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1.
Anticancer Res ; 40(1): 535-543, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892609

RESUMO

BACKGROUND/AIM: To assess the impact of vitamin D supplementation on genomic and metabolomic profiles and relate them to the individual's responsiveness to varying doses of vitamin D3 Patients and Methods: Healthy adults were given either 600, 4000 or 10,000 IUs vitamin D3/day for 6 months. Circulating parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], calcium, peripheral white blood cells broad gene expression and urine and serum metabolomic profiles were evaluated. RESULTS: There was a dose-dependent effect of vitamin D supplementation on serum 25(OH)D, PTH and broad gene expression. Serum calcium levels remained normal for all study subjects and no untoward toxicity was observed. The metabolomic profiles were related to the genomic expression analysis. There were significant inter-individual effects on gene expression and metabolomic profile in response to the same dose of vitamin D3 supplementation, despite similar changes in 25(OH)D and PTH concentrations. CONCLUSION: These results may help explain the variability observed in clinical trials regarding vitamin D's non-calcemic health benefits.


Assuntos
Suplementos Nutricionais , Genômica , Metabolômica , Vitamina D/farmacologia , Adulto , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Hormônio Paratireóideo/sangue , Análise de Componente Principal , Mapas de Interação de Proteínas/efeitos dos fármacos , Vitamina D/análogos & derivados , Vitamina D/sangue
2.
Artigo em Inglês | MEDLINE | ID: mdl-31518684

RESUMO

Generally, fish are thought to have a limited ability to utilize carbohydrate. Postprandial blood glucose is cleared sluggishly in fish, resulting in prolonged hyperglycemia. Facilitative glucose transporters (GLUTs) play an important role in glucose utilization. In the present study, the expression levels of glut2 in different tissues were detected in grass carp. Furthermore, the effects of oral glucose administration on glut2 mRNA expression in the liver, intestine and kidney were investigated, and we also evaluated the response of glut2 mRNA to insulin and glucagon in the primary hepatocytes of grass carp. The expression level of glut2 mRNA was highest in the liver, followed by the intestine and kidney, but lower in other tissues. The result of glucose tolerance test (GTT) showed that serum glucose reached the highest level at 3 h after GTT and recovered to the basic level at 6 h. The glut2 mRNA in the intestine was up-regulated at 1 h after GTT. However, the glut2 mRNA expression in the liver of grass carp was unchanged after GTT for 1, 3, 6 h, and even decreased at 12 h after GTT. In addition, the expression of glut2 mRNA in the primary hepatocytes was enhanced by insulin and glucagon at 3 h post treatment. These results suggested that glut2 expression in the liver of grass carp was sensitive to insulin and glucagon, but not blood glucose. The up-regulation of glut2 by these hormones might be involved in the bi-directional transportation of glucose in the liver.


Assuntos
Cyprinidae/metabolismo , Proteínas de Peixes/metabolismo , Glucagon/metabolismo , Transportador de Glucose Tipo 2/biossíntese , Glucose/farmacologia , Hepatócitos/metabolismo , Insulina/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/metabolismo
3.
Cell Physiol Biochem ; 53(5): 851-864, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31714043

RESUMO

BACKGROUND/AIMS: The growth promoting effect of lysine and betaine as well as the expression of candidate genes reflecting their efficacy, such as ghrelin, leptin, Growth Hormone Secretagogue Receptor (GHS-R), Insulin like Growth Factor (IGF- 1) and Growth Hormone Releasing Hormone (GHRH) was examined in Labeo rohita fingerlings. METHODS: One hundred eighty healthy juveniles from a homologous population were randomly distributed to 15 rectangular tanks of 150 litres capacity. The experiment was carried out for 60 days with five treatment groups consisting T1 (0.25% Betaine), T2 (0.5% Betaine), T3 (0.75% Lysine) and T4 (1.5% Lysine) and control group. The experiment was carried out for 60 days with five treatment groups consisting T1 (0.25% Betaine), T2 (0.5% Betaine), T3 (0.75% Lysine) and T4 (1.5% Lysine) and control group. At the end of trial, the growth parameters such as weight gain, SGR, PER were estimated from the weight of the triplicate groups. The digestive, metabolic and antioxidant enzymes were analysed using spectrophotometric methods. The intestine, brain and liver were sampled from the treatments and expression of different genes ghrelin, leptin, GHSR, IGF-1 and GHRH was also performed by realtime PCR. RESULTS: A significant (P<0.05) increase in weight gain, SGR, PER and lowest FCR was found in T4 group which was significantly (p < 0.05) different from other experimental groups. The highest mRNA expression levels of expression were found in T4 group which was similar to that of ghrelin gene mRNA of T2 group. The significantly (p<0.05) highest GHSR, GHRH and IGF-1 gene expression levels were found in T4 treatment group compared to other groups. CONCLUSION: The present study reveals that the lysine and betaine stimulate growth and expression of ghrelin GHRH, GHS-R and IGF-1 genes. The increase of IGF-I mRNA expression with lysine and betaine supplementation revealed that these compounds act as growth modulators. However, lysine was found to be a more potent modulator of growth compared to betaine.


