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1.
Adv Exp Med Biol ; 1232: 277-282, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893421

RESUMO

Acidification of the cellular microenvironment is found in different pathological states such as inflammation, ischemia and in solid tumors. It can affect cell function and phenotype, and by this aggravate the pathological process. Epithelial cells are a relevant functional part in several normal organs as well as in tumors and will thus be challenged by the acidic extracellular pH (acidosis). Therefore, the impact of acidosis on the expression of different inflammatory mediators (MCP-1, IL-6, osteopontin, iNOS, TNF-α, and COX-2), as well as the role of different signaling pathways regulating the expression, was studied in epithelial normal rat kidney cells (NRK-52E). Acidosis led to an increase in TNF-α expression but a down-regulation of MCP-1, iNOS and COX-2. Expression of IL-6 was only slightly modulated, while osteopontin was not regulated at all. Since acidosis activates ERK1/2 and p38 signaling in NRK-52E cells, the impact of MAP kinase signaling pathways on the expression of the inflammatory markers was analyzed. At normal pH, blocking ERK1/2 or p38 decreased the level of MCP-1, iNOS and partly TNF-α. However, the effect of acidosis on the expression of inflammatory mediators was not affected by inhibition of the MAP kinase pathways. In conclusion, our results show that an acidic microenvironment affects the transcriptional program of epithelial cells. Low pH mostly reduced the expression of pathological relevant genes and might thus repress inflammatory processes induced by epithelial cells.


Assuntos
Acidose , Células Epiteliais , Regulação da Expressão Gênica , Mediadores da Inflamação , Proteínas Quinases p38 Ativadas por Mitógeno , Acidose/metabolismo , Animais , Linhagem Celular , Quimiocina CCL2/genética , Ciclo-Oxigenase 2/genética , Células Epiteliais/metabolismo , Mediadores da Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Óxido Nítrico Sintase Tipo II/genética , Ratos , Fator de Necrose Tumoral alfa/genética
2.
Adv Exp Med Biol ; 1232: 393-399, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893436

RESUMO

Although the existence of the primo vasculature system has been shown in many species, including mice, rats, rabbits and humans, the biological role of this system, including expression of genes and proteins, has not yet been investigated. Especially the transcriptional action by mRNA, which is required for biological action, needs to be studied in primo vasculature biology. Differentially expressed genes in both isolated primo vessels and lymphatic vessels of rabbits were analyzed by RNA sequencing experiments. Primer efficiency and RNA purity of the primo vessels under lipopolysaccharides were confirmed prior to performing real-time qRT-PCR analysis following RNA extraction. We demonstrated that FLT4 was enriched in primo vessels and that several genes, including HSPH1 and EPHB2, were highly expressed in primo vessels compared with lymphatic vessels. Our data show that almost all genes, except HSPA4, were increased or sustained in isolated primo vessels compared with lymphatic vessels (FLT4 2.58 fold, HSPH1 1.83 fold, EPHB2 1.52 fold; whereas HSPA4 decreased 0.50 fold), suggesting primo vessels as a central regulator in diverse physiology. This implies that FLT4, HSPH1, and EPHB2 in high amounts may be involved in the functional activity of primo vessels. Our experimental data show that several genes are highly enriched in primo vessels in the lymphatic vessels of the rabbit.


Assuntos
Regulação da Expressão Gênica , Vasos Linfáticos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Animais , Proteínas de Choque Térmico HSP110/genética , Vasos Linfáticos/metabolismo , RNA Mensageiro/genética , Coelhos , Receptor EphB2/genética , Análise de Sequência de RNA , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética
3.
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
4.
Arch Insect Biochem Physiol ; 103(1): e21642, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31667890

