Vitamin D deficiency is associated with increased risks of chronic obstructive pulmonary disease (COPD). Nevertheless, the mechanisms remain unknown. This study analyzed the correlations between vitamin D levels and inflammation in COPD patients. One hundred and one patients with COPD and 202 control subjects were enrolled. Serum 25(OH)D level and inflammatory cytokines were detected. Serum 25(OH)D was decreased and inflammatory cytokines were increased in COPD patients. According to forced expiratory volume in 1 s, COPD patients were divided into three grades. Furthermore, serum 25(OH)D was gradually decreased in COPD patients ranging from grade 1–2 to 4. Serum 25(OH)D was inversely associated with inflammatory cytokines in COPD patients. Further analysis found that NF-κB and AP-1 signaling were activated in COPD patients. Besides, inflammatory signaling was gradually increased in parallel with the severity of COPD. By contrast, pulmonary nuclear vitamin D receptor was decreased in COPD patients. In vitro experiments showed that 1,25(OH)₂D₃ inhibited LPS-activated inflammatory signaling in A549 cells (human lung adenocarcinoma cell). Mechanically, 1,25(OH)₂D₃ reinforced physical interactions between vitamin D receptor with NF-κB p65 and c-Jun. Our results indicate that vitamin D is inversely correlated with inflammatory signaling in COPD patients. Inflammation may be a vital mediator of COPD progress in patients with low vitamin D levels. Key Points Vitamin D was decreased and inflammation was increased in COPD patients. NF-κB and AP-1 signaling pathways were activated in COPD patients. Vitamin D was inversely correlated with inflammatory signaling in COPD patients.

Studies on the risk factors for intrahepatic cholestasis of pregnancy (ICP) in a population-based cohort are lacking. We assess the prevalence and risk factors of ICP in a Chinese population. In this study, a cohort study was conducted that included 12,200 eligible pregnant women. The overall incidence of ICP in this cohort was 6.06%. With increasing maternal age, the incidence of ICP decreased in women younger than 30 years of age but increased in those older than 30. With increasing pre-pregnancy BMI, the incidence of ICP decreased if the pre-pregnancy BMI was less than 23 kg/m² but increased if it was 23 kg/m² or higher. Further analysis showed that the risk of ICP increased when maternal age was < 25 years (Adjusted RR 2.01; 95% CI 1.64–2.47) or ≥ 35 years (Adjusted RR 1.34; 95% CI 1.02–1.76). Furthermore, an increased risk of ICP was associated with pre-pregnancy underweight (adjusted RR 1.27; 95% CI 1.04–1.56), inadequate gestational weight gain (GWG) (adjusted RR 1.58; 95% CI 1.28–1.96), lower maternal education (adjusted RR 2.96; 95% CI 2.35–3.74), multiparity (adjusted RR 1.54; 95% CI 1.23–1.93), and twin/multiple pregnancies (adjusted RR 2.12; 95% CI 1.25–3.58). Maternal age (< 25 or ≥ 35 years), underweight, inadequate GWG, lower maternal education, multiparity, and twin/multiple pregnancies were identified as risk factors of ICP.

The association between suboptimal pre-pregnancy body mass index (BMI) and small-for-gestational-age (SGA) infants is not well defined. We investigated the association between pre-pregnancy BMI and the risk of SGA infants in a Chinese population. We performed a cohort study among 12029 mothers with a pregnancy. This cohort consisted of pregnant women that were: normal-weight (62.02%), underweight (17.09%), overweight (17.77%) and obese (3.12%). Birth sizes were reduced in the underweight and obese groups compared with the normal-weight group. Linear regression analysis indicated that birth size was positively associated with BMI in both the underweight and normal-weight groups. Further analysis showed that 12.74% of neonates were SGA infants in the underweight group, higher than 7.43% of neonates reported in the normal-weight group (adjusted RR = 1.92; 95% CI: 1.61, 2.30). Unexpectedly, 17.60% of neonates were SGA infants in the obese group, much higher than the normal-weight group (adjusted RR = 2.17; 95% CI: 1.57, 3.00). Additionally, 18.40% of neonates were large-for-gestational-age (LGA) infants in the obese group, higher than 7.26% of neonates reported in the normal-weight group (adjusted RR = 3.00; 95% CI: 2.21, 4.06). These results suggest that pre-pregnancy underweight increases the risk of SGA infants, whereas obesity increases the risks of not only LGA infants, but also SGA infants.

It is increasingly recognized that excessive glucocorticoids induce fetal intrauterine growth restriction (IUGR). Placental 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), a glucocorticoid-catalyzing enzyme, prevents active glucocorticoids from maternal circulation into the fetus, thus protecting against IUGR. Previous studies demonstrated gestational LPS exposure caused fetal IUGR. The aim of the current study was to investigate the effects of LPS on 11β-HSD2 in mice placentas and human placental trophoblasts. Pregnant ICR(CD-1) mice were i.p. injected with LPS (200 μg/kg) on gestational day 16. As expected, gestational LPS exposure downregulated 11β-HSD2 in mice placentas. In vitro, LPS downregulated 11β-HSD2 in human placental trophoblasts. Additional experiment showed that LPS, which activated NF-κB, suppressed rosiglitazone-induced activation of peroxisome proliferator–activated receptor-γ (PPARγ) in mice placentas and human placental trophoblasts. Moreover, NF-κB p65 knockdown and specific NF-κB inhibitor attenuated LPS-induced suppression of PPARγ nuclear translocation in human placental trophoblasts. In addition, NF-κB p65 knockdown attenuated LPS-induced downregulation of 11β-HSD2 in human placental trophoblasts. Mechanically, LPS promoted physical interaction between NF-κB p65 and PPARγ in the cytoplasm and nucleus of placental trophoblasts. Finally, pretreatment with rosiglitazone, a PPARγ agonist, partially alleviated LPS-induced reduction of fetal weight and crown-rump length. Taken together, these results suggest that LPS downregulates 11β-HSD2 through suppressing PPARγ in placental trophoblasts. Placental 11β-HSD2 downregulation may contribute partially to LPS-induced fetal IUGR.