Assuntos
Betaína/farmacologia , Cyprinidae/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Lisina/farmacologia , Ração Animal , Animais , Catalase/metabolismo , Cyprinidae/crescimento & desenvolvimento , Grelina/genética , Grelina/metabolismo , Hormônio Liberador de Hormônio do Crescimento/genética , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Leptina/genética , Leptina/metabolismo , Fígado/enzimologia , Fígado/metabolismo , Receptores de Grelina/genética , Receptores de Grelina/metabolismo , Superóxido Dismutase/metabolismo
4.
Life Sci ; 237: 116890, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31606379

RESUMO

AIMS: Telmisartan (TEL), an angiotensin II type I receptor blocker and PPARγ partial agonist, has been used for to treat hypertension. It is known that PPARγ activation induces bone loss. Therefore, we evaluate the effects of telmisartan on PPARγ protein expression, biomechanics, density and bone microarchitecture of femurs and lumbar vertebrae in SHR ovariectomized animals, a model of hypertension in which preexisting bone impairment has been demonstrated. MAIN METHODS: SHR females (3 months old) were distributed into four groups: sham (S), sham + TEL (ST), OVX (C) and OVX + TEL (CT). TEL (5 mg/kg/day) or vehicle were administered according to the groups. After the protocol, blood pressure was measured and density, microarchitecture and biomechanics of bone were analyzed. Western blotting analysis was performed to evaluate PPARγ protein expression in the bones. KEY FINDINGS: Castration induced a deleterious effect on mineral density and trabecular parameters, with telmisartan enhancing such effects. Telmisartan increased PPARγ levels, which were at their highest when the treatment was combined with castration. As to biomechanical properties, telmisartan reduced the stiffness in the castration group (CT vs. S or C group), as well as resilience and failure load in ST group (vs. all others groups). SIGNIFICANCE: These results demonstrated that telmisartan compromised bone density and microarchitecture in animals that shows preexisting osteoporotic bone disorders, probably via mechanisms associated with increased PPARγ. If this translates to humans, a need for greater caution in the use of telmisartan by patients that have preexisting bone problems, as in the postmenopausal period, may be in order.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Doenças Ósseas/tratamento farmacológico , Osso Esponjoso/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Osteoporose/tratamento farmacológico , PPAR gama/metabolismo , Telmisartan/farmacologia , Animais , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas/metabolismo , Doenças Ósseas/fisiopatologia , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/patologia , Feminino , Osteoporose/metabolismo , Osteoporose/fisiopatologia , PPAR gama/genética , Ratos , Ratos Endogâmicos SHR , Tomografia Computadorizada por Raios X
5.
Life Sci ; 237: 116914, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31622606

RESUMO

AIMS: The aim of the presente study was to examine the effects of oral gallic acid (GA) administration on the brown adipose tissue of obese mice fed with high-fat diet. New mechanisms and interactions pathways in thermogenesis were accessed through bioinformatics analyses. MAIN METHODS: Swiss male mice were divided into four groups and fed during 60 days with: standard diet, standard diet combined with gallic acid, high-fat diet and high-fat diet combined with gallic acid. Body weight, food intake, and blood parameters (glucose tolerance test, total-cholesterol, high-density low-c, triglyceride and glucose levels) were evaluated. Brown and subcutaneous white adipose tissue histological analysis were performed. SIRT1 and PGC1-α mRNA expression in the brown adipose tissue were assessed. KEY FINDINGS: Our main findings showed that the gallic acid improved glucose tolerance and metabolic parameters. These results were accompanied by bioinformatics analyses that evidenced SIRT1 as main target in the thermogenesis process, confirmed as increased SIRT1 mRNA expression was evidenced in the brown adipose tissue. SIGNIFICANCE: Together, the data suggest that the gallic acid effect in brown adipose tissue may improve body metabolism, glucose homeostasis and increase thermogenesis.


Assuntos
Tecido Adiposo Marrom/metabolismo , Biologia Computacional/métodos , Dieta Hiperlipídica/efeitos adversos , Ácido Gálico/farmacologia , Metaboloma/efeitos dos fármacos , Obesidade/metabolismo , Sirtuína 1/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/patologia , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Obesos , Obesidade/tratamento farmacológico , Obesidade/etiologia , Sirtuína 1/genética , Termogênese/efeitos dos fármacos
6.
Rev Assoc Med Bras (1992) ; 65(9): 1144-1150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618328

