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Objective: To explore the relationship of sleep quality and sleep duration with hypertension among adults aged 30-79 years old in Guangzhou. Methods: According to multi-stage stratified cluster sampling, 12 747 residents aged 30-79 years old were sampled and surveyed in Guangzhou from January 2018 to March 2019. Data on general demographic characteristics, sleep quality, sleep duration and hypertension were collected through questionnaire survey, the Pittsburgh sleep quality index (PSQI) and physical examination. Multivariate logistic regression models were used to analyze the putative association between sleep quality, sleep duration and hypertension. Restrictive cubic spline curve was used to draw the dose-response relationship curve between sleep quality, sleep time and hypertension. Results: The mean age of the subjects was (52.68±12.17) years, the prevalence of hypertension was 36.6% (4 664/12 747), the average score of PSQI was (4.70±2.88), and the average sleep time was (7.00±1.32) hours. The prevalence of hypertension was positively associated with the PSQI score. Compared to the subjects with a score less than 3, OR (95%CI) of hypertension with a PSQI score of 3-5, 5-8, ≥9 were 1.14 (1.02-1.27), 1.17 (1.03-1.34), 1.41 (1.21-1.64), respectively. The relationship between sleep duration and hypertension appeared U-shaped. Compared with 6 to 8 hours sleep duration, both sleep duration<6 hours with OR(95%CI) of 1.27(1.12-1.43) or >8 hours with OR(95%CI) of 1.20(1.05-1.38) was associated with hypertension. Conclusion: Both poor sleep quality, longer or shorter sleep duration were responsible for increased risk of cognitive impairment in older Chinese.
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Hipertensão , Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Humanos , Hipertensão/epidemiologia , Pessoa de Meia-Idade , Prevalência , Sono , Transtornos do Sono-Vigília/epidemiologia , Fatores de TempoRESUMO
Dictyostelium discoideum allC RNAi mutant cells are motile and aggregate together, but do not undergo further morphological development. The relatively quick growth rate of allC RNAi mutants compared to wild-type D. discoideum results in a shortened mutant cell cycle. However, at present, little is known about the mechanism underlying this phenomenon. Here, we used semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative RT-PCR, two-dimensional gel electrophoresis, and mass spectrometry/mass spectrometry to elucidate the phenomenon. We found significant downregulation of myosin II heavy chain, D. discoideum calcium-dependent cell adhesion molecule-1 (DdCAD-1) mRNA, DdCAD-1 protein, D. discoideum mRNA for 14-3-3 and 14-3-3 protein, and type A von Willebrand factor domain-containing protein mRNA in allC RNAi mutants. The results suggest that downregulation of the myosin II heavy chain could be one of key factors causing the developmental interruption and that downregulation of the 14-3-3 protein and the type A von Willebrand factor domain-containing protein mRNA plays an important role in shortening the cell cycle of allC RNAi mutants.
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Proteínas 14-3-3/genética , Moléculas de Adesão Celular/biossíntese , Agregação Celular/genética , Pontos de Checagem do Ciclo Celular/genética , Proteínas 14-3-3/biossíntese , Proteínas de Ligação ao Cálcio/biossíntese , Proteínas de Ligação ao Cálcio/genética , Dictyostelium , Regulação da Expressão Gênica/genética , Mutação , Miosina Tipo II/biossíntese , Estrutura Terciária de Proteína , Interferência de RNA , RNA Mensageiro/biossíntese , Fator de von Willebrand/biossínteseRESUMO
UNLABELLED: Bisphosphonates reduce skeletal loss and fracture risk, but their use has been limited in patients with chronic kidney disease. This study shows skeletal benefits of zoledronic acid in an animal model of chronic kidney disease. INTRODUCTION: Bisphosphonates are routinely used to reduce fractures but limited data exists concerning their efficacy in non-dialysis chronic kidney disease. The goal of this study was to test the hypothesis that zoledronic acid produces similar skeletal effects in normal animals and those with kidney disease. METHODS: At 25 weeks of age, normal rats were treated with a single dose of saline vehicle or 100 µg/kg of zoledronic acid while animals with kidney disease (approximately 30% of normal kidney function) were treated with vehicle, low dose (20 µg/kg), or high dose (100 µg/kg) zoledronic acid, or calcium gluconate (3% in the drinking water). Skeletal properties were assessed 5 weeks later using micro-computed tomography, dynamic histomorphometry, and mechanical testing. RESULTS: Animals with kidney disease had significantly higher trabecular bone remodeling compared to normal animals. Zoledronic acid significantly suppressed remodeling in both normal and diseased animals yet the remodeling response to zoledronic acid was no different in normal and animals with kidney disease. Animals with kidney disease had significantly lower cortical bone biomechanical properties; these were partially normalized by treatment. CONCLUSIONS: Based on these results, we conclude that zoledronic acid produces similar amounts of remodeling suppression in animals with high turnover kidney disease as it does in normal animals, and has positive effects on select biomechanical properties that are similar in normal animals and those with chronic kidney disease.
