RESUMEN

In order to provide a thorough summary and analysis over sperm toxicity evaluation of medical devices for human

Asunto(s)

Humanos , Masculino , Técnicas Reproductivas Asistidas , Espermatozoides , Pruebas de Toxicidad

RESUMEN

er to detect the beam quality of the SC200 superconducting cyclotron,measure the beam at the extraction reference and the acceptance of the accelerator is realized.This article mainly introduces the design that use the scintillation screen at the extraction reference to measure the beam profile,position and use the Faraday cup to measure the current intensity with 2.5 level accuracy.The remoted controlling of probes and the acquisition and processing of signal based on LabVIEW and PLC.

Asunto(s)

Terapia de Protones

RESUMEN

Various types of medical devices used in assisted reproductive technologies (ART) should be detected for their safety by strict biological assays. Mouse embryo assay(MEA)has been recognized as one of the most important and standardized methods with the threshold more than 80% of blastocyst formation rate (BR) after 96 h culture of fertilized eggs. The disadvantage using BR for embryonic quality control has been concerned as it is ubiquitously dependent of embryonic morphology and the detailed data including molecular and genetic information is obviously missing and incomplete. This leads to the urgent requirement for more sensitive and efficient assessments for the quality control of ART. This study evaluated the reliability of an immunofluorescent MEA by counting total cell and differential number of the cells in the inner cell mass (ICM) and trophectoderm (TE) in the blastocyst. This method improved the traditional MEA, provided a sensitive and powerful platform to assess embryonic developmental viability and should be suggested as a standard assay to be globally used for the quality control of medical devices and pre-clinical procedures in ART.

Asunto(s)

Animales , Ratones , Blastocisto , Desarrollo Embrionario , Seguridad de Equipos , Reproducibilidad de los Resultados , Técnicas Reproductivas Asistidas

RESUMEN

Brain activities of the mitochondrial enzyme α-ketoglutarate dehydrogenase complex (KGDHC) are reduced in Alzheimer's disease and other age-related neurodegenerative disorders. The goal of the present study was to test the consequences of mild impairment of KGDHC on the structure, protein signaling and dynamics (mitophagy, fusion, fission, biogenesis) of the mitochondria. Inhibition of KGDHC reduced its in situ activity by 23-53% in human neuroblastoma SH-SY5Y cells, but neither altered the mitochondrial membrane potential nor the ATP levels at any tested time-points. The attenuated KGDHC activity increased translocation of dynamin-related protein-1 (Drp1) and microtubule-associated protein 1A/1B-light chain 3 (LC3) from the cytosol to the mitochondria, and promoted mitochondrial cytochrome c release. Inhibition of KGDHC also increased the negative surface charges (anionic phospholipids as assessed by Annexin V binding) on the mitochondria. Morphological assessments of the mitochondria revealed increased fission and mitophagy. Taken together, our results suggest the existence of the regulation of the mitochondrial dynamism including fission and fusion by the mitochondrial KGDHC activity via the involvement of the cytosolic and mitochondrial protein signaling molecules. A better understanding of the link among mild impairment of metabolism, induction of mitophagy/autophagy and altered protein signaling will help to identify new mechanisms of neurodegeneration and reveal potential new therapeutic approaches.

Asunto(s)

Enfermedad de Alzheimer/enzimología , Autofagia/fisiología , Líquido Intracelular/enzimología , Complejo Cetoglutarato Deshidrogenasa/antagonistas & inhibidores , Complejo Cetoglutarato Deshidrogenasa/metabolismo , Mitocondrias/enzimología , Enfermedad de Alzheimer/patología , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Humanos , Líquido Intracelular/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Organofosfonatos/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Succinatos/farmacología

