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Objective: To analyze and evaluate the differences in sex hormones after laparoscopic Roux-en-Y Gastric Bypass Surgery (LRYGB) and laparoscopic sleeve gastrectomy (LSG) in male patients with obesity. Methods: This study was a retrospective cohort study. The inclusion criteria were (1) male patients with obesity who met the surgical indications of the "Chinese Guidelines for Surgical Treatment of Obesity and Type 2 Diabetes" (2019 Edition); (2) patients with a body mass index (BMI) of ≥27.5 kg/m2 and obesity-related metabolic diseases, or patients with severe obesity and a BMI of ≥35 kg/m2; and (3) sex hormone levels checked 1 year after surgery. The exclusion criteria included (1) patients with endocrine diseases (thyrotoxicosis, hyperprolactinemia) and hypothalamic-pituitary lesions and (2) those with severe major organ dysfunction who could not tolerate anesthesia or surgery. According to the above criteria, the clinical data of male patients with obesity admitted to the Gastrointestinal Surgery/Bariatric Center of the First Affiliated Hospital of Jinan University from October 2017 to January 2020 were included. A total of 52 male patients with obesity were included in this study. The mean age, body weight, BMI, and total testosterone level were (29.3±10.2) years, (123.6±35.4) kg, (40.1±11.1) kg/m2, and 7.6 (5.5, 9.1) nmol/L, respectively. Forty-five patients (86.5%) exhibited testosterone deficiency. Among all the patients, 29 underwent LSG (LSG group) and 23 underwent LRYGB surgery (LRYGB group). The main outcome measure was the change in sex hormone levels before and after bariatric surgery in all the patients. The secondary outcome measures were the comparison of changes in sex hormone levels before and after LSG and LRYGB. Results: Pearson correlation analysis showed that preoperative estradiol was positively correlated with waist circumference (R=0.299, P<0.05), hip circumference (R=0.326, P<0.05), and chest circumference (R=0.388, P<0.05). Testosterone was negatively correlated with BMI (R=-0.563, P<0.01), waist circumference (R=-0.521, P<0.01), hip circumference (R=-0.456, P<0.01), chest circumference (R=-0.600, P<0.01), and neck circumference (R=-0.547, P<0.01). One year following bariatric surgery, the serum testosterone (7.6 [5.5, 9.1] nmol/L vs. 13.6 [10.5, 15.4] nmol/L, Z=-5.910, P<0.001), follicle-stimulating hormone (4.7 [2.7, 5.3] IU/L vs. 6.5 [3.6, 7.8] IU/L, Z=-4.658, P<0.001), and progesterone (1.2 [0.4, 1.5] nmol/L vs. 1.9 [0.8, 1.3] nmol/L, Z=-2.542, P=0.011) levels were significantly higher in all the patients. Both estradiol (172.8 [115.6, 217.5] pmol/L vs. 138.3 [88.4, 168.1] pmol/L, Z=-2.828, P=0.005) and prolactin (11.4 [6.4, 14.6] mIU/L vs. 8.6 [4.8, 7.3] mIU/L, Z=-2.887, P=0.004) levels were decreased. In addition to prolactin levels in the LRYGB group, there were statistically significant differences in the levels of estradiol (P=0.030), follicle-stimulating hormone (P < 0.001), luteinizing hormone (P=0.033), progesterone (P=0.034), and testosterone (P<0.001) compared with their preoperative levels. In the LSG group, there were statistically significant differences in the levels of follicle-stimulating hormone (P=0.011), prolactin (P=0.023), and testosterone (P<0.001) compared with their preoperative levels. Conclusion: The degree of obesity in men was negatively correlated with testosterone levels. Both LRYGB and LSG can significantly improve sex hormone levels in male patients with obesity, and testosterone levels show a significant increase after surgery.
