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2.
Ecotoxicol Environ Saf ; 252: 114605, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36753971

RESUMO

BACKGROUND: The omnipresence of human phthalate (PAE) exposure is linked to various adverse health issues, including breast cancer. However, the effects of low-dose PAE exposure on breast cancer stem cells (BCSCs) and the underlying mechanism remain unexplored. METHODS: BCSCs from breast cancer cell lines (MDA-MB-231 and MCF-7) were enriched using a tumorsphere formation assay. Gene and protein expression was detected by measurement of quantitative real-time reverse transcription PCR, western blot, and immunofluorescence assays. Transient transfection assays were used to evaluate the involvement of Gli1, a signaling pathway molecule and ΔNp63α, an oncogene in influencing the PAE-induced characteristics of BCSCs. RESULTS: PAE (butylbenzyl phthalate, BBP; di-butyl phthalate, DBP; di-2-ethylhexyl phthalate, DEHP) exposure of 10-9 M significantly promoted the tumorsphere formation ability in BCSCs. Breast cancer spheroids with a 10-9 M PAE exposure had higher levels of BCSC marker mRNA and protein expression, activated sonic hedgehog (SHH) pathway, and increased mRNA and protein levels of an oncogene, ΔNp63α. Furthermore, suppression of the SHH pathway attenuated the effects of PAEs on BCSCs. And the overexpression of ΔNp63α enhanced PAE-induced characteristics of BCSCs, while low expression of ΔNp63α inhibited the promotion effects of PAEs on BCSCs and the SHH pathway. CONCLUSION: Low-dose PAE exposure promoted the stem cell properties of BCSCs in a ΔNp63α- and SHH-dependent manner. The influence of low-dose exposure of PAEs and its relevance for the lowest observed effect concentrations requires further investigation, and the precise underlying mechanism needs to be further explored.


Assuntos
Neoplasias da Mama , Proteínas Hedgehog , Humanos , Feminino , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Transdução de Sinais , Oncogenes , Células-Tronco Neoplásicas/metabolismo , Linhagem Celular Tumoral
3.
Sci Rep ; 13(1): 1147, 2023 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670177

RESUMO

The aim of the present study was to investigate the role of endoplasmic reticulum (ER) stress in bisphenol A (BPA) - induced hepatic lipid accumulation as well as the protective effects of Sulforaphane (SFN) in this process. Human hepatocyte cell line (LO2) and C57/BL6J mice were used to examine BPA-triggered hepatic lipid accumulation and the underlying mechanism. Hepatic lipid accumulation, triglycerides (TGs) levels, the expression levels of lipogenesis-related genes and proteins in the ER stress pathway were measured. It was revealed that BPA treatment increased the number of lipid droplets, the levels of TG and mRNAs expression of lipogenesis-related genes, and activated the ER stress pathway. These changes were inhibited by an ER stress inhibitor 4-phenylbutyric acid. SFN treatment abrogated BPA-altered hepatic lipid metabolism and ameliorated BPA-induced ER stress-related markers. Together, these findings suggested that BPA activated ER stress to promote hepatic lipid accumulation, and that SFN reversed those BPA effects by alleviating ER stress.


Assuntos
Fígado , Hepatopatia Gordurosa não Alcoólica , Humanos , Animais , Camundongos , Fígado/metabolismo , Metabolismo dos Lipídeos , Estresse do Retículo Endoplasmático , Hepatopatia Gordurosa não Alcoólica/metabolismo , Lipídeos/farmacologia
4.
BMC Public Health ; 20(1): 429, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32238156

RESUMO

BACKGROUND: Vitamin D insufficiency and deficiency in childhood are common. However, the status and influential factors of vitamin D during different ages are not clear. This study aimed to survey vitamin D concentrations in children aged 0 to 6 years and explore its influential factors. METHODS: A total of 6953 children were recruited in Wuxi City of East China from January to December in 2016. Enzyme-linked immunosorbent assay was used to determine the serum concentrations of 25-hydroxyvitamin D [25(OH)D]. RESULTS: The median vitamin D concentrations in the infant group (0-1 years of age) was 69.40 nmol/L, which were higher than that in both the toddlerhood group (1-3 years of age; 62.30 nmol/L) and the preschool group (3-6 years of age; 50.85 nmol/L). In addition, the median vitamin D concentrations were 71.70 nmol/L in summer, which was higher than that in spring (64.25 nmol/L), autumn (62.95 nmol/L) and winter (64.10 nmol/L). However, no difference was observed between genders (P = 0.974). Furthermore, the prevalence of vitamin D deficiency (< 50 nmol/L) was 48.1% in the preschool group (3-6 years of age), which was higher than the 21.2% vitamin D deficiency in the toddlerhood group (1-3 years of age) and the 17.9% vitamin D deficiency in the infant group (0-1 years of age). Interestingly, a nonlinear association between 25(OH) D and air temperature was observed. CONCLUSIONS: A high prevalence of vitamin D deficiency was common in a Chinese population of children 0-6 years old, especially in the preschool-aged children. Therefore, we suggested that we should pay more attention to vitamin D supplementation in Chinese young children.


