Secular increase in the prevalence of gestational diabetes and its associated adverse pregnancy outcomes from 2014 to 2021 in Hebei province, China.

Objective: We aimed to investigate the secular prevalence of gestational diabetes mellitus (GDM) and evaluate its adverse pregnancy outcomes among pregnant women in Hebei province, China. Methods: We analyzed the data from the monitoring information management system for pregnant women in 22 hospitals of Hebei province, China. In this study, 366,212 individuals with singleton live births from 2014 to 2021 were included, of whom 25,995 were diagnosed with gestational diabetes. We described the incidence of common complications and further analyzed the clinical characteristics in GDM patients and the relationship between GDM and adverse pregnancy outcomes. Results: The top 3 pregnancy complications in Hebei province are anemia, gestational hypertension, and GDM. The average incidence of GDM was 7.10% (25,995/366,212). The incidence rate of GDM significantly increased from 2014 to 2021 (χ2 trend = 7,140.663, P < 0.001). The top 3 regions with GDM incidence were Baoding (16.60%), Shijiazhuang (8.00%), and Tangshan (3.80%). The incidence of GDM in urban pregnant women (10.6%) is higher than that in rural areas (3.7%).The difference between the GDM and Non-GDM groups was statistically significant in terms of maternal age, gravidity, parity, education level, and incidence of pregnancy complications (gestational hypertension, heart diseases, and anemia) (P < 0.05). GDM individuals were at significantly increased risk of most assessed adverse pregnancy outcomes, including premature delivery, Cesarean delivery, uterine inertia, neonatal intensive care unit (NICU) admission, Apgar (activity-pulse-grimace-appearance-respiration) score at 1 min, and macrosomia (P < 0.05). The multivariate logistic regression analysis showed that GDM was an independent risk factor in terms of premature birth, Cesarean delivery, uterine inertia, placental abruption, NICU admission, and macrosomia. Conclusion: The risk of adverse pregnancy outcome in pregnant women with GDM is significantly increased. In order to reduce the occurrence of adverse pregnancy outcomes, effective interventions are needed.

Intestinal flora alterations in patients with ulcerative colitis and their association with inflammation.

Ulcerative colitis (UC), which is a type of inflammatory bowel disease, is a chronic intestinal disorder of multifactorial etiology. Numerous studies have indicated an association between UC and intestinal bacteria. However, a limited number of studies regarding the expression of interleukin-17 (IL-17) and interleukin-23 (IL-23) in association with intestinal bacteria have been performed. The aim of the current study was to investigate the gut microbiota alterations in patients with UC, at a number of taxonomic levels, and their relationship with intestinal inflammation by analyzing the protein expression of IL-17 and IL-23. Specimens were collected from 10 healthy controls and 16 patients with UC. A histological examination was performed in colonic tissues, IL-17 and IL-23 protein expression was detected by immunohistochemistry, fecal samples were sequenced using 16S rDNA sequencing and bioinformatics analysis was performed. The UC group exhibited an increased histological score (P<0.01) and upregulated IL-17 and IL-23 expression (P<0.01). At the order level, the bacterial diversity of the UC group was decreased. ß-diversity analyses, including principal component analysis, principal coordinate analysis and non-metric multidimensional scaling, demonstrated that the two groups of samples were separated into two taxonomic categories, as distinct variations were observed in the analysis of group differences (P=0.001). Regarding the differences in species composition between the groups, Enterococcus was indicated to be the species with the greatest difference in abundance compared with the healthy control group (P<0.01), followed by Lactobacillus (P<0.05), Escherichia-Shigella (P<0.05), Bifidobacterium and Bacteroides. In addition, the average optical density of IL-17 was positively correlated with the histological score (ρ=0.669; P=0.035), Enterococcus (r=0.843; P<0.001), Lactobacillus (r=0.737; P=0.001), Bifidobacterium (r=0.773; P<0.001) and Escherichia-Shigella (r=0.663; P=0.005), and the average optical density of IL-23 was positively correlated with the histological score (ρ=0.733; P=0.016), Enterococcus (r=0.771; P<0.001), Lactobacillus (r=0.566; P=0.022), Bifidobacterium (r=0.517; P=0.041) and Escherichia-Shigella (r=0.613; P=0.012). The results of the present study indicated that the intestinal microbiota of patients with UC differed from that of healthy controls at multiple taxonomic levels. The alterations of the intestinal microflora were closely associated with the degree of inflammation. The IL-23/IL-17 axis, as a key factor in the development of UC, maybe associated with the alterations of intestinal microflora. The interaction between intestinal microflora and the IL-23/IL-17 axis may serve an important role in the pathogenesis of UC.

IL-1α induces apoptosis and inhibits the osteoblast differentiation of MC3T3-E1 cells through the JNK and p38 MAPK pathways.