RESUMO

OBJECTIVE: In view of the high incidence of polycystic ovary syndrome (PCOS) and the unsatisfactory therapeutic effects of dimethyldiguanide or clomifene citrate alone, our study aimed to investigate the therapeutic effects of dimethyldiguanide combined with clomifene citrate in the treatment of PCOS. METHODS: A total of 79 patients with POCS and 35 healthy females were included, and endometrial biopsies were obtained. The sterol regulatory element-binding protein-1 (SREBP1) expression in endometrial tissues was detected by qRT-PCR. POC patients were randomly divided into group A (n=40) and group B (n=39). Patients in group A were treated with dimethyldiguanide combined with clomifene citrate, while patients in group B were treated with clomifene citrate alone. The number of mature follicles and cervical mucus score, follicular development rate and single follicle ovulation rate, cycle pregnancy rate, early miscarriage rate, ovulation rate, endometrial thickness, positive rate of three lines sign, follicle stimulating hormone level and luteinizing hormone level were compared between the two groups. RESULTS: The expression level of SREBP1 was higher in PCOS patients than that in the healthy control. SREBP1 expression was inhibited after treatment, while the inhibitory effects of combined treatment were stronger than those of clomifene citrate alone. Compared with clomifene citrate alone, the combined treatment improved cervical mucus score, follicle development rate, single follicle ovulation rate, endometrial thickness, positive rate of three lines sign, and follicle-stimulating hormone level. CONCLUSION: The therapeutic effect of combined treatment is better than clomifene citrate alone in the treatment of PCOS.


Assuntos
Clomifeno/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Muco do Colo Uterino/efeitos dos fármacos , Clomifeno/farmacologia , Quimioterapia Combinada , Endométrio/fisiopatologia , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Folículo Ovariano/efeitos dos fármacos , Indução da Ovulação , Proteína de Ligação a Elemento Regulador de Esterol 1/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Adulto Jovem
7.
Cell Physiol Biochem ; 53(4): 713-730, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31599538

RESUMO

BACKGROUND/AIMS: Renal injury related to hypertension is characterized by glomerular and tubulointerstitial damage. The overactivation of the renin-angiotensin system mainly by angiotensin II (AII) seems to be a main contributor to progressive renal fibrosis. Epithelial to mesenchymal transition (EMT) is a mechanism that promotes renal fibrosis. Owing to heat shock protein 70 (Hsp70) cytoprotective properties, the chaperone exhibits an important potential as a therapeutic target. We investigate the role of Hsp70 on Angiotensin II induced epithelial mesenchymal transition within the Losartan effect in proximal tubule cells (PTCs) from a genetic model of hypertension in rats (SHR). METHODS: Primary cell culture of PTCs from SHR and Wistar Kyoto (WKY) rats were stimulated with AII, treated with Losartan (L), (L+AII) or untreated (Cc). The functional Hsp70 role in Losartan effect, after silencing its expression by cell transfection, was determined by Immunofluorescence; Western blotting; Gelatin Zymography assays; Scratch wound assays; flow cytometry; and Live Cell Time-lapse microscopy. RESULTS: (L) and (L+AII) treatments induced highly organized actin filaments and increased cortical actin in SHR PTCs. However, SHR PTCs (Cc) and (AII) treated cells showed disorganized actin. After Hsp72 knockdown in SHR PTCs, (L) was unable to stabilize the actin cytoskeleton. We demonstrated that (L) and (L+AII) increased E-cadherin levels and decreased vinculin, α-SMA, vimentin, pERK, p38 and Smad2-3 activation compared to (AII) and (Cc) SHR PTCs. Moreover, (L) inhibited MMP-2 and MMP-9 secretion, reduced migration and cellular displacement, stabilizing intercellular junctions. Notably, (L) treatment in shHsp72 knockdown SHR PTCs showed results similar to SHR PTCs (Cc). CONCLUSION: Our results demonstrate that Losartan through Hsp70 inhibits the EMT induced by AII in proximal tubule cells derived from SHR.


Assuntos
Angiotensina II/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/metabolismo , Losartan/farmacologia , Citoesqueleto de Actina/efeitos dos fármacos , Animais , Caderinas/metabolismo , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Adesões Focais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/antagonistas & inibidores , Proteínas de Choque Térmico HSP70/genética , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Vinculina/metabolismo
8.
Cell Physiol Biochem ; 53(4): 687-700, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31577078

RESUMO

BACKGROUND/AIMS: Apelin and its G protein-coupled receptor APJ (gene symbol Aplnr) are strongly expressed in magnocellular vasopressinergic neurons suggesting that the apelin/APJ system plays a key role at the central level in regulating salt and water balance by counteracting the antiduretic action of vasopressin (AVP). Likewise, recent studies revealed that apelin exerts opposite effects to those of vasopressin induced on water reabsorption via a direct action on the kidney collecting duct. However, the underlying mechanisms of the peripheral action of apelin are not clearly understood. Here, we thus investigated the role of the apelin/APJ system in the regulation of water balance in the kidney, and more specifically its involvement in modulating the function of aquaporin-2 (AQP2) in the collecting duct. METHODS: Mouse cortical collecting duct cells (mpkCCD) were incubated in the presence of dDAVP and treated with or without apelin-13. Changes in AQP2 expression and localization were determined by immunoblotting and confocal immunofluorescence staining. RESULTS: Herein, we showed that the APJ was present in mpkCCD cells. Treatment of mpkCCD with apelin-13 reduced the cAMP production and antagonized the AVP-induced increase in AQP2 mRNA and protein expressions. Immunofluorescent experiments also revealed that the AVP-induced apical cell surface expression of AQP2, and notably its phosphorylated isoform AQP2-pS269, was considerably reduced following apelin-13 application to mpkCCD cells. CONCLUSION: Our data reinforce the aquaretic role of the apelin/APJ system in the fine regulation of body fluid homeostasis at the kidney level and its physiological opposite action to the antiduretic activity of AVP.