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Cirugía Bariátrica , Diabetes Mellitus Tipo 2 , Adulto , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/cirugía , Estradiol , Hormona Folículo Estimulante , Humanos , Hormona Luteinizante , Masculino , Obesidad/cirugía , Progesterona , Prolactina , Estudios Retrospectivos , Testosterona , Pérdida de Peso , Adulto JovenRESUMEN
Objective: To establish a clustered management plan for pulmonary care of massive burn casualties (hereinafter referred to as the clustered management plan for pulmonary care), and to explore its application effects. Methods: (1) A clustered care intervention group was established, including the medical and nursing staff from the Department of Burns and Plastic Surgery, Department of Respiratory Medicine, and Department of Infection Control at the Fourth Medical Center of PLA General Hospital (hereinafter referred to as our hospital). Four major links, including pulmonary care assessment, chest and lung physical therapy, artificial airway management, and specialized infection control were sorted out according to the key points and difficulties in pulmonary care for massive burn casualties. Evidence-based nursing methods were employed to retrieve articles related to the above-mentioned four links from PubMed, Chinese Journal Full-Text Database, VIP Database and Wanfang Data using terms of " mass burn, respiratory management and airway management" and terms of ",," , and the clustered management plan for pulmonary care was established based on reading and discussion in combination with clinical practice and experience. (2) In this non-randomized controlled study, the clustered management plan for pulmonary care was applied to 73 massive burn patients (48 males and 25 females, aged 32 (25, 38) years) who were admitted to our hospital from January 2016 to December 2019 and met the inclusion criteria, and they were included into the clustered care group; 43 massive burn patients (25 males and 18 females, aged 35 (17, 45) years) who were admitted to our hospital from January 2013 to December 2015, received routine care and met the inclusion criteria were retrospectively included into routine care group. The pulmonary infection rate and mortality of patients in the two groups were recorded during the hospital stay. Data were statistically analyzed with chi-square test, Mann-Whitney U test, and independent sample t test. Results: (1) The clustered management plan for pulmonary care included a total of 12 specific measures covering four aspects of pulmonary care. The contents in pulmonary care assessment clearly stated to include the previous medical history, history of injury, respiratory status, hoarseness, pulmonary auscultation, etc. Chest and lung physical therapy included how to guide patients to effectively cough and do pursed lip breathing and abdominal breathing exercise, etc. Artificial airway management specified the preparation for the establishment of artificial airway at clinical reception, the observation index and frequency after tracheotomy, the method of humidification, the method and frequency of sputum suction, and the management of mechanical ventilation, etc. Specialized infection control required to strengthen hand hygiene and ventilator management. (2) The pulmonary infection rate and mortality of patients in the clustered care group were 2.74% (2/73) and 4.11% (3/73), respectively, significantly lower than 25.58% (11/43) and 18.60% (8/43) in routine care group (χ(2)=11.986, 5.043, P<0.05 or P<0.01). Conclusions: The clustered management plan for pulmonary care developed for massive burn casualties focuses on the major links and key points. The measures are systemic and comprehensive, simple but precise, and highly operable, covering the entire process of massive burn care, hereby reducing the pulmonary infection rate significantly and improving the success rate of treatment.
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Quemaduras , Adolescente , Adulto , Manejo de la Vía Aérea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Respiración Artificial , Estudios Retrospectivos , Traqueotomía , Adulto JovenRESUMEN
Objective: To investigate the clinical significance of detection of circulating tumor cells (CTCs) in peripheral blood from patients with osteosarcoma (OS) using the iFISH (immunofluorescence and fluorescence in situ hybridization) method. Methods: The live cells recovery rate of immune-magnetic beads was evaluated by live-cell fluorescent tracer technology. The expression of CD45 and CK18 on the cell surface of HOS and HepG2 cells was measured by flow cytometry. And the chromosome aneuploidy was detected by centromeric FISH probe CEP8. Subsequently, 23 OS patients were enrolled and divided into two groups, relapse or metastasis group and primary group. And the prognostic significance of CTCs numbers was analyzed. Results: The live cells recovery rate of immune-magnetic beads was higher than 90%. The flow cytometry results showed that HOS cells were double negative for the surface biomarkers of CD45 and CK18. In addition, the FISH-CEP8 signal abnormality rate were 96.5% in HOS cells. Thus, CTC was identified using the criteria as follows: the cells with CEP8-positive signal >2 accounted for more than 96.5% of the total cells, of which the cells with >3 positive signal were more than 65.0%. Among the enrolled patients, 19 patients had detectable CTCs in the peripheral blood. The CTCs numbers in the relapse or metastasis group and primary group were 2.846±1.281 and 1.400±1.506, respectively. The results showed that the CTCs in patients with recurrence or metastasis were significantly higher than those in primary patients (P=0.021). Conclusions: To our knowledge, this is the first evidence of existence of CTCs in OS patients. The CTCs numbers were positively associated with disease progression and poor prognosis. These results may provide a potential prognostic tool for monitoring metastasis and recurrence in OS patients. Trial registration: Chinese Clinical Trial Registry, ChiCTR-OOC-15005925.
