Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 85
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Ecotoxicol Environ Saf ; 187: 109879, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31677567

RESUMO

Cadmium (Cd) is a major environmental pollutant. Maternal Cd exposure throughout pregnancy caused fetal growth restriction (FGR). However, the pivotal time window of Cd-evoked FGR and its mechanism are unknown. Here, we will establish a murine model to explore the effects of maternal Cd exposure at different stages of gestation on fetal growth and placental progesterone biosynthesis. Pregnant mice were randomly divided into four groups. For Cd groups, mice were given with CdCl2 (150 mg/L) through drinking water at early (GD0-GD6), middle (GD7-GD12) and late (GD13-GD17) gestation, respectively. The controls received reverses osmosis (RO) water. Results showed that maternal cadmium exposure only in late gestation lowered fetal weight and length. Correspondingly, placental Cd level in late gestational Cd exposure is the highest among three different gestational stages. Although gestational Cd exposure had few adverse effects in the weight and diameter of mouse placenta, placental vascular development, as determined by H&E staining and cluster of differentiation-34 (CD-34) immunostaining, was impaired in mice exposed to Cd during late pregnancy. Additionally, late gestational exposure to cadmium markedly reduced progesterone level in maternal serum and placenta. In line, the expression of key progesterone synthetases, including steroidogenic acute regulatory protein (StAR) and 3ß-hydroxyl steroid dehydrogenase (3ß-HSD), was obviously downregulated in placenta from mice was exposed Cd during late pregnancy. These data suggest that maternal Cd exposure during late pregnancy, but not early and middle pregnancy, induces fetal growth restriction partially via inhibiting placental progesterone synthesis.

2.
Sci Rep ; 9(1): 15544, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664141

RESUMO

The association between suboptimal pre-pregnancy body mass index (BMI) and small-for-gestational-age (SGA) infants is not well defined. We investigated the association between pre-pregnancy BMI and the risk of SGA infants in a Chinese population. We performed a cohort study among 12029 mothers with a pregnancy. This cohort consisted of pregnant women that were: normal-weight (62.02%), underweight (17.09%), overweight (17.77%) and obese (3.12%). Birth sizes were reduced in the underweight and obese groups compared with the normal-weight group. Linear regression analysis indicated that birth size was positively associated with BMI in both the underweight and normal-weight groups. Further analysis showed that 12.74% of neonates were SGA infants in the underweight group, higher than 7.43% of neonates reported in the normal-weight group (adjusted RR = 1.92; 95% CI: 1.61, 2.30). Unexpectedly, 17.60% of neonates were SGA infants in the obese group, much higher than the normal-weight group (adjusted RR = 2.17; 95% CI: 1.57, 3.00). Additionally, 18.40% of neonates were large-for-gestational-age (LGA) infants in the obese group, higher than 7.26% of neonates reported in the normal-weight group (adjusted RR = 3.00; 95% CI: 2.21, 4.06). These results suggest that pre-pregnancy underweight increases the risk of SGA infants, whereas obesity increases the risks of not only LGA infants, but also SGA infants.

3.
Environ Pollut ; 254(Pt A): 112991, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31421572

RESUMO

Cadmium (Cd), a ubiquitous environmental pollutant, is known to impair placental development. However, the underlying mechanisms remain unclear. The present study used in vivo and in vitro models to investigate the effects of Cd on apoptosis and autophagy in placental trophoblasts and its mechanism. Pregnant mice were exposed to CdCl2 (4.5 mg/kg) on gestational day (GD) 9. Human JEG-3 cells were exposed to CdCl2 (0-40 µM) for different time points. Gestational Cd exposure obviously lowered the weight and diameter of mouse placentas. Number of TUNEL-positive cells was markedly elevated in Cd-administered mouse placentas and JEG-3 cells. Correspondingly, Cd significantly up-regulated cleaved caspase-3 protein level, a key indicator of apoptosis, in murine placentas and JEG-3 cells. Simultaneously, Cd also triggered autophagy, as determined by an elevation of LC3B-II and p62 protein, and accumulation of LC3-positive puncta, in placental trophoblasts. Chloroquine an autophagy inhibitor, obviously aggravated Cd-induced apoptosis in JEG-3 cells. By contrast, rapamycin, a specific autophagy inducer, significantly alleviated Cd-triggered apoptosis in JEG-3 cells. Mechanistically, autophagy inhibited Cd-induced apoptosis mainly via degrading caspase-9. Co-localizations of p62, a classical autophagic receptor, and caspase-9 were observed in Cd-stimulated human JEG-3 cells. Moreover, p62 siRNAs pretreatment markedly blocked the degradation of caspase 9 proteins via Cd-activated autophagy in JEG-3 cells. Collectively, our data suggest that activation of autophagy inhibits Cd-induced apoptosis via p62-mediated caspase-9 degradation in placental trophoblasts. These findings provide a new mechanistic insight into Cd-induced impairments of placental and fetal development.