Assuntos
Aquaporina 2/metabolismo , Desamino Arginina Vasopressina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Transporte Proteico/efeitos dos fármacos , Animais , Receptores de Apelina/metabolismo , Aquaporina 2/genética , Linhagem Celular , AMP Cíclico/metabolismo , Células HEK293 , Humanos , Túbulos Renais Coletores/citologia , Túbulos Renais Coletores/metabolismo , Camundongos , Fosforilação/efeitos dos fármacos
9.
Int J Nanomedicine ; 14: 7039-7052, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564864

RESUMO

Purpose: In this study, we fabricated multifunctional, electrically conductive composites by incorporating graphene oxide (GO) into a poly (lactic-co-glycolic acid) (PLGA) copolymer for wound repair. Furthermore, the resultant composites were coupled with electrical stimulation to further improve the therapeutic effect of wound repair. Methods: We evaluated the surface morphology of the composites, as well as their physical properties, cytotoxicity, and antibacterial activity, along with the combined effects of composites and electrical stimulation (ES) in a rat model of wound healing. Results: Application of the PLGA/GO composites to full-thickness wounds confirmed their advantageous biological properties, as evident from the observed improvements in wound-specific mechanical properties, biocompatibility, and antibacterial activity. Additionally, we found that the combination of composites and ES improved composite-mediated cell survival and accelerated wound healing in vivo by promoting neovascularization and the formation of type I collagen. Conclusion: These results demonstrated that combined treatment with the PLGA/GO composite and ES promoted vascularization and epidermal remodeling and accelerated wound healing in rats, thereby suggesting the efficacy of PLGA/GO+ES for broad applications associated with wound repair.


Assuntos
Grafite/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Cicatrização , Animais , Antibacterianos/farmacologia , Adesão Celular/efeitos dos fármacos , Adesão Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Forma Celular/efeitos dos fármacos , Forma Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Estimulação Elétrica , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Neovascularização Fisiológica/efeitos dos fármacos , Ratos Sprague-Dawley , Propriedades de Superfície , Cicatrização/efeitos dos fármacos , Cicatrização/genética
10.
Medicine (Baltimore) ; 98(38): e17267, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31568004

RESUMO

Smoking is a substantial risk factor for many respiratory diseases. This study aimed to identify the gene and microRNA changes related to smoking in human airway epithelium by bioinformatics analysis.From the Gene Expression Omnibus (GEO) database, the mRNA datasets GSE11906, GSE22047, GSE63127, and microRNA dataset GSE14634 were downloaded, and were analyzed using GEO2R. Functional enrichment analysis of the differentially expressed genes (DEGs) was enforced using DAVID. The protein-protein interaction (PPI) network and differentially expressed miRNAs (DEMs)- DEGs network were executed by Cytoscape.In total, 107 DEGs and 10 DEMs were determined. Gene Ontology (GO) analysis revealed that DEGs principally enriched in oxidation-reduction process, extracellular space and oxidoreductase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway demonstrated that DEGs were principally enriched in metabolism of xenobiotics by cytochrome P450 and chemical carcinogenesis. The PPI network revealed 15 hub genes, including NQO1, CYP1B1, AKR1C1, CYP1A1, AKR1C3, CEACAM5, MUCL1, B3GNT6, MUC5AC, MUC12, PTGER4, CALCA, CBR1, TXNRD1, and CBR3. Cluster analysis showed that these hub genes were associated with adenocarcinoma in situ, squamous cell carcinoma, cell differentiation, inflammatory response, oxidative DNA damage, oxidative stress response and tumor necrosis factor. Hsa-miR-627-5p might have the most target genes, including ITLN1, TIMP3, PPP4R4, SLC1A2, NOVA1, RNFT2, CLDN10, TMCC3, EPHA7, SRPX2, PPP1R16B, GRM1, HS3ST3A1, SFRP2, SLC7A11, and KLHDC8A.We identified several molecular changes induced by smoking in human airway epithelium. This study may provide some candidate genes and microRNAs for assessing the risk of lung diseases caused by smoking.


Assuntos
Expressão Gênica/efeitos dos fármacos , MicroRNAs/metabolismo , Mucosa Respiratória/metabolismo , Fumar/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Mapas de Interação de Proteínas/efeitos dos fármacos , Mucosa Respiratória/efeitos dos fármacos , Fumar/metabolismo
11.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(8): 702-706, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31638567

