Iptakalim alleviates synaptic damages via targeting mitochondrial ATP-sensitive potassium channel in depression.

Synaptic plasticity damages play a crucial role in the onset and development of depression, especially in the hippocampus, which is more susceptible to stress and the most frequently studied brain region in depression. And, mitochondria have a major function in executing the complex processes of neurotransmission and plasticity. We have previously demonstrated that Iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could improve the depressive-like behavior in mice. But the underlying mechanisms are not well understood. The present study demonstrated that Ipt reversed depressive-like phenotype in vivo (chronic mild stress-induced mice model of depression) and in vitro (corticosterone-induced cellular model). Further study showed that Ipt could upregulate the synaptic-related proteins postsynaptic density 95 (PSD 95) and synaptophysin (SYN), and alleviated the synaptic structure damage. Moreover, Ipt could reverse the abnormal mitochondrial fission and fusion, as well as the reduced mitochondrial ATP production and collapse of mitochondrial membrane potential in depressive models. Knocking down the mitochondrial ATP-sensitive potassium (Mito-KATP) channel subunit MitoK partly blocked the above effects of Ipt. Therefore, our results reveal that Ipt can alleviate the abnormal mitochondrial dynamics and function depending on MitoK, contributing to improve synaptic plasticity and exert antidepressive effects. These findings provide a candidate compound and a novel target for antidepressive therapy.

Iptakalim improves cerebral microcirculation in mice after ischemic stroke by inhibiting pericyte contraction.

Pericytes are present tight around the intervals of capillaries, play an essential role in stabilizing the blood-brain barrier, regulating blood flow and immunomodulation, and persistent contraction of pericytes eventually leads to impaired blood flow and poor clinical outcomes in ischemic stroke. We previously show that iptakalim, an ATP-sensitive potassium (K-ATP) channel opener, exerts protective effects in neurons, and glia against ischemia-induced injury. In this study we investigated the impacts of iptakalim on pericytes contraction in stroke. Mice were subjected to cerebral artery occlusion (MCAO), then administered iptakalim (10 mg/kg, ip). We showed that iptakalim administration significantly promoted recovery of cerebral blood flow after cerebral ischemia and reperfusion. Furthermore, we found that iptakalim significantly inhibited pericytes contraction, decreased the number of obstructed capillaries, and improved cerebral microcirculation. Using a collagen gel contraction assay, we demonstrated that cultured pericytes subjected to oxygen-glucose deprivation (OGD) consistently contracted from 3 h till 24 h during reoxygenation, whereas iptakalim treatment (10 µM) notably restrained pericyte contraction from 6 h during reoxygenation. We further showed that iptakalim treatment promoted K-ATP channel opening via suppressing SUR2/EPAC1 complex formation. Consequently, it reduced calcium influx and ET-1 release. Taken together, our results demonstrate that iptakalim, targeted K-ATP channels, can improve microvascular disturbance by inhibiting pericyte contraction after ischemic stroke. Our work reveals that iptakalim might be developed as a promising pericyte regulator for treatment of stroke.

Oridonin prevents oxidative stress-induced endothelial injury via promoting Nrf-2 pathway in ischaemic stroke.

Oridonin, a natural diterpenoid compound extracted from a Chinese herb, has been proved to exert anti-oxidative stress effects in various disease models. The aim of the present study was to investigate the protective effects of oridonin on oxidative stress-induced endothelial injury in ischaemic stroke. We found oridonin repaired blood-brain barrier (BBB) integrity presented with upregulation of tight junction proteins (TJ proteins) expression, inhibited the infiltration of periphery inflammatory cells and neuroinflammation and thereby reduced infarct volume in ischaemic stroke mice. Furthermore, our results showed that oridonin could protect against oxidative stress-induced endothelial injury via promoting nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf-2). The specific mechanism could be the activation of AKT(Ser473)/GSK3ß(Ser9)/Fyn signalling pathway. Our findings revealed the therapeutic effect and mechanism of oridonin in ischaemic stroke, which provided fundamental evidence for developing the extracted compound of Chinese herbal medicine into an innovative drug for ischaemic stroke treatment.

Automated cartilage segmentation and quantification using 3D ultrashort echo time (UTE) cones MR imaging with deep convolutional neural networks.