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Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Difosfonatos/farmacologia , Imidazóis/farmacologia , Insuficiência Renal Crônica/fisiopatologia , Animais , Fenômenos Biomecânicos , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Remodelação Óssea/fisiologia , Diáfises/efeitos dos fármacos , Diáfises/fisiopatologia , Difosfonatos/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fêmur/efeitos dos fármacos , Fêmur/fisiopatologia , Imidazóis/administração & dosagem , Masculino , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Ratos , Ratos Sprague-Dawley , Tíbia/efeitos dos fármacos , Tíbia/patologia , Tíbia/fisiopatologia , Ácido ZoledrônicoRESUMO
Objective: To analyze the treatment effects and side effects of non-surgical comprehensive treatment for locally advanced hypopharyngeal carcinoma invading cervical esophagus. Methods: A retrospective analysis was performed on sixty-six patients with locally advanced hypopharyngeal carcinoma invade the esophagus. These patients were treated in the Department of Otolaryngology, Head and Neck Surgery of Chinese People's Liberation Army General Hospital between January 2011 and May 2022, including sixty-five males and one female, aged 43-71 years. Treatment regimen consisted of induction chemotherapy and concurrent chemoradiothrapy and epidermal growth factor receptor (EGFR)-targeted therapy, three of these cases were treated with programmed cell death 1 (PD-1) immunotherapy. The Kaplan-Meier method was used for survival analysis. Side effects were evaluated with the established CTCAE (Common Terminology Criteria for Adverse Events) 5.0 criteria. The factors affecting prognosis were analyzed by Cox multivariate regression analysis. Results: Sixty-four (97.0%, 64/66) patients completed the radiotherapy and chemotherapy plan. The most common grade three side effects were radioactive oropharyngeal mucositis (89.1%, 57/64) and leukopenia (23.4%, 15/64). Five (7.8%, 5/64) patients showed grade three hoarseness; two patients (3.1%, 2/64) suffered from grade three swallowing dysfunction and required feeding tube and intravenous nutrition; the remaining patients(89.1%) retained good vocal and swallowing functions. The overall survival (OS) of all patients was 81.5% after one year, 54.0% after three years, and 39.9% after five years; the progression-free survival (PFS) was 78.3% after one year, 54.9% after three years, and 42.6% after five years; local control rate (LCR) was 80.9% after one year, 62.5% after three years, and 52.0% after five years. T4a patients showed better OS, PFS and LCR than T4b patients, with statistically significant differences (χ2=8.10, 8.27, and 6.64, respectively, all P<0.05). Cox multivariate regression analysis showed that lymph node metastasis was an independent factor affecting prognosis (χ2=10.21, P<0.05). Conclusion: Non-surgical comprehensive treatment can provide with another option of radical treatment for locally advanced hypopharyngeal carcinoma with cervical esophagus invasion, offering the patients higher rate of larynx and esophageal preservation with tolerable side effects.
