Homocysteine increases uterine artery blood flow resistance in women with pregnancy loss.

OBJECTIVE: Uterine arterial blood flow is an important factor in embryonic development. Increased uterine artery blood flow resistance may be related to vascular damage. Homocysteine (HCY) can induce injury of endothelial through various pathways. Therefore, we investigate the association between serum HCY levels and uterine artery blood flow in the non-pregnant state in women who have experienced pregnancy loss (PL). METHODS: 364 women eligible for PL were included in the study. The detection of HCY was completed by the Laboratory of Lanzhou University Second Hospital. We divided the patients into three groups: Low-HCY (HCY<10 umol/L, n = 144), Medium-HCY (HCY 10∼15 umol/L, n = 174) and High-HCY (HCY>15 umol/L, n = 46). The patients were subjected to vaginal color Doppler ultrasonography to measure bilateral uterine artery resistance index (RI), pulsatility index (PI) and peak systolic velocity/end diastolic velocity (S/D). RESULT: Among 364 women, the right uterine artery RI in L-HCY, M-HCY, and H-HCY groups were 0.78±0.08, 0.79±0.07 and 0.81±0.07, respectively (P = 0.04). The left uterine artery RI in L-HCY, M-HCY, and H-HCY groups were 0.78±0.08, 0.81±0.07 and 0.81±0.07, respectively (P = 0.01). The right uterine artery RI level and the left uterine artery RI was significantly associated with HCY level (r = 0.103, P = 0.050; r = 0.104, P = 0.047, respectively). Of these, 177 women experienced their next pregnancy, and 33 patients experienced PL again. The pregnancy rate in l-HCY, M-HCY, and HHCY groups were 47.92% (69/144), 49.43% (86/174) and 47.83% (22/46), respectively (P = 0.95). In next pregnancy, the PL rate in l-HCY, M-HCY, and HHCY groups were 8.70% (6/69), 22.58% (22/86) and 22.73% (5/22), respectively (P = 0.03). CONCLUSION: HCY can increase the uterine artery resistance in the non-pregnant state and is associated with the abortion rate of next pregnancy.

Ghrelin ameliorates acute lung injury induced by oleic acid via inhibition of endoplasmic reticulum stress.

AIMS: Acute lung injury (ALI) is associated with excessive mortality and lacks appropriate therapy. Ghrelin is a novel peptide that protects the lung against ALI. This study aimed to investigate whether endoplasmic reticulum stress (ERS) mediates the protective effect of ghrelin on ALI. MAIN METHODS: We used a rat oleic acid (OA)-induced ALI model. Pulmonary impairment was detected by hematoxylin and eosin (HE) staining, lung mechanics, wet/dry weight ratio, and arterial blood gas analysis. Plasma and lung content of ghrelin was examined by ELISA, and mRNA expression was measured by quantitative real-time PCR. Protein levels were detected by western blot. KEY FINDINGS: Rats with OA treatment showed significant pulmonary injury, edema, inflammatory cellular infiltration, cytokine release, hypoxia and CO2 retention as compared with controls. Plasma and pulmonary content of ghrelin was reduced in rats with ALI, and mRNA expression was downregulated. Ghrelin (10nmol/kg) treatment ameliorated the above symptoms, but treatment with the ghrelin antagonists D-Lys3 GHRP-6 (1µmol/kg) and JMV 2959 (6mg/kg) exacerbated the symptoms. ERS induced by OA was prevented by ghrelin and augmented by ghrelin antagonist treatment. The ERS inducer, tunicamycin (Tm) prevented the ameliorative effect of ghrelin on ALI. The decreased ratio of p-Akt and Akt induced by OA was improved by ghrelin treatment, and was further exacerbated by ghrelin antagonists. SIGNIFICANCE: Ghrelin protects against ALI by inhibiting ERS. These results provide a new target for prevention and therapy of ALI.

Expression of FcRs on monocytes among Kawasaki disease patients with coronary artery lesions.

OBJECTIVE: To study expression of Fc gamma receptors (FcRs) on monocytes in Kawasaki disease (KD) patients with coronary artery lesions (CAL). METHODS: 160 newly diagnosed KD patients and 80 health children were enrolled in this study. All patients were scheduled to receive both aspirin and intravenous immunoglobulin (IVIG). Serial blood samples were obtained before and 3days after completing IVIG therapy. The first two-dimensional echocardiographic examination was performed for all KD patients within 10days, and was repeated at 3weeks. CAL was defined by coronary artery Z-scores≥2.5 by echocardiography. Expression of inhibitory and activating FcRs on CD14+ monocytes (MCs) was assessed by flow cytometry. Cytokine expression in MC was evaluated by PCR. RESULTS: Of the 160KD patients enrolled in this study, 36 had coronary artery lesions (KD-CAL+ group), while 124 did not (KD-CAL- group). There was no significant difference in FcRI expression on MCs from KD patients and that of Ctrls. Although FcRIII and FcRIIa levels were significantly higher in KD patients compared with those in Ctrls, there were no significant differences between the KD-CAL+ and KD-CAL- groups. FcRIIb expression in the KD patients was lower than that of Ctrls, meanwhile expression in the KD-CAL+ group was lower than that in the KD-CAL- group. After IVIG therapy, FcRIIb expression increased in KD-CAL+, but did not reach the normal range. A negative correlation was observed between the levels of IL-6, TNF-α and FcRIIb expression. CONCLUSION: Decreased FcRIIb expression on MCs may contribute to the development of coronary artery lesions in patients with KD.