RESUMO

The Colorado potato beetle (Leptinotarsa decemlineata [Say]) is an insect pest that can significantly harm potato plants worldwide. Control of this insect relies heavily on chemical insecticides such as chlorantraniliprole. Nevertheless, the complete molecular signature associated with response to this compound is lacking in L. decemlineata. In this study, amplification and quantification by qRT-PCR (quantitative reverse transcription-polymerase chain reaction) of targets relevant to chlorantraniliprole were undertaken in insects exposed to this chemical. This approach showed modulation of numerous cytochrome P450s, such as CYP350D1 and CYP4Q3, as well as upregulation of microRNAs (miRNAs), including miR-1-3p and miR-305-5p, in chlorantraniliprole-exposed insects. Functional assessment of transcript targets predicted to be regulated by these miRNAs was performed and revealed their likely impact on transcriptional regulation. RNAi-based targeting of CYP350D1 notably provided preliminary evidence of its underlying implication for chlorantraniliprole response in L. decemlineata. Overall, this study strengthens the current knowledge of the molecular changes linked to chlorantraniliprole response in L. decemlineata and provides novel targets with potential relevance to chlorantraniliprole susceptibility in this insect pest of global relevance.


Assuntos
Besouros/efeitos dos fármacos , Besouros/metabolismo , Inseticidas/farmacologia , ortoaminobenzoatos/farmacologia , Animais , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Regulação da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa
5.
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
6.
Artigo em Inglês | MEDLINE | ID: mdl-31526840

RESUMO

The suppressor of cytokine signaling 3 (SOCS3) negatively regulates the responses of various immune cytokines. In this study, we identified socs3s genes of blunt snout bream. 209- and 216-aa long peptides are encoded by socs3a and socs3b genes, respectively. The socs3s mRNAs are expressed consistently during the entire process of embryonic development. Whole-mount in situ hybridization detected socs3a in the eyes and posterior somites at 12 h post fertilization (hpf), transcribed at the otic vesicle at 24 hpf, and transcribed at the eyes, brain, and otic vesicle at 36 hpf; while the socs3b mRNA was transcribed at the notochord at 12 hpf, expressed in the brain, eyes, and tailbud at 24 hpf, and detected in the brain at 36 hpf. The expression of socs3a is slightly different from that of socs3b in tissues of juvenile and adult blunt snout bream. After recombinant human growth hormone (hGH) treatment, the transcript levels of socs3s of blunt snout bream were increased in gills, spleen, kidney, and gonads. After Aerononas hydrophila infection, the mRNA levels of socs3s of blunt snout bream were significantly increased in the liver, spleen, intestine, and kidney tissues. Blunt snout bream were susceptible to various pathogenic microorganisms, we intraperitoneally injected blunt snout bream with A. hydrophila to explore the immune mechanism of socs3s. These results suggested that socs3s of blunt snout bream plays important roles in the regulation of embryonic development and tissue growth, and that socs3s may also play key roles in regulating the bacterial-induced congenital immune response. Socs3s genes has the potential to be used as targeted genes to improve the immunity against bacteria, which is conducive to the improvement of production and breeding.


Assuntos
Cyprinidae/metabolismo , Proteínas de Peixes/biossíntese , Regulação da Expressão Gênica/fisiologia , Proteína 3 Supressora da Sinalização de Citocinas/biossíntese , Animais , Especificidade de Órgãos
7.
Artigo em Inglês | MEDLINE | ID: mdl-31647987

RESUMO

ß-thymosin family comprise a series of heat-stable multifunctional polypeptides involved in actin regulation, anti-inflammation, wound healing, cell migration, angiogenesis, cardiac protection, antimicrobial processes and antiviral immunity. The roles of Tß12 (thymosin-ß12) in marine invertebrates is still largely unknown, especially in terms of antibacterial immunity. In this study, we cloned the Tß12 gene with an ORF of 126 bp coding 41 amino acids from Urechis unicinctus. Tissue distribution analysis by qRT-PCR used TBP as reference gene showed that Tß12 was widely expressed in all tissues, and the transcript levels were the highest in the body wall, followed by the coelomic fluid, and the lowest in the intestines and anal sacs. After LPS (lipopolysaccharides) injection, Tß12 expression in the body was first elevated significantly at 3 h (p < 0.05), indicating that the body wall was the first defense line of the innate immune system; in the coelomic fluid, the Tß12 mRNA levels increased after LPS injection, with a significant increase occurring at 6 h, showing that coelomic fluid functioned as the second defense line of the innate immune system. In the midgut and anal sacs, a significant increase in the Tß12 level occurred at 24 h, suggesting that the midgut and anal sacs may act as accessory organs for the innate immune system. Moreover, U. unicinctus Tß12 recombinants can effectively inhibit the growth of both gram-negative and gram-positive bacteria. These results indicate that U. unicinctus Tß12 plays important roles in innate antibacterial immune responses, which can deepen our understanding of Tß12 in marine invertebrates.