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Carcinoma , Neoplasias Hipofaríngeas , Masculino , Humanos , Feminino , Estudos Retrospectivos , Neoplasias Hipofaríngeas/terapia , Imunoterapia , EsôfagoRESUMO
Objective: To analyze the effectiveness, safety and factors influencing the clinical prognosis of patients with hypopharyngeal carcinoma in T4b by nonsurgical treatments. Methods: The clinical data of 77 patients with T4b hypopharyngeal cancer treated in the College of Otolaryngology Head and Neck Surgery of the Chinese People's Liberation Army General Hospital from January 2010 to June 2021 were analyzed retrospectively. All were males, aged(57.0±8.0)years old. Patients were treated with induction chemotherapy plus concurrent chemoradiotherapy. Kaplan Meier survival analysis was used to compare the effects of different factors on prognosis. Adverse reactions during treatments and the causes of death were analyzed. Results: 98.7% of 77 patients with T4b hypopharyngeal cancer completed the chemotherapy plan and 94.8% completed the radiotherapy plan. The most common adverse reactions were grade 2 radiation oral mucositis (50/77, 64.9%) and grade 2 leukopenia (50/77, 64.9%). The incidence of grade 3 severe hoarseness was 7.8% (6/77), one patient (1.3%) underwent gastrostomy due to dysphagia, and pronunciation and swallowing function were effectively preserved in other patients. The overall survival rate was 71.9% at 1 year, 45.6% at 3 years and 29.7% at 5 years. The location of tumor, the presence of liquefaction necrosis in tumor, the use of molecular targeted drugs and the approach of radiotherapy were independent factors,each of which that affected the prognosis of T4b patients with advanced hypopharyngeal cancer [HR (95%CI) were 1.867(1.085-3.213), 3.018 (1.437-6.335), 0.372 (0.181-0.764) and 2.158 (1.015-4.588), respectively, P<0.05]. The two leading causes of death with high incidence were disease recurrence (12/32, 37.5%) and cervical large vessel rupture and hemorrhage (11/32, 34.4%). Conclusions: Non-surgical comprehensive treatment offers a high laryngeal preservation rate in patients with T4b hypopharyngeal cancer. The location of tumor, the liquefaction necrosis within tumor, the use of molecular targeted drugs, and the approach of radiotherapy are independent prognostic factors.
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Carcinoma de Células Escamosas , Neoplasias Hipofaríngeas , Idoso , Quimiorradioterapia , Humanos , Neoplasias Hipofaríngeas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Interface structure is a basic problem in interface and surface science. It is usually indicated by atomic positions for an ideal interface. But this way is sometimes unsuitable for a mismatch interface, because there are too many atoms under consideration, whose coordinates may confuse our mind in understanding the interface structure. In this case, a 'dislocation representation' is introduced. A misfit dislocation network is used as an effective representation of the interface structure. However, there are two questions on this topic. How to determine the dislocation network structure? And how to relate it to interface dynamics? In this paper, we work on the first question and make an effort to build up the 'dislocation representation' for metal/Al(2)O(3) interfaces.
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Chronic kidney disease (CKD) progression results in musculoskeletal dysfunction that is associated with a higher likelihood of hospitalization and is predictive of hospitalizations and mortality. Despite this, there is a lack of effective interventions to treat the musculoskeletal dysfunction. We studied treadmill running as an intervention to improve musculoskeletal health in a translational rat model that has slowly progressive CKD. CKD rats were subjected to treadmill exercise or no treadmill exercise for 10 weeks (nâ¯=â¯8 each group). Animals ran for 60â¯min, 5 times per week starting at a speed of 8â¯m/min and ending at 18â¯m/min (1â¯m/min increase/week). Treadmill training had no effect on muscle strength (assessed as maximally stimulated torque), half-relaxation time (time from peak torque to 50%) or muscle cross-sectional area. Overall, there were no biochemical improvements related to CKD progression. Skeletal muscle catabolism was higher than non-exercised animals without a concomitant change in muscle synthesis markers or regeneration transcription factors. These results suggest that aerobic exercise, achieved via treadmill running was not protective in CKD animals and actually produced potentially harmful effects (increased catabolism). Given the high prevalence and dramatic musculoskeletal mobility impairment in patients with CKD, there is a clear need to understand how to effectively prescribe exercise in order to benefit the musculoskeletal system.