WITHDRAWN: Decreased level of endogenous ghrelin is involved in the progression of lung injury induced by oleic acid.

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Golgi Phosphoprotein 3 Inhibits the Apoptosis of Human Glioma Cells in Part by Downregulating N-myc Downstream Regulated Gene 1.

BACKGROUND Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development of several human cancers. Our previous study showed that GOLPH3 expression in glioma tissues was related to the severity of the malignancy of the cancer. However, the mechanism by which GOLPH3 affects cell apoptosis is largely unknown. The present study was designed to explore the possible mechanism of GOLPH3 in cell apoptosis. MATERIAL AND METHODS To analyze the biological role of GOLPH3 in glioma cells, we used GOLPH3 small interference RNA in apoptosis of glioma cells. The apoptosis of glioma cells was detected by flow cytometry. The expression level of GOLPH3 and NDRG1 protein was determined by Western blot analyses and immunohistochemical staining, respectively, to evaluate their association with glioma. Tumor tissues were collected from patients with glioma. Normal cerebral tissues were acquired from cerebral trauma patients undergoing internal decompression surgery. RESULTS We confirm that the decrease of GOLPH3 that promotes the apoptosis of glioma cells may be regulated by the activation of NDRG1 and cleaved capcase 3. There was a inverse association between GOLPH3 and NDRG1 in glioma samples. CONCLUSIONS Our findings indicate that GOLPH3 and NDRG1 both play an important role in glioma etiology. Either GOLPH3 or NDRG1 might be a potential candidate for malignant glioma therapy.

Hormones other than aldosterone may contribute to hypertension in 3 different subtypes of primary aldosteronism.

Blood pressure (BP) level is similar in patients with 3 subtypes of primary aldosteronism (PA), even though aldosterone levels may vary. Glucocorticoids and adrenomedullary hormones may be influenced and may contribute to hypertension in PA. The authors' objective was to investigate the influence of PA on adrenal gland secretion and the roles of these hormones in hypertension. Patients diagnosed with PA (229 cases) were enrolled and classified into 3 subgroups: aldosterone-producing adenoma (APA), unilateral nodular adrenal hyperplasia (UNAH), and idiopathic hyperaldosteronism (IHA). Patients with essential hypertension served as the control group (100 cases). Concentration of the above hormones was measured and compared between groups. Level of plasma adrenocorticotrophic hormone (ACTH) in patients with APA was significantly lower than that in patients with IHA (P<.001) and UNAH (P<0.5). The 24-hour urinary free cortisol and adrenomedullary hormone levels were highest in patients with IHA, lower in patients with APA, and lowest in patients with UNAH. Systolic BP level was positively correlated with 8 am plasma cortisol level (r=0.142, P=.039) and plasma ACTH level (r=0.383, P=.016). Cortisol and adrenomedullary hormones were different between PA subtypes and they might involve regulation of BP in those patients.

Lead-induced oxidative damage in steriled seedlings of Nymphoides peltatum.

The effects of increasing concentrations of lead (Pb) on Pb accumulation and its influence on nutrient elements, malondialdehyde (MDA) content, generation of superoxide anion (O2(-·)), hydrogen peroxide (H2O2) content, antioxidant enzymes activities, soluble protein, and photosynthetic pigment, as well as chloroplast ultrastructure in steriled seedlings of Nymphoides peltata (S. G. Gmel.) Kuntze were investigated in order to understand Pb-induced toxicity. The accumulation of Pb was found to increase in a concentration-dependent manner. Nutrient elements (Ca, K, Fe, Mn, and Mo) were also affected. MDA content and O2(-·) generation rate increased progressively, while H2O2 content first boosted up at a low Pb concentration of 12.5 µM but then declined. Guaiacol peroxidase and catalase activities increased alternately, while superoxide dismutase activity gradually fell. Negative correlations were found between Pb and soluble protein and photosynthetic pigment. Moreover, Pb exposure resulted in a significant damage of chloroplasts. Taken together, these findings supported the hypothesis that Nymphoides peltatum underwent oxidative stress induced by Pb. In addition, both the disorder of nutrient elements and the damage to the ultrastructure of chloroplasts were indicative of general disarray in the cellular functions exerted by Pb.