4.
Steroids ; 150: 108445, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31295461

RESUMO

Low vitamin D status has been associated with increased risks of renal cell carcinoma (RCC). This study aimed to analyze the link between low vitamin D status and interleukin (IL)-6/STAT3 hyper-activation in clear cell RCC (ccRCC) patients. Forty-three newly diagnosed ccRCC patients and 86 age- and sex-matched controls were recruited. The association between low vitamin D status and IL-6/STAT3 hyper-activation was analyzed. Proliferation makersand STAT3 signal were evaluated. As expected, serum IL-6 level was higher in ccRCC patients than in controls. Moreover, serum IL-6 level was reversely correlated with serum 25(OH)D in ccRCC patients but not in controls. In addition, STAT3 signaling was hyper-activated in cancerous tissue. CcRCC patients were divided into three groups according to serum 25(OH)D level: vitamin D sufficiency (VitD-S, ≥30 ng/ml), vitamin D insufficiency (VitD-I, ≥20 and <30 ng/ml) or vitamin D deficiency (VitD-D, <20 ng/ml). Serum IL-6 was higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. Cancerous pSTAT3 level was higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The number of pSTAT3+ nuclei in cancerous tissue was more in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The expressions of cancerous PCNA, cyclin D1 and Ki-67, three markers of proliferation, were higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The in vitro experiments showed that active vitamin D3 inhibited LPS-induced STAT3 phosphorylation in ACHN cells. Our results provide evidence that low vitamin D status is correlated with hyper-activation of cancerous IL-6/STAT3 and proliferation in ccRCC patients.

5.
J Immunol ; 203(5): 1198-1207, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31315888

RESUMO

It is increasingly recognized that excessive glucocorticoids induce fetal intrauterine growth restriction (IUGR). Placental 11ß-hydroxysteroid dehydrogenase 2 (11ß-HSD2), a glucocorticoid-catalyzing enzyme, prevents active glucocorticoids from maternal circulation into the fetus, thus protecting against IUGR. Previous studies demonstrated gestational LPS exposure caused fetal IUGR. The aim of the current study was to investigate the effects of LPS on 11ß-HSD2 in mice placentas and human placental trophoblasts. Pregnant ICR(CD-1) mice were i.p. injected with LPS (200 µg/kg) on gestational day 16. As expected, gestational LPS exposure downregulated 11ß-HSD2 in mice placentas. In vitro, LPS downregulated 11ß-HSD2 in human placental trophoblasts. Additional experiment showed that LPS, which activated NF-κB, suppressed rosiglitazone-induced activation of peroxisome proliferator-activated receptor-γ (PPARγ) in mice placentas and human placental trophoblasts. Moreover, NF-κB p65 knockdown and specific NF-κB inhibitor attenuated LPS-induced suppression of PPARγ nuclear translocation in human placental trophoblasts. In addition, NF-κB p65 knockdown attenuated LPS-induced downregulation of 11ß-HSD2 in human placental trophoblasts. Mechanically, LPS promoted physical interaction between NF-κB p65 and PPARγ in the cytoplasm and nucleus of placental trophoblasts. Finally, pretreatment with rosiglitazone, a PPARγ agonist, partially alleviated LPS-induced reduction of fetal weight and crown-rump length. Taken together, these results suggest that LPS downregulates 11ß-HSD2 through suppressing PPARγ in placental trophoblasts. Placental 11ß-HSD2 downregulation may contribute partially to LPS-induced fetal IUGR.