Assuntos
Regulação da Expressão Gênica/imunologia , Imunidade Inata , Poliquetos/imunologia , Timosina/imunologia , Animais , Especificidade de Órgãos/genética , Especificidade de Órgãos/imunologia , Poliquetos/genética , Timosina/genética
8.
Medicine (Baltimore) ; 98(51): e17936, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860948

RESUMO

Clearance of the hepatitis B surface antigen (HBsAg) is the ultimate aim of treatment for patients with chronic hepatitis B (CHB) infection. Genetic, factor age, and gender were reported to be involved in the clearance of HBsAg. However, the rate of HBsAg seroclearance in CHB patients is still low globally and few of the single-nucleotide polymorphism (SNP) had been identified to associated with HBsAg seroclearance in CHB patients.Recently, 3 associated SNPs (rs7944135, rs171941, and rs6462008) were reported in the clearance of HBsAg in the Korean population. However, these SNPs have not been investigated in the CHB Taiwanese population. In present study, these 3 SNPs were genotyped in 2565 Taiwanese CHB patients including 493 CHB patients with HBsAg seroclearance and 2072 without HBsAg seroclearance.We observed that SNP rs7944135 was solely associated with HBsAg seroclearance. Subjects with the AA genotype at rs7944135 of macrophage-expressed gene 1 had a higher susceptibility to HBsAg clearance, compared to those with the AG or GG genotype under the genotypic model (odds ratio [OR] = 1.76. 95% confidence interval [CI] = 1.14-2.72, P = .045). Furthermore, we found a 1.74-fold increased risk of acquiring HBsAg seroclearance associated with the AA genotype compared to AG + GG of rs7944135 under the recessive model (OR = 1.74. 95% CI = 1.13-2.66, P = .014). According to the cumulative fraction curve with the log-rank test revealed that patients with the AA genotype of rs7944135 showed higher susceptibility to occur HBsAg seroclearance (P = .039) and HBV DNA undetectable (P = .0074) compared to those with the AG or GG genotype.This study examined the associations of 3 SNPs (rs7944135, rs171941, and rs6462008) with HBsAg seroclearance, and we identified that rs7944135 is solely associated with HBsAg seroclearance in Taiwanese CHB patients.


Assuntos
Regulação da Expressão Gênica , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Estudos de Coortes , Intervalos de Confiança , DNA Viral/análise , DNA Viral/genética , Feminino , Genótipo , Antígenos de Superfície da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único/imunologia , Estudos Retrospectivos , Testes Sorológicos/métodos , Taiwan
9.
Medicine (Baltimore) ; 98(51): e18110, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860959

RESUMO

OBJECTIVE: To study the potential diagnostic value of plasma miR-200c-3p, miR-100-5p, and miR-1826 levels in knee osteoarthritis (KOA). METHODS: Real-time quantitative PCR (RT-PCR) was used to measure the expression levels of serum miR-200c-3p, miR-100-5p, and miR-1826 in 150 KOA patients and 150 control controls. In addition, the levels of DNMT3A, ZEB1, MMP13, and CTNNB1 mRNAs in the synovial fluid were also measured by RT-PCR. RESULTS: The expression levels of miR-100-5p, miR-200c-3p, and miR-1826 in the synovial fluid of 150 KOA patients were significantly lower than those in 54 controls (P < .001). In the synovial fluid, the miR-100-5p and DNMT3A mRNA levels, miR-100-5p and ZEB1 mRNA levels, miR-200c-3p and MMP13 mRNA levels, and miR-1826 and CTNNB1 mRNA levels were all negatively correlated (r = -0.83, -0.81, -0.83, -0.58, respectively). The AUCs of the diagnosis for KOA using the plasma levels of miR-200c-3p, miR-100-5p, and miR-1826 were 0.755, 0.845, and 0.749, respectively. CONCLUSION: The plasma levels of miR-200c-3p, miR-100-5p, and miR-1826 are of potentially high value in the diagnosis of KOA.