RESUMEN

OBJECTIVE: To study the mechanism of Wnt/ß-catenin signaling pathway in the enhanced malignant phenotype of A549 cells of human non-small cell lung cancer induced by the anti-angiogenesis therapy. METHODS: The siRNA technique was employed to inhibit the expression of vascular endothelial growth factor (VEGF) in A549 cells and simulate the clinical course of anti-angiogenesis therapy. Real-time PCR and western blot were used to study the change in the expression of Wnt/ß-catenin signaling molecules at the mRNA and protein level respectively, as well as the effect on the epithelial mesenchymal transition in A549 cells. The proliferation and invasion abilities of tumor cells were detected to discuss the mechanism of Wnt/ß-catenin signaling pathway in the enhanced malignant phenotype of non-small cell lung cancer induced by the anti-angiogenesis therapy. RESULTS: The specific siRNA could significantly inhibit the expression of VEGF in cells to simulate the anti-angiogenesis therapy. Under the action of 50 nM VEGF siRNA, the proliferation ability of A549 significantly increased (P < 0.05). After being treated with VEGF siRNA, the invasion ability of cells increased. Twenty-four hours after the transcription of 50 nM siRNA into cells, the number of cells that come through the membrane was 278.3 ± 12.9. Compared with the Ctrl siRNA group, when VEGF was inhibited, the expression of ß-catenin and Cyclin D1 increased by 86% and 55% respectively. Meanwhile, the expression of E-cadherin decreased, while the one of vimentin increased. CONCLUSIONS: siRNA can significantly inhibit the expression of VEGF. For the anti-angiogenesis therapy, the inhibited expression of VEGF can activate the Wnt/ß-catenin signaling pathway to cause the epithelial mesenchymal transition and then the enhanced malignant phenotype of non-small cell lung cancer.

RESUMEN

To explore the associated proteins of the hypothalamus in aging rat models with intervention by Qiongyugao(QYG) based on iTRAQ technology, find out the target protein candidates and investigate the mechanism of delaying aging for Qiongyugao. The results showed that Qiongyugao increased GSH-Px activity in serum and SOD activity in liver; the total protein count identified by iTRAQ was 3 522, FDR<1%. There were 20 kinds of differential proteins between the blank group and model group; there were 295 kinds of differential proteins between model group and QYG group, and 40 kinds of them had a difference multiple ≥1.30 (the maximum value was 1.47). Compared with blank group, there were 14 kinds of proteins that were down-regulated in model group and up-regulated in QYG group. Combined with literature search and gene function search, 12 kinds of target protein candidates were screened out ： ST18, Ptprc, PSMB8, INPP4B, Shc3, Pik3r1, PIP5K1C, Nampt, Rasgrp2, Asah2, Pdpk1, and Map2k7. The expression of nuclear factor-kappa B (NF-κB) in the hypothalamic inflammatory pathway was detected by Western blot and the results showed that its expression level in model group(0.96) was higher than that in control group(0.85), while its expression level in QYG group(0.89) was lower than that in model group. Q-PCR results showed that the relative mRNA expression levels of PIP5K1C and Ptprc in model group were significantly lower than those in blank group(P<0.01); while compared with the model group, the mRNA expression levels of PIP5K1C and Ptprc in QYG group were significantly increased(P<0.01) . This result was consistent with proteomics data. QYG may delay aging by regulating hypothalamic inflammatory reaction.

Asunto(s)

Envejecimiento , Medicamentos Herbarios Chinos/farmacología , Hipotálamo/efectos de los fármacos , Animales , Antígenos Comunes de Leucocito/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Ratas