RESUMO

Objective To analyze the changes and correlation between inflammation and Klotho expression in kidney tissue of mice with acute kidney injury (AKI) induced by cisplatin, and to explore the role and possible mechanism of Klotho in AKI induced by cisplatin. Methods Eighteen male C57BL/6 mice were randomly divided into 0-day group, 1-day group and 3-day group with 6 mice in each group. The mice were killed at 0, 1 and 3 days after a single intraperitoneal injection of 25 mg/kg of cisplatin, and the serum and kidney tissues were collected. The content of serum creatinine (Scr) and blood urea nitrogen (BUN) were measured by biochemical analyzer, and the pathological changes of kidney tissues were observed by HE staining. Neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor α (TNF-α), NLR family pyrin domain containing 3 (NLRP3), Klotho, signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 (p-STAT3), nuclear factor-kappa B (NF-κB), phosphorylated NF-kappa B (p-NF-κB) were detected by Western blot analysis. Spearman rank correlation test was used to analyze the correlations. Results The content of serum Scr and BUN in 1-day and 3-day groups were significantly higher than those in 0-day group, and inflammatory cell infiltration, renal tubular epithelial cell exfoliation, edema and accumulation of cell fragments were seen in 1-day and 3-day groups. In the 3-day group, the content of NGAL, TNF-α, NLRP3, p-STAT3, STAT3, p-NF-κB and NF-κB proteins in renal tissues significantly increased, and the expression of TNF-α, p-STAT3 and STAT3 increased in a time-dependent manner. The expression of Klotho decreased in a time-dependent manner in the 1-day and 3-day groups, and the expression of NGAL, TNF-α, NLRP3, p-STAT3, and p-NF-κB were significantly negatively correlated with the expression of Klotho. Conclusion The activation of STAT3/NF-κB pathway by Klotho is involved in the regulation of the occurrence and development of AKI induced by cisplatin in mice.


Assuntos
Lesão Renal Aguda , Cisplatino , Regulação da Expressão Gênica , Glucuronidase , Rim , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/fisiopatologia , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Glucuronidase/genética , Rim/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Distribuição Aleatória
12.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(8): 721-726, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31638570

RESUMO

Objective To study the effects of compound porcine cerebroside and ganglioside injection (CPCGI) on brain injury and expression of cerebellin 4 (CBLN4) in neonatal mice after intrauterine hypoxia. Methods A total of 15 healthy adult pregnant mice were randomly divided into 3 groups: control group with 3 mice, model group and CPCGI treatment group with 6 mice in each group. From the 14th day of pregnancy, the pregnant mice in the CPCGI treatment group and model group were put into the animal hypoxia box to produce the intrauterine hypoxia fetal mouse models. After the delivery of mother, the neonatal mice in the CPCGI treatment group and model group were given CPCGI (1 mL/kg) and PBS via abdominal cavity, respectively, while the control group received no treatment. At 40 days postpartum, the memory ability of mice was trained with a platform jumper test. After the platform test, the brain tissue of the mice was taken out. The expression of neurogenolase (NSE), interleukin-1 beta (IL-1ß), CBLN4 and synaptophsin (SYN) were detected by immunofluorescence staining. The relative expression of CBLN4 protein in the hippocampus of mice was detected by Western blot analysis. Results Compared with the control group, hypoxia caused a significant decrease in learning and memory ability of newborn mice, and CPCGI could significantly improve the memory of mice. After hypoxia, the expression of NSE, CBLN4 and SYN in the neonatal cerebellum significantly decreased, and the expression of IL-1ß significantly increased. The expression of NSE, CBLN4 and SYN in CPCGI treatment group was significantly higher than those in the model group, and the expression of IL-1ß was significantly lower than that in the model group. Conclusion CPCGI can reduce neuronal damage in neonatal mice after hypoxia, which may be related to the reduction of IL-1ß expression and the promotion of synaptic reconstruction.


Assuntos
Lesões Encefálicas , Cerebrosídeos , Gangliosídeos , Regulação da Expressão Gênica , Hipóxia , Animais , Animais Recém-Nascidos , Lesões Encefálicas/tratamento farmacológico , Cerebrosídeos/farmacologia , Cerebrosídeos/uso terapêutico , Feminino , Gangliosídeos/farmacologia , Gangliosídeos/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Hipóxia/tratamento farmacológico , Hipóxia/genética , Camundongos , Gravidez , Suínos
13.
Endocrinology ; 160(10): 2339-2352, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504411

RESUMO

Osteoporosis is a complication of diabetes mellitus (DM). The pathology of diabetic osteoporosis is distinct from postmenopausal osteoporosis, and there are no specific treatment guidelines for diabetic osteoporosis. In the current study, this issue was addressed by evaluating the effect of osteoporosis medications, such as the anabolic agent PTH [teriparatide (TPTD)] and the antiresorptive agents calcitonin [elcatonin (ECT)] and bisphosphonate [risedronate (RIS)], on bone metabolism as well as on glucose and lipid metabolism in spontaneously diabetic Torii (SDT) fatty rats, which are a model of type 2 DM (T2DM). The medicines were injected subcutaneously into 8-week-old male SDT fatty rats three times weekly for 8 weeks. TPTD treatment in SDT fatty rats increased the osteoblast number and function on trabecular bone in vertebrae, and increased the trabecular bone mass, bone mineral density (BMD), and mechanical strength of vertebrae. Additionally, TPTD improved cortical bone structure and increased BMD. RIS decreased the osteoclast number and function, which led to an increase in vertebral bone mineral content and BMD in the femoral diaphysis, and mechanical strength was increased in the vertebrae. ECT showed no clear effects on bone mass or metabolism. Similar to diabetic lesions, all of the drugs had no effects on hyperglycemia, pancreas morphology, or serum insulin and glucagon levels. However, triglyceride levels and lipid droplets in fatty liver were decreased in the TPTD group. These results suggest that TPTD may be useful for treating fatty liver in addition to osteoporosis in T2DM.