Assuntos
Regulação da Expressão Gênica , MicroRNAs/genética , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/genética , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Western Blotting , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/sangue , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real/métodos , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais
10.
Biomed Khim ; 65(5): 388-397, 2019 Aug.
Artigo em Russo | MEDLINE | ID: mdl-31666411

RESUMO

Fibrates are well-known agonists of the PPAR family (peroxisome proliferator-activated receptors). This class of drugs is used for the treatment of dyslipidemia and atherosclerosis. Fenofibrate is one of the members of this class of synthetic PPARα receptor ligands. The oral administration of 0.3% fenofibrate caused a decrease in strength due to loss of body weight in laboratory animals when improving behavioural features. Analysis of the mitochondrial DNA of liver cells showed a genotoxic effect of fenofibrate, due to accumulation of reactive oxygen species, which could be attributed to activation of peroxisomal ß-oxidation processes, as well as to the lack of increase in the expression of genes encoding antioxidant defense proteins. Treatment with fenofibrate did not cause brain mtDNA damage. It has been shown that fenofibrate induced mitochondrial ß-oxidation in the brain, as indicated by the increased expression of the Acadm and Cpt1a and Ppargc1a and Ppara. The study found no effect of fenofibrate on the increase of mitochondrial biogenesis in brain and liver cells. Thus, we can conclude that fenofibrate significantly affects lipid metabolism in the liver and brain, but in the liver it is associated with an increase of oxidative stress, resulting in mtDNA oxidative damage. However, fenofibrate-induced increase in the expression of Ppargc1a is not associated with an increase of mitochondrial biogenesis. This is consistent with the recent suggestion that PGC-1α might not be a master regulator of mitochondrial biogenesis.


Assuntos
Encéfalo/efeitos dos fármacos , Dano ao DNA , Ácidos Graxos/metabolismo , Fenofibrato/farmacologia , Fígado/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Regulação da Expressão Gênica , Fígado/metabolismo , Camundongos
11.
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
12.
DNA Cell Biol ; 38(11): 1188-1196, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31603699

RESUMO

The mammary gland is an important organ for lactation in dairy goats. Mammary gland development and lactation functions are primarily regulated by natural hormones and certain crucial regulatory factors. Nedd4 family-interacting protein 1 (Ndfip1) can specifically bind to neural precursor cell-expressed, developmentally downregulated protein 4 (Nedd4) family members to participate in ubiquitination, which in turn regulates a range of biological processes in the body. However, the effects of Ndfip1 expression regulation at the post-transcriptional level on the development of mammary gland cells have not been previously reported. To study the regulation of Ndfip1 at post-transcriptional level, the overexpression and interference vectors of Ndfip1 were constructed, and co-transfected into the primary mammary gland epithelial cells cultured in vitro with miR-143 mimics and inhibitor. Dual luciferase reporter gene system, real-time quantitative polymerase chain reaction, western blotting, cholecystokinin octapeptide assays, and flow cytometry were used to identify their regulation and function. As a result, Ndfip1 was targeted and regulated by miR-143, which influences the development of mammary gland epithelial cells in dairy goats cultured in vitro. This study will lay an experimental foundation for further understanding the functions of Ndfip1 and miR-143.