RESUMEN

OBJECTIVE@#To study the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of A549 cells of human non-small cell lung cancer induced by the anti-angiogenesis therapy.@*METHODS@#The siRNA technique was employed to inhibit the expression of vascular endothelial growth factor (VEGF) in A549 cells and simulate the clinical course of anti-angiogenesis therapy. Real-time PCR and western blot were used to study the change in the expression of Wnt/β-catenin signaling molecules at the mRNA and protein level respectively, as well as the effect on the epithelial mesenchymal transition in A549 cells. The proliferation and invasion abilities of tumor cells were detected to discuss the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of non-small cell lung cancer induced by the anti-angiogenesis therapy.@*RESULTS@#The specific siRNA could significantly inhibit the expression of VEGF in cells to simulate the anti-angiogenesis therapy. Under the action of 50 nM VEGF siRNA, the proliferation ability of A549 significantly increased (P < 0.05). After being treated with VEGF siRNA, the invasion ability of cells increased. Twenty-four hours after the transcription of 50 nM siRNA into cells, the number of cells that come through the membrane was 278.3 ± 12.9. Compared with the Ctrl siRNA group, when VEGF was inhibited, the expression of β-catenin and Cyclin D1 increased by 86% and 55% respectively. Meanwhile, the expression of E-cadherin decreased, while the one of vimentin increased.@*CONCLUSIONS@#siRNA can significantly inhibit the expression of VEGF. For the anti-angiogenesis therapy, the inhibited expression of VEGF can activate the Wnt/β-catenin signaling pathway to cause the epithelial mesenchymal transition and then the enhanced malignant phenotype of non-small cell lung cancer.

RESUMEN

AIM: To investigate the effects of external counterpulsation combined with laser photocoagulation for treatment of non-proliferative diabetic retinopathy. METHODS: A prospective study method were used from Aug. 2013 to Feb. 2016. A total of 104 cases in our hospital for treatment of non - proliferative stage of diabetic retinopathy patients were selected as the research object, and all the patients were equally divided into observation group and control group, 52 cases in each group according to the order of admission. Patients in control group were treated with panretinal laser photocoagulation treatment. The observation group were given external counterpulsation combined with laser photocoagulation for treatment, observed the prognosis in the two groups. RESULTS: The total efficiency in the observation group and the control group were 98. 1% and 84. 6%, the observation group was significantly higher than the control group (P0. 05). CONCLUSION: External counterpulsation combined with laser photocoagulation treatment has good safety in the treatment of non-proliferative diabetic retinopathy, it can promote eye artery blood flow speed, thereby improve the therapeutic effect.

RESUMEN

Objective: To study the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of A549 cells of human non-small cell lung cancer induced by the anti-angiogenesis therapy. Methods: The siRNA technique was employed to inhibit the expression of vascular endothelial growth factor (VEGF) in A549 cells and simulate the clinical course of anti-angiogenesis therapy. Real-time PCR and western blot were used to study the change in the expression of Wnt/β-catenin signaling molecules at the mRNA and protein level respectively, as well as the effect on the epithelial mesenchymal transition in A549 cells. The proliferation and invasion abilities of tumor cells were detected to discuss the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of non-small cell lung cancer induced by the anti-angiogenesis therapy. Results: The specific siRNA could significantly inhibit the expression of VEGF in cells to simulate the anti-angiogenesis therapy. Under the action of 50 nM VEGF siRNA, the proliferation ability of A549 significantly increased (P < 0.05). After being treated with VEGF siRNA, the invasion ability of cells increased. Twenty-four hours after the transcription of 50 nM siRNA into cells, the number of cells that come through the membrane was 278.3 ± 12.9. Compared with the Ctrl siRNA group, when VEGF was inhibited, the expression of β-catenin and Cyclin D1 increased by 86% and 55% respectively. Meanwhile, the expression of E-cadherin decreased, while the one of vimentin increased. Conclusions: siRNA can significantly inhibit the expression of VEGF. For the anti-angiogenesis therapy, the inhibited expression of VEGF can activate the Wnt/β-catenin signaling pathway to cause the epithelial mesenchymal transition and then the enhanced malignant phenotype of non-small cell lung cancer.