OBJECTIVE: To develop a fully automated full-thickness cartilage segmentation and mapping of T1, T1ρ, and T2*, as well as macromolecular fraction (MMF) by combining a series of quantitative 3D ultrashort echo time (UTE) cones MR imaging with a transfer learning-based U-Net convolutional neural networks (CNN) model. METHODS: Sixty-five participants (20 normal, 29 doubtful-minimal osteoarthritis (OA), and 16 moderate-severe OA) were scanned using 3D UTE cones T1 (Cones-T1), adiabatic T1ρ (Cones-AdiabT1ρ), T2* (Cones-T2*), and magnetization transfer (Cones-MT) sequences at 3 T. Manual segmentation was performed by two experienced radiologists, and automatic segmentation was completed using the proposed U-Net CNN model. The accuracy of cartilage segmentation was evaluated using the Dice score and volumetric overlap error (VOE). Pearson correlation coefficient and intraclass correlation coefficient (ICC) were calculated to evaluate the consistency of quantitative MR parameters extracted from automatic and manual segmentations. UTE biomarkers were compared among different subject groups using one-way ANOVA. RESULTS: The U-Net CNN model provided reliable cartilage segmentation with a mean Dice score of 0.82 and a mean VOE of 29.86%. The consistency of Cones-T1, Cones-AdiabT1ρ, Cones-T2*, and MMF calculated using automatic and manual segmentations ranged from 0.91 to 0.99 for Pearson correlation coefficients, and from 0.91 to 0.96 for ICCs, respectively. Significant increases in Cones-T1, Cones-AdiabT1ρ, and Cones-T2* (p < 0.05) and a decrease in MMF (p < 0.001) were observed in doubtful-minimal OA and/or moderate-severe OA over normal controls. CONCLUSION: Quantitative 3D UTE cones MR imaging combined with the proposed U-Net CNN model allows a fully automated comprehensive assessment of articular cartilage. KEY POINTS: • 3D UTE cones imaging combined with U-Net CNN model was able to provide fully automated cartilage segmentation. • UTE parameters obtained from automatic segmentation were able to reliably provide a quantitative assessment of cartilage.

Recognizing the Chinese Pioneer of Neuraxial Labor Analgesia: Dr Guang-Bo Zhang and Her Unpublished Manuscript From More Than a Half-Century Ago.

Dr Guang-Bo Zhang was the first anesthesiologist to administer and study the effects of labor epidural analgesia in China. Between September 1963 and March 1964, she conducted an observational study evaluating the effects of neuraxial analgesia for laboring women. She presented her research and prepared an article; however, due to the Great Proletarian Cultural Revolution (Cultural Revolution), which began in 1966, her work went unpublished. She successfully preserved her unpublished article, notes, and slides throughout the Cultural Revolution by hiding them in a countryside location near Beijing. These 54-year-old, previously unpublished documents represent the first known clinical trial of neuraxial labor analgesia conducted in China.

High glucose downregulates the effects of autophagy on osteoclastogenesis via the AMPK/mTOR/ULK1 pathway.

Diabetes is a chronic disease that disrupts the balance between bone formation and bone desorption, which can lead to osteoporosis, increasing the risk of fracture. However, compared with osteoblasts, the biological effects of hyperglycemia on osteoclastogenesis remain to be elucidated. Therefore, we investigated the impact of glucose at different concentrations (5.5, 10.5, 15.5, 20.5, 25.5, and 30.5 mM) on osteoclastogenesis using RAW264.7 cells. Cell proliferation was measured with the cell counting kit-8 assay, and osteoclastogenesis was detected with tartrate-resistant acid phosphatase staining and bone resorption assays, as well as protein cathepsin K expression. Compound C, the AMP-activated protein kinase (AMPK) pathway inhibitor, was used to examine the relationship between the AMPK/mTOR/ULK1 signaling pathway and autophagy in osteoclasts. Autophagy was evaluated with transmission electron microscopy and immunofluorescence microscopy and associated proteins were detected with western blotting. The pharmacological autophagic reagents bafilomycin A1, 3-methyladenine, and rapamycin were used to determine the effect of autophagy on osteoclastogenesis. Our results showed that glucose negatively affected osteoclast formation and function but did not affect the proliferation of RAW264.7 cells. Suppression of the AMPK/mTOR/ULK1 signaling axis decreased autophagy in glucose-mediated osteoclast. Furthermore, High levels of glucose decreased autophagy level in osteoclasts. Additionally, interfering with autophagy affected osteoclast formation and function. These findings clarify the mechanisms underlying the effects of glucose-mediated osteoclastogenesis and will help identify novel therapeutic strategies for the protection of skeletal health in diabetic osteoporosis.