Assuntos
Apoptose/genética , Células Epiteliais/fisiologia , Cabras , Lactação/genética , Glândulas Mamárias Animais/fisiologia , Proteínas de Membrana/genética , MicroRNAs/fisiologia , Animais , Células Cultivadas , Indústria de Laticínios , Células Epiteliais/metabolismo , Feminino , Regulação da Expressão Gênica , Cabras/genética , Cabras/metabolismo , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/metabolismo
13.
Life Sci ; 237: 116896, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31605707

RESUMO

AIMS: Population-based studies have shown that exercise has anti-atherosclerotic effects, but the mechanisms underlying this cardiac protection are poorly understood. The aim of this study was to investigate if the anti-atherosclerotic effects of exercise are associated with changes in neuropeptide Y (NPY) expression in apolipoprotein E-deficient (ApoE-/-) mice. MAIN METHODS: Thirty-one male ApoE-/- mice were randomly divided into regular exercise (5 days/week), occasional exercise (1-2 days/week), and sedentary groups. After 8 weeks, atherosclerotic burden and plaque stability were measured by histological and morphological analysis. Quantitative real-time PCR and immunohistochemistry were used to measure the expression of NPY and its receptors in the aorta. KEY FINDINGS: Eight weeks of occasional exercise was equally effective as regular exercise at preventing atherosclerotic plaque formation and enhancing atherosclerotic plaque stability. This was shown by increased plaque collagen and smooth muscle cell content and decreased plaque lipid and macrophage content. The expression of NPY and its receptors in the vasculature was decreased in the regular exercise and occasional exercise groups, and this expression was significantly correlated with the progress of atherosclerosis. Moreover, exercise may reduce the activity of macrophages by down-regulating the expression of NPY Y1 receptors, thereby reducing the release of inflammatory cytokines. SIGNIFICANCE: These results suggest that exercise training can attenuate plaque burden and enhance atherosclerotic plaque stability. The anti-atherosclerotic effect of exercise appears to be, at least in part, dependent on down-regulation of the expression of NPY and its receptors (especially Y1 receptors) in the aorta.


Assuntos
Apolipoproteínas E/fisiologia , Aterosclerose/prevenção & controle , Regulação da Expressão Gênica , Inflamação/prevenção & controle , Neuropeptídeo Y/metabolismo , Condicionamento Físico Animal , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/etiologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Neuropeptídeo Y/genética
14.
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
15.
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
16.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 31(4): 404-409, 2019 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-31612676

RESUMO

OBJECTIVE: To investigate the expression of some genes in Pomacea canaliculata infected with Angiostrongylus cantonensis, so as to provide insight into the preliminary understanding of the interactions between Angiostrongylus cantonensis and its intermediate host Pomacea canaliculata. METHODS: P. canaliculata was fed with rat faces containing the first-stage larvae of A. cantonensis. Three to five P. canaliculata was sampled 1, 10 days and 20 days after feeding, and the hemolymph, hepatopancreas, kidney, intestinal tract, head-foot and gill tissues were collected, while uninfected P. canaliculata served as controls. Total RNA was extracted from various tissues of P. canaliculata at different time points post-infection, and transcribed reversely into cDNA. Based on previous transcriptome sequencing results, 10 genes associated with immune defense, signal transduction, cell growth and metabolism, stress response were selected, and the gene expression was determined in the hemolymph tissues of P. canaliculata 1, 10 days and 20 days post-infection with A. cantonensis using real-time fluorescent quantitative PCR assay, and the α-tubulin gene expression was quantified in the hepatopancreas, kidney, head-foot, intestinal tract and gill tissues of P. canaliculata infected with A. cantonensis. RESULTS: Higher CELA1 gene expression was detected in the infection group than in the control group 1 (t = 12.32, P < 0.05), 10 days (t = 23.51, P < 0.05) and 20 days post-infection (t = 34.92, P < 0.05), and the CELA1 expression increased with the time of infection. The GST gene expression was (7.26 ± 1.80) times higher in the infection group than in the control group 1 day post-infection, and was significantly lower in the infection group than in the control group 10 days (t = 23.89, P < 0.05) and 20 days post-infection (t = 19.83, P < 0.05). Higher ferritin gene expression was found in the infection group than in the control group 10 days post-infection (t = 32.76, P < 0.05), and higher CRT gene expression was seen in the infection group than in the control group 1 (t = 7.23, P < 0.05), 10 days (t = 5.78, P < 0.05) and 20 days post-infection (t = 6.32, P < 0.05). In addition, the greatest α-tubulin gene expression was observed in the the hepatopancreatic tissues of P. canaliculata (F = 17.58, P < 0.05), and the α-tubulin gene expression altered in various tissues of P. canaliculata post-infection with A. cantonensis, with the most remarkable reduction of α - tubulin gene expression seen in the hepatopancreatic tissues (P < 0.05). CONCLUSIONS: Following A. cantonensis infection in P. canaliculata, the expression of multiple genes is altered, and the expression of α-tubulin gene is inhibited in multiple tissues. The findings provide a basis for the further elucidation of the interactions between P. canaliculata and A. cantonensis.


