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Studies increasingly show that social connectedness plays a key role in determining survival, in addition to natural and anthropogenic environmental factors. Few studies, however, integrated social, non-social and demographic data to elucidate what components of an animal's socio-ecological environment are most important to their survival. Female giraffes (Giraffa camelopardalis) form structured societies with highly dynamic group membership but stable long-term associations. We examined the relative contributions of sociability (relationship strength, gregariousness and betweenness), together with those of the natural (food sources and vegetation types) and anthropogenic environment (distance from human settlements), to adult female giraffe survival. We tested predictions about the influence of sociability and natural and human factors at two social levels: the individual and the social community. Survival was primarily driven by individual- rather than community-level social factors. Gregariousness (the number of other females each individual was observed with on average) was most important in explaining variation in female adult survival, more than other social traits and any natural or anthropogenic environmental factors. For adult female giraffes, grouping with more other females, even as group membership frequently changes, is correlated with better survival, and this sociability appears to be more important than several attributes of their non-social environment.
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Girafas , Animais , Meio Ambiente , Feminino , Alimentos , Fatores SociológicosRESUMO
BACKGROUND AND OBJECTIVE: Osteoclast precursors (OPs) re-migrate from the bone surface into blood vessels through sphingosine-1-phosphate receptor 1 (S1PR1) expression. T cells also express S1PR1, mediating their migration from the lymph nodes into blood vessels. OP and T-cell migration are one of the sequential steps related to osteoclast formation. To characterize the role of S1PR1 in osteoclast formation induced by periodontitis, we investigated the effect of S1PR1-binding molecule FTY720 (FTY) on the number of OPs and T cells in periodontal tissue and peripheral blood of rats with ligature-induced periodontitis. MATERIAL AND METHODS: Rats were divided into four groups; control (Con), FTY, periodontitis (Peri), and periodontitis+FTY (Peri+FTY) groups. Ligatures were placed around the first molars in the left and right mandibles. The rats were intraperitoneally injected with vehicle or 3 mg/kg FTY daily until they were killed. The number of osteoclasts and cluster of differentiation (CD)11b, CD3 and receptor activator of NF-κB ligand (RANKL)-positive cells in first molar furcation were counted by tartrate-resistant acid phosphatase or immunohistochemistry staining. The number of CD11b- and CD3-positive cells in peripheral blood was estimated by flow cytometry. RESULTS: The number of osteoclasts in the Peri group was higher than Con, Peri+FTY and FTY groups (p < 0.05) and CD11b, CD3 and RANKL-positive cells were also higher in the Peri group than other groups in furcation (p < 0.05). While CD11b-positive cells in furcation of the Peri+FTY group were lower than the Peri group (p < 0.05), they were higher in peripheral blood (p < 0.05). Dissimilar to CD11b-positive cells, CD3-positive cells in the Peri+FTY group were lower in peripheral blood as well as furcation than the Peri group (p < 0.05). RANKL-positive cells in furcation of the Peri+FTY group were also lower than Peri group (p < 0.05). CONCLUSION: These results indicate that FTY may facilitate re-migration of OPs from the alveolar bone surface into blood vessels, blocking T-cell migration from the lymph nodes into blood vessels and subsequently reducing osteoclast formation induced by periodontitis. This suggests that S1PR1-S1P binding may play a role in osteoclast formation of periodontitis by modulating OP and T-cell migration.
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Cloridrato de Fingolimode/farmacologia , Imunossupressores/farmacologia , Osteoclastos/efeitos dos fármacos , Periodontite/metabolismo , Perda do Osso Alveolar/metabolismo , Animais , Modelos Animais de Doenças , Citometria de Fluxo , Defeitos da Furca/metabolismo , Defeitos da Furca/patologia , Ligadura , Masculino , Osteoclastos/metabolismo , Periodontite/patologia , Ratos , Ratos Sprague-Dawley , Linfócitos T/metabolismoRESUMO
The Korean traditional hot sauce gochujang has been reported to have biological activities. Different kinds of gochujang products were prepared based on combinations of a fungal rice koji with two kinds of bacterial soybean mejus. Diets that included gochujang products were fed to rats and anti-obesity effects were investigated. Gochujang products reduced body weight gains, epididymal fat weights, and triglyceride levels in the serum and the liver. Effects were exerted by the diet that included the non-fermented gochujang mixture, increased using a fungal rice koji, and further enhanced using a bacterial soybean meju. Dietary effects were apparently induced via inhibition of the lipogenic enzymes fatty acid synthase, malic enzyme, and lipoprotein lipase by gochujang products in epididymal adipose tissues, and inhibition of glucose-6-phosphate dehydrogenase in the liver. High levels of capsaicin and genistein in gochujang products are considered to contribute to anti-obesity effects.