Assuntos
Estações do Ano , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Fatores Etários , Povo Asiático , Criança , Pré-Escolar , China/epidemiologia , Cidades , Suplementos Nutricionais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Prevalência , Inquéritos e Questionários , Temperatura , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Vitaminas
5.
J Trace Elem Med Biol ; 43: 148-152, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28126204

RESUMO

Our objective was to evaluate the relationship between iron level and thyroid function during the first trimester of pregnancy in Eastern China. This was a hospital-based, cross-sectional observational study. A total of 1764 pregnant women were enrolled during their first trimester of gestation in Wuxi city. Serum ferritin (SF), hemoglobin (Hb), urinary iodine concentrations (UIC), thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) were measured and evaluated in pregnant women. The median of TSH,FT4 and FT3 were 1.53mIU/L,10.43pmol/L and 4.50pmol/L respectively. The median UIC was 200µg/L and the median Hb was 126g/L. Of all the women, 1.76% of the subjects had iron deficiency anaemia (IDA) (SF<20µg/L and Hb<105g/L), and 39.06% of the population had iron deficiency (ID) (SF<15µg/L). Compared with SF>100µg/L group, the FT4 level was significantly lower in SF<20µg/L group (P=0.031) and in SF 20-100µg/L group (P=0.048). The TSH value of SF>20µg/L group was significantly higher than that in SF 20-100µg/L group (P=0.038) and SF>100µg/L group(P=0.034). There was an inverse linear relationship between TSH and FT4 after log transformation (r=0.245,P=0.000). Moreover, spearman's correlation analysis showed that UIC were correlated with SF and FT3 (all P<0.001) and iodine status more than adequate was associated with reduced serum ferritin concentration and FT3 levels. Thus, it is recommended that iron deficiency and iron deficiency anaemia shoud be evaluated and treated to combat thyroid dysfunction during the first trimester of pregnancy, Meanwhile, an increased attention should be paid on iodine nutritional status among this pregnant women simultaneous iron deficiency and thyroid dysfunction.


Assuntos
Ferro/sangue , Estudos Transversais , Feminino , Humanos , Iodo/sangue , Gravidez , Primeiro Trimestre da Gravidez , Testes de Função Tireóidea , Glândula Tireoide/metabolismo , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
6.
Artigo em Inglês | MEDLINE | ID: mdl-27483296

RESUMO

BACKGROUND: Regulation of iron transfer from mother to fetus via the placenta is not fully understood and the relationship between stored iron status in the mothers' serum and gestational diabetes (GDM) in case-control studies is controversial. The present study aimed to detect circulating soluble transferrin receptor (sTfR) and ferritin levels in maternal and umbilical cord blood. We also examined the expression of hepcidin (Hep), transferrin receptor (TfR1), and ferroportin (FPN) in the placenta in pregnant women with and without GDM at full term. METHODS: Eighty-two women participated (42 with GDM and 40 without GDM [controls]). Maternal samples were collected at 37-39 weeks' gestation. Umbilical cord blood was collected at birth. Ferritin and sTfR levels in maternal serum and umbilical cord blood, and Hep, TfR1, and FPN protein expression in plac enta were compared between the GDM and non-GDM groups. Serum ferritin (SF) was measured by electrochemiluminescence assay and sTfR was measured by ELISA. Hep, TfR1, and FPN expression was measured by immunohistochemistry. RESULTS: Maternal serum sTfR levels were significantly elevated in the GDM group compared with the non-GDM group (p = 0.003). SF levels in cord blood in the GDM group were significantly higher than those in the non-GDM group (p = 0.003). However, maternal hemoglobin and SF, and umbilical cord sTfR levels were not different between the groups. In placental tissue, FPN expression was higher and hepcidin expression was lower in the GDM group compared with the non-GDM group (p = 0.000 and p = 0.044, respectively). There was no significant difference in TfR1 between the groups (p = 0.898). CONCLUSIONS: Women with GDM transport iron more actively than those without GDM at term pregnancy. Maternal iron metabolism in GDM may play a role in fetal/placental iron demand and in the overall outcome of pregnancy.