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Neoplasias Óseas/sangre , Hibridación Fluorescente in Situ/métodos , Células Neoplásicas Circulantes/patología , Osteosarcoma/sangre , Aneuploidia , Biomarcadores de Tumor/análisis , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Recuento de Células , Técnica del Anticuerpo Fluorescente , Humanos , Antígenos Comunes de Leucocito/análisis , Recurrencia Local de Neoplasia , Osteosarcoma/química , Osteosarcoma/genética , Osteosarcoma/secundario , PronósticoRESUMEN
Hypertensive disorders in pregnancy remain a leading cause of maternal and perinatal mortality and morbidity. We aim to study urotensin II (UII) and its association with the markers of endoplasmic reticulum stress (ERS) in placentas of patients with severe preeclampsia (SPE). Thirty-three patients with hypertensive disorders in pregnancy and twenty-two healthy pregnant women designated as healthy controls were recruited. Expression levels of UII, UII receptor (GPR14) and the markers of ERS in placenta specimens of patients were performed. Plasma and urinary UII levels were measured by radioimmunoassay method. Our study showed that the plasma levels of UII in patients with hypertensive disorders during pregnancy were significantly higher than that of the healthy control group. However, the urinary levels of UII had no difference in two groups. The expression level of mRNA and protein of UII, CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose regulation protein 78 in placentas of SPE was significantly increased. Immunohistochemical analyses show that the expression levels of UII and ERS markers were mainly located in the cytoplasm of placental trophoblastic cells. Moreover, expression level of UII mRNA and protein was positively correlated with that of the markers of ERS. The positive correlation between UII and ERS markers expression level also corresponded with the level of patient's systolic blood pressure and proteinuria. In conclusion, we first verify that expression of UII is associated with ERS in patients with SPE. Our results indicate that UII may trigger ERS in placental trophoblastic cells in patients with preeclampsia.
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Presión Sanguínea/fisiología , Estrés del Retículo Endoplásmico/genética , Regulación de la Expresión Génica , Placenta/metabolismo , Preeclampsia/genética , ARN Mensajero/genética , Urotensinas/genética , Adulto , Western Blotting , Femenino , Humanos , Inmunohistoquímica , Preeclampsia/sangre , Preeclampsia/fisiopatología , Embarazo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Índice de Severidad de la Enfermedad , Urotensinas/biosíntesisRESUMEN
The objective of this study was to determine the effect of forage: concentrate ratio (F:C) on growth performance, ruminal fermentation and blood metabolites of housing-feeding yaks. Thirty-two Maiwa male yaks (initial body weight = 207.99±3.31 kg) were randomly assigned to four dietary treatments (8 yaks per treatment). Experimental diets were: A, B, C, D which contained 70:30, 60:40, 50:50 and 40:60 F:C ratios, respectively. Dry matter intake and average daily gain in yaks fed the C and D diets were greater (p<0.05) than yaks fed the A and B diets. No differences were found in ruminal NH3-N, total volatile fatty acids, acetate, butyrate, valerate, and isovalerate concentrations. The propionate concentration was increased (p<0.05) in the C and D groups compared with the A and B diets. In contrast, the acetate to propionate ratio was decreased and was lowest (p<0.05) in the C group relative to the A and B diets, but was similar with the D group. For blood metabolites, no differences were found in serum concentrations of urea-N, albumin, triglyceride, cholesterol, low density lipoprotein, alanine aminotransferase, and aspartate aminotransferase (p>0.05) among treatments. Treatment C had a higher concentration of total protein and high density lipoprotein (p<0.05) than A and B groups. In addition, there was a trend that the globulin concentration of A group was lower than other treatments (p = 0.079). Results from this study suggest that increasing the level of concentrate from 30% to 50% exerted a positive effect on growth performance, rumen fermentation and blood metabolites in yaks.
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Colitis-associated colorectal cancer (CAC) is the most serious complication of inflammatory bowel disease (IBD). Excessive complement activation has been shown to be involved in the pathogenesis of IBD. However, its role in the development of CAC is largely unknown. Here, using a CAC model induced by combined administration of azoxymethane (AOM) and dextran sulfate sodium (DSS), we demonstrated that complement activation was required for CAC pathogenesis. Deficiency in key components of complement (e.g., C3, C5, or C5a receptor) rendered tumor repression in mice subjected to AOM/DSS. Mechanistic investigation revealed that complement ablation dramatically reduced proinflammatory cytokine interleukin (IL)-1ß levels in the colonic tissues that was mainly produced by infiltrating neutrophils. IL-1ß promoted colon carcinogenesis by eliciting IL-17 response in intestinal myeloid cells. Furthermore, complement-activation product C5a represented a potent inducer for IL-1ß in neutrophil, accounting for downregulation of IL-1ß levels in the employed complement-deficient mice. Overall, our study proposes a protumorigenic role of complement in inflammation-related colorectal cancer and that the therapeutic strategies targeting complement may be beneficial for the treatment of CAC in clinic.