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BACKGROUND AND OBJECTIVES: Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts are formed in sequential steps: proliferation and differentiation of hematopoietic progenitors into quiescent osteoclast precursors (QOPs), followed by fusion of QOPs. In this study, we investigated whether enhancement of osteoclast formation by periodontitis is derived from the stimulation of proliferation of hematopoietic progenitors or the differentiation of QOPs into osteoclasts. MATERIAL AND METHODS: Ligatures were placed around the first molars in the left mandibles of Fischer 344 inbred rats. The rats received drinking water containing bromodeoxyuridine (BrdU) (which can be incorporated into dividing nuclei) after ligation during the experimental period. The number of inflammatory cells in the distal area was counted. Alveolar bone loss was histologically estimated by measuring the distance from the cementoenamel junction to the alveolar bone crest in the distal area and determining the percentage of periodontal ligament area in the furcation. The number of osteoclasts and percentage of BrdU(+) nuclei in total osteoclasts nuclei were counted after TRAP and BrdU double labeling. RESULTS: The number of polymorphonuclear cells increased on day 1 and then rapidly decreased. The number of mononuclear cells increased in a time-dependent manner up to day 5 and remained the same until day 10. Alveolar bone loss of ligatured teeth increased in a time-dependent manner. The number of osteoclasts peaked on day 3 then gradually decreased. At peak, the percentage of BrdU(+) nuclei in total osteoclasts nuclei in the distal and furcation areas were 7.9% and 4.1%, respectively. CONCLUSION: These results indicate that most of the osteoclasts formed after periodontitis induction are derived from preformed QOPs, suggesting that enhancement of osteoclast formation by periodontitis might be mainly caused by stimulating the differentiation of QOPs into osteoclasts.
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Osteoclastos/fisiologia , Periodontite/patologia , Células-Tronco/fisiologia , Perda do Osso Alveolar/patologia , Processo Alveolar/patologia , Animais , Bromodesoxiuridina , Contagem de Células , Diferenciação Celular/fisiologia , Núcleo Celular/patologia , Contagem de Leucócitos , Leucócitos Mononucleares/patologia , Masculino , Neutrófilos/patologia , Osteoclastos/patologia , Ratos , Ratos Endogâmicos F344 , Fosfatase Ácida Resistente a Tartarato/análise , Fatores de Tempo , Colo do Dente/patologiaRESUMO
BACKGROUND AND OBJECTIVE: Experimental models showing variable diabetic status are necessary to understand the relationship between diabetes and periodontitis. The streptozotocin (STZ)-induced diabetes model allows control of diabetic status by nicotinamide (NA), which protects against STZ-induced ß-cell necrosis. Therefore, we compared diabetic characteristics and alveolar bone loss in STZ- and STZ-NA-treated rats with periodontitis. MATERIAL AND METHODS: STZ-treated rats were generated by intravenous (IV) administration of STZ (50 mg/kg). STZ-NA-treated rats were induced by intraperitoneal administration of NA (270 mg/kg) 15 min before IV administration of STZ (65 mg/kg). Periodontitis was induced by ligature around the left mandibular first molar 1 wk after injection. Blood glucose level, glucose tolerance and serum insulin levels were determined at day 0 and/or 20 after ligature. At day 20, tibia bone loss was assessed using micro-computed tomography and hematoxylin and eosin staining. Alveolar bone loss was histologically measured as the distance of the cementoenamel junction to the alveolar bone crest in distal and the percentage of periodontal ligament area in the first molar furcation, respectively. The number of inflammatory cells, receptor activator of nuclear factor kappa-B ligand (RANKL)-positive cells and the area of osteoid were determined. RESULTS: In STZ-treated rats, obvious hyperglycemia over 300 mg/dL and severe body weight loss were observed. The insulin level was approximately 14% compared to that of control rats. STZ-NA-treated rats were impaired in glucose tolerance compared to control rats; however, body weight and insulin levels were not significantly different. Tibia bone loss was increased in STZ-treated rats, but significant change was not observed in STZ-NA-treated rats compared to control rats. In ligatured teeth, alveolar bone loss was increased in both STZ- and STZ-NA-treated rats compared to control rats. Alveolar bone loss, the number of inflammatory cells and RANKL-positive cells in STZ-treated rats were greater than in STZ-NA-treated rats. The area of osteoid decreased in STZ-treated rats compared to control, but not STZ-NA-treated rats. CONCLUSION: These results indicate that STZ- and STZ-NA-treated rats exhibit diabetic characteristics similar to type 1 diabetes mellitus and a pre-diabetic state, respectively. In addition, alveolar bone loss in response to periodontitis and tibia loss depend on diabetic status. Diabetic status-dependent bone remodeling imbalance and inflammation could affect the alveolar bone loss in the two models. Both STZ- and STZ-NA-treated rats may be useful to investigate differences in periodontitis sensitivity associated with diabetic status and to develop therapeutic agents for periodontitis in patients with diabetes.