RESUMEN

To explore the associated proteins of the hypothalamus in aging rat models with intervention by Qiongyugao(QYG) based on iTRAQ technology, find out the target protein candidates and investigate the mechanism of delaying aging for Qiongyugao. The results showed that Qiongyugao increased GSH-Px activity in serum and SOD activity in liver; the total protein count identified by iTRAQ was 3 522, FDR<1%. There were 20 kinds of differential proteins between the blank group and model group; there were 295 kinds of differential proteins between model group and QYG group, and 40 kinds of them had a difference multiple ≥1.30 (the maximum value was 1.47). Compared with blank group, there were 14 kinds of proteins that were down-regulated in model group and up-regulated in QYG group. Combined with literature search and gene function search, 12 kinds of target protein candidates were screened out ： ST18, Ptprc, PSMB8, INPP4B, Shc3, Pik3r1, PIP5K1C, Nampt, Rasgrp2, Asah2, Pdpk1, and Map2k7. The expression of nuclear factor-kappa B (NF-κB) in the hypothalamic inflammatory pathway was detected by Western blot and the results showed that its expression level in model group(0.96) was higher than that in control group(0.85), while its expression level in QYG group(0.89) was lower than that in model group. Q-PCR results showed that the relative mRNA expression levels of PIP5K1C and Ptprc in model group were significantly lower than those in blank group(P<0.01); while compared with the model group, the mRNA expression levels of PIP5K1C and Ptprc in QYG group were significantly increased(P<0.01) . This result was consistent with proteomics data. QYG may delay aging by regulating hypothalamic inflammatory reaction.

RESUMEN

Reversible post-translation modifications of proteins are common in all cells and appear to regulate many processes. Nevertheless, the enzyme(s) responsible for the alterations and the significance of the modification are largely unknown. Succinylation of proteins occurs and causes large changes in the structure of proteins; however, the source of the succinyl groups, the targets, and the consequences of these modifications on other proteins remain unknown. These studies focused on succinylation of mitochondrial proteins. The results demonstrate that the α-ketoglutarate dehydrogenase complex (KGDHC) can serve as a trans-succinylase that mediates succinylation in an α-ketoglutarate-dependent manner. Inhibition of KGDHC reduced succinylation of both cytosolic and mitochondrial proteins in cultured neurons and in a neuronal cell line. Purified KGDHC can succinylate multiple proteins including other enzymes of the tricarboxylic acid cycle leading to modification of their activity. Inhibition of KGDHC also modifies acetylation by modifying the pyruvate dehydrogenase complex. The much greater effectiveness of KGDHC than succinyl-CoA suggests that the catalysis owing to the E2k succinyltransferase is important. Succinylation appears to be a major signaling system and it can be mediated by KGDHC. Reversible post-translation modifications of proteins are common and may regulate many processes. Succinylation of proteins occurs and causes large changes in the structure of proteins. However, the source of the succinyl groups, the targets, and the consequences of these modifications on other proteins remains unknown. The results demonstrate that the mitochondrial α-ketoglutarate dehydrogenase complex (KGDHC) can succinylate multiple mitochondrial proteins and alter their function. Succinylation appears to be a major signaling system and it can be mediated by KGDHC.

Asunto(s)

Acilcoenzima A/metabolismo , Complejo Cetoglutarato Deshidrogenasa/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Animales , Encéfalo/metabolismo , Línea Celular , Células Cultivadas , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Sirtuinas/metabolismo