[Effects of intrathecal injection of IRF8 SiRNA on pain threshold and activation of spinal cord microglia in rats with postoperative persistent pain].

Objective: To investigate the effects of intrathecal injection of IRF8 SiRNA on the pain threshold and activation of spinal cord microglia in rats with postoperative persistent pain. Methods: One hundred and twenty male Sprague-Dawley rats were randomly divided into sham group (SH, n=12), SMIR group (SM, n=48), SMIR + DEPC group (SD, n=12) and SMIR + irf8 SiRNA group (SS, n=48). In the SM group, the persistent postsurgical pain(PPsP) model was established according to the skin/muscle incision and retraction (SMIR), and the SH group was only incised without retracted. The SD group and SS group received intrathecal catheterization one week before SMIR, the SS group was injected with 20 µl of IRF8 SiRNA solution (dissolved in DEPC-treated water, 150 pmol) intrathecally on the 5th and 6th day after SMIR, and the SD group was injected with the same amount of DEPC-treated water. The paw withdrawal threshold (PWT) of each group was measured and recorded before SMIR and on the 1st, 3rd, 7th, 12th, 22nd and 33rd days after SMIR. Western blot was used to detect the expression of Iba-1 in the dorsal horn of spinal cord on the 12th days after SMIR, and the saphenous nerves in the SH group and SM group were collected to observe their ultrastructural changes under electron microscope. The flow cytometry was used to detect the activation of microglia in spinal cord dorsal horn before SMIR and on the 1st, 3rd, 7th, 12th, 22nd and 33rd days after SMIR in the SM group and SS group. Results: Compared with D0, the PWT of SM group was decreased on the 1th to 22nd day after SMIR (P＜0.05 or P＜0.01), and returned to normal level on the 33rd day after SMIR (P＞ 0.05). Compared with the SH group, the PWT of the SM group was decreased on the 1th to 22nd day after SMIR (P＜0.05 or P＜ 0.01). However, compared with the SD group, the PWT of the SS group was increased on the 7th to 22nd day after SMIR (P＜0.05 or P＜0.01). Compared with SH group, the PWT of SS group was decreased on the 7th to 22nd day after SMIR (P＜0.05 or P＜0.01). The average thickness of saphenous nerve myelin was (377.0 3±69.60) nm in the SH group and (369.50±73.26) nm in the SM group, and there was no significant difference between the two groups (P＞0.05). Compared with the SH group, the expression level of Iba-1 was increased significantly (P＜0.01) in the SM group. Compared with the SD group, the expression of Iba-1 was inhibited (P＜0.05) in the SS group, and compared with the SH group, the expression of Iba-1 was also statistically different (P＜0.05) in the SS group, while the expression of Iba-1 was not statistically significant between the SM group and the SD group (P＞0.05). Compared with D0, the activation ratio of microglia was increased significantly on the 3rd to 22nd day after SMIR (P＜0.01) in the SM group , while the activation of microglia reached a peak on 3rd day after SMIR (P＜0.01) in the SS group. After intrathecal administration, the activation rate of microglia in the spinal dorsal horn of the SS group was decreased significantly, and compared with the SM group, it was decreased significantly on the 7th to 12th day after SMIR (P＜0.01). Conclusion: The significant and persistent mechanical hyperalgesia in PPsP induced by SMIR was caused non-obvious peripheral nerve injury, which may be mediated by the activation of microglia in the dorsal horn of the spinal cord. IRF8 SiRNA administrated by intrathecal injection could inhibit the activation of microglia and reverse SMIR-induced hyperalgesia.

Neuronal extracellular vesicle derived miR-98 prevents salvageable neurons from microglial phagocytosis in acute ischemic stroke.