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Perda do Osso Alveolar/etiologia , Diabetes Mellitus Experimental/complicações , Niacinamida/administração & dosagem , Periodontite/complicações , Complexo Vitamínico B/administração & dosagem , Animais , Glicemia/análise , Peso Corporal , Matriz Óssea/patologia , Reabsorção Óssea/etiologia , Diabetes Mellitus Experimental/sangue , Defeitos da Furca/etiologia , Gengiva/patologia , Teste de Tolerância a Glucose , Hiperglicemia/sangue , Hiperglicemia/complicações , Insulina/sangue , Células Secretoras de Insulina/efeitos dos fármacos , Leucócitos Mononucleares/patologia , Masculino , Dente Molar/patologia , Neutrófilos/patologia , Ligante RANK/análise , Ratos , Ratos Endogâmicos F344 , Estreptozocina , Tíbia/patologia , Redução de Peso , Microtomografia por Raio-X/métodosRESUMO
BACKGROUND AND OBJECTIVE: Epigallocatechin-3-gallate (EGCG) is known for its beneficial properties, including anti-inflammatory and anti-oxidative activities. Recently, reports have suggested that EGCG plays a pivotal role in regulating cytokine expression and osteoclastic activity. In the present study, we investigated whether orally administered EGCG has a therapeutic effect on ligature-induced periodontitis. MATERIALS AND METHODS: Forty-eight Sprague-Dawley rats were treated with EGCG or phosphate-buffered saline. Periodontitis was induced by tying a ligature for 7 d. After removing ligation, EGCG (200 mg/kg) or phosphate-buffered saline was administered via oral gavage on a daily basis. Rats were killed after 1, 2 and 4 wk of administration. Histologic and histomorphometric analyses, tartrate resistant acid phosphatase staining and immunohistochemistry were carried out. RESULTS: In the control group, bone loss did not recover even after the causative factor of periodontitis was eliminated. On the other hand, distance from cemento-enamel junction to alveolar bone crest, long junctional epithelium and collagen destruction were reduced in the EGCG group. Decreased interleukin (IL)-6 expression was shown from the early stage of EGCG administration, followed by reduced tumor necrosis factor (TNF) expression at week 4 EGCG group. The CT area showed a higher decrease of IL-6 expression between the control and EGCG group than alveolar bone area. Downregulation of TNF and IL-6 expression led to a decrease in osteoclast number and activity, which resulted in reduced bone loss. CONCLUSIONS: Systemic administration of EGCG could have a therapeutic effect on damaged periodontal tissue. Inhibited cytokine expression, including TNF and IL-6 is responsible for the reduction in osteoclast formation, osteoclastic activity and collagen destruction.
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Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Catequina/análogos & derivados , Periodontite/tratamento farmacológico , Fosfatase Ácida/análise , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/patologia , Processo Alveolar/efeitos dos fármacos , Processo Alveolar/patologia , Animais , Biomarcadores/análise , Catequina/uso terapêutico , Colágeno/efeitos dos fármacos , Regulação para Baixo , Inserção Epitelial/efeitos dos fármacos , Inserção Epitelial/patologia , Imuno-Histoquímica , Interleucina-6/análise , Isoenzimas/análise , Masculino , Osteoclastos/efeitos dos fármacos , Periodontite/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fosfatase Ácida Resistente a Tartarato , Fatores de Tempo , Colo do Dente/efeitos dos fármacos , Colo do Dente/patologia , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
Structural abnormalities include various types of translocations, inversions, deletions, duplications and isochromosomes. Structural abnormalities of the Y chromosome are estimated to affect less than 1% of the newborn male population and are particularly hazardous for male reproductive function. The objective of this study was to characterize a group of patients with structural abnormalities of the Y chromosome. All patients who visited our laboratory between 2007 and 2010 underwent cytogenetic investigations. Among these, we detected 26 patients with structural abnormalities of the Y chromosome. To confirm the structural Y chromosome alterations, we used special bandings, FISH and multiplex PCR to detect Y chromosome microdeletions. Of the 26 patients presented here, 11 had an isodicentric Y chromosome, 7 had an inversion, 3 had a translocation, 2 had a derivative, 2 had a Yqs and 1 had a deletion. Sixteen were diagnosed with azoospermia, 8 as normal fertile males and 1 as a man who was unable to donate semen due to mental retardation. One of the patients having 45,X/46,X,idic(Y) was reported to be phenotypically female with primary amenorrhea and without uterus. Deletions of the AZFbc region were correlated with the sperm concentration (p < 0.05), but no correlation with the levels of FSH, LH, testosterone, prolactin and estradiol were found. The present report shows that the precise identification of structural Y chromosome aberrations may be clinically important for genetic counseling and assisted reproductive technology treatment.