Interleukin (IL)-1 is a proinflammatory cytokine that plays important roles in inflammation and host responses to infection. The present study aimed to evaluate the effects of IL-1α on the apoptosis and differentiation of osteoblasts, and to elucidate the mechanism responsible for these effects in the osteoblast­like cell line MC3T3-E1. The MC3T3-E1 cells were non-treated or treated with IL-1α. Following treatment, cell viability, alkaline phosphatase (ALP) activity and caspase-3 activity were evaluated. The expression of osteoblast-specific genes as well as Bax, Bcl-2 and caspase-3 were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The protein levels of Bax, Bcl-2, caspase-3 and the phosphorylation of mitogen-activated protein kinases (MAPKs, also known as MAP kinases) were evaluated using western blot analysis. The MAPK signaling pathway was blocked by pre-treatment with MAPK inhibitors SB203580, PD98059 and SP600125. IL-1α treatment induced a significant decrease in cell viability and ALP activity in the MC3T3-E1 cells. IL-1α also significantly decreased the mRNA expression and protein levels of osteoblast-related genes in the MC3T3-E1 cells. On the other hand, IL-1α significantly upregulated the mRNA expression and protein levels of Bax and caspase-3 as well as caspase-3 activity, whereas Bcl-2 expression was decreased in the MC3T3-E1 cells. Furthermore, IL-1α activated the apoptotic signaling pathway by increasing the phosphorylation of c-Jun N-terminal kinase (JNK) and p38-MAPK, whereas it inhibited the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Moreover, pre-treatment with MAPK inhibitors attenuated the phosphorylation of JNK, p38 and Bax expression enhanced by IL-1α. However, MAPK inhibitors markedly increased the protein expression of osteoblast-related genes and Bcl-xL in the MC3T3-E1 cells downregulated by IL-1α. Taken together, these findings suggest that IL-1α induces the apoptosis of osteoblasts and inhibits osteoblast differentiation by activating the JNK and the p38 MAPK pathways.

Lipopolysaccharide (LPS) induces the apoptosis and inhibits osteoblast differentiation through JNK pathway in MC3T3-E1 cells.

Bone degradation is a serious complication of chronic inflammatory diseases such as septic arthritis, osteomyelitis, and infected orthopedic implant failure. Up to date, effective therapeutic treatments for bacteria-caused bone destruction are limited. In our previous study, we found that LPS promoted osteoclast differentiation and activity through activation of mitogen-activated protein kinases (MAPKs) pathway such as c-Jun N-terminal kinases (JNK) and extracellular signal regulated kinase (ERK1/2). The current study was to evaluate the mechanism of LPS on the apoptosis and osteoblast differentiation in MC3T3-E1 cells. MC3T3-E1 osteoblasts were non-treated, treated with LPS. After treatment, the cell viability, the activity of alkaline phosphatase (ALP) and caspase-3 were measured. The expressions of osteoblast-specific genes and Bax, Bcl-2, and caspase-3 were determined by real-time quantitative polymerase chain reaction (qPCR). Protein levels of Bax, Bcl-2, caspase-3, and phosphorylation of MAPKs were measured using Western blotting assays. The MAPK signaling pathway was blocked by pretreatment with JNK inhibitor SP600125. LPS treatment induced a significant decrease in cell metabolism, viability, and ALP activity in MC3T3-E1 cells. LPS also significantly decreased mRNA expressions of osteoblast-related genes in MC3T3-E1 cells. On the other hand, LPS significantly upregulated mRNA expressions and protein levels of Bax and caspase-3 as well as activation of caspase-3, whereas decreased Bcl-2 expression in MC3T3-E1 cells. Furthermore, LPS significantly promoted MAPK pathway including the phosphorylation of JNK and the phosphorylation of ERK1/2; moreover, pretreatment with JNK inhibitor not only attenuated both of phosphorylation-JNK and ERK1/2 enhanced by LPS in MC3T3-E1 cells, but also reversed the downregulated expressions of osteoblast-specific genes including ALP and BSP induced by LPS. In conclusion, LPS could induce osteoblast apoptosis and inhibit osteoblast differentiation via activation of JNK pathway.

Prodigiosin found in Serratia marcescens y2 initiates phototoxicity in the cytomembrane

Background: Light can be absorbed by bacterial pigment and affects its growth. Prodigiosin is a red pigment found in various bacterial species. The purpose of this study was to investigate the impacts of light on prodigiosin production, biomass formation, and membrane integrity of Serratia marcescens y2. Results: S. marcescens y2 grew better and produced more intracellular prodigiosin in darkness than in illumination. The pigment leakage ratio from cells was detected more in light than in darkness conditions. Ethidium bromide uptake assay could visually prove the prodigiosin-related loss of membrane integrity under illumination. A higher concentration of malondialdehyde (MDA) was detected in light-treated culture than in darkness. Tests of different light treatments (red, yellow, blue and green) showed that the maximum extracellular pigment and the minimum biomass formation and intracellular pigment were obtained in green light. Conclusions: Prodigiosin could absorb light, and then initiate phototoxicity damage of the cytomembrane.