Hirudin ameliorates diabetic nephropathy by inhibiting Gsdmd-mediated pyroptosis.

Our group previously reported that hirudin ameliorated diabetic nephropathy (DN) in streptozotocin (STZ)-injected rats, but the mechanism remained largely unknown. Therefore, we further explored its possible mechanism. We subcutaneously injected 5 U hirudin into STZ-induced WT mice or Gasdermin D (Gsdmd)-/- (KO) mice daily for 12 weeks, respectively, and evaluated their kidney injury. Next, glomerular endothelial cells (GECs), renal tubular epithelial cells (RTECs), and bone-marrow-derived macrophages (BMDMs) were isolated from WT mice and treated with hirudin in the presence of high glucose/lipopolysaccharides and ATP to measure the release of interleukin-18 and interleukin-1ß. Kidney injury induced by STZ injection was significantly ameliorated by hirudin through inhibiting Gsdmd-mediated pyroptosis in the mice, not Caspase 1-mediated apoptosis. Meanwhile, hirudin also suppressed pyroptosis in primary GECs, RTECs, and BMDMs in vitro. Moreover, the deletion of Gsdmd reduced pyroptosis and kidney injury both in vivo and in vitro. We also found that hirudin regulated the expression of Gsdmd by inhibiting interferon regulatory factor 2 (Irf2). Hirudin ameliorated Gsdmd-mediated pyroptosis by inhibiting irf2, leading to the improvement of kidney injury. Therefore, hirudin might serve as a potential therapeutic strategy to treat DN.

CMKLR1 Antagonist Alpha-NETA Protects against Diabetic Nephropathy in Mice.

INTRODUCTION: Diabetic nephropathy (DN) is a common complication in diabetic patients. Chemerin, a novel adipokine, has been associated with renal damage in DN. The chemerin chemokine-like receptor 1 (CMKLR1) has been reported to participate in DN. In this study, we aimed to investigate the effect of a CMKLR1 antagonist, 2-(anaphthoyl)ethyltrimethylammonium iodide (α-NETA), on DN. METHODS: To induce diabetes, 8-week-old male C57BL/6J mice were given a single intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Diabetic mice were randomly assigned to receive daily doses of 0, 5, or 10 mg/kg α-NETA for 4 weeks. RESULTS: α-NETA dose-dependently induced body weight and reduced fasting blood glucose levels in STZ-induced diabetic mice. Furthermore, α-NETA significantly reduced the expressions of renal injury markers, including serum creatinine, kidney weight/body weight, urine volume, total proteins, and albumin in the urine, and increased creatinine clearance. Periodic acid-Schiff staining also indicated that α-NETA could effectively ameliorate renal injuries in DN mice. In addition, α-NETA inhibited renal inflammation and the expressions of chemerin and CMKLR1 in mice with DN. CONCLUSION: In summary, our findings suggested that α-NETA has beneficial effects on the management of DN. Specifically, α-NETA effectively ameliorated renal damage and inflammation in a dose-dependent manner in mice with DN. Thus, targeting the chemerin and CMKLR1 axis with α-NETA may be a promising therapeutic strategy for the treatment of DN.

[Application of micro-bolus injection and piezoelectric sensors to improve the safety of radiopharmaceuticals bolus injection].

Radiopharmaceutical dynamic imaging typically necessitates intravenous injection via the bolus method. However, manual bolus injection carries the risk of handling errors as well as radiological injuries. Hence, there is potential for automated injection devices to replace manual injection methods. In this study, the effect of micro-bolus pulse injection technology was compared and verified by radioactive experiments using a programmable injection pump, and the overall bubble recognition experiment and rat tail vein simulation injection verification were performed using the piezoelectric sensor preloading method. The results showed that at the same injection peak speed, the effective flushing volume of micro-bolus pulse flushing (about 83 µL/pulse) was 49.65% lower than that of uniform injection and 25.77% lower than that of manual flushing. In order to avoid the dilution effect of long pipe on the volume of liquid, the use of piezoelectric sensor for sealing preloading detection could accurately predict the bubbles of more than 100 µL in the syringe. In the simulated injection experiment of rat tail vein, when the needle was placed in different tissues by preloading 100 µL normal saline, the piezoelectric sensor fed back a large difference in pressure attenuation rate within one second, which was 2.78% in muscle, 17.28% in subcutaneous and 54.71% in vein. Micro-bolus pulse injection method and piezoelectric sensor sealing preloading method have application potential in improving the safety of radiopharmaceutical automatic bolus injection.