6.
Oxid Med Cell Longev ; 2019: 1897316, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019650

RESUMO

Background: Cellular stress is involved in ischemia/reperfusion- (I/R-) induced acute kidney injury (AKI). This study is aimed at investigating the effects of pretreatment with cholecalciferol on renal oxidative stress and endoplasmic reticulum (ER) stress during I/R-induced AKI. Methods: I/R-induced AKI was established by cross-clamping renal pedicles for 90 minutes and then reperfusion. In the Chol + I/R group, mice were orally administered with three doses of cholecalciferol (25 µg/kg) at 1, 24, and 48 h before ischemia. Renal cellular stress and kidney injury were measured at different time points after reperfusion. Results: I/R-induced AKI was alleviated in mice pretreated with cholecalciferol. In addition, I/R-induced renal cell apoptosis, as determined by TUNEL, was suppressed by cholecalciferol. Additional experiment showed that I/R-induced upregulation of renal GRP78 and CHOP was inhibited by cholecalciferol. I/R-induced renal IRE1α and eIF2α phosphorylation was attenuated by cholecalciferol. Moreover, I/R-induced renal GSH depletion, lipid peroxidation, and protein nitration were blocked in mice pretreated with cholecalciferol. I/R-induced upregulation of renal NADPH oxidases, such as p47phox, gp91phox, and nox4, was inhibited by cholecalciferol. I/R-induced upregulation of heme oxygenase- (HO-) 1, gshpx and gshrd, was attenuated in mice pretreated with cholecalciferol. Conclusions: Pretreatment with cholecalciferol protects against I/R-induced AKI partially through suppressing renal cellular stress response.


Assuntos
Lesão Renal Aguda/etiologia , Lesão Renal Aguda/patologia , Colecalciferol/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Rim/patologia , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/complicações , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Glutationa/metabolismo , Rim/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos ICR , NADPH Oxidases/metabolismo , Receptores de Calcitriol/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
7.
Int Immunopharmacol ; 69: 235-244, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30738993

RESUMO

Several epidemiological reports demonstrated that vitamin D deficiency elevated risk of preterm delivery. We investigate the effects of oral cholecalciferol (VD3) supplementation on lipopolysaccharide (LPS)-induced preterm delivery. Pregnant mice were randomly assigned to either oral VD3 (25 µg/kg) or corn oil once daily from gestational day (GD)13 to GD15, and were intraperitoneally injected with either LPS (200 µg/kg) or normal saline on GD15. As expected, LPS was effective in inducing preterm delivery and fetal death. LPS-induced preterm delivery and fetal death were alleviated in VD3-pretreated mice. LPS-induced down-regulation of genes for placental progesterone biosynthetic enzymes was blocked in VD3-pretreated mice. LPS-induced reduction of serum progesterone was correspondingly attenuated by VD3. Although oral VD3 had no effect on estradiol production, it attenuated LPS-induced up-regulation of placental ERß in mice. LPS-induced placental COX-2 up-regulation and serum PGF2α elevation were alleviated in VD3-pretreated mice. Additionally, LPS-evoked elevations of the placental Tnfα, Il1ß, Mcp1 and Mip2 mRNAs were attenuated by VD3. VD3 promoted placental vitamin D receptor nuclear translocation and simultaneously alleviated LPS-induced nuclear translocation of NF-κB p65 and p50 subunits. These results provide evidence that oral VD3 supplementation alleviates LPS-induced preterm delivery and fetal demise partially through regulating placental steroid hormones and prostaglandins.


Assuntos
Colecalciferol/uso terapêutico , Suplementos Nutricionais , Placenta/metabolismo , Nascimento Prematuro/dietoterapia , Receptores de Calcitriol/metabolismo , Administração Oral , Animais , Estradiol/metabolismo , Feminino , Humanos , Inflamação , Lipopolissacarídeos/imunologia , Camundongos , Camundongos Endogâmicos ICR , Gravidez , Progesterona/metabolismo , Prostaglandinas/metabolismo
8.
Int Immunopharmacol ; 66: 177-184, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30468885