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OBJECTIVE: To investigate the efficacy of induction chemotherapy (ICT) followed by concurrent chemotherapy and helical tomotherapy (HT) in the patients with T4b squamous cell carcinoma of nasal cavity and paranasal sinus (SCCNP) for orbital organ preservation and high quality of life. METHODS: A total of 26 patients with the orbital involvement of T4b SCCNP between May 2008 and March 2013 were analyzed retrospectively. There were 17 males and 9 females; the average age was 54.7 years. The median follow-up time was 25 months (range 4-77 months). The patients received 1-2 cycles ICT with TP (docetaxel 70 mg/m(2) on day 1 and cisplatin 40 mg/m(2) on day 1-2, every 3 weeks) or TPF (docetaxel 70 mg/m(2) on day 1 and cisplatin 70 mg/m(2) on day 1-2, 5-fu 700 mg/m(2) on day 1-5, every 3 weeks), followed by concurrent HT (60-70 Gy) and chemotherapy with TP and/or epidermal growth factor receptor (EGFR) inhibitor. The Kaplan-Meier method was used to determine the 3-year overall survival rate and local control rate. Side-effects were evaluated with the established common terminology criteria for adverse events (CTCAE) version 4.0 criteria. RESULTS: All patients completed the planned chemotherapy and 96.2%(25/26)patients completed the planned radiotherapy. The 3-year overall survival rate, the local control rate and real orbital preservation rate were 56.7%, 79.5% and 80.0% respectively. The most common acute side effects higher than grade 2 were oral mucositis, radiodermatitis and dry eye syndrome. CONCLUSION: The strategy including ICT followed by CCRT and/or EGFR inhibitor is an effective treatment for T4b SCCNP patients, with minimal toxicities, higher 3-year OS rate and orbital preservation rate, and also provides a new treatment option for T4b SCCNP patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Nasais/tratamento farmacológico , Neoplasias Nasais/radioterapia , Tratamentos com Preservação do Órgão , Antineoplásicos , Carcinoma de Células Escamosas/mortalidade , Cisplatino/administração & dosagem , Terapia Combinada/métodos , Docetaxel , Receptores ErbB/antagonistas & inibidores , Feminino , Fluoruracila/administração & dosagem , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Cavidade Nasal , Neoplasias Nasais/mortalidade , Neoplasias dos Seios Paranasais/tratamento farmacológico , Neoplasias dos Seios Paranasais/radioterapia , Qualidade de Vida , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Taxa de Sobrevida , Taxoides/administração & dosagem , Resultado do TratamentoRESUMO
In the past, tolerance mechanisms have focused on processes that involve elimination (deletion) or paralysis (anergy) of immune responses. It is now becoming clearer that peripheral tolerance to antigen depends on the generation of regulatory cells that function to maintain the tolerant state. The development of peripheral tolerance may require that the immune system utilize several strategies, including deletion, anergy, and immunoregulatory pathways, and these strategies may overlap. Recent investigations using animal models of transplantation tolerance have demonstrated that immunoregulatory CD4 mechanisms may play a central role in limiting organ-destructive immune responses. In this Overview, we discuss the rationale behind the need for invoking active regulatory mechanisms in peripheral immunologic tolerance and summarize the data that support or refute a CD4 regulatory mechanism.