Kaempferol regulates MAPKs and NF-κB signaling pathways to attenuate LPS-induced acute lung injury in mice.

Recent studies show that mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways are two pivotal roles contributing to the development of lipopolysaccharide (LPS)-induced acute lung injury (ALI). The present study aimed to investigate the protective effect of kaempferol (Kae), a naturally occurring flavonoid compound, on ALI and explore its possible mechanisms. Male BALB/c mice with ALI, induced by intranasal instillation of LPS, were treated or not with Kae (100 mg/kg, intragastrically) 1h prior to LPS exposure. Kae treatment attenuated pulmonary edema of mice with ALI after LPS challenge, as it markedly decreased the lung W/D ratio of lung samples, protein concentration and the amounts of inflammatory cells in BALF. Similarly, LPS mediated overproduction of proinflammatory cytokines in BALF, including TNF-α, IL-1ß and IL-6, was strongly reduced by Kae. Histological studies demonstrated that Kae substantially inhibited LPS-induced alveolar wall thickness, alveolar hemorrhage and leukocytes infiltration in lung tissue with evidence of reduced myeloperoxidase (MPO) activity. Kae also efficiently increased superoxide dismutase (SOD) activity of lung sample when compared with LPS group, which was obviously reduced by LPS administration. In addition, Western blot analysis indicated that the activation of MAPKs and NF-κB signaling pathways stimulated by LPS was significantly blocked by Kae. Taken together, our results suggest that Kae exhibits a protective effect on LPS-induced ALI via suppression of MAPKs and NF-κB signaling pathways, which may involve the inhibition of tissue oxidative injury and pulmonary inflammatory process.

[Subcellular distribution and phytotoxicity of cadmium in Alternanthera philoxeroides leaves].

A hydroponic experiment was conducted to study the subcellular distribution of Cd and mineral elements in Alternanthera philoxeroides leaves and the leaves anti-oxidative capacity and chlorophyll, soluble protein, and phytochelatins (PCs) contents under the stress of different concentration (0, 0.05, 0.1, 0.2, 0.4 mmol x L(-1)) Cd. With the increasing concentration of Cd in culture medium, the Cd content in all subcellular components of A. philoxeroides leaves increased significantly, and mainly distributed in cell wall, followed by in soluble fractions, and in chloroplast and mitochondria. When the Cd concentration in the medium exceeded 0.2 mmol x L(-1), the Cd was more allocated in soluble fractions than in cell wall. Cd stress resulted in an obvious imbalance of mineral elements uptake. With the increasing concentration of Cd, the Ca content in all subcellular components, especially in cell wall, increased significantly, whereas the P and K contents in cell wall and soluble fractions as well as the Mg and Fe contents in chloroplast decreased. In the meantime, the soluble protein and chlorophyll contents showed a decreasing trend, the glutathione and ascorbic acid contents decreased after an initial increase, the total anti-oxidative capacity (T-AOC) increased progressively, and the PCs accumulated in large quantity. These results suggested that A. philoxeroides had definite resistance to the water body Cd, and there was a dosage-effect relationship between the Cd enrichment in the subcellular components of A. philoxeroides leaves and the phytotoxicity of Cd. The imbalance of the mineral elements in subcellular components and the decrease of soluble protein and chlorophyll contents in chloroplast indicated the obvious phytotoxicity of Cd, while the massive accumulation of Ca in cell wall and the increased levels of PCs and T-AOC suggested the stronger resistance of A. philoxeroides to Cd stress. There was a definite correlation between the PCs production by A. philoxeroides and the toxicity of Cd, suggesting that the PCs could be considered as a sensitive biomarker for estimating the Cd phytotoxicity.

Immunomodulatory effects of cinobufagin isolated from Chan Su on activation and cytokines secretion of immunocyte in vitro.

The objective of this study was to evaluate the immunomodulatory effects of cinobufagin (CBG) isolated from Chan Su (Venenum Bufonis) in vitro. In this paper, our results show that CBG significantly stimulated cell proliferation of splenocytes and peritoneal macrophages (PMΦ) and markedly enhanced the phagocytic activation of PMΦ. CBG also significantly increased CD4(+)CD8(+) double-positive T-cell populations and the percentage of S-phase cells of splenic lymphocytes. The levels of several Th1 cytokines, including interferon-γ and tumor necrosis factor-α, are significantly increased after CBG treatment, whereas the levels of the Th2 cytokine interleukin-4 and interleukin-10 are significantly decreased. As a result, the ratio of Th1/Th2 also increased. Taken together, these results indicated that CBG had potential immune system regulatory effects and suggested that this compound could be developed as a novel immunotherapeutic agent to treat immune-mediated diseases such as cancer.