Extracellular vesicles (EVs), as a novel intercellular communication carrier transferring cargo microRNAs (miRNAs), could play important roles in the brain remodeling process after ischemic stroke. However, the detailed mechanisms involved in EVs derived miRNAs-mediated cellular interactions in the brain remain unclear. Several studies indicated that microRNA-98 (miR-98) might participate in the pathogenesis of ischemic stroke. Here, we showed that expression of miR-98 in penumbra field kept up on the first day but dropped sharply on the 3rd day after ischemic stroke in rats, indicating that miR-98 could function as an endogenous protective factor post-ischemia. Overexpression of miR-98 targeted inhibiting platelet activating factor receptor-mediated microglial phagocytosis to attenuate neuronal death. Furthermore, we showed that neurons transferred miR-98 to microglia via EVs secretion after ischemic stroke, to prevent the stress-but-viable neurons from microglial phagocytosis. Therefore, we reveal that EVs derived miR-98 act as an intercellular signal mediating neurons and microglia communication during the brain remodeling after ischemic stroke. The present work provides a novel insight into the roles of EVs in the stroke pathogenesis and a new EVs-miRNAs-based therapeutic strategy for stroke.

Expert consensus of Chinese Association for the Study of Pain on the application of ozone therapy in pain medicine.

This consensus was compiled by first-line clinical experts in the field of pain medicine and was organized by the Chinese Association for the Study of Pain. To reach this consensus, we consulted a wide range of opinions and conducted in-depth discussions on the mechanism, indications, contraindications, operational specifications and adverse reactions of ozone iatrotechnique in the treatment of pain disorders. We also referred to related previous preclinical and clinical studies published in recent years worldwide. The purpose of this consensus is to standardize the rational application of ozone iatrotechnique in pain treatment, to improve its efficacy and safety and to reduce and prevent adverse reactions and complications in this process.

Lipoxin A(4) inhibited hepatocyte growth factor-induced invasion of human hepatoma cells.

AIM: Inflammation is a critical component of tumor progression. Lipoxin A(4) (LXA(4)) has been approved for potent anti-inflammatory properties. Recently, it was reported that LXA(4) repressed the expression and activity of cyclooxygenase-2 (COX-2), which is essential for invasion. However, there are few reports dealing with its effects on cancer. To explore whether LXA(4) regulate invasion, the effects of LXA(4) and its receptor agonist BML-111 on hepatocyte growth factor (HGF)-induced invasion of hepatoma cells and the possible mechanisms were researched. METHODS: Lipoxin A(4) receptor (ALX) expression in HepG2 cells were measured through reverse transcription polymerase chain reaction and western blot. Cytotoxicity of LXA(4) and BML-111 to HepG2 cells was detected by MTT and ((3)H)-TdR incorporation assay. Cell migration and invasion assays were performed using a Boyden chemotaxis chamber. COX-2 expression was detected by real-time polymerase chain reaction and western blot, respectively. Moreover, the expressions of matrix metalloproteinases (MMP)-2, MMP-9, IkappaBalpha and nuclear factor-kappaB (NF-kappaB) p65 were observed via western blot, and NF-kappaB transcriptional activity was tested by transfections and luciferase activities assay. RESULTS: ALX expression was detected in HepG2 cells, and suitable concentrations of LXA(4) and BML-111 had no cytotoxicity to cells. LXA(4) and BML-111 inhibited HGF-induced migration and invasion; downregulated COX-2, MMP-2 and -9; restrained HGF-induced IkappaBalpha degradation, NF-kappaB translocation and the transcriptional activity of NF-kappaB in HepG2 cells. Furthermore, exogenous PGE2 could reverse the inhibitory effects of LXA(4) also BML-111 on HGF-induced invasion and migration partially. CONCLUSION: LXA(4) inhibited HGF-induced invasion of HepG2 cells through NF-kappaB/COX-2 signaling pathway partially.

Effect of lncRNA HULC knockdown on rat secreting pituitary adenoma GH3 cells.

Pituitary adenoma is one of the most common tumors in the neuroendocrine system. This study investigated the effects of long non-coding RNAs (lncRNAs) highly up-regulated in liver cancer (HULC) on rat secreting pituitary adenoma GH3 cell viability, migration, invasion, apoptosis, and hormone secretion, as well as the underlying potential mechanisms. Cell transfection and qRT-PCR were used to change and measure the expression levels of HULC, miR-130b, and FOXM1. Cell viability, migration, invasion, and apoptosis were assessed using trypan blue staining assay, MTT assay, two-chamber transwell assay, Guava Nexin assay, and western blotting. The concentrations of prolactin (PRL) and growth hormone (GH) in culture supernatant of GH3 cells were assessed using ELISA. The targeting relationship between miR-130b and FOXM1 was verified using dual luciferase activity. Finally, the expression levels of key factors involved in PI3K/AKT/mTOR and JAK1/STAT3 pathways were evaluated using western blotting. We found that HULC was highly expressed in GH3 cells. Overexpression of HULC promoted GH3 cell viability, migration, invasion, PRL and GH secretion, as well as activated PI3K/AKT/mTOR and JAK1/STAT3 pathways. Knockdown of HULC had opposite effects and induced cell apoptosis. HULC negatively regulated the expression of miR-130b, and miR-130b participated in the effects of HULC on GH3 cells. FOXM1 was a target gene of miR-130b, which was involved in the regulation of GH3 cell viability, migration, invasion, and apoptosis, as well as PI3K/AKT/mTOR and JAK1/STAT3 pathways. In conclusion, HULC tumor-promoting roles in secreting pituitary adenoma might be via down-regulating miR-130b, up-regulating FOXM1, and activating PI3K/AKT/mTOR and JAK1/STAT3 pathways.