Assuntos
Antígenos CD/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Diabetes Gestacional/metabolismo , Ferritinas/metabolismo , Sangue Fetal/metabolismo , Hepcidinas/metabolismo , Ferro/metabolismo , Placenta/metabolismo , Receptores da Transferrina/metabolismo , Adulto , Estudos de Casos e Controles , China/epidemiologia , Diabetes Gestacional/fisiopatologia , Feminino , Idade Gestacional , Humanos , Ferro/sangue , Fenômenos Fisiológicos da Nutrição Materna , Troca Materno-Fetal/fisiologia , Placenta/fisiopatologia , Gravidez , Terceiro Trimestre da Gravidez
7.
Arterioscler Thromb Vasc Biol ; 34(7): 1539-47, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24790141

RESUMO

OBJECTIVE: Interleukin-8 (IL-8) receptors IL8RA and IL8RB (IL8RA/B) on neutrophil membranes bind to IL-8 with high affinity and play a critical role in neutrophil recruitment to sites of injury and inflammation. This study tested the hypothesis that administration of rat pulmonary arterial endothelial cells (ECs) overexpressing IL8RA/B can accelerate the adhesion of ECs to the injured lung and inhibit monocrotaline-induced pulmonary inflammation, arterial thickening and hypertension, and right ventricular hypertrophy. APPROACH AND RESULTS: The treatment groups included 10-week-old ovariectomized Sprague-Dawley rats that received subcutaneous injection of PBS (vehicle), a single injection of monocrotaline (monocrotaline alone, 60 mg/kg, SC), monocrotaline followed by intravenous transfusion of ECs transduced with the empty adenoviral vector (null-EC), and monocrotaline followed by intravenous transfusion of ECs overexpressing IL8RA/B (1.5 × 10(6) cells/rat). Two days or 4 weeks after monocrotaline treatment, endothelial nitric oxide synthase, inducible nitric oxide synthase, cytokine-induced neutrophil chemoattractant-2ß (IL-8 equivalent in rat), and monocyte chemoattractant protein-1 expression, neutrophil and macrophage infiltration into pulmonary arterioles, and arteriolar and alveolar morphology were measured by histological and immunohistochemical techniques. Proinflammatory cytokine/chemokine protein levels were measured by Multiplex rat-specific magnetic bead-based sandwich immunoassay in total lung homogenates. Transfusion of ECs overexpressing IL8RA/B significantly reduced monocrotaline-induced neutrophil infiltration and proinflammatory mediator (IL-8, monocyte chemoattractant protein-1, inducible nitric oxide synthase, cytokine-induced neutrophil chemoattractant, and macrophage inflammatory protein-2) expression in lungs and pulmonary arterioles and alveoli, pulmonary arterial pressure, and pulmonary arterial and right ventricular hypertrophy and remodeling. CONCLUSIONS: These provocative findings suggest that targeted delivery of ECs overexpressing IL8RA/B is effective in repairing the injured pulmonary vasculature.


Assuntos
Células Endoteliais/transplante , Terapia Genética/métodos , Hipertensão Pulmonar/prevenção & controle , Monocrotalina , Artéria Pulmonar/metabolismo , Receptores de Interleucina-8/biossíntese , Adenoviridae/genética , Animais , Pressão Arterial , Células Cultivadas , Quimiocina CCL2/metabolismo , Quimiocinas CXC/metabolismo , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Hipertensão Pulmonar Primária Familiar , Feminino , Vetores Genéticos , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/genética , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/fisiopatologia , Hipertrofia Ventricular Direita/prevenção & controle , Macrófagos/metabolismo , Infiltração de Neutrófilos , Neutrófilos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ovariectomia , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Ratos , Ratos Sprague-Dawley , Receptores de Interleucina-8/genética , Transdução Genética , Regulação para Cima , Função Ventricular Direita , Remodelação Ventricular
8.
Am J Physiol Heart Circ Physiol ; 305(4): H590-8, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23771691

RESUMO

The endothelium is a dynamic component of the cardiovascular system that plays an important role in health and disease. This study tested the hypothesis that targeted delivery of endothelial cells (ECs) overexpressing neutrophil membrane IL-8 receptors IL8RA and IL8RB reduces acute myocardial infarction (MI)-induced left ventricular (LV) remodeling and dysfunction and increases neovascularization in the area at risk surrounding the infarcted tissue. MI was created by ligating the left anterior descending coronary artery in 12-wk-old male Sprague-Dawley rats. Four groups of rats were studied: group 1: sham-operated rats without MI or EC transfusion; group 2: MI rats with intravenous vehicle; group 3: MI rats with transfused ECs transduced with empty adenoviral vector (Null-EC); and group 4: MI rats with transfused ECs overexpressing IL8RA/RB (1.5 × 106 cells post-MI). Two weeks after MI, LV function was assessed by echocardiography; infarct size was assessed by triphenyltetrazolium chloride (live tissue) and picrosirus red (collagen) staining, and capillary density and neutrophil infiltration in the area at risk were measured by CD31 and MPO immunohistochemical staining, respectively. When compared with the MI + vehicle and MI-Null-EC groups, transfusion of IL8RA/RB-ECs decreased neutrophil infiltration and pro-inflammatory cytokine expression and increased capillary density in the area at risk, decreased infarct size, and reduced MI-induced LV dysfunction. These findings provide proof of principle that targeted delivery of ECs is effective in repairing injured cardiac tissue. Targeted delivery of ECs to infarcted hearts provides a potential novel strategy for the treatment of acute MI in humans.