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Tolerância Imunológica , Animais , Células Apresentadoras de Antígenos/fisiologia , Linfócitos T CD4-Positivos/fisiologia , Anergia Clonal/imunologia , Humanos , Tolerância Imunológica/fisiologia , Interleucina-2/fisiologiaRESUMO
The use of cell-specific monoclonal antibodies provides a means by which the emergence, differentiation and maturation of retinal neurons can be studied. The present study investigates the labelling of ganglion cells in the developing rabbit retina by a ganglion cell-specific monoclonal antibody, AB5(12,13). AB5 labelling of ganglion cells was observed as early as day postnatal. By 6-8 days postnatal, AB5-labelled ganglion cells had begun differentiating into the various ganglion cell subtypes observed in the adult retina. This differentiation process appeared to continue throughout the first 3 weeks postnatal. The AB5 monoclonal antibody was also used in a double-label paradigm with an anti-gamma-aminobutyric acid (GABA) polyclonal antibody to differentiate the GABAergic ganglion cells from other GABAergic elements in the retina and to study their development. GABAergic ganglion cells were first observed at 3 days postnatal and by 6 days postnatal, it was possible to observe a wide variety of GABAergic ganglion cells ranging from small cells to large alpha-type cells. The appearance of AB5 labelling in ganglion cells at relatively early stages of development suggests that the AB5 monoclonal antibody may be a useful tool for studying the development of ganglion cell structure, distribution, synaptic relationships and neurochemical specificity.
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Retina/crescimento & desenvolvimento , Células Ganglionares da Retina/fisiologia , Ácido gama-Aminobutírico/análise , Envelhecimento , Animais , Animais Recém-Nascidos , Anticorpos Monoclonais , Imuno-Histoquímica , Coelhos , Retina/citologia , Células Ganglionares da Retina/citologiaRESUMO
We examined the time course of insulin-like growth factor binding protein (IGFBP) secretion and hormonal regulation of IGFBP and IGF-I secretion in porcine stromal vascular (S-V) cultures. Primary cultures of S-V cells derived from porcine adipose tissue were exposed to serum-free media with or without hormone treatment. Time course studies indicated that secretion of four IGFBP (IGFBP-1, -2, -3 and -4) by porcine S-V cells increased with time during the first 3 d after the switch to serum-free conditions and then decreased gradually. Growth hormone treatment stimulated secretion of each IGFBP by 47 +/- 4.7, 46 +/- 10.2, 70 +/- 13.2, and 49 +/- 5.6%, respectively, over control levels. The secretion of IGFBP-1, -2, -3, and -4 was enhanced by 91 +/- 18, 80 +/- 16, 74 +/- 12, and 263 +/- 48%, respectively, in T4-treated S-V cultures compared with untreated cultures. In contrast, dexamethasone reduced the abundance of the IGFBP by 28 to 50% of control levels. Insulin-like growth factor I secretion (844.63 +/- 35.98 pg/mL) in vitro (3 d conditioned media) was increased (P < .05) by GH (1,302.45 +/- 12.95 pg/mL) and T4 (1,291.60 +/- 86.4 pg/mL) and decreased (P < .05) by dexamethasone (552.5 +/- 30.2 pg/mL) (n = 4, S-V cell pools, P < .05). In addition to preadipocytes, other cells in S-V cultures also secrete IGFBP. In conclusion, the secretion of IGF-I and IGFBP by S-V cells is differentially regulated by hormones in vitro.