Value of fasting plasma glucose to screen gestational diabetes mellitus before the 24th gestational week in women with different pre-pregnancy body mass index.

BACKGROUND: Gestational diabetes mellitus (GDM) is usually diagnosed between 24th and 28th gestational week using the 75-g oral glucose tolerance test (OGTT). It is difficult to predict GDM before 24th gestational week because fast plasma glucose (FPG) decreases as the gestational age increases. It is controversial that if FPG ≥5.1 mmol/L before 24th gestational week should be intervened or not. The aim of this study was to evaluate the value of FPG to screen GDM before 24th gestational week in women with different pre-pregnancy body mass index (BMI). METHODS: This was a multi-region retrospective cohort study in China. Women who had a singleton live birth between June 20, 2013 and November 30, 2014, resided in Beijing, Guangzhou and Chengdu, and received prenatal care in 21 selected hospitals, were included in this study. Pre-pregnancy BMI, FPG before the 24th gestational week, and one-step GDM screening with 75 g-OGTT at the 24th to 28th gestational weeks were extracted from medical charts and analyzed. The pregnant women were classified into four groups based on pre-pregnancy BMI: Group A (underweight, BMI < 18.5 kg/m), Group B (normal, BMI 18.5-23.9 kg/m), Group C (overweight, BMI 24.0-27.9 kg/m) and Group D (obesity, BMI ≥28.0 kg/m). The trend of FPG before 24th week of gestation was described, and the sensitivity and specificity of using FPG before the 24th gestational week to diagnose GDM among different pre-pregnancy BMI groups were reported. Differences in the means between groups were evaluated using independent sample t-test and analysis of variance. Pearson Chi-square test was used for categorical variables. RESULTS: The prevalence of GDM was 20.0% (6806/34,087) in the study population. FPG decreased gradually as the gestational age increased in all pre-pregnancy BMI groups until the 19th gestational week. FPG was higher in women with higher pre-pregnancy BMI. FPG before the 24th gestational week and pre-pregnancy BMI could be used to predict GDM. The incidence of GDM in women with FPG ≥5.10 mmol/L in the 19th to 24th gestational weeks and pre-pregnancy overweight or obesity was significantly higher than that in women with FPG ≥5.10 mmol/L and pre-pregnancy BMI <24.0 kg/m (78.5% [62/79] vs. 52.9% [64/121], χ = 13.425, P < 0.001). CONCLUSIONS: FPG decreased gradually as the gestational age increased in all pre-pregnancy BMI groups until the 19th gestational week. Pre-pregnancy overweight or obesity was associated with an increased FPG value before the 24th gestational week. FPG ≥5.10 mmol/L between 19 and 24 gestational weeks should be treated as GDM in women with pre-pregnancy overweight and obesity.

Catechin protects rat cardiomyocytes from hypoxia-induced injury by regulating microRNA-92a.

