Elevated C-reactive protein and complement C3 levels are associated with preterm birth: a nested case-control study in Chinese women.

BACKGROUND: Currently, there are many studies researched the associations between maternal serum inflammatory indicators (i.e. ferritin, C-reactive protein [CRP], C3 and C4) and preterm birth (PTB). The results, however, are inconsistent. Therefore, the aim of this study was to estimate the relationship between maternal serum inflammatory indicators and PTB in a nested case-control (NCC)study. METHODS: A NCC study was conducted by Guangxi Birth Cohort Study which enrolled a total of 6203 pregnant women between 50/7 and 346/7 weeks of gestational age (wGA) from six cities in China between 2015 and 2016. There were 206women who delivered preterm (< 370/7 wGA), and 412 women who delivered term birth, those women were matched by maternal age, birth place, gender of infants, and wGA at blood collection. The inflammatory indicators were quantified by immunoturbidimetric methods. RESULTS: Highest quartile concentrations of all inflammatory indicators were determined versus median. After adjusting for maternal age, high levels of CRP (CRP > 16.60 mg/L) are related to the risk of PTB (OR = 2.16, 95% CI: 1.02-4.56, p = 0.044) in the first trimester. The association of C3 was extremely related to those who delivered PTB (OR = 2.53, 95% CI: 1.14-5.64, p = 0.023) in the first trimester. Moreover, no significant associations were found in C4 (p = 0.079) and ferritin (p = 0.067) between PTB. CONCLUSIONS: Elevated concentrations of CRP and C3 in the first trimester were associated with increased risk of PTB. Inflammatory indicators may act a pivotal part in early diagnosis and prognosis of PTB.

Serum multiple cytokines for the prediction of spontaneous preterm birth in asymptomatic women: A nested case-control study.

BACKGROUND: Current biomarkers such as fetal fibronectin and cervical length are accurate predictors of spontaneous preterm birth (sPTB) in women with clinically suspected preterm risk; however, these are not effective for predicting the risk of sPTB in asymptomatic women. Therefore, we performed this study with the objective of determining whether the combinations of specific serum cytokines could accurately predict the sPTB risk in asymptomatic women. METHODS: We conducted a nested case-control study with 129 incident sPTB cases and 258 individually matched controls who participated in an ongoing birth cohort study. The maternal serum levels of the selected 35 cytokines were measured. We evaluated the relationship between the multiple cytokines and sPTB risk using conditional logistic regression and elastic net model. RESULTS: A panel of cytokines was significantly associated with an increased risk of sPTB. The odds ratio (OR) of sPTB per standard deviation (SD) increase of the predictive model score was 1.57 (95% CI 1.25-1.97) for the cytokines model. The combination of the selected serum cytokines was substantially more effective in predicting the risk for sPTB, as the receiver-operator characteristic curve (AUC) values were 0.546 and 0.559 in the single cytokine model and it improved to 0.642 in the multiple cytokines model (PAUC difference = 0.02 for TNF-α vs. multiple cytokines; PAUC difference = 0.05 for TRAIL vs. multiple cytokines). Moreover, the prediction was more accurate in overweight pregnant women, with an AUC = 0.879. CONCLUSIONS: The current study suggested that the combination of selected serum cytokines can more effectively predict the risk of sPTB in asymptomatic women compared with the use of single cytokine.

Dual RNA-Seq uncovers the function of an ABC transporter gene in the host-pathogen interaction between Epinephelus coioides and Pseudomonas plecoglossicida.

As an important pathogen in aquaculture, Pseudomonas plecoglossicida has caused heavy losses. The expression of an ABC transporter gene-L321_23611 of P. plecoglossicida at 18 °C was found significant higher than those at 28 °C by RNA-seq and qRT-PCR. RNAi significantly reduced the content of L321_23611 mRNA in P. plecoglossicida with a maximal decrease of 89.2%. Compared with the wild type strain, the infection of L321_23611-RNAi strain resulted in the reduction in mortality and the onset time delay of a kind of marine teleosts, Epinephelus coioides. The results of dual RNA-seq showed that the RNAi of L321_23611 resulted in a significant change in both pathogen and host transcriptome in the spleens of infected E. coioides. The result of GO and KEGG analysis from dual RNA-seq data showed both host genes of chemokine signaling pathway, coagulation and complement system, hematopoietic cell lineage pathway as well as hemoglobin complex GO term and pathogenic genes of bacterial-type flagellum-dependent cell mortality GO term and flagellar assembly, biosynthesis of amino acids and lysine biosynthesis systems pathways were mainly affected by L321_23611 gene of P. plecoglossicida. The results indicated that: 1. ABC transporter gene-L321_23611 was a virulent gene of P. plecoglossicida. 2. Both the activation of the host immune pathways and depression of pathogenic virulence-related pathways facilitated E. coioides to remove L321_23611-RNAi strain than the wild type strain of P. plecoglossicida.