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Carcinogénesis/inmunología , Colitis/patología , Neoplasias Colorrectales/patología , Activación de Complemento/fisiología , Interleucina-17/metabolismo , Interleucina-1beta/metabolismo , Animales , Transformación Celular Neoplásica/inmunología , Transformación Celular Neoplásica/metabolismo , Colitis/inmunología , Colitis/metabolismo , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/metabolismo , Progresión de la Enfermedad , Citometría de Flujo , Immunoblotting , Inmunohistoquímica , Mucosa Intestinal/metabolismo , Intestinos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/inmunologíaRESUMEN
Neutrophil infiltration is a key event in chronic intestinal inflammation and associated colorectal cancer, but how these cells support cancer development is poorly understood. In this study, using a mouse model of colitis-associated cancer (CAC), we have demonstrated that infiltrated neutrophils produce large amounts of interleukin-1 (IL)-1ß that is critical for the development of CAC. Depletion of neutrophil or blockade of IL-1ß activity significantly reduced mucosal damage and tumor formation. This protumorigenic function of IL-1ß was mainly attributed to increased IL-6 secretion by intestine-resident mononuclear phagocytes (MPs). Furthermore, commensal flora-derived lipopolysaccharide (LPS) was identified to trigger IL-1ß expression in neutrophils. Importantly, accumulation of IL-1ß-expressing neutrophils was seen in lesions of patients suffering from ulceratic CAC and these infiltrated neutrophils induced IL-6 production by intestinal MPs in an IL-1ß-dependent manner. Overall, these findings reveal that in CAC milieu, infiltrating neutrophils secrete IL-1ß that promotes tumorigenesis by inducing IL-6 production by intestinal MPs.
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Carcinogénesis/inmunología , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/inmunología , Neoplasias del Colon/etiología , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Infiltración Neutrófila/inmunología , Animales , Modelos Animales de Enfermedad , Citometría de Flujo , Humanos , Inmunohistoquímica , Ratones , Ratones Desnudos , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND AND PURPOSE: We recently reported a novel -62 G/A polymorphism within ataxin 8 (ATXN8) gene promoter region, with -62 G displaying significantly higher luciferase activity compared with -62 A. Phenotypic variability in spinocerebellar ataxia type 8 (SCA8) has been suggested, and large SCA8 repeats were found in patients with Parkinson's disease (PD). We aimed to investigate the association of ATXN8 -62 G/A polymorphism with the risk of Taiwanese PD, and identify the trans-acting factor modulating the ATXN8 promoter activity. METHODS: A case-control study in a cohort of 569 PD cases and 547 ethnically matched controls was conducted by polymerase chain reaction (PCR) and restriction enzyme analysis. The trans-acting factor binding to the ATXN8 promoter was examined by chromatin immunoprecipitation (ChIP)-PCR assay, cDNA co-transfection and luciferase reporter assay. RESULTS: When genotype distribution was calculated by comparing the rare AA genotype with the GG + GA genotypes (recessive model), a significant difference was found (P = 0.035, 1 df). Individuals carrying AA genotype exhibited a decreased risk of developing PD (odds ratio: 0.73; 95% CI: 0.55-0.98, P = 0.035). After stratification by age, individuals over 60 years of age carrying AA genotype demonstrated a further decrease in the risk of developing PD (odds ratio: 0.64; 95% CI: 0.43-0.96, P = 0.030). ChIP-PCR and cDNA over-expression revealed that CCAAT/enhancer-binding protein alpha binds to the ATXN8 proximal promoter to upregulate ATXN8 expression in neuroblastoma SK-N-SH cells. CONCLUSIONS: Our data suggest that ATXN8 -62 G/A polymorphism plays a role in Taiwanese PD susceptibility.
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Predisposición Genética a la Enfermedad/genética , Proteínas del Tejido Nervioso/genética , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas/genética , Adulto , Anciano , Anciano de 80 o más Años , Western Blotting , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Factores de Riesgo , Taiwán , Adulto JovenRESUMEN
New innovations and novel approaches to peripheral arterial occlusive disease have brought enormous benefits to the vascular patient. Diseases that were once manageable only by surgical intervention are now easily and successfully treated by minimally invasive procedures. While the early days of percutaneous intervention were filled with inventions of new devices, today the focus centers on using modern technology and manufacturing to further improve upon these devices. Advances in guidewires and catheters have allowed us to visualize and treat lesions in nearly any vessel, and technology is guiding us towards specialized applications for specific lesions in specific vessels. However, one of the big hurdles remaining in treating arterial occlusive diseases is the rate of restenosis and the need for reinterventions. The location and architecture of these vessels make them uniquely difficult to treat, and call for new technology to address these challenges. Current developments of drug-eluting and bioabsorbable stents are at the forefront of new advancements specifically directed at improving current patency and restenosis rates; perhaps the next step in percutaneous intervention will rely on nanotechnology and the molecular surface engineering that may achieve a new era of devices that are able to target specific cell ligands or proteins to prevent the inflammatory and proliferative response from vessels. The present review will focus on the current literature regarding technological devices in peripheral percutaneous interventions and clinical applications. Future advancements in materials engineering and biotechnology will continue to improve the current standard of percutaneous intervention for peripheral arterial occlusive diseases.