Assuntos
Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Teriparatida/farmacologia , Animais , Glicemia , Densidade Óssea/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Fígado/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos
14.
Aquat Toxicol ; 215: 105286, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31479757

RESUMO

Chlorpyrifos (CPF) is an environmental pollutant with increasing importance due to its high toxicity to fish and aquatic animals. In the present study, we divided 120 common carp (Cyprinus carpio L.) into two groups including control group and CPF group, CPF group was exposed to 14.5 µg/L CPF for 30 d. 17 miRNAs were differentially expressed in CPF group head kidney tissues according to the results of miRNAome analysis. In addition, histopathological examination and electron microscopy proved that CPF exposure could lead to damage of head kidney and obvious apoptosis characteristics. The possible target genes of miRNA were predicted using online target gene prediction websites, miRNAome sequencing, GO and KEGG enrichment. miRNAome results showed that expression of miR-731 and miR-2188-3p in CPF group was 0.48 time and 0.45 time as control group, respectively. qRT-PCR results proved the reality of miRNAome. During CPF exposure, mRNA expression of TLR pathway genes and its downstream genes involved in autophagy and apoptosis pathway including TLR1, TLR2, TLR7, TLR9, MyD88, IRAK1, IRAK4, IRF7, PI3K, AKT, mTOR, Caspase3, Caspase8 and Bax were differentially increased under CPF exposure, along with ATG13 and Bcl2 decreased at the same time. Western blot results indicated that apoptosis related protein Caspase3 and Caspase8 were differentially up-regulated in the CPF group. In summary, CPF exposure could induce apoptosis while inhibited autophagy in head kidney of common carp via the regulation of miR-2188-3p and miR-731 by targeting TLR pathway. These results provide new insights for unveiling the biological effects of CPF and miRNAs in common carp.


Assuntos
Apoptose/genética , Carpas/genética , Clorpirifos/toxicidade , Rim Cefálico/lesões , MicroRNAs/metabolismo , Transdução de Sinais , Receptores Toll-Like/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Autofagia/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Ontologia Genética , Rim Cefálico/efeitos dos fármacos , Rim Cefálico/metabolismo , Rim Cefálico/ultraestrutura , MicroRNAs/química , MicroRNAs/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Transdução de Sinais/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade
15.
Artigo em Inglês | MEDLINE | ID: mdl-31473330

RESUMO

Estradiol (E2) is a sex steroid hormone that modulates multiple physiological processes in teleosts. The aim of this study was to explore the role of E2 in the hepatic lipid metabolism of hybrid tilapia. The hybrid tilapias were injected with different concentrations of E2 (0 mg/kg, 10 mg/kg, 25 mg/kg and 50 mg/kg) and ICI 182,780 (ICI) (35 mg/kg) (an E2 receptor antagonist). Subsequently, the liver lipid depositions were analyzed by tissue sections with oil red O staining. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and nonesterified fatty acids (NEFAs) were assayed from the fish in different groups. Genes related to very low-density lipoprotein (VLDL) assembly, lipoprotein lipase and lipoprotein receptors, fatty acid uptake and triacylglycerol metabolism were determined by quantitative RT-PCR. The results showed that 50 mg/kg E2 injections enlarged the lipid droplets significantly. Simultaneously, the E2 injections tended to upregulate TC, TG, LDL, and HDL in the serum. The 50 mg/kg E2 group showed a significantly higher expression of the VLDL assembly genes but depressed levels of LDLR and LRP1. In addition, FABP3, FABP11a and DGAT2 were significantly elevated, while CD36 and ACO1 decreased in the 50 mg/kg E2 injection. The ICI injection inhibited the expression of MTP, LPL, LRP1, CD36, FABP11a, ACO1 and FAS in tilapia livers. These results demonstrated that by stimulating the expression of genes associated with the VLDL assembly, inhibiting lipoprotein lipase and lipoprotein receptor-related genes and promoting the rate-limiting enzyme in the synthesis of the TG, E2 induced deposition of lipids in the livers of hybrid tilapia. Overall, the results suggest a role for E2 in fish lipid metabolisms that provide new clues to illustrate the sex steroid function in energy metabolism in livers.