Assuntos
Cromossomos Humanos Y/genética , Aberrações dos Cromossomos Sexuais , Adulto , Azoospermia/genética , Bandeamento Cromossômico , Deleção Cromossômica , Inversão Cromossômica , Feminino , Humanos , Hibridização in Situ Fluorescente , Infertilidade Masculina , Cariotipagem , Masculino , Pessoa de Meia-Idade , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Translocação Genética , Adulto JovemRESUMO
OBJECTIVES: This study compared the effects of consuming different forms (bite size, puree) and two fruit types (guava, papaya) on glycemic response (GR) in elderly and young adults. DESIGN: This study was conducted using a randomized, crossover design. PARTICIPANTS: Nineteen healthy participants (9 elderly, 10 young adults) were recruited from the general public in Singapore. INTERVENTION: Participants consumed glucose (reference food) on three occasions and test fruits (guava bites, guava puree, papaya bites, and papaya puree) on one occasion each. MEASUREMENTS: Blood glucose was analyzed prior to consuming the test food, at 15, 30, 45, 60, 90 and 120 minutes after food consumption. RESULTS: The incremental area under the blood glucose response curve (iAUC) over 120 minutes for all the treatments was significantly lower than glucose (all P < 0.001). All fruit forms and types studied were low glycemic index (GI) (guava bites: 29; papaya bites: 38; papaya puree: 42; guava puree: 47), albeit a significant difference in GI between the treatments was found (P = 0.003). Elderly exhibited significantly greater GR than young participants (P = 0.019). CONCLUSION: Although fruit form influences GR in the elderly and young adults, all fruit types and forms studied were found to be low GI. This study indicates that fruits are a valuable source of nutrient irrespective of the form of delivery in elderly and young adults. This study was registered at www.anzctr.org.au as ACTRN12614000655640.
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Frutas/metabolismo , Índice Glicêmico/fisiologia , Adulto , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Adulto JovemRESUMO
AIM: PGC-1α4 is a novel regulator of muscle hypertrophy; however, there is limited understanding of the regulation of its expression and role in many (patho)physiological conditions. Therefore, our purpose was to elicit signalling mechanisms regulating gene expression of Pgc1α4 and examine its response to (patho)physiological stimuli associated with altered muscle mass. METHODS: IL-6 knockout mice and pharmacological experiments in C2C12 myocytes were used to identify regulation of Pgc1α4 transcription. To examine Pgc1α4 gene expression in (patho)physiological conditions, obese and lean Zucker rats with/without resistance exercise (RE), ageing mice and muscle regeneration from injury were examined. RESULTS: In IL-6 knockout mice, Pgc1α4mRNA was ~sevenfold greater than wild type. In C2C12 cells, Pgc1α4mRNA was suppressed ~70% by IL-6. Suppression of Pgc1α4 by IL-6 was prevented by MEK-ERK-MAPK inhibition. RE led to ~260% greater Pgc1α4mRNA content in lean rats. However, obese Zucker rats exhibited ~270% greater Pgc1α4mRNA than lean, sedentary with no further augmentation by RE. No difference was seen in IL-6mRNA or ERK-MAPK phosphorylation in Zucker rats. Aged mice demonstrated ~50% lower Pgc1α4mRNA and ~fivefold greater ERK-MAPK phosphorylation than young despite unchanged Il-6mRNA. During muscle regeneration, Pgc1α4 content is ~30% and IL-6mRNA >threefold of uninjured controls 3 days following injury; at 5 days, Pgc1α4 was >twofold greater in injured mice with no difference in IL-6mRNA. CONCLUSION: Our findings reveal a novel mechanism suppressing Pgc1α4 gene expression via IL-6-ERK-MAPK and suggest this signalling axis may inhibit Pgc1α4 in some, but not all, (patho)physiological conditions.