[Application of automatic injection device based on automatic hemostasis in injection of radiopharmaceutical bolus injection].

In clinical practice, radiopharmaceutical dynamic imaging technology requires the bolus injection method to complete injection. Due to the failure rate and radiation damage of manual injection, even experienced technicians still bear a lot of psychological burden. This study combined the advantages and disadvantages of various manual injection modes to develop the radiopharmaceutical bolus injector, and explored the application of automatic injection in the field of bolus injection from four aspects: radiation protection, occlusion response, sterility of injection process and effect of bolus injection. Compared with the current mainstream manual injection method, the bolus manufactured by the radiopharmaceutical bolus injector based on the automatic hemostasis method had a narrower full width at half maximum and better repeatability. At the same time, radiopharmaceutical bolus injector had reduced the radiation dose of the technician's palm by 98.8%, and ensured more efficient vein occlusion recognition performance and sterility of the entire injection process. The radiopharmaceutical bolus injector based on automatic hemostasis has application potential in improving the effect and repeatability of bolus injection.

Enterocins: Classification, Synthesis, Antibacterial Mechanisms and Food Applications.

Enterococci, a type of lactic acid bacteria, are widely distributed in various environments and are part of the normal flora in the intestinal tract of humans and animals. Although enterococci have gradually evolved pathogenic strains causing nosocomial infections in recent years, the non-pathogenic strains have still been widely used as probiotics and feed additives. Enterococcus can produce enterocin, which are bacteriocins considered as ribosomal peptides that kill or inhibit the growth of other microorganisms. This paper reviews the classification, synthesis, antibacterial mechanisms and applications of enterocins, and discusses the prospects for future research.

[Association between fruit intake during pregnancy and blood glucose metabolism].

OBJECTIVE: To examine the association between fruit intake and blood glucose metabolism. METHODS: Healthy singleton pregnant women with 6-14 weeks of gestation were selected in a maternal-and-child health care institution in Chengdu from February to July 2017. Dietary information was obtained by 3-day 24-hour dietary recall during each trimester, and the average daily total fruit intake per person were calculated. According to the Dietary guidelines for Chinese pregnant women(2016), insufficient rates of fruits were calculated, and the participants were divided into insufficient intake group, suitable intake group and higher intake group. Multiple linear regression was used to analyze the association between fruit intake during pregnancy and fasting blood glucose, 1-h plasma glucose and 2-h plasma glucose. Log-binomial regression model was used to analyze the association between fruit intake during pregnancy and the risk of gestational diabetes mellitus(GDM). RESULTS: Valid samples of 1453 cases in early pregnancy, 1049 cases in middle pregnancy were included, the age was(28.5±4.0)years old. The average fruit intake during the early and middle pregnancy(M(P25, P75)) were 279.7(180.8, 415.2) g/d and 232.0(100.0, 390.0) g/d, respectively. The insufficient rates were 18.8% and 43.2%, respectively. After adjusting for age, pre-pregnancy BMI, education level, family income, family history of diabetes, parity, physical activity, energy, vegetables, grains, red meat, and beverages, multiple linear regression result showed that compared with the insufficient fruit intake group, in the suitable fruit intake group, the fasting blood glucose level was decreased(ß=-0.071, 95%CI-0.111--0.003). Results of log binomial regression analysis showed that when compared with the fruit suitable intake group during the second trimester, the insufficient intake group may increase the risk of GDM(RR=1.13, 95% CI 1.11-1.58); no association between fruit intake during the early pregnancy and blood glucose metabolism was observed. CONCLUSION: Fruit intake during pregnancy is associated with blood glucose metabolism. The appropriate amount of fruit intake may improve fasting blood glucose and insufficient intake of fruits during the second trimester may increase the risk of GDM.

A low-carbohydrate dietary pattern characterised by high animal fat and protein during the first trimester is associated with an increased risk of gestational diabetes mellitus in Chinese women: a prospective cohort study.

