Role and mechanism of the p-JAK2/p-STAT3 signaling pathway in follicular development in PCOS rats.

OBJECTIVE: To identify the association between the phosphorylated Janus kinase 2/phosphorylated signal transducer and activator of transcription (p-JAK2/p-STAT3) signaling pathway and follicular development in polycystic ovary syndrome (PCOS) rats, and explore the underlying mechanism. To evaluate the role of exogenous JAK2 inhibitor AG490 in the model and the associations among luteinizing hormone/choriogonadotropin receptor (LHCGR), follicle-stimulating hormone receptor (FSHR), cytochrome P450 17α (CYP17a), cytochrome P450 19 (CYP19), and PCOS. RESULTS: Rat models of PCOS was established. PCOS rats were intraperitoneally treated with double-distilled water (ddH2O)/DMSO/AG490. The rate of ovarian morphological recovery in the AG490 group was significantly higher compared with the DMSO group (83.3 % vs 9.1 %, X2 = 12.68, P < 0.001). Moreover, the short in the time the estrous cycle was resumed in the AG490 group (hazard ratio = 16.32, P < 0.001) compared with the DMSO group. Compared with the controls, p-JAK2, p-STAT3, LHCGR, and CYP17a expression levels were increased whereas that of FSHR and CYP19 were decreased in the ovaries of PCOS rats. However, an opposite trend was observed after treatment with AG490. Software prediction revealed that the p-STAT3 bound to the promoter regions of LHCGR, FSHR, CYP17a, and CYP19 genes. This finding was confirmed by results of correlation analysis (R = 0.834, -0.836, 0.875 and -0.712, respectively, all P < 0.001). CONCLUSION: This study demonstrated that the p-JAK2/p-STAT3 signaling pathway was involved in follicular development in PCOS rats by upregulating LHCGR and CYP17a expression, and downregulating that of FSHR and CYP19. AG490 treatment exerted beneficial effects. LHCGR, FSHR, CYP17a, and CYP19 are candidate genes associated with follicular development in PCOS rats.

Experimental and numerical investigation of stiffened angle connection in a minor axis.

The bolted angle connections which are simple, fast, cost-effective, high quality, and no site welding have been recognized as their excellent performance. The moment-rotation behavior of both major and minor axis should be both taken into considering, however, the lack of research on minor axis limits the more comprehensive application. Five monotonic tests were carried out to investigate the influence under different parameters, and a new type connection were considered and detailed. Refined finite element models were built to validate the experimental results and to do several parametric analyses on initial rotational stiffness and plastic moment resistance, including of a presence of stiffened seat angle, angle thickness, and prying force. Furthermore, a new simplified plate method was proposed for calculating stiffness of stiffened angle and web in bending. The stiffened angle gives a significant increase at the moment-resisting capacity and the initial stiffness, the ultimate rotation of all tested specimens was beyond 0.067rad. The initial stiffness and plastic moment resistance of the joints were also controlled by the column web. The presence of the stiffener in the compression zone has the none effect on initial stiffness. The numerical analysis has captured the failure reason for weld and more attention should be paid to welding of stiffener in engineering design and practice. Adding stiffener at the top-and-seat angle joint can reduce the prying force of bolt, but it still cannot be ignored. The theoretical results were in good agreement with the experimental data and finite element results; therefore, it can be used to guide the design and selection of joints.

CoQ10 alleviate preeclampsia symptoms by enhancing the function of mitochondria in the placenta of pregnant rats with preeclampsia.

Objective: To assess whether supplementation with Coenzyme Q10 (CoQ10) during pregnancy alleviate preeclampsia symptoms and the underlying mechanism in the rats with preeclampsia. Methods: Forty-five pregnant Wistar rats were equally divided into three groups randomly and received subcutaneous saline injection (control group, n = 15) or 200 mg/kg L-NAME injection to induce preeclampsia symptoms (PE group, n = 30). The PE rats were treated by distilled water (PE+DW group, n = 15) and CoQ10 (PE+CoQ10 group, n = 15) on day 15 to 21 of gestation randomly. Physiological characteristics such as urine volume, total urine protein, blood pressure, number and weight of pups were recorded. Fluorescent dye was used to detect mitochondrial membrane potential in placenta. Real-time fluorescent quantitative PCR was used to detect the expression of mitochondrial DNA(mtDNA) in placenta. Results: There was no statistic difference among all the three groups on day 10 of gestation in SBP and 24-h proteinuria (P > 0.05). Whereas, SBP and 24-h proteinuria were significantly higher in PE group than control group on day 15 and 21 of gestation (P < 0.05). SBP and 24-h proteinuria were significantly lower in PE+CoQ10 group than PE+DW group on day 21 of gestation (P < 0.05). The number and weight of normal pups were significantly lower in PE group than the control group (P < 0.05), which were most notably in distilled water group, and the number and weight of normal pups were markedly bigger in PE+CoQ10 group rats compared to PE+DW (P < 0.05). The PE+CoQ10 group showed a significantly higher in level of mitochondrial membrane potential than PE+DW group. The expression of mtDNA was significantly higher in the PE+CoQ10 group compared with PE+DW group (P < 0.05). Conclusions: CoQ10 can alleviate preeclampsia symptoms and enhance the function of mitochondria in the placenta.