RESUMO

Acute lung injury (ALI) is a common disease that may result in acute respiratory failure and death. However, there are still no effective treatments for ALI. Several studies have shown that farnesoid X receptor (FXR) has an anti-inflammatory effect. We investigated the effects of obeticholic acid (OCA), an agonist of FXR, on Lipopolysaccharide (LPS)-induced ALI in mice. Sixty male mice were randomly divided into six groups, and orally administered with or without OCA once daily for 3 consecutive days before LPS (1.0 mg/kg). Animals were sacrificed at 0 h, 2 h or 6 h after LPS. As expected, OCA enhanced pulmonary FXR activity. OCA prevented LPS-induced ALI. Additional experiment showed that OCA alleviated LPS-induced up-regulation of pulmonary pro-inflammatory and chemokine genes. Moreover, OCA also repressed LPS-induced the release of TNF-α and KC in serum and bronchoalveolar lavage fluid. In contrast, OCA further up-regulated LPS-induced the expression of Il-10, an anti-inflammatory cytokine. Further study showed that OCA inhibited LPS-evoked NF-κB signaling in the lungs. OCA attenuated LPS-induced ERK1/2, JNK, p38 and Akt phosphorylation in the lungs. Overall, these results suggest that OCA prevent LPS-induced ALI may be through enhancing pulmonary FXR activity and then blockading several inflammatory signaling pathways.

9.
Life Sci ; 212: 241-250, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30300654

RESUMO

AIMS: The aim of the study was to investigate the effects of high-fat diets before pregnancy and/or during pregnancy on fetal development. MAIN METHODS: Female mice were fed with standard diets (SD) or high-fat diets (HFD). After 12 weeks, females were mated. In the SD + SD and HFD + SD groups, pregnant mice were fed with standard diets. In the SD + HFD and HFD + HFD groups, pregnant mice were fed with high-fat diets. All pregnant mice were sacrificed on gestational day (GD) 16. KEY FINDINGS: Fetal weight and crown-rump length were increased in SD + HFD-fed mice, whereas were decreased in HFD + SD-fed mice. The levels of CRP and TNF-α in maternal serum and amniotic fluid were elevated in all HFD-fed mice. Placenta weight was elevated in SD + HFD-fed but not in HFD + SD-fed mice. Blood sinusoid areas, and the number of Ki67-positive cells, a marker of cell proliferation, were elevated in placental labyrinth layer of SD + HFD-fed mice, but decreased in HFD + SD-fed mice. Finally, placental Fatp1, a fatty acid transporter gene, was up-regulated in SD + HFD-fed mice. By contrary, placental Fatp1, and Snat2, an amino acid transporter, were down-regulated in HFD + SD-fed mice. Moreover, the levels of placental FATP4 and SNAT2 were up-regulated in SD + HFD-fed mice. SIGNIFICANCE: HFD before pregnancy and HFD during pregnancy differentially disturb fetal growth development. HFD before pregnancy-induced fetal SGA might be partially attributed to inflammatory cytokines and mediators derived from maternal adipose tissue. By contrary, HFD during pregnancy-induced fetal overweight may be partially attributed to the increase of placental nutrient transport capacity.

10.
Eur J Pharmacol ; 838: 60-68, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30196109

RESUMO

It is increasingly recognized that farnesoid X receptor (FXR) has anti-inflammatory and antioxidant activities. The present study investigated the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, on renal inflammation and oxidative stress in a model of sepsis-induced acute kidney injury. All mice except controls were intraperitoneally injected with lipopolysaccharide (LPS, 2.0 mg/kg). In the OCA + LPS group, mice were orally pretreated with three doses of OCA (5 mg/kg) at 48, 24 and 1 h before LPS injection. Interestingly, OCA pretreatment alleviated LPS-induced renal dysfunction and pathological damage. Moreover, OCA pretreatment repressed renal inflammatory cytokines and chemokines during LPS-induced acute kidney injury. In addition, OCA blocked nuclear translocation of nuclear factor kappa B (NF-κB) p65 and p50 subunits in tubular epithelial cells of renal cortex. Additional experiment showed that OCA pretreatment attenuated LPS-induced renal glutathione depletion, lipid peroxidation and protein nitration. Moreover, OCA pretreatment inhibited the upregulation of renal NADPH oxidase and inos genes during LPS-induced acute kidney injury. In conclusion, OCA pretreatment protects against sepsis-induced acute kidney injury through inhibiting renal inflammation and oxidative stress. These results provide evidence for roles of FXR as an important regulator of inflammation and oxidative stress in the kidney.