RESUMEN

Thiamine dependent enzymes are diminished in Alzheimer's disease (AD). Thiamine deficiency in vitro and in rodents is a useful model of this reduction. Thiamine interacts with cellular calcium stores. To directly test the relevance of the thiamine dependent changes to dynamic processes in AD, the interactions must be studied in cells from patients with AD. These studies employed fibroblasts. Mitochondrial dysfunction including reductions in thiamine dependent enzymes and abnormalities in calcium homeostasis and oxidative processes occur in fibroblasts from Alzheimer's Disease (AD) patients. Bombesin-releasable calcium stores (BRCS) from the endoplasmic reticulum (ER) are exaggerated in fibroblasts from patients with AD bearing a presenilin-1 (PS-1) mutation and in control fibroblasts treated with oxidants. ER calcium regulates calcium entry into the cell through capacitative calcium entry (CCE), which is reduced in fibroblasts and neurons from mice bearing PS-1 mutations. Under physiological conditions, mitochondria and ER play important and interactive roles in the regulation of Ca(2+) homeostasis. Thus, the interactions of mitochondria and oxidants with CCE were tested. Inhibition of ER Ca(2+)-ATPase by cyclopiazonic acid (CPA) stimulates CCE. CPA-induced CCE was diminished by inhibition of mitochondrial Ca(2+) export (-60%) or import (-40%). Different aspects of mitochondrial Ca(2+) coupled to CPA-induced-CCE were sensitive to select oxidants. The effects were very different when CCE was examined in the presence of InsP3, a physiological regulator of ER calcium release, and subsequent CCE. CCE under these conditions was only mildly reduced (20-25%) by inhibition of mitochondrial Ca(2+) export, and inhibition of mitochondrial Ca(2+) uptake exaggerated CCE (+53%). However, t-BHP reversed both abnormalities. The results suggest that in the presence of InsP3, mitochondria buffer the local Ca(2+) released from ER following rapid activation of InsP3R and serve as a negative feedback to the CCE. The results suggest that mitochondrial Ca(2+) modifies the depletion and refilling mechanism of ER Ca(2+) stores.

Asunto(s)

Señalización del Calcio , Calcio/metabolismo , Retículo Endoplásmico/metabolismo , Mitocondrias/metabolismo , Tiamina/fisiología , Enfermedad de Alzheimer/patología , Animales , Células Cultivadas , Fibroblastos/metabolismo , Homeostasis , Humanos , Indoles/farmacología , Inositol 1,4,5-Trifosfato/fisiología , Receptores de Inositol 1,4,5-Trifosfato/fisiología , Transporte Iónico , Masculino , Ratones , Ratones Mutantes Neurológicos , Neuronas/metabolismo

RESUMEN

To investigate the expression of vascular endothelial cell growth factor (VEGF) and its receptors in vitreous of patients with diabetic retinopathy ( DR), and to discuss its role in the development of DR. ●METHODS: Selected 13 patients (16 eyes) with DR and 15 healthy people (15 eyes), the expression of VEGF and its receptors (fms-like tyrosine kinase-1, Flt-1 and kinase insert domain containing receptor, KDR) were evaluated by immunohistochemistry in vitreous. The levels of VEGF, the Flt-1 and KDR in vitreous of patients with DR were examined with enzyme linked immunosorbent assay (ELlSA). ● RESULTS: lmmunohistochemical staining showed that the expression of VEGF, Flt-1 and KDR in vitreous vessel membrane of patients with DR was increased significantly. And the levels of VEGF, Flt - 1 and KDR in vitreous of patients with DR were obviously higher than that in the control group (P ● CONCLUSlON: VEGF, Flt - 1 and KDR were widely expressed in vitreous of patients with DR, and were positively related to micro-angiogenesis of DR patients. lt proved that VEGF and its receptors played important roles in the occurrence and development of DR.

