low RFI (LRFI, high efficiency, n = 9) and high RFI (HRFI, low efficiency, n = 9) groups to investigate the differences in microbial composition and functions. RESULTS: The relative abundances of butyrate producers, including the Clostridium, Butyrivibrio, Eubacterium and Blautia genera, were higher in HRFI cows than in LRFI cows (P < 0.05). Four carbohydrate metabolic pathways (glycolysis/gluconeogenesis, pentose phosphate pathway, fructose and mannose metabolism, and butanoate metabolism) and one energy metabolism pathway (methane metabolism), were more abundant in HRFI animals (P < 0.05). Quorum sensing and DNA replication pathways were more abundant in HRFI cows. For CAZyme profiles, 14 out of 19 genes encoding carbohydrates-deconstructing enzymes were more abundant in HRFI cows (P < 0.05). Seven Lachnospiraceae species associated with carbohydrate metabolism and quorum sensing may contribute to the difference in feed efficiency. Moreover, the LRFI cows had lower abundances of Methanosphaera (P < 0.01), Methanobrevibacter ruminantium (P = 0.09) and methanogenesis functions (P = 0.04). CONCLUSIONS: The rumen microbiota of low-efficiency cows has stronger abilities to degrade carbohydrates and produce methane, and quorum sensing pathways could also be associated with differences in feed efficiency. This study provides a deeper understanding of the microbial ecology of dairy cows with different feed efficiencies and highlights the possibility of modulating the rumen microbiome or microbial functions to improve the feed efficiency of dairy cows.