Assuntos
Angiostrongylus cantonensis , Gastrópodes , Interações Hospedeiro-Parasita , Infecções por Strongylida , Tubulina (Proteína) , Angiostrongylus cantonensis/fisiologia , Animais , Gastrópodes/genética , Gastrópodes/parasitologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Interações Hospedeiro-Parasita/genética , Larva , Ratos , Tubulina (Proteína)/genética
17.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 31(4): 446-449, 2019 Jul 23.
Artigo em Chinês | MEDLINE | ID: mdl-31612687

RESUMO

Macrophage migration inhibitory factor (MIF), a type of pleiotropic immunoregulatory cytokine with a specific structure, participates in the regulation of host cell growth and migration and immune responses. Following parasitic infections, hosts may produce MIF and then participate in the parasite-host interactions. In addition, parasites may secrete parasite-derived MIF, and they jointly participate in parasite-host interactions. This paper reviews the regulation of MIF gene expression following parasitic infections, the role of MIF in parasite-host immune system interactions, and important signaling pathways of MIF-mediated immune responses.


Assuntos
Interações Hospedeiro-Parasita/imunologia , Fatores Inibidores da Migração de Macrófagos , Parasitos , Animais , Regulação da Expressão Gênica/imunologia , Fatores Inibidores da Migração de Macrófagos/imunologia , Parasitos/imunologia , Transdução de Sinais/imunologia
18.
Life Sci ; 236: 116899, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31614145

RESUMO

AIMS: The aim of our study is to illustrate the role of amphiregulin in trophoblast invasiveness and underlying signal cascades. MAIN METHODS: An immortalized human early extravillous cell line, HTR-8/SVneo, was used for this investigation. Matrigel-transwell invasion assay was used for testing the effects of amphiregulin on cell invasiveness. MMP9 and MMP2 mRNA expression level and activity were measured using Rt-qPCR and zymographic analysis. Cell signals involved in the invasion process were verified using western blot and specific inhibitors. KEY FINDINGS: Our results showed that amphiregulin could promote HTR-8/SVneo cell invasiveness without interfering cell proliferation, and significantly upregulate the expression of MMP9 and TIMP-1 mRNAs as well as the ratio of MMP9/TIMP-1. Using specific inhibitors for MEK and PI3K signaling further indicated that, both ERK1/2 and Akt signal pathways were required for amphiregulin-induced cell invasiveness. The co-ordination between ERK1/2 and Akt signaling pathway was needed for the upregulation of MMP9 mRNA, while ERK1/2 was more essential for the upregulation of TIMP-1 mRNA. Meanwhile, we first put forward that the deficiency of amphiregulin expression in trophoblast might be compensated by the upregulation of epidermal growth factor receptor (EGFR) and heparin-binding EGF (HB-EGF) mRNA. SIGNIFICANCE: ERK1/2 and Akt signaling pathways mediate amphiregulin-induced upregulation of MMP9 mRNA and the MMP9/TIMP-1 ratio, which subsequently contribute to amphiregulin-promotion of HTR-8/SVneo cell invasion.