Background: Myocardial infarction (MI) is a serious condition, caused by acute, persistent ischemia or hypoxia of a coronary artery and responsible for heart failure and sudden death. This study aimed to investigate the effects of catechin, one of the main active components of green tea, on hypoxia-induced MI cell model, as well as the underlying possible mechanism. Methods: Cell viability, proliferation, apoptosis, and the expression of microRNA-92a (miR-92a) after hypoxia stimulation and/or catechin treatment were assessed using cell counting kit-8 (CCK-8) assay, western blotting, annexin V-FITC/PI staining and qRT-PCR, respectively. miRNA transfection was performed to change the expression of miR-92a. The effects of miR-92a on hypoxia and catechin-treated H9c2 cell viability, proliferation and apoptosis were evaluated. Finally, western blotting was conducted to measure the expression of core factors in the c-Jun N-terminal kinase (JNK) signaling pathway. Results: Hypoxia stimulation significantly inhibited H9c2 cell viability and proliferation, induced cell apoptosis and up-regulated miR-92a expression. Catechin markedly protected H9c2 cells from hypoxia-induced viability loss, proliferation inhibition, and apoptosis enhance, as well as miR-92a expression increase. Furthermore, suppression of miR-92a enhanced the protective effects of catechin on hypoxia-induced H9c2 cells. Overexpression of miR-92a had opposite effects. Catechin activated the JNK pathway in H9c2 cells by down-regulating miR-92a. Conclusion: Catechin protected H9c2 cells from hypoxia-induced injury by regulating miR-92a and JNK signaling pathway. Our findings facilitate the understanding of the protective activity of catechin in hypoxia-induced MI cell injury and provide a theoretical basis for further explore treatment of MI by using catechin.

Analysis of correlation factors and pregnancy outcomes of hypertensive disorders of pregnancy - a secondary analysis of a random sampling in Beijing, China.

OBJECTIVE: We aimed to assess the prevalence and risk factors for hypertensive disorders and to study the main pregnancy outcomes in the Beijing area of China. STUDY DESIGN: This study randomly sampled 15 hospitals in Beijing from Jun 2013 to Nov 2013 and evaluated 15 194 deliveries. Logistic regression analysis was used to study the association between risk factors and hypertensive disorders. Pregnancy outcomes included preterm birth, cesarean delivery and small for gestational age (SGA). RESULTS: The prevalence of hypertensive disorders, preeclampsia (PE) and severe PE was 4.4, 2.7 and 1.8%, respectively. The risk factors for hypertensive disorders and severe PE were maternal body mass index before pregnancy, gestational weight gain (GWG), gestational diabetes and pre-gestational diabetes, and third trimester cholesterol (CHOL) levels. First trimester high-density lipoprotein was a protective factor for severe PE. The incidence of hypertensive disorders increased with maternal age. Preterm delivery, cesarean delivery and small infant size for gestational age were more prevalent in the severe PE group compared with the non-hypertensive group. CONCLUSIONS: In the Beijing area of China, maternal body mass index before pregnancy, GWG, maternal complications of gestational diabetes and pre-gestational diabetes, and third trimester CHOL levels are risk factors for both hypertensive disorders of pregnancy and severe PE. First trimester high-density lipoprotein is a protective factor for severe PE. Severe preeclampsia leads to a higher incidence of preterm delivery, cesarean delivery and SGA infants.

Risk of adverse pregnancy outcomes stratified for pre-pregnancy body mass index.

OBJECTIVE: To estimate the risk of adverse maternal and perinatal outcomes in women with different pre-pregnancy body mass index (BMI). METHODS: We conducted a cohort study with 14 451 singleton pregnancies in 15 medical centers in Beijing between 20 June 2013 and 30 November 2013 using cluster random sampling. We divided participants into four groups based on pre-pregnancy BMI: Group A (underweight): BMI < 18.5 kg/m(2), Group B (normal): 18.5-23.9 kg/m(2), Group C (overweight): 24-27.9 kg/m(2), Group D (obesity): ≥28 kg/m(2). We used multivariate analysis to evaluate the association of the risk of adverse pregnancy outcomes and pre-pregnancy BMI. RESULTS: The prevalence of maternal overweight and obesity was 14.82% (2142/14 451) and 4.71% (680/14 451) in the study population, respectively. Higher pre-pregnancy BMI is associated with higher prevalence of gestational diabetes (GDM), macrosomia, Cesarean section (C-section), preeclampsia and postpartum hemorrhage. Pre-pregnancy overweight or obesity increases the risk of adverse pregnancy outcomes, regardless of GDM status. CONCLUSIONS: Pre-pregnancy overweight or obesity is associated with increased risk of adverse pregnancy outcomes. Nutrition counseling is recommended before pregnancy in women who have overweight or obesity.

Lipoxin A4 inhibits NF-κB activation and cell cycle progression in RAW264.7 cells.