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Regulação da Expressão Gênica/fisiologia , Músculo Esquelético/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/biossíntese , Transdução de Sinais/fisiologia , Envelhecimento/fisiologia , Animais , Interleucina-6/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/lesões , Obesidade/fisiopatologia , Condicionamento Físico Animal/fisiologia , Ratos , Ratos ZuckerRESUMO
AIM: Mitochondria-encoded proteins are necessary for oxidative phosphorylation; however, no report has examined how physical activity (PA) and obesity affect mitochondrial mRNA translation machinery. Our purpose was to determine whether Western diet (WD)-induced obesity and voluntary wheel running (VWR) impact mitochondrial mRNA translation machinery and whether expression of this machinery is dictated by oxidative phenotype. METHODS: Obesity was induced with 8-wk WD feeding, and in the final 4 wks, half of mice were allowed VWR. Mitochondrial mRNA translation machinery including initiation factors (mtIF2/3), elongation factor Tu (TUFM) and translational activator (TACO1), and mitochondria-encoded proteins (CytB and ND4) was assessed by immunoblotting. The relation of mitochondrial mRNA translation to muscle oxidative phenotype was assessed using PGC-1α transgenic overexpression (MCK-PGC-1α vs. wild-type mice) and comparing across muscle groups in wild-type mice. RESULTS: mtIF3 and TACO1 proteins were ~45% greater in VWR than sedentary (SED), and TACO1 and mtIF2 proteins were ~60% and 125% greater in WD than normal chow (NC). TUFM protein was ~50% lower in WD-SED than NC-SED, but ~50% greater in WD-VWR compared to NC-SED. CytB and ND4 were ~40% greater in VWR and ND4 was twofold greater with WD. TUFM, TACO1, ND4 and CytB were greater in MCK-PGC-1α compared to wild-type, and mtIF2/3 contents were not different. In oxidative muscle (soleus), mitochondrial translation machinery was elevated compared to mixed (gastrocnemius) or glycolytic (extensor digitorum longus) muscles. CONCLUSION: These data suggest a novel mechanism promoting mitochondrial function by translation of mitochondrial protein following PA. This may act to promote muscle health by PA in obesity.
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Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Condicionamento Físico Animal/fisiologia , Biossíntese de Proteínas/fisiologia , RNA Mensageiro/metabolismo , Animais , Citocromos b/genética , Citocromos b/metabolismo , Dieta Ocidental , Regulação da Expressão Gênica , Camundongos , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Mitocôndrias Musculares/genética , Obesidade/genética , Fosforilação Oxidativa , Fator Tu de Elongação de Peptídeos/genética , Fator Tu de Elongação de Peptídeos/metabolismo , RNA Mensageiro/genéticaRESUMO
Deoxyribonuclease activities were examined in isoelectric focusing fractions of non-histone, chromatin-associated and nucleoplasmic proteins of isolated normal human lymphoblastoid and mouse melanoma cell nuclei using parallel procedures. A very similar series of eight DNA endonucleases, each active on calf thymus DNA and containing no exonuclease activity, were found in the chromatin proteins of both cell lines. Several differences were observed: an activity in human cells at pI 6.6 was absent from murine cells, and there was an increased activity in mouse cells at pI 4.4 and a decreased activity at pI 7.3, as compared with corresponding human cell activities. Assay of these fractions against supercoiled, circular phage PM2 DNA showed greater activity among the fractions with acidic pI valves and slightly lower activities in the murine cells than in the human cells. Analysis of the nucleoplasmic fractions showed a series of DNA endonuclease and exonuclease activities which were again very similar between the two cell lines, although greater endonuclease activity at pI 4.4 occurred in mouse than in human nucleoplasm. These results demonstrate an entire series of deoxyribonuclease activities in both chromatin and nucleoplasm which are nearly identical in two very different mammalian cell lines, suggesting that many of these enzymes are ubiquitous in mammalian cell nuclei.