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Dexametasona/farmacologia , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Hormônio do Crescimento/farmacologia , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Suínos/metabolismo , Tiroxina/farmacologia , Adipócitos/citologia , Adipócitos/metabolismo , Análise de Variância , Animais , Western Blotting/veterinária , Células Cultivadas , Relação Dose-Resposta a Droga , Células-Tronco/citologia , Células-Tronco/metabolismo , Fatores de TempoRESUMO
Previous studies have shown that the responsiveness of porcine preadipocytes to glucocorticoids increases progressively with fetal age. In the current study, the development of fetal glucocorticoid receptors in porcine preadipocytes was examined in primary cultures derived from 50-, 75-, and 105-d fetal and 7-d postnatal porcine adipose tissue. Three dams were used for each fetal age group and three young pigs were used for the postnatal studies. Using [3H]dexamethasone as the radioligand, cytosolic glucocorticoid receptors were measured in preadipocytes. There was an age-related increase in the number of glucocorticoid receptors during fetal development. The number of glucocorticoid receptors was very low in 50-d fetal porcine preadipocytes (1.350 +/- .178 fmol/mg of protein) and increased progressively to a peak at 105 d (8.990 +/- .741 fmol/mg of protein). This represents an approximate sixfold increase in receptor number between these two ages (P < .05). After birth, the glucocorticoid receptor number significantly decreased compared with that of 105-d fetuses (2.766 +/- .218 fmol/mg of protein, P < .05). Furthermore, the dissociation constant (Kd) of the glucocorticoid receptor in 105-d fetal preadipocytes was numerically smaller than the Kd of receptors derived from other age groups, although only significantly lower than that of the 75-d group (P < .05). Insulin markedly increased the number and binding affinity of glucocorticoid receptors in preadipocytes, indicating its potential involvement in regulation of glucocorticoid receptors. The effect of glucocorticoids on differentiation in preadipocytes is, at least in part, mediated by the number of glucocorticoid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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Adipócitos/metabolismo , Animais Recém-Nascidos/crescimento & desenvolvimento , Receptores de Glucocorticoides/metabolismo , Células-Tronco/metabolismo , Suínos/embriologia , Adipócitos/química , Adipócitos/citologia , Envelhecimento/fisiologia , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Citosol/química , Dexametasona , Feminino , Insulina/farmacologia , Gravidez , Receptores de Glucocorticoides/análise , Receptores de Glucocorticoides/efeitos dos fármacos , Células-Tronco/química , Células-Tronco/citologia , Suínos/crescimento & desenvolvimento , TrítioRESUMO
The effects of fetal hypophysectomy (hypox) and age on insulin-like growth factor-I (IGF-I) response, receptor binding and IGF-I & IGF binding protein secretion by porcine preadipocytes was examined. Primary cultures of stromal vascular (S-V) cells derived from fetal and postnatal adipose tissue were established and exposed to test media (different concentrations of pig serum with or without IGF-I) for morphological study or to serum-free media for measuring IGF-I receptor binding and IGF-I & IGFBPs secretion. Conditioned media were collected and subjected to IGF-I RIA and ligand blot and immunoblot analysis. IGF-I significantly stimulated total cell growth (determined by DNA levels) and increased fat cell cluster number and lipid deposition in porcine S-V cultures (determined by image analysis). Although the pattern of response to IGF-I was similar in fetal and postnatal cultures, the response was greater in fetal cultures. The mitogenic and adipogenic response of fetal preadipocytes to IGF-I was impaired by fetal hypox. Specific IGF-I binding sites on fetal preadipocytes had a higher binding affinity for IGF-I (Kd = 2.82 +/- 0.28 nM) than did postnatal preadipocytes (Kd = 7.28 +/- 1.52 nM, P < 0.05). Preadipocytes secreted IGF-I and four IGF-BPs (BP-1, -2, -3, and -4) in a developmentally regulated manner. For example, IGFBP-2, and -3 were predominant binding proteins secreted by fetal preadipocytes which represented 47% and 30% of the total, respectively. IGFBP-1 was the major binding protein secreted by postnatal preadipocytes. Furthermore, fetal cells secreted greater amounts of IGF-I in cultures than did postnatal cells (2428 +/- 205 pg/ml vs. 870 +/- 31 pg/ml, P < 0.05). Fetal hypox caused a decrease from 47% to 68% of control values in all four IGFBPs secreted by preadipocytes. The changes in IGF-I receptor binding and IGF-I and IGFBP secretion by preadipocytes may account for altered response of preadipocytes to IGF-I. Thus, secretion of IGF-I and IGFBPs, IGF-I binding and response of porcine preadipocytes were affected by age and fetal hypox. The results indicated that locally produced IGF-I and IGFBPs may play a critical paracrine/autocrine role during fetal adipose development.