Assuntos
Células Endoteliais/transplante , Terapia Genética/métodos , Infarto do Miocárdio/terapia , Miocárdio/metabolismo , Receptores de Interleucina-8/biossíntese , Remodelação Ventricular , Adenoviridae/genética , Animais , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/imunologia , Células Endoteliais/metabolismo , Vetores Genéticos , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Masculino , Infarto do Miocárdio/genética , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/imunologia , Miocárdio/patologia , Neovascularização Fisiológica , Infiltração de Neutrófilos , Ratos , Ratos Sprague-Dawley , Receptores de Interleucina-8/genética , Proteínas Recombinantes de Fusão/biossíntese , Fatores de Tempo , Transdução Genética , Transfecção , Regulação para Cima , Disfunção Ventricular Esquerda/genética , Disfunção Ventricular Esquerda/imunologia , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/prevenção & controle , Função Ventricular Esquerda
9.
Biol Trace Elem Res ; 149(3): 412-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22628058

RESUMO

Undernutrition during pregnancy and/or lactation plays an important role on the overall health of offspring later in life. Using a rodent model, the present study was conducted to examine the effect of fetal and early postnatal iron deficiency on iron metabolism in adult animals. Rats were treated with three stages of low or normal iron diets from gestation until the end of the study. During the first stage (4 weeks prior to 3 weeks after pregnancy, total 7 weeks), two groups of adult females (dams) were fed with either a low-iron (7.4 mg iron/kg, group LD) or control-iron (274 mg/kg, group CD) diet. During the second stage (from 3 to 13 weeks of age, total 10 weeks), all pups from stage 1 (both the LD and CD groups) were placed on a control-iron diet for 10 weeks (groups LD-CD and CD-CD, respectively). During the third stage (from 13 to 29 weeks of age, total 16 weeks), both LD-CD and CD-CD groups from stage 2 were fed with a low-iron (named LD-CD-LD and CD-CD-LD groups, respectively). We found that the live birth rate of the offspring of the LD dams (84.7 %) was significantly lower than that of the CD dams (95.4 %). During stage 2, the mean body weight of the LD-CD male or LD-CD female rats exceeded the CD-CD male rats (p < 0.05). Compared with the CD-CD-LD rats, the LD-CD-LD rats had significantly increased total iron binding capacity, and higher levels of transferrin, serum erythropoietin (EPO), renal EPO mRNA, duodenal divalent metal transporter-1, and renal transferrin receptors. These findings indicate that rats with an early-life experience of iron deficiency (during pregnancy and the nursing period) can develop stronger iron absorption capabilities in adulthood.


Assuntos
Deficiências de Ferro , Ferro/metabolismo , Animais , Feminino , Feto/metabolismo , Masculino , Ratos , Ratos Wistar
10.
Wei Sheng Yan Jiu ; 38(6): 692-5, 2009 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-20047224

RESUMO

OBJECTIVE: To explore the effect of low-iron intervene in pregnant rat on hematologic parameters of its offspring in adulthood. METHODS: Wistar female rats at the age of six weeks were divided into two groups randomly: experimental group were feeded with low-iron diet, control group were feeded with iron-sufficient diet. They were mated with healthy male rats after four weeks and the iron intervention were carried out until the lactation period end. Iron-sufficient diet were then given to all rats for ten weeks and this period were called iron balancing period. After that control group and experimental group were divided into two groups respectively and all the rats were killed to detect Hb, RET, RDW, FEP, SI, SF, TIBC et al after sixteen weeks. RESULTS: Iron intervention in pregnant rats resulted in the iron deficiency of their offspring. In comparison with control group, Hb and RET of the offspring whose mother feeded with low-level iron diet in pregnancy were significantly elevated after four and six weeks in intervention again. While TIBC were also higher than those of control when intervention period was ended. CONCLUSION: Iron deficiency during pregnant rats produce long-dated affect on iron intake of their offspring in growth phase and adulthood, but it did not show stronger capability of anti-anemia than control rats.


Assuntos
Animais Recém-Nascidos/sangue , Deficiências de Ferro , Ferro da Dieta/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal , Fenômenos Fisiológicos da Nutrição Pré-Natal , Ração Animal , Animais , Animais Recém-Nascidos/crescimento & desenvolvimento , Feminino , Masculino , Exposição Materna , Gravidez , Distribuição Aleatória , Ratos , Ratos Wistar
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