Assuntos
Estradiol/farmacologia , Proteínas de Peixes/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/metabolismo , Tilápia/metabolismo , Triglicerídeos/biossíntese , Animais , Cruzamentos Genéticos , Relação Dose-Resposta a Droga , Feminino , Proteínas de Peixes/genética , Masculino , Tilápia/genética , Triglicerídeos/genética
16.
Aquat Toxicol ; 215: 105289, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31491707

RESUMO

Mifepristone (RU486), a clinical abortion agent and potential endocrine disruptor, binds to progestin and glucocorticoid receptors and has multiple functional importance in reproductive physiology. A long-term exposure of RU486 resulted in masculinization of female fish, however, the epigenetic landscape remains elusive. Recent studies demonstrated that long non-coding RNAs (lncRNAs) might play potential roles in epigenetic modulation of sex differentiation, ovarian cancer and germline stem cell survival. To further understand the influence of RU486 exposure on epigenetic regulation, we performed a comparative investigation on sex-biased gonadal lncRNAs profiles using control XX/XY and RU486-induced sex reversed XX Nile tilapia (Oreochromis niloticus) by RNA-seq. In total, 962 sexually differentially expressed lncRNAs and their target genes were screened from the gonads of control and sex reversed fish. In comparison with the control XX group, sex reversal induced by RU486 treatment led to significant up-regulation of 757 lncRNAs and down-regulation of 221 lncRNAs. Hierarchical clustering analysis revealed that global lncRNA expression profiles in RU486-treated XX group clustered into the same branch with the control XY, whereas XX control group formed a separate branch. The KEGG pathway enrichment analysis showed that the cis-target genes between RU486-XX and control-XX were concentrated in NOD - like receptor signaling pathway, Cell adhesion molecules (CAMs) and Biosynthesis of amino acids. Real-time PCR and in situ hybridization experiments demonstrate that lncRNAs showing intense fluctuation during RU486 treatment are also sexually dimorphic during early sex differentiation, which further proves the intimate relationship between lncRNAs and sex differentiation and sexual transdifferentiation. Taken together, our data strongly indicates that a long-term exposure of RU486 resulted in sex reversal of XX female fish and the altered expression of sexually dimorphic lncRNAs might partially account for the sex reversal via epigenetic modification.


Assuntos
Ciclídeos/genética , Ciclídeos/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Gônadas/metabolismo , Mifepristona/toxicidade , Progestinas/antagonistas & inibidores , RNA Longo não Codificante/genética , Caracteres Sexuais , Animais , Feminino , Genoma , Gônadas/efeitos dos fármacos , Masculino , Fases de Leitura Aberta/genética , Ovário/efeitos dos fármacos , Ovário/metabolismo , RNA Longo não Codificante/metabolismo , Reprodutibilidade dos Testes , Testículo/efeitos dos fármacos , Testículo/metabolismo , Fatores de Tempo , Distribuição Tecidual/efeitos dos fármacos , Transcrição Genética/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade
17.
Life Sci ; 236: 116836, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31493479

RESUMO

AIMS: The present experiment was conceptualised to explore the therapeutic response of tetramethylpyrazine (TMP), a major active constituent of Ligusticum chuanxiong, a Chinese traditional medicinal plant, in high-fat diet (HFD)-streptozotocin (STZ)-induced diabetes in rats and to identify the possible mechanism of action. MAIN METHODS: Dose-reliant effect of oral treatment of TMP (100, 150 and 200 mg/kg/day) for 28 days was evaluated by calculating the alteration in body weight, level of fasting blood glucose (FBG), plasma insulin, homeostasis model assessment (HOMA), serum lipids, oral glucose & intraperitoneal insulin tolerance and glycosylated haemoglobin in HFD-STZ-induced type-2 diabetic (T2D) rats and underlying molecular mechanisms of TMP was also studied. KEY FINDINGS: TMP treatment prominently reduced the level of FBG, glycosylated haemoglobin and revived body weight gain and level of serum insulin dose-dependently in diabetic rats. TMP treatment considerably improved insulin resistance, as observed in oral glucose tolerance and insulin tolerance tests. Moreover, dose-dependent reduction in the level of pro-inflammatory cytokines, C-reactive protein (CRP) and interleukin-6 (IL-6) was observed and their level was found to be significantly reduced in highest dose TMP (200 mg/kg) treated diabetic rats, pointing towards TMP mediated recovery of insulin signalling and a decrease in insulin resistance. The expressions of p-PI3K-p85/p-Akt/GLUT-4 were also significantly up-regulated by TMP (200 mg/kg), suggesting the connection of the PI3K/Akt signal pathway in the anti-hyperglycemic action of TMP. SIGNIFICANCE: These findings suggest that TMP may be used as a potential agent for type-2 diabetes treatment.


Assuntos
Diabetes Mellitus Experimental/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Regulação da Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirazinas/farmacologia , Animais , Glicemia , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Transportador de Glucose Tipo 4/genética , Masculino , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Wistar , Transdução de Sinais , Vasodilatadores/farmacologia
18.
Aquat Toxicol ; 215: 105282, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31509759

RESUMO

Aquatic ecosystems are now chronically polluted by a cocktail of many chemical substances. There is now clear evidence of associations between exposure to pollutants and greater susceptibility to pathogens. The aim of the present study was to characterize the defense capacities of rainbow trout (Oncorhynchus mykiss), chronically exposed to pendimethalin (PD), to subsequent experimental challenge with the infectious hematopoietic necrosis virus (IHNV). Immunological responses were examined at different organizational levels, from individuals to gene expression. No negative effects of PD were noted on the Fulton index nor on the liver or spleen somatic indices (LSI; SSI) before viral infection, but the infectious stress seems to generate a weak but significant decrease in Fulton and LSI values, which could be associated with consumption of energy reserves. During the viral challenges, the distribution of cumulative mortality was slightly different between infected groups. The impact of the virus on fish previously contaminated by PD started earlier and lasted longer than controls. The proportion of seropositive fish was lower in the fish group exposed to PD than in the control group, with similar quantities of anti-IHNV antibodies secreted in positive fish, regardless of the treatment. While no significant differences in C3-1 expression levels were detected throughout the experiment, TNF1&2, TLR3, Il-1ß and IFN expression levels were increased in all infected fish, but the difference was more significant in fish groups previously exposed to herbicide. On the other hand, ß-def expression was decreased in the pendimethalin-IHNV group compared to that in fish only infected by the virus (control-IHNV group).