We aimed to examine the association between low-carbohydrate diet (LCD) scores during the first trimester and gestational diabetes mellitus (GDM) risk in a Chinese population. A total of 1455 women were included in 2017. Dietary information during the first trimester was collected by 24-h dietary recalls for 3 d. The overall, animal and plant LCD scores, which indicated adherence to different low-carbohydrate dietary patterns, were calculated. GDM was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test at 24-28 weeks gestation. Log-binomial models were used to estimate relative risks (RR) and 95 % CI. The results showed that the multivariable-adjusted RR of GDM from the lowest to the highest quartiles of the overall LCD score were 1·00 (reference), 1·15 (95 % CI 0·92, 1·42), 1·30 (95 % CI 1·06, 1·60) and 1·24 (95 % CI 1·01, 1·52) (P = 0·026 for trend). Multivariable-adjusted RR (95 % CI) of GDM from the lowest to the highest quartiles of the animal LCD score were 1·00 (reference), 1·20 (95 % CI 0·96, 1·50), 1·41 (95 % CI 1·14, 1·73) and 1·29 (95 % CI 1·04, 1·59) (P = 0·002 for trend). After additional adjustment for gestational weight gain before GDM diagnosis, the association of the overall LCD score with GDM risk was non-significant, while the association of animal LCD score with GDM risk remained significant. In conclusion, a low-carbohydrate dietary pattern characterised by high animal fat and protein during the first trimester is associated with an increased risk of GDM in Chinese women.

Specific fruit but not total fruit intake during early pregnancy is inversely associated with gestational diabetes mellitus risk: a prospective cohort study.

OBJECTIVES: Fruit intake may influence gestational diabetes mellitus (GDM) risk. However, prospective evidence remains controversial and limited. The current study aimed to investigate whether total fruit and specific fruit intake influence GDM risk. DESIGN: A prospective cohort study was conducted. Dietary information was collected by a 3-d 24-h dietary recall. All participants underwent a standard 75-g oral glucose tolerance test at 24-28 gestational weeks. Log-binomial models were used to estimate the association between fruit intake and GDM risk, and the results are presented as relative risks (RR) and 95 % CI. SETTING: Southwest China. PARTICIPANTS: Totally, 1453 healthy pregnant women in 2017. RESULTS: Total fruit intake was not associated with lower GDM risk (RR of 1·03 (95 % CI 0·83, 1·27) (Ptrend = 0·789)). The RR of GDM risk was 0·73 for the highest anthocyanin-rich fruit intake quartile compared with the lowest quartile (95 % CI 0·56, 0·93; Ptrend = 0·015). A higher grape intake had a linear inverse association with GDM risk (Q4 v. Q1: RR = 0·65; 95 % CI 0·43, 0·98; Ptrend = 0·044), and after further adjustment for anthocyanin intake, the inverse association tended to be non-linear (Q4 v. Q1: RR = 0·65; 95 % CI 0·44, 0·98; Ptrend = 0·079). However, we did not find an association between glycaemic index-grouped fruit, glycaemic load-grouped fruit or other fruit subtype intake and GDM risk. CONCLUSIONS: In conclusion, specific fruit intake (particularly anthocyanin-rich fruit and grapes) but not total fruit intake was inversely associated with GDM risk.

Associations between Maternal Lipid Profiles and Pregnancy Complications: A Prospective Population-Based Study.

OBJECTIVE: To investigate whether plasma lipid profiles are independently associated with pregnancy complications including gestational diabetes mellitus (GDM), hypertensive disorder complicating pregnancy (HDCP), and intrahepatic cholestasis of pregnancy (ICP). STUDY DESIGN: A prospective study was conducted among 1,704 pregnant women at three medical institutions in Chengdu, China. The concentrations of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured at gestational weeks 12 ± 1, 24 ± 1, and 34 ± 1. Logistic regression models were used to estimate the association between lipid profiles and pregnancy complications. Receiver operating characteristic analysis was performed to determine the value of lipid profiles to predict GDM and HDCP. RESULTS: After adjusting for potential confounders, TG, TC, and LDL-C in the first trimester were independently associated with GDM (TG: odds ratio [OR] =2.00, 95% confidence interval [CI]: 1.57-2.56; TC: OR = 1.38, 95% CI: 1.16-1.64; LDL-C: OR = 1.43, 95% CI: 1.14-1.79) and HDCP (TG: OR = 2.42, 95% CI: 1.56-3.78, TC: OR = 1.64, 95% CI: 1.04-2.57; LDL-C: OR = 1.87, 95% CI: 1.07-3.25). The TC concentration during the whole pregnancy (first trimester: OR = 1.53, 95% CI: 1.13-2.08; second trimester: OR = 1.31, 95% CI: 1.06-1.61; third trimester: OR = 1.39, 95% CI: 1.17-2.04) and LDL-C in the last two trimesters (second trimester: OR = 1.62, 95% CI: 1.30-2.04; third trimester: OR = 1.56, 95% CI: 1.29-1.88) were positively associated with ICP. HDL-C in the third trimester was negatively associated with the risk of ICP (OR = 0.46, 95% CI: 0.22-0.98). Combining lipid profiles in the first trimester with the other common predictors to predict GDM or HDCP owned stronger predictive power with the largest area under the curve (GDM: 0.643 [95% CI: 0.613-0.673], HDCP: 0.707 [95% CI: 0.610-0.804]) than either indicator alone. CONCLUSION: Maternal lipid profiles during the whole pregnancy are significantly associated with GDM, HDCP, and ICP. Combining lipid profiles in the first trimester with the other common predictors could effectively improve the power of predicting GDM and HDCP.