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Núcleo Celular/enzimologia , Desoxirribonucleases/metabolismo , Linfócitos/enzimologia , Melanoma/enzimologia , Animais , Linfoma de Burkitt/enzimologia , Linhagem Celular , Desoxirribonucleases/isolamento & purificação , Humanos , Camundongos , Neoplasias Experimentais/enzimologia , Nucleoproteínas/análiseRESUMO
AIM: Obesity is classified as a metabolic disorder that is associated with delayed muscle regeneration following damage. For optimal skeletal muscle regeneration, inflammation along with extracellular matrix remodelling and muscle growth must be tightly regulated. Moreover, the regenerative process is dependent on the activation of myogenic regulatory factors (MRFs) for myoblast proliferation and differentiation. The purpose of this study was to determine how obesity alters inflammatory and protein synthetic signalling and MRF expression at the onset of muscle regeneration in mice. METHODS: Forty-eight male C57BL/6J mice (3 weeks old) were randomly assigned to either a high-fat diet (HFD, 60% fat) or a lean diet (10% fat) for 12 weeks. At 15 weeks, bupivacaine was injected into the tibialis anterior (TA) of the injured group (n = 5-8/group) and PBS was injected into the control (n = 5-6). The TA was excised 3 or 28 days after injection. RESULTS: We demonstrated impaired muscle regeneration in obese mice. The obese mice had reduced IL-6, MyoD and IGF-1 mRNA abundance compared to the lean mice (P < 0.05). Three days following muscle damage, TNF-α mRNA and protein levels of P-STAT3 and P-Akt were 14-fold, fourfold and fivefold greater in the lean mice respectively. However, there were no differences observed in the obese injured group compared to the uninjured group. Moreover, p70S6K1 was threefold greater in lean injured mice compared to uninjured but was reduced by 28% in the obese injured mice. CONCLUSION: Obese mice have impaired inflammatory and protein synthetic signalling that may negatively influence muscle regeneration.
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Dieta Hiperlipídica , Inflamação/metabolismo , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Regeneração/fisiologia , Animais , Modelos Animais de Doenças , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
INTRODUCTION: To investigate the association between pregnancies with small for gestational age (SGA) neonates and the concentration of cell-free fetal DNA or cell-free total DNA in maternal plasma during the first and second trimesters using tissue-specific epigenetic characteristics of the SERPINB5 gene. METHODS: A nested case-control study was conducted with maternal plasma collected at 11 to 26 gestational weeks from 51 women with SGA neonates and 102 controls. We performed a real-time quantitative methylation-specific PCR to quantify concentrations of unmethylated-SERPINB5 (U-SERPINB5) as a cell-free fetal DNA marker and methylated-SERPINB5 (M-SERPINB5) as a cell-free total DNA marker. RESULTS: A positive correlation was observed between U-SERPINB5 and M-SERPINB5 concentrations in both control (r = 0.363, p < 0.001) and SGA groups (r = 0.548, p < 0.001). Moreover, the concentration of U-SERPINB5 or M-SERPINB5 was significantly positive correlated with gestational age at sampling in both controls (U-SERPINB5: r = 0.397, p < 0.001; M-SERPINB5: r = 0.275, p = 0.005) and SGA (U-SERPINB5: r = 0.274, p = 0.052; M-SERPINB5: r = 0.439, p = 0.001). However, the concentration of U-SERPINB5 or M-SERPINB5 was not correlated with birthweight. At 11-14 weeks, U-SERPINB5 and M-SERPINB5 concentrations in SGA did not differ significantly from those of controls. There were also no statistically significant differences in the concentrations of U-SERPINB5 and M-SERPINB5 between SGA and controls at 15-26 weeks of gestation. DISCUSSION: Our findings suggest that U-SERPINB5 and M-SERPINB5 concentrations in maternal plasma during early pregnancy are not associated with pregnancies who delivered SGA neonates.
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Retardo do Crescimento Fetal/sangue , Recém-Nascido Pequeno para a Idade Gestacional , Placenta/metabolismo , Primeiro Trimestre da Gravidez/sangue , Segundo Trimestre da Gravidez/sangue , Serpinas/genética , Adulto , Estudos de Casos e Controles , Metilação de DNA , Epigênese Genética , Feminino , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/metabolismo , Feto/metabolismo , Idade Gestacional , Humanos , Gravidez , Primeiro Trimestre da Gravidez/genética , Segundo Trimestre da Gravidez/genética , Serpinas/sangue , TranscriptomaRESUMO
INTRODUCTION: Down syndrome (DS) is the most common aneuploidy, caused by an extra copy of all or part of chromosome 21 (chr21). Differential microRNA (miRNA) expression is involved in many human diseases including DS. However, the genome-wide changes in miRNA expression in DS fetal placentas have yet to be determined, and the function of these changes is also unclear. METHODS: We profiled genome-wide miRNA expression in placenta samples from euploid or DS fetuses by using microarray technology and predicted the functions of differentially expressed miRNAs using bioinformatics tools. RESULTS: Thirty-four miRNAs were significantly differentially expressed in the DS placenta compared with the normal placenta (16 up-regulated and 18 down-regulated). However, expression of chr21-derived miRNAs did not change. Predicted target genes included 7434 genes targeted by up-regulated miRNAs and 6071 genes targeted by down-regulated miRNAs. Seventy-six of these target genes were located on chr21 (10 genes controlled by down-regulated miRNAs and 34 genes by up-regulated miRNAs, and 32 genes by both). Target genes on chr21 were significantly associated with DS and DS-related disorders, such as mental retardation, neurobehavioral manifestations, and congenital abnormalities. DISCUSSION: To our knowledge, this is the first genome-wide study to comprehensively survey placental miRNAs in DS fetuses. Our results provide new insight into miRNA expression in placentas of fetuses with DS. Additionally, our findings indicate that the differentially expressed miRNAs in the DS placenta may potentially affect various pathways related to DS pathogenesis.