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Arteriopatías Oclusivas/terapia , Procedimientos Endovasculares/instrumentación , Angioplastia de Balón/instrumentación , Aterectomía/instrumentación , Catéteres , Dispositivos de Protección Embólica , Diseño de Equipo , Humanos , StentsRESUMEN
BACKGROUND: Cisplatin-based chemotherapy is a standard treatment of metastatic urothelial carcinoma (UC), though carboplatin-based chemotherapy is frequently substituted due to improved tolerability. Because comparative effectiveness in clinical outcomes of cisplatin- versus carboplatin-based chemotherapy is lacking, a meta-analysis was carried out. METHODS: PubMed was searched for articles published from 1966 to 2010. Eligible studies included prospective randomized trials evaluating cisplatin- versus carboplatin-based regimens in patients with metastatic UC. Individual patient data were not available and survival data were inconsistently reported. Therefore, the analysis focused on overall response (OR) and complete response (CR) rates. The Mantel-Haenszel method was used for combining trials and calculating pooled risk ratios (RRs). RESULTS: A total of 286 patients with metastatic UC from four randomized trials were included. Cisplatin-based chemotherapy was associated with a significantly higher likelihood of achieving a CR [RR = 3.54; 95% confidence interval (CI) 1.48-8.49; P = 0.005] and OR (RR = 1.34; 95% CI 1.04-1.71; P = 0.02). Survival end points could not be adequately assessed due to inconsistent reporting among trials. CONCLUSIONS: Cisplatin-based, as compared with carboplatin-based, chemotherapy significantly increases the likelihood of both OR and CR in patients with metastatic UC. The impact of improved response proportions on survival end points could not be assessed.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Cisplatino/uso terapéutico , Investigación sobre la Eficacia Comparativa , Neoplasias Urológicas/tratamiento farmacológico , Carcinoma de Células Transicionales/secundario , Femenino , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Urológicas/secundarioRESUMEN
Sonic hedgehog (Shh) is a soluble signaling protein that is crucial in regulating cell proliferation, migration and differentiation, axonal guidance and neural progenitor cell survival during nervous system development. Recent evidence suggests that the Shh plays an important role in adulthood in regulating structural plasticity. Here we investigated the expression of Shh in temporal lobe epileptic foci in patients and experimental animals in order to explore the probable relationship between Shh expression and temporal lobe epilepsy (TLE). The Shh expression was assessed in 30 human brain tissues derived from patients undergoing operation for intractable TLE and was also detected in 12 histological normal temporal lobes from controls. Meanwhile, we investigated the Shh expression in the temporal neocortex and hippocampus from lithium-pilocarpine-treated rats on days 1, 3, 7, 14, 30, and 60 post-seizure, and from control rats. Expression of Shh was assessed by immunohistochemistry, immunofluorescence, and Western blot analysis. Shh was mainly expressed in neurons in temporal lobe epileptic foci in humans and experimental rats. Compared to the control group, Shh expression was enhanced in the temporal neocortex of patients with intractable TLE. In experimental rats, Shh expression gradually increased from 7 to 60 days post-seizure in temporal neocortex and elevated from 3 to 60 days in hippocampus with the peak levels at 30 days as compared with the control group. These results suggest that Shh may play an important role in the development of TLE.
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Epilepsia del Lóbulo Temporal/metabolismo , Epilepsia del Lóbulo Temporal/fisiopatología , Proteínas Hedgehog/biosíntesis , Plasticidad Neuronal/genética , Lóbulo Temporal/metabolismo , Lóbulo Temporal/fisiopatología , Adolescente , Adulto , Animales , Modelos Animales de Enfermedad , Epilepsia del Lóbulo Temporal/genética , Femenino , Proteínas Hedgehog/genética , Humanos , Masculino , Persona de Mediana Edad , Ratas , Ratas Sprague-Dawley , Regulación hacia Arriba/genética , Adulto JovenRESUMEN
Myocarditis is an inflammation of the myocardium which often follows virus infections. Coxsackievirus B3 (CVB3), as a marker of the enterovirus group, is one of the most important infectious agents of virus-induced myocarditis. Using a CVB3-induced myocarditis model, we show that injection α-galactosylceramide (α-GalCer), a ligand for invariant natural killer (NK) T (iNK T) cells, can protect the mice from viral myocarditis. After the systemic administration of α-GalCer in CVB3 infected mice, viral transcription and titres in mouse heart, sera and spleen were reduced, and the damage to the heart was ameliorated. This is accompanied by a better disease course with an improved weight loss profile. Compared with untreated mice, α-GalCer-treated mice showed high levels of interferon (IFN)-γ and interleukin (IL)-4, and reduced proinflammatory cytokines and chemokines in their cardiac tissue. Anti-viral immune response was up-regulated by α-GalCer. Three days after CVB3 infection, α-GalCer-administered mice had larger spleens. Besides NK T cells, more macrophages and CD8(+) T cells were found in these spleens. Upon stimulation with phorbol myristate acetate plus ionomycin, splenocytes from α-GalCer-treated mice produced significantly more cytokines [including IFN-γ, tumour necrosis factor-α, IL-4 and IL-10] than those from untreated mice. These data suggest that administration of α-GalCer during acute CVB3 infection is able to protect the mice from lethal myocarditis by local changes in inflammatory cytokine patterns and enhancement of anti-viral immune response at the early stage. α-GalCer is a potential candidate for viral myocarditis treatment. Our work supports the use of anti-viral treatment early to reduce the incidence of virus-mediated heart damage.