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Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Receptor IGF Tipo 1/metabolismo , Tecido Adiposo/citologia , Envelhecimento/metabolismo , Animais , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Desenvolvimento Embrionário e Fetal , Feminino , Feto/metabolismo , Hipofisectomia , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Gravidez , SuínosRESUMO
We have previously found that uremic human serum upregulates RUNX2 in vascular smooth muscle cells (VSMCs), and that RUNX2 is upregulated in areas of vascular calcification in vivo. To confirm the role of RUNX2, we transiently transfected a dominant-negative RUNX2 (DeltaRUNX2) construct in bovine vascular smooth muscle cells (BVSMCs). Blocking RUNX2 transcriptional activity significantly decreased uremic serum induced alkaline phosphatase (ALP) activity (268+/-34 vs 188+/-9.5 U/g protein, P<0.05) and osteocalcin expression (172+/-17 vs 125+/-9 ODU, P<0.05). To determine the mechanism by which uremic serum upregulates RUNX2, we examined cell signaling pathways. BVSMCs were incubated in the presence or absence of inhibitors and RUNX2 expression and ALP activity were determined. The results demonstrate that the cyclic AMP (cAMP)/protein kinase A (PKA), but not protein kinase C, signaling pathway is involved in uremic serum-induced RUNX2 expression and ALP activity in BVSMCs. To examine potential uremic 'toxins', we measured bone morphogenetic protein (BMP)-2 concentration and found that uremic serum contained increased BMP-2 (uremic serum=169+/-33 pg/ml, normal serum=117+/-15 pg/ml, P<0.05). The incubation of BVSMCs with noggin, an inhibitor of BMP, decreased RUNX2 expression. In addition, BMP-2 secretion progressively increased during calcification and uremic serum enhanced its secretion compared to normal serum. In conclusion, this study demonstrates that RUNX2 transcriptional activity is critical in uremic serum-induced bone matrix protein expression in BVSMCs and that the cAMP/PKA pathway is involved. BMP-2 is also increased in uremic serum and can upregulate RUNX2 and calcification in vitro in VSMCs.
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Proteínas Sanguíneas/farmacologia , Proteínas Morfogenéticas Ósseas/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Músculo Liso Vascular/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Uremia/sangue , Fosfatase Alcalina/metabolismo , Animais , Aorta Torácica/citologia , Proteína Morfogenética Óssea 2 , Proteínas Morfogenéticas Ósseas/sangue , Calcificação Fisiológica , Proteínas de Transporte/metabolismo , Proteínas de Transporte/farmacologia , Bovinos , Técnicas de Cultura de Células , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , AMP Cíclico/metabolismo , Músculo Liso Vascular/citologia , Osteocalcina/metabolismo , Fator de Crescimento Transformador beta/sangue , Regulação para CimaRESUMO
The cluster expansion method is applied to electronic excitations and a set of effective cluster densities of states (ECDOS) is defined, analogous to effective cluster interactions (ECIs). The ECDOSs are used to generate alloy thermodynamic properties as well as the equation of state (EOS) of electronic excitations for the fcc Ni-Al systems. When parent clusters have a small size, the convergence of the expansion is not so good but the electronic density of state (DOS) is well reproduced. However, the integrals of the DOS such as the cluster expanded free energy, entropy, and internal energy associated with electronic excitations are well described at the level of the tetrahedron-octahedron cluster approximation, indicating that the ECDOS is applicable to produce electronic ECIs for cluster variation method (CVM) or Monte Carlo calculations. On the other hand, the Gruneisen parameter, calculated with first-principles methods, is no longer a constant and implies that the whole DOS profile should be considered for EOS of electronic excitations, where ECDOS adapts very well for disordered alloys and solid solutions.