Assuntos
Síndrome de Down/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , MicroRNAs/metabolismo , Modelos Biológicos , Placenta/metabolismo , Adulto , Células Cultivadas , Amostra da Vilosidade Coriônica , Cromossomos Humanos Par 21/metabolismo , Biologia Computacional , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Síndrome de Down/patologia , Feminino , Perfilação da Expressão Gênica , Genômica/métodos , Hospitais Gerais , Hospitais Urbanos , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Placenta/patologia , Gravidez , Primeiro Trimestre da Gravidez , República da CoreiaRESUMO
Receptor activator of NF-kappaB (RANK) is a recently cloned member of the tumor necrosis factor receptor (TNFR) superfamily, and its function has been implicated in osteoclast differentiation and dendritic cell survival. Many of the TNFR family receptors recruit various members of the TNF receptor-associated factor (TRAF) family for transduction of their signals to NF-kappaB and c-Jun N-terminal kinase. In this study, the involvement of TRAF family members and the activation of the JNK pathway in signal transduction by RANK were investigated. TRAF1, 2, 3, 5, and 6 were found to bind RANK in vitro. Association of RANK with each of these TRAF proteins was also detected in vivo. Expression of RANK in cultured cells also induced the activation of JNK, which was blocked by a dominant-negative form of JNK. Furthermore, by employing various C-terminal deletion mutants of RANK, the regions responsible for TRAF interaction and JNK activation were identified. TRAF5 was determined to bind to the C-terminal 11 amino acids and the other TRAF members to a region N-terminal to the TRAF5 binding site. The domain responsible for JNK activation was localized to the same region where TRAF1, 2, 3, and 6 bound, which suggests that these TRAF molecules might mediate the RANK-induced JNK activation.
Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Proteínas de Transporte , Glicoproteínas de Membrana , Proteínas Quinases Ativadas por Mitógeno , Proteínas/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Linhagem Celular , Ativação Enzimática , Células HeLa , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno , Testes de Precipitina , Ligação Proteica , Proteínas/genética , Ligante RANK , Receptor Ativador de Fator Nuclear kappa-B , Receptores do Fator de Necrose Tumoral/química , Receptores do Fator de Necrose Tumoral/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Deleção de Sequência , Transdução de Sinais , Fator 1 Associado a Receptor de TNF , Fator 2 Associado a Receptor de TNF , Fator 3 Associado a Receptor de TNF , Fator 5 Associado a Receptor de TNF , Fator 6 Associado a Receptor de TNF , TransfecçãoRESUMO
A semiquantitative chromatographic technique was developed and standardized using water/chloroform extracts of foods which are spotted onto heat-activated silica gel thin layer chromatographic (TLC) plates, run in butanol/acetic acid/ether/water, developed in acids anisaldehyde, and quantitated planimetrically using Purdy and Truter's formula. Clinically significant amounts of lactose were found in low-calorie sweeteners, breads, yogurt, margarine, penicillin, Gantrisin, and other commonly ingested nondairy substances.
Assuntos
Carboidratos/análise , Análise de Alimentos , Lactose/análise , Bebidas/análise , Pão/análise , Cromatografia em Camada Fina/métodos , Laticínios/análise , Estudos de Avaliação como Assunto , Alimentos Infantis/análise , Preparações Farmacêuticas/análise , Sacarose/análise , Edulcorantes/análiseRESUMO
The nickel and vanadium contents of nine institutional diets were determined by atomic absorption spectrometry with background correction. The following values were obtained for nickel: mean concentration, 0.27 +/- 0.02 microgram/g (dry weight); range, 0.19 and 0.41 microgram/g; mean intake, 165 +/- 11 microgram/day or 75 +/- 10 microgram/1000 cal. The respective values for vanadium were: 0.032 +/- 0.004 microgram/g (dry weight); 0.019 to 0.050 microgram/g; 20.4 +/- 2.3 microgram/day or 8.9 +/- 1.0 microgram/1000 cal. Thus, vanadium is present at approximately one order of magnitude less than nickel.