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Infecciones por Coxsackievirus/prevención & control , Galactosilceramidas/farmacología , Miocarditis/prevención & control , Miocardio/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Células Cultivadas , Infecciones por Coxsackievirus/complicaciones , Infecciones por Coxsackievirus/mortalidad , Citocinas/genética , Citocinas/metabolismo , Enterovirus Humano B/genética , Enterovirus Humano B/fisiología , Ensayo de Inmunoadsorción Enzimática , Galactosilceramidas/administración & dosificación , Corazón/efectos de los fármacos , Corazón/virología , Interacciones Huésped-Patógeno/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Miocarditis/etiología , Miocarditis/mortalidad , Miocardio/inmunología , Miocardio/patología , Células T Asesinas Naturales/efectos de los fármacos , Células T Asesinas Naturales/inmunología , Células T Asesinas Naturales/metabolismo , ARN Viral/genética , ARN Viral/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Transcripción Genética/efectos de los fármacos , Carga Viral/efectos de los fármacosRESUMEN
The inverse association of the functional ubiquitin carboxy-terminal hydrolase L1 (UCHL1) S18Y variant with Parkinson's disease (PD) among Caucasian populations has been debated. We conducted a large-scale analysis to investigate the age-of-onset effect of the UCHL1 variant in PD among ethnic Chinese. Individual data sets from 5 centers comprising a total of 4088 study subjects were analyzed. In the univariate analysis, only data from 1 center showed a trend towards a protective effect among young subjects. However, in the combined analysis, no significant association between the UCHL1 variant and PD was detected (A allele frequency 0.531 vs. 0.528, p=0.87, OR 1.01, 95% CI 0.92-1.1). Among subjects less than 60 years old, the OR is 0.99 (95% CI 0.84-1.16, p=0.88). A multivariate logistic regression analysis showed that family history, UCHL1 variant and the interaction of UCHL1 variant and age at onset (p=0.816) were not significantly associated with PD.
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Variación Genética/genética , Enfermedad de Parkinson/enzimología , Enfermedad de Parkinson/genética , Ubiquitina Tiolesterasa/genética , Adolescente , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/etnología , Pueblo Asiatico/genética , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Singapur/epidemiología , Singapur/etnología , Taiwán/epidemiología , Taiwán/etnología , Ubiquitinación/genética , Adulto JovenRESUMEN
BACKGROUND: Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher's disease, among patients with Parkinson's disease. We aimed to ascertain the frequency of GBA mutations in an ethnically diverse group of patients with Parkinson's disease. METHODS: Sixteen centers participated in our international, collaborative study: five from the Americas, six from Europe, two from Israel, and three from Asia. Each center genotyped a standard DNA panel to permit comparison of the genotyping results across centers. Genotypes and phenotypic data from a total of 5691 patients with Parkinson's disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel-Haenszel procedure used to estimate odds ratios across centers. RESULTS: All 16 centers could detect two GBA mutations, L444P and N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of patients and 3% of controls, and among non-Ashkenazi Jewish subjects, either mutation was found in 3% of patients and less than 1% of controls. GBA was fully sequenced for 1883 non-Ashkenazi Jewish patients, and mutations were identified in 7%, showing that limited mutation screening can miss half the mutant alleles. The odds ratio for any GBA mutation in patients versus controls was 5.43 across centers. As compared with patients who did not carry a GBA mutation, those with a GBA mutation presented earlier with the disease, were more likely to have affected relatives, and were more likely to have atypical clinical manifestations. CONCLUSIONS: Data collected from 16 centers demonstrate that there is a strong association between GBA mutations and Parkinson's disease.