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The predilection for beta(2)-microglobulin (beta(2)M) amyloid deposition in articular structures is unique compared to other forms of amyloid; this article focuses on possible pathogenic mechanisms. The synovium and/or cartilage appear to be important in the pathogenesis of beta(2)M amyloidosis (A beta(2)M), as amyloid is not found in the shafts of long bones. The concentration of beta(2)M in the joint fluid parallels that in serum. Once in the joint space, evidence suggests that the beta(2)M binds to collagen in cartilage as the initial site of deposition. This binding may serve as the first step in subsequent amyloid formation, although this remains to be proven. beta(2)M has been shown to have many direct effects on synovial fibroblasts, including induction of the release of cytokines, metalloproteinases, cyclooxygenase-2, and vascular cell adhesion molecule-1 (VCAM-1). The release of these inflammatory mediators that lead to tissue degradation is also observed in other forms of arthritis. Thus beta(2)M itself may elicit the release of inflammatory mediators from synovial fibroblasts even in the absence of cellular infiltrates.
Assuntos
Amiloidose/metabolismo , Cartilagem Articular/metabolismo , Membrana Sinovial/metabolismo , Microglobulina beta-2/metabolismo , Amiloidose/etiologia , Humanos , Ligação Proteica , Diálise Renal/efeitos adversosRESUMO
Studies were conducted to determine the influence of thyroxine (T4) in vivo on preadipocyte development and insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs) secretion in stromal-vascular (S-V) cultures. Fetal pigs were hypophysectomized (hypox) at 70 days of gestation, implanted with T4 pellets, and fetuses from the dam at 75 days of gestation. In a second experiment, hypox and T4 implantation were performed at 75 days and fetal pigs removed at 95 days of gestation. Primary cultures of stromal vascular (S-V) cells derived from fetal adipose tissue were established. Cultures were stained for morphological analysis and conditioned media were collected for IGF-1 determination by radioimmunoassay (RIA) and IGFBP analysis by Western blotting. After only 5 days of T4 treatment, fat cell cluster number and size and lipid deposition in cultures were significantly increased compared to cultures from untreated hypox fetuses. Fetal hypox reduced IGF-I secretion by preadipocytes at both ages and T4 treatment completely normalized IGF-I secretion (p < 0.05). Four IGFBPs (BP-1, BP-2, BP-3 & BP-4) detected in S-V cultures derived from 95-day fetuses were decreased in concentration by hypox by 44 +/- 9.4%, 32 +/- 9.7%, 42 +/- 12% and 53 +/- 6.9%. In cultures derived from T4 treated hypox fetuses, the levels of these four IGFBPs were increased by 187 +/- 25%, 239 +/- 38%, 190 +/- 5% and 347 +/- 43% over control values, respectively. In cultures from 75-day fetuses, only IGFBP-2 (major one) and BP-1 (minor one) were detected and their secretion was also decreased by hypox and elevated by T4 treatment (190 +/- 49.5%, 156 +/- 30%, respectively, of controls). The results provide direct evidence that T4 has a major influence on fetal preadipocyte development. T4 stimulated production of IGF-I and IGFBP in fetal S-V cultures, which in turn, may have mediated the capability of T4 to enhance fetal adipose tissue development.
Assuntos
Adipócitos/citologia , Tecido Adiposo/embriologia , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Tiroxina/farmacologia , Adipócitos/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/fisiologia , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Meios de Cultivo Condicionados , Feminino , Idade Gestacional , Hipofisectomia , Gravidez , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Células Estromais/fisiologia , Suínos , Tiroxina/administração & dosagem , Tiroxina/sangueRESUMO
We present an exact mathematical description of beam shaping and indicate that a rigorous solution does not exist: only an optimal solution can be found. An optimization method is proposed to search for the solution. The simulation results for an example are given in detail.
RESUMO
We first discuss the discrete fractional Fourier transform and present some essential properties. We then propose a recursive algorithm to implement phase retrieval from two intensities in the fractional Fourier transform domain. This approach can significantly simplify computational manipulations and does not need an initial phase estimate compared with conventional iterative algorithms. Simulation results show that this approach can successfully recover the phase from two intensities.