Assuntos
Anfirregulina/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Trofoblastos/metabolismo , Trofoblastos/patologia , Movimento Celular , Proliferação de Células , Células Cultivadas , Feminino , Regulação da Expressão Gênica , Humanos , Metaloproteinase 9 da Matriz/genética , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Gravidez , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais , Inibidor Tecidual de Metaloproteinase-1/genética
19.
Life Sci ; 236: 116906, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31614147

RESUMO

AIMS: The anti-hyperglycemic action of metformin on skeletal muscles is presently unclear. Long noncoding RNAs (lncRNAs) are implicated in multiple cellular functions. This study aims to explore the role of lncRNAs in the glucometabolic action of metformin on skeletal muscle cells. MAIN METHODS: Metformin accumulation was assessed using [14C]-metformin. A lncRNA array was used to investigate metformin-regulated lncRNAs in C2C12 skeletal muscle cells. Knockdown studies were applied to evaluate the function of lncRNA Dreh. A colorimetric assay was used for the measurement of medium glucose concentration; glucose transport was assessed using [3H]-2-deoxyglucose; real-time PCR was used for RNA expression analysis, and western blotting was used to assess protein expression in myotubes. A Dreh overexpression plasmid was transfected into the cells. KEY FINDINGS: Metformin accumulated in C2C12 myotubes. Metformin reduced medium glucose concentration and repressed lncRNA Dreh expression in the myotubes. Knockdown of Dreh in the myotubes resulted in reduced glucose concentration in the culture medium, increased glucose transport, and increased levels of GLUT4 protein in the plasma membrane. Overexpression of Dreh attenuated the glucose-lowering effect of metformin in myotubes. SIGNIFICANCE: The glucoregulatory actions of metformin are mediated in part by a lncRNA, Dreh, in the skeletal muscle cells. Dreh is a novel regulator for glucose transport and could be a therapeutic target for diabetes.


Assuntos
Glucose/metabolismo , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , RNA Longo não Codificante/genética , Animais , Transporte Biológico , Linhagem Celular , Regulação da Expressão Gênica , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Camundongos , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/efeitos dos fármacos , Músculo Esquelético/citologia , Músculo Esquelético/efeitos dos fármacos
20.
Protein Pept Lett ; 26(10): 751-757, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618170

RESUMO

BACKGROUND: NMAAP1 plays a role in regulating macrophage differentiation to the M1 type and exerting antitumoral functions. It is not clear what role and mechanism NMAAP1 does play in the reversal of macrophages from M1 to M2. METHODS: We detected the typing of macrophages with high or low expression of NMAAP1 by QPCR and ELISA, and detected the colocalization of NMAAP1 and endogenous IP3R by laser confocal microscopy, and detected the protein expression in cells by Western-blotting. RESULTS: Our study found that knockdown NMAAP1 in RAW264.7 cells induced macrophage polarization to the M2 type and up-regulation of NMAAP1 in RAW264.7 cells maintain M1 Phenotype even in the presence of IL-4, a stronger inducer of the M2 type. Additionally, Coimmunoprecipitation revealed a protein-protein interaction between NMAAP1 and IP3R and then activates key molecules in the PKC-dependent Raf/MEK/ERK and Ca2+/CaM/CaMKII signaling pathways. Activation of PKC (Thr638/641), ERK1/2 (Thr202/Tyr204) and CaMKII (Thr286) is involved in the regulation of cell differentiation. CONCLUSION: NMAAP1 interacts with IP3R, which in turn activates the PKC-dependent Raf/MEK/ERK and Ca2+/CaM/CaMKII signaling pathways. These results provide a new explanation of the mechanism underlying M1 differentiation.


Assuntos
Cálcio/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Macrófagos/metabolismo , Proteínas de Membrana/metabolismo , Transdução de Sinais , Animais , Diferenciação Celular , Citocinas/metabolismo , Regulação da Expressão Gênica , Humanos , Macrófagos/citologia , Proteínas de Membrana/genética , Camundongos , Fenótipo , Ligação Proteica , Células RAW 264.7 , RNA Interferente Pequeno/metabolismo , Regulação para Cima
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