Mutual regulation between miR-21 and the TGFß/Smad signaling pathway in human bronchial fibroblasts promotes airway remodeling.

OBJECTIVE: Airway remodeling is an important pathological feature of asthma. Excessive deposition of extracellular matrix (e.g., collagen) secreted from fibroblasts is a major factor contributing to airway remodeling. Currently, the mechanism by which collagen continues to be oversynthesized in the airway remains unclear. In this study, we investigated the role of the microRNA-21 (miR-21) and TGFß/Smad signaling pathway in human bronchial fibroblasts (HBFs), and explored the regulatory mechanism of airway remodeling. METHODS: HBFs were cultured in vitro and treated with the transforming growth factor ß (TGFß), receptor inhibitor (SB431542), and TGFß1. miR-21 and Smad7 overexpressing lentiviruses, as well as an miR-21 interfering lentivirus were constructed and transfected into HBFs. Western blotting was used to determine the expression of airway remodeling-related proteins and proteins in the TGFß/Smad signaling pathway. miR-21 expression was measured by quantitative real-time PCR. RESULTS: The high expression of miR-21 induced by TGFß1 was reduced following the treatment with the SB431542 in HBFs. Smad7 overexpression inhibited the elevated expression of the COL I protein induced by miR-21 overexpression in HBFs. Inhibiting miR-21 expression upregulated the level of Smad7 protein, thus reducing the expression of airway remodeling-related proteins induced by TGFß1 stimulation in HBFs. CONCLUSIONS: TGFß1 can induce miR-21 expression in HBFs through the TGFß/Smad signaling pathway to promote airway remodeling. miR-21 downregulates Smad7, activates the TGFß/Smad signaling pathway, and promotes airway remodeling. Mutual regulation between miR-21 and the TGFß/Smad signaling pathway in HBFs promotes airway remodeling.

[Changes in serum inflammatory factors in wheezing infants with community-acquired pneumonia].

OBJECTIVE: To study whether infantile wheezing pneumonia has similar immune mechanisms to asthma by determining the levels of serum inflammatory factors in wheezing infants with community-acquired pneumonia (CAP). METHODS: Forty-two infants with CAP but without wheezing, 47 infants with CAP and wheezing, and 30 healthy infants as a control were recruited in the study. The peripheral blood levels of C-reactive protein, procalcitonin, soluble triggering receptor expressed on myeloid cell-l, interferon-γ, interleukin-4, interleukin-10, and periostin were compared in the three groups. RESULTS: The serum levels of procalcitonin, soluble triggering receptor expressed on myeloid cell-l, interleukin-4 and interleukin-10 in the two CAP groups were higher than in the control group (P<0.05). The ratio of interferon-γ/interleukin-4 in the wheezing pneumonia group was lower than in the non-wheezing pneumonia and control groups (P<0.05). The serum level of periostin in the wheezing pneumonia group was higher than in the non-wheezing pneumonia and control groups (P<0.05). CONCLUSIONS: The unbalanced ratio of interferon-γ/interleukin-4 and airway eosinophilic inflammation in wheezing infants with pneumonia suggest infantile pneumonia with wheezing may has similar immune mechanisms to asthma.

[Roles of allergen testing in vitro and impulse oscillometry for lung function measurements in children with cough variant asthma].

OBJECTIVE: To study the roles of allergen testing in vitro and impulse oscillometry for lung function measurements in preschool children with cough variant asthma (CVA). METHODS: ethodsForty-four preschool children with acute asthma, 41 with chronic asthma, 46 with CVA, and 35 healthy preschool children as control were recruited in the study. Inhaled allergen, food allergen, and mite-specific IgE were determined by Pharmacia UniCAP System. Serum eosinophil cationic protein (ECP) and total IgE levels were measured. Lung function was assessed by impulse oscillometry. RESULTS: The positive rates of inhaled allergen and food allergen, and total IgE levels in the CVA, acute asthma and chronic asthma groups were higher than those in the control group (P<0.01). However, no significant differences were found among the three case groups. The serum ECP levels in the CVA group were lower than those in the acute asthma group (P<0.01), but did not show differences when compared with the chronic asthma group. The impulse oscillometry demonstrated that the respiratory total impedance (Zrs), airway resistance at 5 Hz (R5), airway resistance at 20 Hz (R20), subtracting R5 from R20 (R5-R20) and resonant frequency (Fres) in the CVA, acute asthma and chronic asthma groups were higher than those in the control group (P<0.01). Zrs, R5, R20, R5-R20, and Fres in the CVA and chronic asthma groups were lower than those in the acute asthma group (P<0.01). Serum ECP levels were positively correlated with Zrs, R5, R5-R20 and Fres (P<0.05) in the CVA and chronic asthma groups. CONCLUSIONS: The measurements of allergens, serum ECP and impulse oscillometry for lung function are helpful for the evaluation of airway inflammation and airway obstruction in preschool children with CVA.