Assuntos
Análise de Alimentos , Níquel/análise , Vanádio/análise , Inquéritos sobre Dietas , Dieta Redutora , Dieta Hipossódica , HumanosRESUMO
Two MAP kinases, MK1 and MK2, were cloned from Capsicum annuum (pepper) cv. Subicho using a parsley MAP kinase gene as a heterologous probe. MK1 and MK2 encode stress-inducible protein kinases that can contribute to the response to wounding, UV-C, and cold. MK1 has a 92% amino acid identity with WIPK of tobacco. It was transcriptionally induced in response to wounding. In contrast, no detectable MK1 transcript was found in unwounded leaves of pepper. MK2 has a high level of amino acid homology to MAP kinases, such as NTF4 and SIPK and was constitutively expressed in all tissues. Both MK transcripts were downregulated by UV-C treatment. Each MK protein activation was independently wound-inducible in a cultivar dependent manner. MK1 is phosphorylated in cv. Pungchon but not cv. Subicho; whereas, the MK2 protein activation by wounding is restricted to cv. Subicho. In addition, de novo synthesis of the MK1 protein and tyrosine phosphorylation was rapidly and transiently induced in cv. Pungchon by wounding. In contrast, it is highly unlikely that the MK1 protein is produced in cv. Subicho, even though there is an abundant expression of MK1 mRNA after wounding in this cultivar. In Escherichia coli, which overexpresses MK1, autophosphorylation is observed at conserved threonine and tyrosine phosphorylation sites.
Assuntos
Capsicum/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Proteínas Quinases Ativadas por Mitógeno/genética , Plantas Medicinais , Sequência de Aminoácidos , Clonagem Molecular , Temperatura Baixa , DNA Complementar/isolamento & purificação , Ativação Enzimática/fisiologia , Ativação Enzimática/efeitos da radiação , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Dados de Sequência Molecular , Fosforilação , Folhas de Planta/enzimologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , RNA Mensageiro/análise , Raios Ultravioleta , CicatrizaçãoRESUMO
We investigated behavioral responses to noxious cold and heat stimuli in mice. Similar to the hot-plate test, mice showed licking or jumping responses on a cold-plate (0 degrees C). The sensitivity to noxious heat (55 degrees C) was not correlated to the sensitivity to noxious cold, indicating that nociceptive processing of cold and heat are different. Behavioral responses to noxious cold are inhibited by systemic morphine or intrathecal administration of morphine. Lesion of the medial frontal cortex, including the anterior cingulate cortex, or selective activation of two types of opioid receptors in the anterior cingulate cortex produces dose-dependent antinociceptive effects on behavioral responses to noxious cold stimuli. These results suggest that activation of opioid receptors in the anterior cingulate cortex can produce powerful antinociception.
Assuntos
Comportamento Animal/fisiologia , Temperatura Baixa , Giro do Cíngulo/fisiologia , Temperatura Alta , Dor/fisiopatologia , Analgésicos Opioides/farmacologia , Animais , Ala(2)-MePhe(4)-Gly(5)-Encefalina/farmacologia , D-Penicilina (2,5)-Encefalina/farmacologia , Injeções Espinhais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Morfina/farmacologia , Entorpecentes/farmacologia , Nociceptores/efeitos dos fármacos , Nociceptores/fisiologia , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologiaRESUMO
Alfentanil, a short-acting and powerful analgesic, when injected peripherally to rats (0.5 mg/kg) produced a catatonic state characterized by a rigid akinesia. The present study was designed to explore the neuroanatomical location of the opiate receptors mediating the alfentanil induced catatonia. The catatonic effect of alfentanil was measured using a bar test and depression of locomotor activity in rats tested in photocell cages during an active nocturnal phase of their cycle. Methylnaloxonium HCl (MN), a quaternary derivative of naloxone which does not readily cross the blood-brain barrier, injected into the lateral ventricle significantly reduced the catatonia at doses of 0.125-2.0 micrograms as measured in both the locomotor and bar test. MN perfusion of similar doses directly into the nucleus raphe pontis, but not in the caudate nucleus significantly antagonized the catatonia. These data complement results on alfentanil-induced muscular rigidity (Blasco et al., see companion paper) where EMG indices of rigidity in rats were reversed by microinjections of low doses of MN (0.125 and 0.5 microgram) in the nucleus raphe pontis, but not the caudate nucleus even at a high dose (4.0 micrograms). Together these results suggest that the region of the nucleus raphe pontis is an important neural substrate for opiate-induced muscular rigidity, and that the catatonic state produced by opiates depends on more diffuse opiate receptor activation of which one important component may be the nucleus raphe pontis.