[Influencing factors of insufficient and excessive folate intake in early pregnancy in Chengdu in 2017].

OBJECTIVE: To investigate the folate intake level of early pregnant women and its influencing factors in Chengdu. METHODS: The healthy singleton pregnant women with 8-14 weeks of pregnancy in an obstetrical clinic of maternal-and-child health care institution in Chengdu in 2017 were selected as the object of the study. The basic information of pregnant women was collected by questionnaire survey, and the dietary intake of all kinds of food in early pregnancy was collected by 3-day 24-hour dietary recall method, and the average daily intake of folate was calculated according to China Food Composition(2018). A self-designed questionnaire was used to collect the use of folic acid supplements in pregnant women in the past one month, and the average daily intake of folic acid supplements was calculated. According to the Chinese Dietary Reference Intakes(2013), the folate intake <600 µg DFE/d was defined as insufficient, and folic acid supplements intake ≥1000 µg/d was defined as excessive. The influencing factors of folate intake were analyzed by binary Logistic regression model. RESULTS: A total of 1579 valid samples were included. The average folate intake of early pregnant women in Chengdu was 865.8(778.6, 1461.0) µg DFE/d, the average dietary folate intake was 145.4(101.9, 200.7) µg/d, and the average folic acid supplements intake was 400.0(400.0, 800.0) µg/d. The rate of insufficient intake of folate in early pregnancy was 12.1%, and the rate of excessive intake of folic acid supplements was 13.0%. Compared with the primiparous group, the risk of insufficient folate intake was higher in the multiparous group(OR=1.708, 95%CI 1.175-2.482). Compared with the low income group, risk of insufficient folate intake in the medium and high income group was lower(OR=0.660, 95%CI 0.477-0.913); taking folic acid supplements before pregnancy has a lower risk of overdose of folic acid than the non-taking group(OR=0.594, 95%CI 0.423-0.835). CONCLUSION: The phenomenon of insufficient intake of total folate and excessive intake of folic acid supplements coexists among women in early pregnancy in Chengdu, and the rational use of folic acid supplements is worthy of attention.

[Prospective study of red meat intake in the first and second trimesters and the risk of gestational diabetes mellitus in Chengdu in 2017].

OBJECTIVE: To evaluate the red meat intake of pregnant women in Chengdu area and explore the effect of red meat intake in the first and second trimesters on gestational diabetes mellitus(GDM). METHODS: From February to July 2017, a prospective study was conducted among healthy singleton pregnant women within 8-14 weeks of gestation in a prenatal clinic of maternal-and-child medical institution in Chengdu City through purposive sampling. Data on maternal demographic characteristics was collected through questionnaire in early pregnancy. 3-day 24 hour dietary recall was used to collect dietary intake information in the first and second trimesters. The 75 g oral glucose tolerance test(OGTT)was conducted at 24 to 28 weeks of gestation, and GDM was diagnosed according to the Guidelines for the Diagnosis and Treatment of Pregnancy Diabetes in China(2014). Multivariate unconditional Logistic regression model was used to explore the association between tertiles of red meat intake and the risk of GDM in the first and second trimesters. RESULTS: A total of 985 valid samples were followed up. The mean intake of total meat and red meat in middle pregnancy(102. 9 g/d and 74. 6 g/d) was higher than that in early pregnancy(70. 7 g/d and 52. 0 g/d). The difference was statistically significant(P<0. 05). Red meat accounted for 73. 6% and 72. 5% of total meat intake in early and middle pregnancy, respectively. After adjusting the confounding factors, multivariate unconditional Logistic regression analysis showed the risk of GDM was 1. 499 times(95%CI 1. 028-2. 185) in the highest red meat intake(>86 g/d)women compared with the lowest red meat intake(<44 g/d) women in the second trimester. No association was found between red meat intake in the first trimester and the occurrence of GDM(OR=1. 029, 95%CI 0. 716-1. 481). CONCLUSION: Pregnant women in Chengdu area have excessive intake of red meat in the second trimester. Higher intake of red meat in the second trimester(>86 g/d) may increase the risk of gestational diabetes.