11.
PLoS One ; 13(8): e0202910, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30153273

RESUMO

Previous studies have shown that folate levels were decreased in patients with type 2 diabetes (T2D) and further lowered in T2D patients with cognitive impairment. However, whether folate deficiency could cause T2D and subsequent cognitive dysfunction is still unknown. The present study aimed to explore the effects of chronic folate deficiency (CFD) on glucose and lipid metabolism and cognitive function in mice. Seven-week-old mice were fed with either a CFD or control diet for 25 weeks. Serum folate was significantly reduced, whereas serum total homocysteine was significantly increased in the CFD group. Moreover, CFD induced obesity after a 6-week diet treatment, glucose intolerance and insulin resistance after a 16-week-diet treatment. In addition, CFD reduced the hepatic p-Akt/Akt ratio in response to acute insulin administration. Moreover, CFD increased serum triglyceride levels, upregulated hepatic Acc1 and Fasn mRNA expression, and downregulated hepatic Cd36 and ApoB mRNA expression. After a 24-week diet treatment, CFD induced anxiety-related activities and impairment of spatial learning and memory performance. This study demonstrates that folate deficiency could induce obesity, glucose and lipid metabolism disorders and subsequent cognitive dysfunction.

12.
Placenta ; 65: 7-14, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29908644

RESUMO

INTRODUCTION: Several reports demonstrated that cadmium (Cd) had proinflammatory activities. The present study aimed to investigate whether Cd induces inflammatory cytokines in mouse placenta and human trophoblast cells. METHODS: Human JEG-3 cells were treated with different concentration of CdCl2 (0-50 µM) or CdCl2 (25 µM) for different times. The pregnant mice were administered with CdCl2 (3.0 mg/kg, i.p.) on GD15. RESULTS: TNF-α, IL-8 and IL-6 mRNAs were elevated in CdCl2-treated JEG-3 cells. Several inflammatory cytokines were up-regulated in Cd-treated placenta of mice. Moreover, keratinocyte chemokine (KC), a functional analogue of human IL-8, was increased in maternal serum and amniotic fluid from CdCl2-exposed mice. Additional experiment showed that gestational Cd exposure activated Akt signaling in mouse placenta. Co-culture with CdCl2 elevated pAkt level in JEG-3 cells in concentration- and time-dependent manners. LY294002, a specific inhibitor of PI3K, blocked CdCl2-evoked Akt phosphorylation in JEG-3 cells. Concomitantly, LY294002 inhibited CdCl2-induced IL-8 in JEG-3 cells. N-acetylcysteine (NAC), an antioxidant and a glutathione precursor, blocked CdCl2-evoked Akt phosphorylation in mouse placenta and human trophoblast cells. Additionally, NAC attenuated Cd-induced up-regulation of KC in amniotic fluid. DISCUSSION: Cd induces inflammatory cytokines partially through activating Akt signaling in mouse placenta and human trophoblast cells. NAC may be exploited for prevention of Cd-induced placental inflammation.

13.
J Steroid Biochem Mol Biol ; 182: 14-20, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29684478

RESUMO

Vitamin D deficiency is especially prevalent in pregnant women and children. Our recent study demonstrated that vitamin D deficiency in early life disturbed testicular development. This study investigated the effects of vitamin D deficiency in early life on prostatic hyperplasia in middle-aged mice. In control group, dams and their male pups were fed with standard-chow diets. In VDD group, dams were fed with vitamin D deficient (VDD) diets throughout pregnancy and lactation. After weaning, male pups continued to be fed with VDD diets. As expected, prostate weight was elevated and prostatic hyperplasia was observed in VDD-fed mice. The number of prostatic Ki-67-positive epithelial cells, a proliferation marker, was increased in VDD-fed mice. Further analysis found that vitamin D deficiency promoted inflammatory infiltration and stromal fibrosis in prostate of middle-aged mice. Moreover, vitamin D deficiency activated NF-κB and up-regulated Il-6 mRNA in prostate of middle-aged mice. In addition, vitamin D deficiency activated prostatic STAT3, a proliferation pathway in middle-aged mice. Of interest, VDD-induced prostatic inflammation and hyperplasia were partially reversed when VDD diets was replaced with standard diets. These results provide evidence that vitamin D deficiency in early life promotes prostatic hyperplasia in middle-aged mice through exacerbating local inflammation.