RESUMEN

Comparisons of the clinical characteristics of contemporaneous pandemic (H1N1) 2009 influenza A virus (A(H1N1)pdm09)- and seasonal influenza viruses-infected patients are important for both clinical management and epidemiological studies. A prospective multicenter observational study was conducted using a preestablished sentinel surveillance system in Guangzhou, China during 2009. In this study, the clinical presentations of patients with either acute respiratory infection or community-acquired pneumonia were recorded, and nasopharyngeal swab samples were collected for detection of respiratory virus strains using cell cultures or real-time reverse transcription/real-time polymerase chain reaction. Comparisons of the clinical features between A(H1N1)pdm09- and seasonal influenza viruses-infected patients were conducted accordingly. Of the 1,498 patients examined, 265 tested positive for A(H1N1)pdm09, 286 were positive for seasonal influenza A viruses, and 137 for influenza B viruses. The predominant virus was influenza B before the emergence of A(H1N1)pdm09 (epidemiological week [EW] 1-EW 21); then, predominantly non-A(H1N1)pdm09 influenza A and, later, A(H1N1)pdm09, which peaked in EW 46. Compared with the common seasonal influenza-infected patients, A(H1N1)pdm09-infected patients were younger, and had a higher proportion of these patients reported prior contact with infected individuals (P < 0.001, by χ(2) test). However, few significant differences were observed in clinical symptoms and severity among any of the infections caused by the different influenza A strains. Our hospital-based network served as a useful source of information during A(H1N1)pdm09 monitoring. Viral distribution in Guangzhou was characterized by a sharp rise in A(H1N1)pdm09-infected patients in September 2009. Similar to seasonal influenza A-infected cases, A(H1N1)pdm09 cases had a very small proportion of severe cases.

Asunto(s)

Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/epidemiología , Gripe Humana/fisiopatología , Pandemias , Estaciones del Año , Adolescente , Adulto , Anciano , China , Femenino , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/genética , Masculino , Persona de Mediana Edad , Vigilancia de Guardia , Adulto Joven

RESUMEN

Understanding the molecular sequence of events that culminate in multiple abnormalities in brains from patients that died with Alzheimer's disease (AD) will help to reveal the mechanisms of the disease and identify upstream events as therapeutic targets. The activity of the mitochondrial α-ketoglutarate dehydrogenase complex (KGDHC) in homogenates from autopsy brain declines with AD. Experimental reductions in KGDHC in mouse models of AD promote plaque and tangle formation, the hallmark pathologies of AD. We hypothesize that deficits in KGDHC also lead to the abnormalities in endoplasmic reticulum (ER) calcium stores and cytosolic calcium following K(+) depolarization that occurs in cells from AD patients and transgenic models of AD. The activity of the mitochondrial enzyme KGDHC was diminished acutely (minutes), long-term (days), or chronically (weeks). Acute inhibition of KGDHC produced effects on calcium opposite to those in AD, while the chronic or long-term inhibition of KGDHC mimicked the AD-related changes in calcium. Divergent changes in proteins released from the mitochondria that affect endoplasmic reticulum calcium channels may underlie the selective cellular consequences of acute versus longer term inhibition of KGDHC. The results suggest that the mitochondrial abnormalities in AD can be upstream of those in calcium.

Asunto(s)

Enfermedad de Alzheimer/enzimología , Calcio/fisiología , Complejo Cetoglutarato Deshidrogenasa/deficiencia , Mitocondrias/enzimología , Proteínas Mitocondriales/deficiencia , Enfermedad de Alzheimer/fisiopatología , Animales , Línea Celular Tumoral , Células Cultivadas , Complejo Cetoglutarato Deshidrogenasa/antagonistas & inhibidores , Complejo Cetoglutarato Deshidrogenasa/genética , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas Mitocondriales/antagonistas & inhibidores , Proteínas Mitocondriales/genética