Hirudin Reduces the Expression of Markers of the Extracellular Matrix in Renal Tubular Epithelial Cells in a Rat Model of Diabetic Kidney Disease Through the Hypoxia-Inducible Factor-1α (HIF-1α)/Vascular Endothelial Growth Factor (VEGF) Signaling Pathway.

BACKGROUND This study aimed to investigate the effects of hirudin on the production of extracellular matrix (ECM) factors by renal tubular epithelial cells in a rat model of diabetic kidney disease (DKD) and HK-2 human renal tubule epithelial cells. MATERIAL AND METHODS Sprague-Dawley rats were divided into the normal control group (n=10), the normal control+hirudin group (n=10), the DKD model group (n=12) and the DKD+hirudin group (n=12). At the end of the study, renal histopathology was undertaken, and the expression of type IV collagen, fibronectin, hypoxia-inducible factor-1alpha (HIF-1alpha), and vascular endothelial growth factor (VEGF) were evaluated using immunohistochemistry, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). HK-2 cells were cultured in glucose and treated with hirudin. Protein and mRNA expression of fibronectin, type IV collagen, HIF-1alpha, and VEGF were evaluated following knockdown or overexpression of HIF-1alpha. RESULTS Hirudin significantly improved renal function in the rat model of DKD (P<0.01), and significantly down-regulated the expression of fibronectin, type IV collagen, HIF-1alpha, and VEGF proteins (P<0.05). The expression of ECM associated proteins was increased in HK-2 cells treated with high glucose and reduced in the high glucose+shRNA HIF-1alpha group (P<0.05). Compared with the control group, the expression of ECM associated proteins was increased in the HIF-1alpha over-expressed group, and decreased following treatment with hirudin (P<0.05). CONCLUSIONS Hirudin reduced the expression of markers of ECM by inhibiting the HIF-1alpha/VEGF signaling pathway in DKD renal tubular epithelial cells.

Excessive gestational weight gain in the first trimester is associated with risk of gestational diabetes mellitus: a prospective study from Southwest China.

OBJECTIVE: To evaluate the effects of gestational weight gain (GWG) in the first trimester (GWG-F) and the rate of gestational weight gain in the second trimester (RGWG-S) on gestational diabetes mellitus (GDM), exploring the optimal GWG ranges for the avoidance of GDM in Chinese women. DESIGN: A population-based prospective study was conducted. Gestational weight was measured regularly in every antenatal visit and assessed by the Institute of Medicine (IOM) criteria (2009). GDM was assessed with the 75-g, 2-h oral glucose tolerance test at 24-28 weeks of gestation. Multivariable logistic regression was performed to assess the effects of GWG-F and RGWG-S on GDM, stratified by pre-pregnancy BMI. In each BMI category, the GWG values corresponding to the lowest prevalence of GDM were defined as the optimal GWG range. SETTING: Southwest China. PARTICIPANTS: Pregnant women (n 1910) in 2017. RESULTS: After adjusting for confounders, GWG-F above IOM recommendations increased the risk of GDM (OR; 95 % CI) among underweight (2·500; 1·106, 5·655), normal-weight (1·396; 1·023, 1·906) and overweight/obese women (3·017; 1·118, 8·138) compared with women within IOM recommendations. No significant difference was observed between RGWG-S and GDM (P > 0·05) after adjusting for GWG-F based on the previous model. The optimal GWG-F ranges for the avoidance of GDM were 0·8-1·2, 0·8-1·2 and 0·35-0·70 kg for underweight, normal-weight and overweight/obese women, respectively. CONCLUSIONS: Excessive GWG in the first trimester, rather than the second trimester, is associated with increased risk of GDM regardless of pre-pregnancy BMI. Obstetricians should provide more pre-emptive guidance in achieving adequate GWG-F.

Antibacterial Efficacy and Mechanism of Mannosylerythritol Lipids-A on Listeria monocytogenes.