14.
Mol Cell Endocrinol ; 474: 272-283, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-29614340

RESUMO

An adverse intrauterine environment may be an important factor contributing to the development of type 2 diabetes in later life. The present study investigated the longitudinal effects of maternal lipopolysaccharide (LPS) exposure during the third trimester on glucose metabolism and sex hormone balance in the offspring. Pregnant mice were intraperitoneally injected with LPS (50 µg/kg) daily from gestational day (GD) 15 to GD17. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were assessed at postnatal day (PND) 60 and PND120. Sex hormones, their receptors, and metabolic enzymes (aromatase) were measured in male offspring at different phases of development (PND14: juvenile; PND35: adolescence; PND60: adulthood; and PND120: middle age). LPS-exposed male offspring exhibited glucose intolerance and insulin resistance by GTT and ITT at middle age, accompanied by an increase in fasting blood glucose and reductions in serum insulin levels and hepatic phosphorylated (p) -AKT/AKT ratio. However, glucose intolerance and insulin resistance were not observed in LPS-exposed female offspring. Maternal LPS exposure upregulated hepatic aromatase proteins and mRNA levels in male offspring at all time points. At adolescence, the testosterone/estradiol ratio (T/E2) was markedly reduced in LPS-exposed male offspring. Moreover, maternal LPS exposure significantly increased hepatic estrogen receptor (ER) α expressions and decreased hepatic androgen receptor (AR) expressions in male offspring. At adulthood, maternal LPS exposure increased serum estradiol levels, decreased serum testosterone levels and elevated hepatic ERß expressions in male offspring. In conclusion, maternal LPS exposure upregulated aromatase expressions, followed by a reduction in the T/E2 ratio and an alteration in sex hormone receptor activity, which might be involved in the development of glucose metabolism disorders in middle-aged male offspring. This study provides a novel clue and direction to clarify the pathogenesis of maternal infection-related diabetes in male offspring.

15.
J Nutr Sci Vitaminol (Tokyo) ; 64(1): 26-33, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29491269

RESUMO

The aim of this study was to investigate the effects of folic acid on impaired wound healing in diabetic mice. Male mice were divided into three groups: group 1, the non-diabetic mice (control); group 2, the streptozotocin (STZ)-induced type 1 diabetic mice; and group 3, the diabetic mice that received a daily dose of 3 mg/kg folic acid via oral gavage. Full-thickness excision wounds were created with 8-mm skin biopsy punches. Each wound closure was continuously evaluated until the wound healed up. Wound healing was delayed in diabetic mice compared with the non-diabetic mice. There were significantly reduced levels of hydroxyproline content (indicator of collagen deposition) and glutathione in diabetic wounds, whereas levels of lipid peroxidation and protein nitrotyrosination were increased. Daily supplementation with folic acid restored diabetes-induced healing delay. Histopathology showed that folic acid supplementation accelerated granulation tissue formation, proliferation of fibroblasts, and tissue regeneration in diabetic mice. Interestingly, folic acid alleviated diabetes-induced impaired collagen deposition in wounds. Moreover, folic acid significantly decreased levels of lipid peroxidation, protein nitrotyrosination and glutathione depletion in diabetic wounds. In conclusion, our results indicate that folic acid supplementation may improve impaired wound healing via suppressing oxidative stress in diabetic mice.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Ácido Fólico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Glutationa/metabolismo , Hidroxiprolina/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pele/efeitos dos fármacos , Pele/metabolismo
16.
Sci Rep ; 8(1): 3020, 2018 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-29445226

RESUMO

Ethanol is a widely used beverage and abused drug. Alcoholism causes severe damage to human health and creates serious social problems. Understanding the mechanisms underlying ethanol actions is important for the development of effective therapies. Alcohol has a wide spectrum of effects on physiological activities and behaviours, from sensitization to sedation and even intoxication with increasing concentrations. Animals develop tolerance to ethanol. However, the underlying mechanisms are not well understood. In Caenorhabditis elegans, NPR-1 negatively regulates the development of acute tolerance to ethanol. Here, using in vivo Ca2+ imaging, behavioural tests and chemogenetic manipulation, we show that the soluble guanylate cyclase complex GCY-35/GCY-36-TAX-2/TAX-4 signalling pathway in O2 sensory neurons positively regulates acute functional tolerance in npr-1 worms.