RESUMEN

<p><b>OBJECTIVE</b>To analyze the correlation between mitral regurgitation grading and left ventricular ejection fraction in elderly patients (>60 years of age) in a 2-year follow-up.</p><p><b>METHODS</b>A total of 455 patients with the diagnosis of at least mild mitral regurgitation by echocardiography were divided into ischemic mitral regurgitation (IMR) group and non-ischemic regurgitation (NIMR) group. The patients were followed up with echocardiography every 6 months and the data were analyzed at the end of 24 months.</p><p><b>RESULTS</b>Mitral regurgitation grade was inversely correlated with left ventricular ejection fraction (LVEF). Patients with moderate and severe IMR had a lower LVEF than those with NIMR (P<0.05). After adjustment for age, sex, body mass index, high blood pressure, diabetes, atrial fibrillation and cardiomyopathy, the mean LVEF at 2 years was lowered by 2.7% (1.4%-4.1%), 2.7% (1.3%-4.0%), and 5.2% (3.5%-6.9%) in mild, moderate and severe IMR patients, respectively (P<0.04), and by 3.2% (1.6%-4.8%), and 3.0% (1.4%-4.5%), and 1.7%(-0.5%-3.9%) in mild, moderate and severe NIMR patients (P=0.30).</p><p><b>CONCLUSION</b>The mean LVEF in IMR patients is significantly lowered compared to that in NIMR patients. The grade of mitral regurgitation is inversely correlated with the regurgitation area in IMR patients. Stratified management might help improve LVEF in severe IMR patients.</p>

Asunto(s)

Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Estudios de Seguimiento , Insuficiencia de la Válvula Mitral , Volumen Sistólico , Disfunción Ventricular Izquierda

RESUMEN

Diminished thiamine (vitamin B1) dependent processes and oxidative stress accompany Alzheimer's disease (AD). Thiamine deficiency in animals leads to oxidative stress. These observations suggest that thiamin may act as an antioxidant. The current experiments first tested directly whether thiamin could act as an antioxidant, and then examined the physiological relevance of the antioxidant properties on oxidant sensitive, calcium dependent processes that are altered in AD. The first group of experiments examined whether thiamin could diminish reactive oxygen species (ROS) or reactive nitrogen species (RNS) produced by two very divergent paradigms. Dose response curves determined the concentrations of t-butyl-hydroperoxide (t-BHP) (ROS production) or 3-morpholinosydnonimine ((SIN-1) (RNS production) to induce oxidative stress within cells. Concentrations of thiamine that reduced the RNS in cells did not diminish the ROS. The second group of experiments tested whether thiamine alters oxidant sensitive aspects of calcium regulation including endoplasmic reticulum (ER) calcium stores and capacitative calcium entry (CCE). Thiamin diminished ER calcium considerably, but did not alter CCE. Thiamine did not alter the actions of ROS on ER calcium or CCE. On the other hand, thiamine diminished the effect of RNS on CCE. These data are consistent with thiamine diminishing the actions of the RNS, but not ROS, on physiological targets. Thus, both experimental approaches suggest that thiamine selectively alters RNS. Additional experiments are required to determine whether diminished thiamine availability promotes oxidative stress in AD or whether the oxidative stress in AD brain diminishes thiamine availability to thiamine dependent processes.

Asunto(s)

Calcio/metabolismo , Oxidantes/farmacología , Tiamina/farmacología , Células Cultivadas , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Masculino , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

Resveratrol, a polyphenol found in red wine, peanuts, soy beans, and pomegranates, possesses a wide range of biological effects. Since resveratrol's properties seem ideal for treating neurodegenerative diseases, its ability to diminish amyloid plaques was tested. Mice were fed clinically feasible dosages of resveratrol for forty-five days. Neither resveratrol nor its conjugated metabolites were detectable in brain. Nevertheless, resveratrol diminished plaque formation in a region specific manner. The largest reductions in the percent area occupied by plaques were observed in medial cortex (-48%), striatum (-89%) and hypothalamus (-90%). The changes occurred without detectable activation of SIRT-1 or alterations in APP processing. However, brain glutathione declined 21% and brain cysteine increased 54%. The increased cysteine and decreased glutathione may be linked to the diminished plaque formation. This study supports the concept that onset of neurodegenerative disease may be delayed or mitigated with use of dietary chemo-preventive agents that protect against beta-amyloid plaque formation and oxidative stress.