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Glucosilceramidasa/genética , Mutación , Enfermedad de Parkinson/genética , Anciano , Estudios de Casos y Controles , Genotipo , Humanos , Judíos/genética , Modelos Logísticos , Persona de Mediana Edad , Análisis Multivariante , Oportunidad RelativaRESUMEN
Previous studies indicated the beneficial effects of glial cell line-derived neurotrophic factor (GDNF) and transplanted neural stem cells (NSCs) on stroke. Here, we explored whether transplantation of neural stem cells (NSCs) modified by GDNF gene provides a better therapeutic effect than native NSCs after stroke. Primary rat NSCs were transfected with GDNF plasmid (GDNF/NSCs, labeled by green fluorescent protein from AdEasy-1, GFP). Adult rats were subjected to two-hour middle cerebral artery occlusion and reperfusion, followed by infusion of NSCs (labeled with5-bromo-2'-deoxyuridine before infusion, BrdU), GDNF/NSCs and saline at 3 days after reperfusion (NSCs group, GDNF/NSCs group, control group), respectively. All rats were sacrificed at 1, 2, 3, 5, and 7 weeks after reperfusion. Modified Neurological Severity Scores (mNSS) test and H and E staining were respectively performed to evaluate neurological function and lesion volume. Immunohistochemistry was used to identify implanted cells and observe the expressions of Synaptophysin (Syp) and postsynaptic density-95 (PSD-95) and caspase-3. TdT-mediated dUTP-biotin nick-end labeling (TUNEL) was employed to observe apoptotic cells. Western blotting was used to detect brain-derived neurotrophic factor (BDNF) and NT-3 protein expression. Significant recovery of mNSS was found in GDNF/NSCs rats at 2 and 3 weeks after reperfusion compared with NSCs rats. Lesion volume in the NSCs and GDNF/NSCs groups was reduced significantly compared with control group. The number of NSCs in the GDNF/NSCs group was significantly increased in comparison with NSCs group. Moreover, Syp-immunoreactive product at 2 and 3 weeks after reperfusion and PSD-95 immunoreactive product in the GDNF/NSCs group were significantly increased compared with NSCs group. In contrast, caspase-3 positive cells and TUNEL-positive cells in the GDNF/NSCs group were significantly decreased compared with NSCs group. Significant increase of BDNF protein in the GDNF/NSCs and NSCs groups was observed compared to the control group at different time points of reperfusion, and GDNF/NSCs grafting significantly increased BDNF protein expression compared to NSCs grafting. In addition, significant increase of NT-3 protein in GDNF/NSCs and NSCs groups was detected only at 1 week of reperfusion compared to control group. The results demonstrate that grafting NSCs modified by GDNF gene provides better neuroprotection for stroke than NSCs grafting alone.
Asunto(s)
Isquemia Encefálica/terapia , Terapia Genética/métodos , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Neuronas/trasplante , Trasplante de Células Madre/métodos , Animales , Western Blotting , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Homólogo 4 de la Proteína Discs Large , Femenino , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Infarto de la Arteria Cerebral Media/terapia , Péptidos y Proteínas de Señalización Intracelular , Masculino , Proteínas de la Membrana/biosíntesis , Factor de Crecimiento Nervioso/biosíntesis , Ratas , Ratas Wistar , Recuperación de la Función , Sinaptofisina/biosíntesis , TransfecciónRESUMEN
Intraosseous transcutaneous amputation prostheses (ITAP) rely on the integrity of the soft tissue-implant interface as a barrier to exogenous agents, and in the prevention of avulsion and marsupilization. This experimental work aimed at the in vivo evaluation of soft tissue attachment to Ti alloy (Ti6Al4V) transcutaneous custom-made screws treated by a micro-arc oxidation (MAO) method. Prior to implantation, the surface of the MAO treated implants was analyzed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and x-ray diffraction (XRD). The experimental model comprised implantation of 16 transcutaneous screws (two groups: MAO and machined (control); total eight implants/group) in the medial aspect of the left tibia of eight female goats. The animals were euthanized at eight weeks and the samples harvested and processed for histological and histomorphometrical analysis of soft tissue attachment to the implant surface. Significant higher soft tissue attachment was observed in the MAO-modified group compared to the control. The in vivo data indicated that MAO-modified Ti alloy could be a useful biomaterial for tissue engineering and benefit applications where bone-anchored transcutaneous implants are used.
Asunto(s)
Materiales Biocompatibles/química , Tornillos Óseos , Tejido Conectivo/anatomía & histología , Tibia/citología , Tibia/cirugía , Titanio/química , Aleaciones , Animales , Tejido Conectivo/fisiología , Tejido Conectivo/cirugía , Galvanoplastia/métodos , Análisis de Falla de Equipo , Femenino , Cabras , Oxidación-Reducción , Tamaño de la Partícula , Proyectos Piloto , Diseño de Prótesis , Propiedades de SuperficieRESUMEN
Single crystalline ZnO nanowires were synthesized by hydrothermal process and then formed nano-tubes by acidic etching these nanowires in acetic solution at 85 degrees C. The nanotube diameter can be easily controlled by dividing the nanowires growth and etching process. The ZnO nanotubes remain single crystalline hexagonal structure after the etching process. The defects existed in the nanowires and the dangling bonds of the nanowires' surface play the important roles for the etching process. An etching model for forming ZnO nanotubes is proposed, which can be proved by our experimental results.