Mannosylerythritol lipids-A (MEL-A) is a novel biosurfactant with excellent surface activity and potential biomedical applications. In this study, we explored the antibacterial activity and the underlying mechanisms of MEL-A against the important food-borne pathogen Listeria monocytogenes. The bacterial growth and survival assays revealed a remarkable antibacterial activity of MEL-A. Since MEL-A is a biosurfactant, we examined the cell membrane integrity and morphological changes of MEL-A-treated bacteria by biochemical assays and flow cytometry analysis and electron microscopes. The results showed obvious damaging effects of MEL-A on the cell membrane and morphology. To further explore the antibacterial mechanism of MEL-A, a transcriptome analysis was performed, which identified 528 differentially expressed genes (DEGs). Gene ontology (GO) analysis revealed that the gene categories of membrane, localization and transport were enriched among the DEGs, and the analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways demonstrated significant changes in the maltodextrin ABC transporter system and stress response system. Furthermore, the growth of L. monocytogenes could also be significantly inhibited by MEL-A in milk, a model of a real food system, suggesting that MEL-A could be potentially applied as an natural antimicrobial agent to control food-borne pathogens in the food industry.

[Anxiety and depression on gestational diabetes mellitus in early pregnancy].

OBJECTIVE: To investigate the effects of anxiety and depression on gestational diabetes mellitus(GDM) in early pregnancy. METHODS: A prospective study was conducted in 2017 to select 1426 single-child healthy pregnant women of 8-14 weeks from the Sichuan Provincial Hospital for Women and Children through a deliberate sampling method. The age was(28. 6±4. 0) years old. Basic information such as age, pre-pregnancy weight, parity, and gravidity of pregnant women was collected through questionnaire survey. The anxiety self-rating scale(SAS) and depression self-rating scale(SDS) were used to collect information of anxiety and depression in pregnant women, and their anxiety and depressive symptoms were evaluated according to the result of Chinese norm. At 24 to 28 weeks of gestation, the oral glucose tolerance test(OGTT) was conducted. GDM was diagnosed according to the Guidelines for the Diagnosis and Treatment of Pregnancy Diabetes in China(2014). Multivariate unconditional Logistic regression was adopted to analyze the effects of anxiety and depression on GDM in pregnant women. RESULTS: The incidence of GDM in early pregnancy anxiety group and depression group was 41. 8% and 33. 6%, respectively. The incidence of anxiety, depression, and anxiety combined with depression were 7. 7%, 10. 5% and 4. 8%, respectively. The incidence of anxiety and depression in the group of pregnant women younger than 30 years old(9. 0% and 11. 7%) was higher than that in the group of pregnant women older than 30 years old(5. 3% and 8. 1%). The prevalence of anxiety and depression in the group of nulliparous women(8. 8% and 11. 9%) was higher than that in the group of multiparous women(5. 4% and 6. 4%). The difference was statistically significant(P<0. 05). After adjusting the confounding factors such as age, pre-pregnancy body mass index, family history of diabetes, gravidity, parity, energy intake, conception, education, occupation, smoking and drinking, the result showed that the risk of GDM in anxious pregnant women was increased, compared with that in non-anxious pregnant women in early pregnancy(OR=1. 556, 95% CI 1. 014-2. 387). However, the association between early pregnancy depression and the occurrence of GDM was not found(P>0. 05). Compared with the non-anxiety group in the early pregnancy, the risk of GDM in the anxiety group was increased both in pregnant women under 30 years old(OR=1. 654, 95% CI 1. 004-2. 726) and nulliparous women(OR=1. 633, 95% CI 1. 013-2. 634). No correlation between anxiety and risk of GDM was observed in pregnant women over 30 years old and multiparous women(P>0. 05). CONCLUSION: Anxiety in early pregnancy increases the risk of GDM. Pregnant women under 30 years old and and nulliparous women are at high risk of anxiety.

[A Prospective Study of the Relationship Between Dietary Patterns during the Second Trimester of Pregnancy and Gestational Weight Gain].