The effect of a LysR-type transcriptional regulator gene of Pseudomonas plecoglossicida on the immune responses of Epinephelus coioides.

As an important pathogen in aquaculture, Pseudomonas plecoglossicida has caused heavy losses. It was determined with RNA-seq that the expression of a LysR-type transcriptional regulator gene (L321_20267) of P. plecoglossicida at 18 °C was significantly higher than that at 28 °C, which was verified by quantitative real-time PCR (qRT-PCR). RNAi significantly reduced the content of L321_20267 mRNA in P. plecoglossicida, with a maximal decrease of 90.63%. Compared with the wild-type strain, infection with the L321_20267-RNAi strain resulted in a 50% reduction in mortality and an onset time delay of Epinephelus coioides, as well as alleviation of the symptoms in E. coioides spleens. Compared with the wild-type strain of P. plecoglossicida, the L321_20267-RNAi strain resulted in a significant change in the spleen transcriptome of infected E. coioides. The results of GO and KEGG analysis showed that genes of serine hydrolase activity, the antigen processing and presentation pathway, the B cell receptor signalling pathway and the chemokine signalling pathway were most affected by the L321_20267 gene of P. plecoglossicida. Meanwhile, the immune genes were related to different numbers of miRNAs and lncRNAs, and some miRNAs were related to more than one gene. The results indicated that 1. L321_20267 is a virulence gene of P. plecoglossicida; 2. the upregulation of the immune pathways facilitated E. coioides to remove the L321_20267-RNAi strain compared with the wild-type strain of P. plecoglossicida; and 3. the immune genes were regulated by miRNA and lncRNA in a complex manner.

Low Serum Sex Hormone-Binding Globulin Associated with Insulin Resistance in Men with Nonalcoholic Fatty Liver Disease.

The presence of nonalcoholic fatty liver disease (NAFLD) is a strong risk predictor for type 2 diabetes (T2D). A reduction in sex hormone-binding globulin (SHBG) is associated with NAFLD. Low SHBG is also associated with insulin resistance (IR). However, very limited data are available for the association of SHBG and IR in patients with NAFLD. The study aims to clarify the association between SHBG and IR in patients with NAFLD. In this cross-sectional study, 334 men with NAFLD were recruited. SHBG, total testosterone, free testosterone, total cholesterol, triglyceride, insulin, and glucose concentrations were measured. Homeostatic model assessment (HOMA)-IR and HOMA-ß were calculated. Spearman's correlations and multiple linear regressions were used to analyze the association between SHBG and IR. Men with moderate-severe NAFLD had higher waist circumference, BMI, total cholesterol, triglyceride, insulin, HOMA-IR, HOMA-ß, and free testosterone, but lower SHBG than the mild NAFLD. The moderate-severe NAFLD group exhibited higher HOMA-IR (2.38±1.35 vs. 4.16±2.84, p<0.001) and lower SHBG (25.89±11.89 vs. 30.13±12.97 nmol/l, p<0.001) than the other group. SHBG value was negatively correlated with insulin, and HOMA-IR, but was not significantly correlated with glucose and testosterone. The multiple linear regression analysis showed that SHBG was significantly associated with insulin (ß=- 0.241, p<0.001), and HOMA-IR (ß=- 0.229, p<0.001), even adjusting for potential confounders. In conclusion, low serum SHBG is associated with IR in men with NAFLD.

16S rRNA gene sequencing reveals altered composition of gut microbiota in individuals with kidney stones.