Assuntos
Herbicidas/toxicidade , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Vírus da Necrose Hematopoética Infecciosa/fisiologia , Oncorhynchus mykiss/genética , Oncorhynchus mykiss/imunologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/veterinária , Compostos de Anilina/toxicidade , Animais , Doenças dos Peixes/genética , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Regulação da Expressão Gênica/efeitos dos fármacos , Oncorhynchus mykiss/virologia , Infecções por Rhabdoviridae/genética , Infecções por Rhabdoviridae/patologia , Poluentes Químicos da Água/toxicidade
19.
Chemosphere ; 226: 874-882, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31509916

RESUMO

The exposure and health effects of fluoride are an ongoing topic that has attracted worldwide attention. Fluoride exposure disturbs the testicular development, sexual hormone levels and spermatogenesis. However, as to whether fluoride interferes with acrosome formation which is essential for production of capable spermatozoa during spermatogenesis still remains unclear. The objective was to determine the effects of fluoride on the acrosome formation and to further elucidate the potential mechanism of impaired reproductive function. For this, forty adult rats were assigned into four groups. The control group received distilled water, while the other three groups were treated with 25, 50 and 100 mg NaF/L via drinking water for 56 d, respectively. Testes were processed for total RNA extraction and western blot analysis. Three samples of each group were fixed in 2.5% glutaraldehyde solution for transmission electron microscopy analysis. From the results, we first found that fluoride decreased the expression of mRNA and protein levels of Zpbp1, Spaca1 and Dpy19l2 of seven markers during acrosome biogenesis in testes. Furthermore, fluoride damaged not only the acrosome structure, but also the structure of the nuclear lamina which was observed to be discontinuous and partially missing by transmission electron microscopy. Moreover, the results indicated that the altered structure in nuclear lamina maybe due to reduced LMNB2 expression in testis induced by fluoride. In a nutshell, fluoride exposure could restrain acrosome biogenesis during spermatogenesis and contribute to the elucidation of the underlying mechanisms of fluoride-induced male reproductive toxicity.


Assuntos
Acrossomo/patologia , Fluoretos/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/patologia , Testículo/patologia , Acrossomo/efeitos dos fármacos , Acrossomo/metabolismo , Animais , Proteínas do Ovo/genética , Proteínas do Ovo/metabolismo , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas de Plasma Seminal/genética , Proteínas de Plasma Seminal/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo
20.
Int J Nanomedicine ; 14: 5831-5848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534327

RESUMO

Purpose: In order to accelerate the tendon-bone healing processes and achieve the efficient osteointegration between the tendon graft and bone tunnel, we aim to design bioactive electrospun nanofiber membranes combined with tendon stem/progenitor cells (TSPCs) to promote osteogenic regeneration of the tendon and bone interface. Methods: In this study, nanofiber membranes of polycaprolactone (PCL), PCL/collagen I (COL-1) hybrid nanofiber membranes, poly(dopamine) (PDA)-coated PCL nanofiber membranes and PDA-coated PCL/COL-1 hybrid nanofiber membranes were successfully fabricated by electrospinning. The biochemical characteristics and nanofibrous morphology of the membranes, as well as the characterization of rat TSPCs, were defined in vitro. After co-culture with different types of electrospun nanofiber membranes in vitro, cell proliferation, viability, adhesion and osteogenic differentiation of TSPCs were evaluated at different time points. Results: Among all the membranes, the performance of the PCL/COL-1 (volume ratio: 2:1 v/v) group was superior in terms of its ability to support the adhesion, proliferation, and osteogenic differentiation of TSPCs. No benefit was found in this study to include PDA coating on cell adhesion, proliferation and osteogenic differentiation of TSPCs. Conclusion: The PCL/COL-1 hybrid electrospun nanofiber membranes are biocompatible, biomimetic, easily fabricated, and are capable of supporting cell adhesion, proliferation, and osteogenic differentiation of TSPCs. These bioactive electrospun nanofiber membranes may act as a suitable functional biomimetic scaffold in tendon-bone tissue engineering applications to enhance tendon-bone healing abilities.


Assuntos
Materiais Biocompatíveis/farmacologia , Osso e Ossos/fisiologia , Membranas Artificiais , Nanofibras/química , Células-Tronco/citologia , Tendões/citologia , Engenharia Tecidual/métodos , Animais , Osso e Ossos/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Nanofibras/ultraestrutura , Osteogênese , Ratos Sprague-Dawley , Células-Tronco/efeitos dos fármacos
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