RESUMEN
Endoplasmic reticulum (ER) chaperone heat shock 70 kDa protein 5 (HSPA5/GRP78) is known to be involved in the metabolism of amyloid precursor protein and neuronal death in Alzheimer's disease (AD) could arise from dysfunction of the ER. Through a case-control study and an expression assay, we investigated the association of HSPA5 -415 G/A (rs391957), -370 C/T (rs17840761) and -180 del/G (rs3216733) polymorphisms with Taiwanese AD. The overall genotype and allele frequency distribution at the completely linked -415 G/A and -180 del/G sites showed significant difference between AD cases and controls (P = 0.020 and 0.009, respectively). A decrease in risk of developing AD was demonstrated for -415 AA/-180 GG genotype [OR = 0.38, 95% confidence interval (CI) = 0.18-0.75, P = 0.007] and -415 A/-180 G allele (OR = 0.69, 95% CI = 0.51-0.91, P = 0.009). The HSPA5 transcriptional activity of the -415 A/-180 G allele was significantly lower than that of the -415 G/-180 del alleles, whereas induction of HSPA5 expression after ER stress was markedly increased in the cells with the -415 A/-180 G allele. Therefore, our preliminary results may suggest a protective role of the HSPA5 -415 A/-180 G allele in Taiwanese AD susceptibility.
Asunto(s)
Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Proteínas de Choque Térmico/biosíntesis , Proteínas de Choque Térmico/genética , Chaperonas Moleculares/biosíntesis , Chaperonas Moleculares/genética , Anciano , Alelos , ADN/genética , Chaperón BiP del Retículo Endoplásmico , Femenino , Expresión Génica/fisiología , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Oportunidad Relativa , Polimorfismo Genético/genética , Regiones Promotoras Genéticas/genética , Factores de Riesgo , Taiwán/epidemiología , Células Tumorales CultivadasRESUMEN
BACKGROUND AND PURPOSE: This study examines whether angiotensin-converting enzyme (ACE) gene polymorphisms are associated with the risk of spontaneous deep intracerebral hemorrhage (SDICH) in Taiwan using a case-control study. METHODS: Totally, 217 SDICH patients and 283 controls were recruited. Associations of ACE A-240T and ACE I/D polymorphisms with SDICH were examined under the additive model and adjusted for gender, age, body mass index, total cholesterol level, smoking history, alcohol use, hypertension, and use of ACE inhibitors. RESULTS: Hypertension, diabetes mellitus, family history of spontaneous intracerebral hemorrhage (SICH), and low cholesterol level increase risk of female SDICH, whereas hypertension, alcohol use, smoking history, family history of SICH, and low cholesterol level are an important risk factor for male SDICH. After adjusting for covariates, only haplotype ACE T-D (OR = 2.7, 95% CI, 1.1-6.5, P = 0.02) was associated with female SDICH. CONCLUSIONS: This study demonstrates that environmental risk factors play a major role and ACE polymorphisms play a minor role in contributing risk of SDICH in Taiwan.
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Hemorragia Cerebral/genética , Predisposición Genética a la Enfermedad/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético/genética , Anciano , Estudios de Casos y Controles , Hemorragia Cerebral/fisiopatología , Colesterol/sangre , Análisis Mutacional de ADN , Ambiente , Femenino , Frecuencia de los Genes , Marcadores Genéticos/genética , Pruebas Genéticas , Genotipo , Haplotipos , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Mutación , Factores de Riesgo , Caracteres Sexuales , TaiwánRESUMEN
The lateral film growth rate of CH4, C2H4, CO2, CH4 + C2H4, and CH4 + C3H8 hydrates in pure water were measured at four fixed temperatures of 273.4, 275.4, 277.4, and 279.4 K by means of suspending a single gas bubble in water. The results showed that the lateral growth rates of mixed-gas CH4 + C2H4 hydrate films were slower than that of pure gas (CH4 or C2H4) for the same driving force and that of mixed-gas CH4 + C3H8 hydrate film growth was the slowest. The dependence of the thickness of hydrate film on the driving force was investigated, and it was demonstrated that the thickness of hydrate film was inversely proportional to the driving force. It was found that the convective heat transfer control model reported in the literature could be used to formulate the lateral film growth rate v(f) with the driving force DeltaT perfectly for all systems after introduction of the assumption that the thickness of hydrate films is inversely proportional to the driving force DeltaT; i.e., v(f) = psiDeltaT(5/2) is correct and independent of the composition of gas and the type of hydrate. The thicknesses of different gas hydrate films were estimated, and it is demonstrated that the thicknesses of mixed-gas hydrate films were thicker than those of pure gases, which was qualitatively consistent with the experimental result.