Nephrolithiasis is a common urological disease with high prevalence and recurrence rates. Characterizing gut microbiome profiles of nephrolithiasis patients may provide valuable insights and potential biomarkers for the disease. Therefore, we explored the relation between gut microbiome and nephrolithiasis using 16S ribosomal RNA (rRNA) gene sequencing. 13 patients with multiple kidney stones and 13 matched healthy controls were recruited. A decreasing trend in number of observed species in nephrolithiasis patients was detected, although statistical significance was not reached (p = 0.086). The inter-group variability in community structure by beta diversity analysis showed a clear separation between nephrolithiasis patients and healthy controls. Twenty genera differentiated significantly in relative abundance between nephrolithiasis patients and healthy controls (all p < 0.05). Among the 20 genera, Phascolarctobacterium, Parasutterella, Ruminiclostridium_5, Erysipelatoclostridium, Fusicatenibacter and Dorea were correlated with the concentration of the trace elements in blood, including potassium, sodium, calcium and chlorinum. Characteristic microbiome in nephrolithiasis patients was also identified by linear discriminant analysis effect size (LEfSe). These findings may provide novel and non-invasive potential diagnostic biomarkers for nephrolithiasis, and contribute to prevention and treatment of nephrolithiasis from the perspective of maintaining micro-ecological equilibrium in gut.

HIPK2 polymorphisms rs2058265, rs6464214, and rs7456421 were associated with kidney stone disease in Chinese males not females.

BACKGROUND AND AIM: Recent studies have shown that genetic factors are involved in the development of kidney stone disease (KSD). A case-control association analysis was performed to investigate the association between homeodomain-interacting protein kinase 2 (HIPK2; OMIM *606868) polymorphisms and KSD. METHODS: A total of 890 KSD patients and 920 healthy subjects were analyzed. Polymorphisms were genotyped using SNPscanTM high-throughput SNP classification technology. The genotypic and allelic frequencies in KSD patients and healthy individuals were analyzed using a Chi-square test. RESULTS: The genotype and allele distributions of the three polymorphisms (rs2058265, rs6464214, and rs7456421 in HIPK2) displayed strong associations with KSD in males (rs2058265: odds ratio [OR] 2.480,95%confidence interval [CI] 1.205-5.106, p = 0.014; rs6464214: OR 2.466, 95%CI 1.198-5.078, p = 0.014; rs7456421: OR 2.846, 95%CI 1.362-5.947, p = 0.005; perallele: r2058265T, OR 1.357, 95%CI 1.073-1.715, p = 0.011; rs6464214G, OR 1.340, 95%CI 1.060-1.693, p = 0.014; rs7456421C, OR 1.356, 95%CI 1.073-1.713, p = 0.011). Patients carrying the T allele of rs2058265, the G allele of rs6464214, or the C allele of rs7456421 showed higher systolic blood pressure, creatinine, and uric acid levels compared with wild-genotype individuals after adjusting for age, gender, and body mass index (p < 0.005). CONCLUSION: The association of HIPK2 gene polymorphisms with KSD was only observed in males but not in females. HIPK2 gene polymorphisms were also involved in the changes of KSD-related metabolic traits.

Breast cancer in postmenopausal women is associated with an altered gut metagenome.

BACKGROUND: Increasing evidence suggests that gut microbiota play a role in the pathogenesis of breast cancer. The composition and functional capacity of gut microbiota associated with breast cancer have not been studied systematically. METHODS: We performed a comprehensive shotgun metagenomic analysis of 18 premenopausal breast cancer patients, 25 premenopausal healthy controls, 44 postmenopausal breast cancer patients, and 46 postmenopausal healthy controls. RESULTS: Microbial diversity was higher in breast cancer patients than in controls. Relative species abundance in gut microbiota did not differ significantly between premenopausal breast cancer patients and premenopausal controls. In contrast, relative abundance of 45 species differed significantly between postmenopausal patients and postmenopausal controls: 38 species were enriched in postmenopausal patients, including Escherichia coli, Klebsiella sp_1_1_55, Prevotella amnii, Enterococcus gallinarum, Actinomyces sp. HPA0247, Shewanella putrefaciens, and Erwinia amylovora, and 7 species were less abundant in postmenopausal patients, including Eubacterium eligens and Lactobacillus vaginalis. Acinetobacter radioresistens and Enterococcus gallinarum were positively but weakly associated with expression of high-sensitivity C-reactive protein; Shewanella putrefaciens and Erwinia amylovora were positively but weakly associated with estradiol levels. Actinomyces sp. HPA0247 negatively but weakly correlated with CD3+CD8+ T cell numbers. Further characterization of metagenome functional capacity indicated that the gut metagenomes of postmenopausal breast cancer patients were enriched in genes encoding lipopolysaccharide biosynthesis, iron complex transport system, PTS system, secretion system, and beta-oxidation. CONCLUSION: The composition and functions of the gut microbial community differ between postmenopausal breast cancer patients and healthy controls. The gut microbiota may regulate or respond to host immunity and metabolic balance. Thus, while cause and effect cannot be determined, there is a reproducible change in the microbiota of treatment-naive patients relative to matched controls.