Asunto(s)

Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Antioxidantes/uso terapéutico , Suplementos Dietéticos , Placa Amiloide/genética , Placa Amiloide/patología , Estilbenos/uso terapéutico , Animales , Antioxidantes/farmacocinética , Ácido Ascórbico/metabolismo , Benzotiazoles , Western Blotting , Encéfalo/metabolismo , Ventrículos Cerebrales/patología , Cisteína/metabolismo , Femenino , Glutatión/metabolismo , Hipocampo/patología , Humanos , Inmunohistoquímica , Masculino , Ratones , Ratones Transgénicos , Resveratrol , Sirtuina 1 , Sirtuinas/metabolismo , Estilbenos/farmacocinética , Tiazoles , Factores de Transcripción/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo

RESUMEN

<p><b>OBJECTIVE</b>To investigate the effect of obstructive sleep apnea syndrome (OSAS) on blood lipid and blood glucose in elderly hypertensive patients.</p><p><b>METHOD</b>a One hundred and seven elderly hypertensive patients received examinations by polysomnography and according to the apnea-hypopnea index (AHI), the patients were divided into four groups, namely uncomplicated hypertension group (n=23) and 3 hypertension groups with mild (n=31), moderate (n=29) and severe (n=24) OSAS. The fasting and 2-hour postprandial plasma glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), Apo-A, and Apo-B of these patients were measured.</p><p><b>RESULTS</b>aCompared with the non-OSAS patients, all the OSAS patients showed increased fasting and 2-hour postprandial plasma glucose, HbA1c, TC, TG, LDL and TC/HDL, and the increments were statistically significant in severe OSAS patients (P<0.05). The level of HDL was lowered in the OSAS groups, showing significant difference between severe OSAS group and the non-OSAS group (P<0.05). Apo-A level was lowered and Apo-B increased in the OSAS groups, but the differences were not statistically significant (P>0.05).</p><p><b>CONCLUSIONS</b>OSAS may produce harmful affect on the blood glucose and blood lipids in elderly hypertensive patients.</p>

Asunto(s)

Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glucemia , Metabolismo , Hipertensión , Sangre , Lípidos , Sangre , Polisomnografía , Apnea Obstructiva del Sueño , Sangre

RESUMEN

Type 1 diabetes mellitus (T1DM) is an auto-immune disease while oral administrating its autoantigens could be a treatment of T1DM. To express human insulin gene (ins) in lactic acid bacteria (LAB) for oral vaccine, ins gene was replaced by LAB bias codon and an 8-amino-acid-residue linker peptide forming a beta-turn was designed to link insulin chain A and B. After synthesized by primer annealing method, the whole ins gene was fused with signal peptide sequence SP(Usp45), subcloned into a LAB secretory expressive vector pSW501 and then introduced to Lactococcus lactis (L. lactis) MG1363 and Lactobacillus casei (Lb. casei ) ATCC27092 respectively. Western blot showed that the expression product (SP(Usp45)-INS protein) targeted mainly at the cell wall while little was found in cytoplasm or supernatant. The highest expression level emerged in exponential phase when the optical density at 600nm of the culture was 0.4. The culture of the recombinant strain Lb. casei/pSW501 was administered to non-obese diabetic (NOD) mice orally. ELISA and Western blot results showed that the recombinant strain could induce SP(Usp45)-INS-specific antibodies and raise IL-4 level (38.583 +/- 2.083 pg/mL, P < 0.05) in the mice' s sera. Expression of insulin in the food-grade vehicle LAB could induce oral immune tolerance in NOD mice and protect it from pancreas injury, suggesting it might be a new way to the treatment of T1DM.

Asunto(s)

Diabetes Mellitus Tipo 1/tratamiento farmacológico , Insulina/genética , Lacticaseibacillus casei/genética , Lactococcus lactis/genética , Proteínas Recombinantes/biosíntesis , Administración Oral , Animales , Secuencia de Bases , Humanos , Insulina/uso terapéutico , Ratones , Ratones Endogámicos NOD , Datos de Secuencia Molecular , Proteínas Recombinantes/uso terapéutico