OBJECTIVE: To study dietary patterns during the second trimester of pregnancy and to investigate the relationship between dietary patterns and gestational weight gain (GWG). METHODS: A prospective cohort study was conducted to select healthy singleton pregnant women at 8-14 weeks of gestation in a maternal and child health care institution in Chengdu city. Food items and quantities were collected at 8-14, 24-28, 32-36 weeks of gestation by using the 3-day 24-hour dietary recall and energy intakes were calculated. Dietary patterns during the second trimester were established by factor analysis and factor scores were calculated. The weight of pregnant women was measured at 8-14, 24-28 weeks of gestation and 1 week before delivery, and the total GWG and the GWG rates in the second and third trimesters were calculated. Multiple linear regression analyses were used to analyze the association between dietary patterns and GWG. RESULTS: A total of 1 004 samples were included. Three dietary patterns were identified: Milk-egg-whole grain pattern, Beverage-dessert pattern and Traditional pattern. The average total GWG was (13.2±4.5) kg. The average weight gain rate was (0.4±0.2) kg/week in the second trimester. The average weight gain rate was (0.5±0.3) kg/week in the third trimester. After adjusting for confounding factors including maternal age, body mass index before pregnancy, dietary energy intake, physical activity, multiple linear regression analysis showed that the factor score of Beverage-dessert pattern was positively associated with the total GWG and the weight gain rate in the third trimester ( ß=0.370, 95% confidence interval ( CI): (0.103, 0.636), P=0.007; ß=0.014, 95% CI: (0.000, 0.027), P=0.049, respectively), and the factor score of Traditional pattern was negatively associated with the total GWG ( ß=-0.285, 95% CI: (-0.555, -0.015), P=0.039). There was no association between the Milk-egg-whole grain pattern and GWG. CONCLUSION: Dietary patterns during the second trimester of pregnancy are associated with GWG. The Beverage-dessert pattern may increase the total GWG and weight gain rate in the third trimester. The traditional pattern may help control the total GWG.

[Associations of Dairy Consumption during Pregnancy and Neonatal Birth Body Mass: a Prospective Study].

OBJECTIVE: To investigate the dairy product intake during pregnancy in Southwest China and to explore its relationship with neonatal birth body mass. METHODS: A prospective study was conducted to select healthy singleton pregnant women at 8-14 weeks of gestation in a maternal and fetal health care institution in Chengdu City. Dairy product consumption during the first, second, third trimester of pregnancy were collected by 24-hour dietary recalls at 8-14 weeks, 24-28 weeks and 32-36 weeks of pregnancy, respectively, and the total milk intake and milk consumption rate were calculated. According to the dietary guidelines for Chinese pregnant women (2016), the recommended amount of milk (300 g/d) was used as the standard to calculate the compliance rate. The respondents were divided into three groups: no dairy consumption group, insufficient dairy consumption group and suitable dairy consumption group. The gestational age at delivery and neonatal birth body mass were collected by the hospital information system. Logistic regression model was used to analyze the association between milk intake during pregnancy and neonatal birth body mass. RESULTS: A total of 962 pregnant women were included. The average milk intake in the first, second and third trimester of pregnancy were 125.0 (0, 236.1) g/d, 208.3 (0, 284.7) g/d and 250.0 (150.0, 416.7) g/d, respectively, with the compliance rates of 12.6%, 33.2% and 48.4%, respectively. The average neonatal birth body mass was (3 225.0±399.8) g. The incidence of small for gestational age (SGA) and large for gestational age (LGA) was 8.3% and 3.9%, respectively. Compared with no dairy consumption group in the second trimester of pregnancy, the risk of SGA was lower in suitable dairy consumption group (odds ratio (OR)=0.786, 95% confidence interval (CI): 0.385-0.976). Compared with no dairy consumption group in the third trimester of pregnancy, the risk of SGA was lower in insufficient dairy consumption group and suitable dairy consumption group (OR=0.672, 95%CI: 0.477-0.821 and OR=0.497, 95%CI: 0.116-0.807, respectively). No association was observed between milk intake in the first trimester and neonatal birth body mass, and milk intake in the second and third trimester of pregnancy was not associated with the risk of LGA. CONCLUSION: Insufficient milk intake of pregnant women is a significant problem in southwest China and needs to be improved. Milk intake during pregnancy is associated with neonatal birth body mass, and increased milk intake in the second and third trimester of pregnancy may reduce the risk of SGA.

ERp44 depletion exacerbates ER stress and aggravates diabetic nephropathy in db/db mice.

Diabetic nephropathy (DN) is a major complication of diabetes, and the dysfunction of endoplasmic reticulum (ER) plays an important role in its pathogenesis. ERp44, an ER resident chaperone protein, has been implicated in the modulation of ER stress, however, its role and mechanism in DN are not determined. Here, we show that ERp44 expression is upregulated in the glomeruli of db/db mice, a rodent model of type 2 diabetes. When ERp44 is depleted by in vivo shRNA-mediated knockdown, the features associated with DN including albuminuria level and glomerular basement membrane (GBM) thickness are aggravated, therefore suggesting a detrimental role of ERp44 depletion in DN progression. We further show that ERp44 depletion exacerbates ER stress in DN in db/db mice, and that attenuating ER stress with the chemical chaperone TUDCA remarkably diminishes the aggravated DN features caused by ERp44 depletion. These results suggest that the exacerbated ER stress is a critical factor for the detrimental effect of ERp44 depletion on DN progression in db/db mice. Thus, our study links the role of ERp44 in DN with ER stress regulation and may offer a potential therapeutic strategy to interfere DN progression.

Visfatin regulates the production of lipopolysaccharide-induced inflammatory cytokines through p38 signaling in murine macrophages.

Visfatin plays an important role in regulation of inflammatory cytokines. However, the role of visfatin under bacterial stress condition is not fully explored yet. Therefore, the present study was conducted for the better understanding of the regulation mechanism of visfatin on the production of inflammatory cytokines under lipopolysaccharide (LPS) stress in RAW264.7 murine macrophages. Enzyme Linked Immuno-sorbent Assay (ELISA) results showed that, as compared to the control group, visfatin significantly up-regulated the levels of interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor (TNF)-α (P < 0.05). Compared to the LPS group, the levels of IL-1ß, IL-10, TNF-α was down-regulated in visfatin + LPS group (P < 0.05). After adding p38 inhibitor, SB203580 to culture, the production of IL-1ß, IL-6, IL-10, TNF-α was significantly reduced as compared to visfatin only (P < 0.01). The results showed that visfatin may regulate the production of IL-1ß, IL-6, IL-10, TNF-α through the p38 signaling pathway. As compared to the PBS group, phosphorylayed p38 (P-p38) level in visfatin group was significantly decreased (P < 0.05). Compared with LPS group, P-p38 level was significantly decreased in visfatin + LPS group (P < 0.05). Hence, it is concluded that visfatin can significantly increase the levels of IL-1ß, IL-10 and TNF-α in normal conditions, while their levels significantly decrease during inflammation. Moreover, visfatin participates in the inflammatory response through the p38 mitogen-activated protein kinase (MAPK) signal pathway by the up-regulation of p38 and down-regulation of P-p38 levels.

Urotensin II Induces ER Stress and EMT and Increase Extracellular Matrix Production in Renal Tubular Epithelial Cell in Early Diabetic Mice.

BACKGROUND/AIMS: Urotensin II (UII) and its receptor are highly expressed in the kidney tissue of patients with diabetic nephropathy (DN). The aim of this study is to examine the roles of UII in the induction of endoplasmic reticulum stress (ER stress) and Epithelial-mesenchymal transition (EMT) in DN in vivo and in vitro. METHODS: Kidney tissues were collected from patients with DN. C57BL/6 mice and mice with UII receptor knock out were injected with two consecutive doses of streptozotocin to induce diabetes and were sacrificed at 3th week for in vivo study. HK-2 cells in vitro were cultured and treated with UII. Markers of ER stress and EMT, fibronectin and type IV collagen were detected by immunohistochemistry, real time PCR and western blot. RESULTS: We found that the expressions of protein of UII, GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were upregulated while E-cadherin protein was downregulated as shown by immunohistochemistry or western blot analysis in kidney of diabetic mice in comparison to normal control; moreover expressions of GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were inhibited while E-caherin expression was enhanced in kidney in diabetic mice with UII receptor knock out in comparison to C57BL/6 diabetic mice. In HK-2 cells, UII induced upregulation of GRP78, CHOP, ALPHA-SMA, fibroblast-specifc protein 1(FSP-1), fibronectin and type collagen and downregulation of E-cadherin. UII receptor antagonist can block UII-induced ER stress and EMT; moreover, 4-PBA can inhibit the mRNA expression of ALPHA-SMA and FSP1 induced by UII in HK-2 cells. CONCLUSIONS: We are the first to verify UII induces ER stress and EMT and increase extracellular matrix production in renal tubular epithelial cell in early diabetic mice. Moreover, UII may induce renal tubular epithelial EMT via triggering ER stress pathway in vitro, which might be the new pathogenic pathway for the development of renal fibrosis in DN.