Lipoxins (LXs), including lipoxin A4 (LXA4), etc., have been approved for potent anti-inflammatory and immunomodulatory properties. Based on the important roles of macrophages in inflammation and immunomodulation, we investigate the effects of LXA4 on lipopolysaccharide (LPS)-induced proliferation and the possible signal transduction pathways in RAW264.7 macrophages. RAW264.7 cells were treated in vitro with or without LPS in the absence or presence of LXA4. [(3)H]-TdR incorporation assay and flow cytometry were used for detecting cell proliferation and cycle, respectively. Moreover, Western blot was applied to evaluate the protein expression levels of Cyclin E, IκBα, nuclear factor-κB (NF-κB), and IκB kinase (IKK). Our research showed that LXA4 suppressed LPS-induced proliferation, increased the proportion of the G0/G1 phase, decreased the proportion of the S phase, and downregulated the expression of Cyclin E. Besides these, LXA4 suppressed LPS-induced IκBα degradation, NF-κB translocation, and the expression of IKK. The data suggested that LXA4 inhibited LPS-induced proliferation through the G0/G1 phase arrest in RAW264.7 macrophages, and the inhibitory effect might depend on NF-κB signaling transduction pathway.

Effect of lncRNA HULC knockdown on rat secreting pituitary adenoma GH3 cells

Pituitary adenoma is one of the most common tumors in the neuroendocrine system. This study investigated the effects of long non-coding RNAs (lncRNAs) highly up-regulated in liver cancer (HULC) on rat secreting pituitary adenoma GH3 cell viability, migration, invasion, apoptosis, and hormone secretion, as well as the underlying potential mechanisms. Cell transfection and qRT-PCR were used to change and measure the expression levels of HULC, miR-130b, and FOXM1. Cell viability, migration, invasion, and apoptosis were assessed using trypan blue staining assay, MTT assay, two-chamber transwell assay, Guava Nexin assay, and western blotting. The concentrations of prolactin (PRL) and growth hormone (GH) in culture supernatant of GH3 cells were assessed using ELISA. The targeting relationship between miR-130b and FOXM1 was verified using dual luciferase activity. Finally, the expression levels of key factors involved in PI3K/AKT/mTOR and JAK1/STAT3 pathways were evaluated using western blotting. We found that HULC was highly expressed in GH3 cells. Overexpression of HULC promoted GH3 cell viability, migration, invasion, PRL and GH secretion, as well as activated PI3K/AKT/mTOR and JAK1/STAT3 pathways. Knockdown of HULC had opposite effects and induced cell apoptosis. HULC negatively regulated the expression of miR-130b, and miR-130b participated in the effects of HULC on GH3 cells. FOXM1 was a target gene of miR-130b, which was involved in the regulation of GH3 cell viability, migration, invasion, and apoptosis, as well as PI3K/AKT/mTOR and JAK1/STAT3 pathways. In conclusion, HULC tumor-promoting roles in secreting pituitary adenoma might be via down-regulating miR-130b, up-regulating FOXM1, and activating PI3K/AKT/mTOR and JAK1/STAT3 pathways.

BML-11, a lipoxin receptor agonist, protected carbon tetrachloride-induced hepatic fibrosis in rats.

Inflammation plays an important role in the occurrence and development of fibrosis. Lipoxins (LXs) and BML-111 (lipoxin A4 agonist) have been approved for potent anti-inflammatory properties. Previously, we and others had showed LXs and BML-111 could protect acute hepatic injury, inhibit the growth and invasion of hepatic tumor. However, there are few reports dealing with their effects on hepatic fibrosis. To explore whether LXs and the analog could interrupt the process of hepatic fibrosis, the effects of BML-111 on tetrachloride-induced hepatic fibrosis were observed and the possible mechanism were discussed. Sprague-Dawley rats were induced liver fibrosis by carbon tetrachloride (CCl4) for 10 weeks with or without BML-111, and the histopathology and collagen content were employed to quantify hepatic necro-inflammation and fibrosis. Moreover, the expression levels of α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1), and platelet-derived growth factor (PDGF) were examined via Western blot or ELISA. Rats treated with BML-111 improved hepatic necro-inflammation and inhibited hepatic fibrosis in association with reduction of α-SMA expression and decreased collagen deposition. Furthermore, BML-111 could downregulate the expressions of TGF-ß1 and PDGF significantly. BML-111 played a critical protective role in CCl4-induced hepatic fibrosis through inhibiting the levels of TGF-ß1 and PDGF in rats.