18.
Sci Rep ; 8(1): 3608, 2018 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-29483547

RESUMO

Gestational vitamin D deficiency (VDD) has been linked with adverse pregnant outcomes. To investigate influent factors of gestational VDD and its relation to the incidence of preterm delivery, total 3598 eligible mother-and-singleton-offspring pairs were recruited. For serum 25(OH)D concentration, 941 pregnant women were sufficient, 1260 insufficient, and 1397 deficient. Further analysis showed that VDD was more prevalent in winter than in other seasons. Underweight but not overweight was a risk factor for gestational VDD. Multivitamin use reduced risk of gestational VDD. Interestingly, 8.23% delivered preterm infants among subjects with VDD (adjusted RR: 4.02; 95% CI: 2.33, 6.92) and 3.81% among subjects with gestational vitamin D insufficiency (VDI) (adjusted RR: 2.07; 95% CI: 1.16, 3.71). Moreover, 2.59% delivered early preterm infants among subjects with VDD (adjusted RR: 2.97; 95% CI: 1.41, 6.24) and 0.49% among subjects with VDI (adjusted RR: 0.54; 95% CI: 0.19, 1.51). The incidence of late preterm delivery was 5.64% among subjects with VDD (adjusted RR: 3.90; 95% CI: 2.26, 6.72) and 3.32% among subjects with VDI (adjusted RR: 2.09; 95% CI: 1.17, 3.74). In conclusion, pre-pregnancy BMI, seasonality and multivitamin use are influent factors of gestational vitamin D status. Gestational VDD is associated with an increased risk of preterm delivery in Chinese population.

19.
PLoS One ; 13(1): e0191667, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29373603

RESUMO

Cadmium (Cd) is a developmental toxicant that induces fetal growth restriction (FGR). Placental endoplasmic reticulum (ER) stress is associated with FGR. This study investigated the effects of N-acetylcysteine (NAC) on Cd-induced placental ER stress and FGR. Pregnant mice were intraperitoneally injected with CdCl2 daily from gestational day (GD)13 to GD17. As expected, Cd reduced fetal weight and crown-rump length. Cd decreased the internal space of blood vessels in the placental labyrinth layer and inhibited placental cell proliferation. Several genes of growth factors, such as Vegf-a, placental growth factor, Igf1 and Igf1r, and several genes of nutrient transport pumps, such as Glut1, Fatp1 and Snat2, were down-regulated in placenta of Cd-treated mice. Moreover, Cd evoked placental ER stress. Of interest, NAC alleviated Cd-induced FGR. Additional experiment showed that NAC inhibited Cd-induced impairment of placental development and placental ER stress. Therefore, NAC may be exploited for prevention of Cd-induced placental insufficiency and FGR.


Assuntos
Acetilcisteína/farmacologia , Cádmio/toxicidade , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Retardo do Crescimento Fetal/prevenção & controle , Placenta/efeitos dos fármacos , Animais , Regulação para Baixo/efeitos dos fármacos , Feminino , Camundongos , Gravidez , Reação em Cadeia da Polimerase em Tempo Real
20.
J Clin Res Pediatr Endocrinol ; 10(1): 38-43, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28825589

RESUMO

OBJECTIVE: To evaluate the effect of intrahepatic cholestasis of pregnancy (ICP) on neonatal birth weight. METHODS: Potential articles were identified by searching PubMed and Web of Science databases on April 30th, 2017. Using the Mantel-Haenszel random-effects or fixed-effects model, outcomes were summarized through weighted mean difference (WMD) and 95% confidence intervals (CI). Potential publication bias was tested using a funnel plot and the methods of Egger's regression and Begg's test. RESULTS: A total of eight studies were included in our meta-analysis. Six studies reported data on neonatal birth weight in ICP and control pregnancies. Pooled data from the six studies showed that the birth weight in the ICP group was significantly lighter than in the control group. The overall pooled WMD was -175 g (95% CI: -301, -48). Meanwhile, pooled data from the other two studies indicated that the birth weight in the late-onset ICP group was heavier than in the early-onset ICP group (WMD: 267 g, 95% CI: 168, 366). CONCLUSION: Neonatal birth weights in ICP pregnancies were lower than in normal pregnancies. Furthermore, early-onset ICP is associated with a lower birth weight than late-onset ICP.


Assuntos
Peso ao Nascer , Colestase Intra-Hepática , Complicações na Gravidez , Feminino , Humanos , Recém-Nascido , Gravidez
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA