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BACKGROUND AIMS: Chronic allograft vasculopathy (CAV) remains a predominant contributor to late allograft failure after organ transplantation. Several factors have already been shown to facilitate the progression of CAV, and there is still an urgent need for effective and specific therapeutic approaches to inhibit CAV. Human mesenchymal-like endometrial regenerative cells (ERCs) are free from the deficiencies of traditional invasive acquisition methods and possess many advantages. Nevertheless, the exact immunomodulation mechanism of ERCs remains to be elucidated. METHODS: C57BL/6 (B6) mouse recipients receiving BALB/c mouse donor abdominal aorta transplantation were treated with ERCs, negative control (NC)-ERCs and interleukin (IL)-37-/-ERCs (ERCs with IL-37 ablation), respectively. Pathologic lesions and inflammatory cell infiltration in the grafts, splenic immune cell populations, circulating donor-specific antibody levels and cytokine profiles were analyzed on postoperative day (POD) 40. The proliferative capacities of Th1, Th17 and Treg subpopulations were assessed in vitro. RESULTS: Allografts from untreated recipients developed typical pathology features of CAV, namely endothelial thickening, on POD 40. Compared with untreated and IL-37-/-ERC-treated groups, IL-37-secreting ERCs (ERCs and NC-ERCs) significantly reduced vascular stenosis, the intimal hyperplasia and collagen deposition. IL-37-secreting ERCs significantly inhibited the proliferation of CD4+T cells, reduced the proportions of Th1 and Th17 cells, but increased the proportion of Tregs in vitro. Furthermore, in vitro results also showed that IL-37-secreting ERCs significantly inhibited Th1 and Th17 cell responses, abolished B-cell activation, diminished donor-specific antibody production and increased Treg proportions. Notably, IL-37-secreting ERCs remarkably downregulated the levels of pro-inflammatory cytokines (interferon-γ, tumor necrosis factor-α, IL-1ß, IL-6 and IL-17A) and increased IL-10 levels in transplant recipients. CONCLUSIONS: The knockdown of IL-37 dramatically abrogates the therapeutic ability of ERCs for CAV. Thus, this study highlights that IL-37 is indispensable for ERC-mediated immunomodulation for CAV and improves the long-term allograft acceptance.
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Trasplante de Corazón , Animales , Humanos , Ratones , Aloinjertos , Inmunoterapia , Interleucinas , Ratones Endogámicos BALB C , Ratones Endogámicos C57BLRESUMEN
Background: A tumor occurs because of abnormal cell multiplication caused by many variables like a significant disturbance in the regulation of cell growth and the instability of chromosome mitosis. Budding uninhibited by benzimidazoles 1 (BUB1), BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B), and budding uninhibited by benzimidazoles 3 (BUB3) are key regulators of mitosis, and their abnormal expression is highly correlated with breast cancer (BrCa), sarcoma, hepatic carcinoma, and other malignant tumors. However, the occurrence of BUBs (BUB1, BUB1B, and BUB3) and the development of BrCa have not been systematically explained. Methods: Find out the target gene by looking up literature on PubMed and CNKI. Using the R software, TCGA, GEO, Kaplan-Meier Plotter, TIMER, and other databases, we studied the level of transcription, genetic changes, and physiological functions of BUBs in BrCa patients and their relationship with the origin, development, prognosis, immunity, and drug resistance of BrCa patients. Findings. We found that the high expression level of BUBs in BrCa tissues proposed a poor prognosis. The multivariate Cox regression analysis suggested that BUB1B and BUB3 might be independent prognostic factors of BrCa. In addition, the Metascape functional enrichment analysis showed that BUBs may be involved in the composition of the spindle, chromosome, and other structures and play a role in mitosis, sister chromatid separation, and other processes. Pathway enrichment suggests that BUBs may affect the cell cycle and lead to abnormal proliferation. Meanwhile, we also found that BUB3 can negatively regulate B lymphocytes, and BUB1 and BUB1B inhibit immune responses by promoting the secretion level of checkpoint molecules of the immune system, leading to immune escape of tumor cells. Conclusion: We speculate that BUB1, BUB1B, and BUB3 may be therapeutic targets for BrCa patients and also provide new therapeutic strategies for BrCa treatment.
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Neoplasias de la Mama , Proteínas de Ciclo Celular/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Bencimidazoles , Biomarcadores , Neoplasias de la Mama/genética , Carcinogénesis , Proteínas de Ciclo Celular/genética , Transformación Celular Neoplásica , Femenino , Humanos , Pronóstico , Proteínas Serina-Treonina Quinasas/genéticaRESUMEN
Interleukin (IL)-37 is a novel defined cytokine that belongs to IL-1 family, which possesses potent anti-inflammatory and immunosuppressive properties. The IL-37 protein mainly exists in the cytoplasm of monocytes and is also expressed in epithelial cells and T cells. IL-37 is produced as a precursor which works in mature or immature isoforms without a classic signal peptide, and negatively regulates TLR agonist- mediated signaling pathway, proinflammatory cytokines, and IL-1R ligands. IL-37 has been found to be elevated and plays an anti-tumor role in various types of tumors, such as hepatocellular carcinoma, non-small cell lung cancer, and cervical cancer. The tumor microenvironment (TME) refers to the cellular environment where the tumor or cancer stem cells exist. At present, growing evidence shows that changes in TME can regulate metabolism, immunity, secretion, and function, so as to inhibit or promote the progression of the tumor. Therefore, a thorough understanding of the TME is essential for the occurrence and development of tumors. In this review, we will summarize the role of IL-37 in the microenvironment of different tumors, hoping to provide novel perspectives towards the mechanism, prevention, and treatment of tumors.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Citocinas/metabolismo , Humanos , Interleucina-1 , Transducción de Señal , Microambiente TumoralRESUMEN
Endometrial regenerative cells (ERCs) are a new type of mesenchymal-like stromal cells, and their therapeutic potential has been tested in a variety of disease models. SDF-1/CXCR4 axis plays a chemotaxis role in stem/stromal cell migration. The aim of the present study was to investigate the role of SDF-1/CXCR4 axis in the immunomodulation of ERCs on the experimental colitis. The immunomodulation of ERCs in the presence or absence of pretreatment of SDF-1 or AMD3100 was examined in both in vitro cell culture system and dextran sulphate sodium-induced colitis in mice. The results showed that SDF-1 increased the expression of CXCR4 on the surface of ERCs. As compared with normal ERCs, the SDF-1-treated, CXCR4 high-expressing ERCs more significantly suppressed dendritic cell population as well as stimulated both type 2 macrophages and regulatory T cells in vitro and in vivo. Meanwhile, SDF-1-pretreated ERCs increased the generation of anti-inflammatory factors (e.g., IL-4, IL-10) and decreased the pro-inflammatory factors (e.g., IL-6, TNF-α). In addition, SDF-1-pretreated CM-Dil-labeled ERCs were found to engraft to injured colon. Our results may suggest that an SDF-1-induced high level of CXCR4 expression enhances the immunomodulation of ERCs in alleviating experimental colitis in mice.
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Quimiocina CXCL12/farmacología , Colitis/metabolismo , Endometrio/citología , Compuestos Heterocíclicos/farmacología , Receptores CXCR4/metabolismo , Animales , Bencilaminas , Células Cultivadas , Quimiocina CXCL12/uso terapéutico , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Ciclamas , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Compuestos Heterocíclicos/uso terapéutico , Humanos , Masculino , Ratones Endogámicos BALB C , Bazo/citología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/metabolismoRESUMEN
INTRODUCTION: The tumor cells could escape from the immune elimination through the immunoediting mechanisms including the generation of immunosuppressive or immunoregulative cells. By contrast, allograft transplantation could activate the immune system and induce a strong allogenic response. The aim of this study was to investigate the efficacy of allogenic skin transplantation in the inhibition of tumor growth through the activation of allogenic immune response. METHODS: Full-thickness skin transplantation was performed from C57BL/6 (H-2b) donors to BALB/c (H-2d) recipients that were receiving subcutaneous injection of isogenic CT26 colon cancer cells (2â¯×â¯106 cells) at the same time. The tumor size and pathological changes, cell populations and cytokine profiles were evaluated at day 14 post-transplantation. RESULTS: The results showed that as compared to non-transplant group, the allogenic immune response in the skin-grafting group inhibited the growth of tumors, which was significantly associated with increased numbers of intra-tumor infiltrating lymphocytes, increased populations of CD11c+MHC-classII+CD86+ DCs, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD19+ B cells, as well as decreased percentage of CD4+CD25+Foxp3+ T cells in the spleens. In addition, the levels of serum IgM and IgG, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were significantly higher within the tumor in skin transplant groups than that in non-transplant group. CONCLUSIONS: Allogenic skin transplantation suppresses the tumor growth through activating the allogenic immune response, and it may provide a new immunotherapy option for the clinical refractory tumor treatment.
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Vasculopathy is one of the primary pathological changes in chronic rejection of vascularized allograft transplantation. Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells with immunosuppressive effect. B7-H1 is a negative costimulator that mediates active immune suppression. The aim of this study was to investigate the requirement of B7-H1 in the immunoregulation of ERCs in preventing transplant vasculopathy of aorta allografts. The results showed that B7-H1 expression on ERCs was upregulated by IFN-γ in a dose-dependent manner and it was required for ERCs to inhibit the proliferation of peripheral blood mononuclear cells (PBMCs) in vitro. ERCs could alleviate transplant vasculopathy, as the intimal growth of transplanted aorta was limited, and the preventive effects were correlated with an increase in the percentages of CD11c+MHC class IIlowCD86low dendritic cells, CD68+CD206+ macrophages, and CD4+CD25+Foxp3+ T cells, as well as a decrease in the percentages of CD68+ macrophages, CD3+CD4+ T cells, CD3+CD8+ T cells, and donor-reactive IgM and IgG antibodies. Moreover, overexpression of B7-H1 by IFN-γ can promote the immunosuppressive effect of ERCs. These results suggest that overexpression of B7-H1 stimulated by IFN-γ is required for ERCs to prevent the transplant vasculopathy, and this study provides a theoretical basis for the future clinical use of human ERCs.
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Warfarin is used as anticoagulant and Compound Danshen prescription (CDP) is able to promote blood circulation. The combination might produce a synergic effect for patients of coronary heart diseases (CHDs) with atrial fibrillation (AF). Whether the combination increases the bleeding risk of warfarin is unclear, so the effects of Compound Danshen dripping pill (CDDP) on the pharmacokinetics (PK) and pharmacodynamics (PD) profiles of warfarin was investigated in patients. The dose and blood concentrations of warfarin, the four indicators of blood coagulation, prothrombin time, activated partial thromboplatin time, thrombin time, fibrinogen, and international normalized ratio value were compared when with and without CDDP treatment. The population PK (PPK) and PPK-PD models were established to assess patient demographics, genetic polymorphisms and CDDP as covariates. And the Seattle Angina Questionnaire was used to evaluate clinical efficacy, and the bleeding risk of combination was analyzed. The results indicated that CDDP had little influence on PK and PD profiles of warfarin in most patients and the combination of CCDP and warfarin would be a promising alternative regime for CHD with AF patients. The study was registered on China Clinical Trial Registry with number ChiCTR-ONRC-13003523.
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OBJECTIVE: To explore the effects of maternal high-fat (HF) diet-induced obesity on fetal growth and the expression of placental nutrient transporters. METHODS: Maternal obesity was established in rats by 8 weeks of pre-pregnancy fed HF diet, while rats in the control group were fed normal (CON) diet. Diet-induced obesity (DIO) rats and diet-induced obesity-resistant (DIR) rats were selected according to body weight gain over this period. After copulation, the CON rats were divided into two groups: switched to HF diet (CON-HF group) or maintained on the CON diet (CON-CON group). The DIO rats and DIR rats were maintained on the HF diet throughout pregnancy. Pregnant rats were euthanized at day 21 gestation, fetal and placental weights were recorded, and placental tissue was collected. Reverse transcription-polymerase chain reaction was used to determine mRNA expression of placental nutrient transporters. Protein expression was determined by Western blot. RESULTS: Average fetal weight of DIO dams was reduced by 6.9%, and the placentas of CON-HF and DIO dams were significantly heavier than the placentas of CON-CON and DIR dams at day 21 of gestation (p<0.05). The fetal/placental weight ratio of DIO dams was significantly reduced compared with the fetal/placental weight ratio of CON-CON dams (p<0.05). The mRNA expression of GLUT-1 and SNAT-2 were not significantly different between groups. The mRNA and protein expression levels of CD36, FATP-1, and FATP-4 in DIO dams were decreased significantly (p<0.05). CONCLUSION: Maternal obesity induced by a HF diet led to intrauterine growth retardation and down-regulated the expression of placental fatty acid transporters.
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Proteínas de Transporte de Ácidos Grasos/genética , Desarrollo Fetal/fisiología , Obesidad , Placenta/metabolismo , Complicaciones del Embarazo , Animales , Dieta Alta en Grasa , Proteínas de Transporte de Ácidos Grasos/metabolismo , Ácidos Grasos/metabolismo , Femenino , Masculino , Fenómenos Fisiologicos Nutricionales Maternos , Obesidad/genética , Obesidad/fisiopatología , Embarazo , Complicaciones del Embarazo/genética , Complicaciones del Embarazo/fisiopatología , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND AND OBJECTIVES: This study evaluated the association of maternal excessive gestational weight gain with saturated and polyunsaturated fatty acid concentrations in maternal and cord serum. METHODS AND STUDY DESIGN: We included 77 pairs of women and their newborns and classified them into three groups as follows: mothers with normal gestational weight gain and their babies with normal birth weight in group I (30 pairs), mothers with excessive gestational weight gain and their babies with normal birth weight in group II (30 pairs), and mothers with excessive gestational weight gain and their macrosomic babies in group III (17 pairs). Serum fatty acid concentrations were determined through gas chromatography-mass spectrometry. RESULTS: No remarkable difference in maternal dietary intake was observed among the three groups. C16:0, C18:0, eicosapentaenoic acid, and docosahexaenoic acid concentrations were significantly higher in group III mothers than in group I mothers. Compared with group I neonates, total saturated and polyunsaturated fatty acid concentrations were significantly lower but total n-3 polyunsaturated fatty acid and docosahexaenoic acid concentrations were significantly higher in group II neonates (p<0.05). The n-6: n-3 ratio in maternal and cord serum was approximately 10:1 and 1.5:1, respectively. CONCLUSION: Women with excessive gestational weight gain who deliver a macrocosmic neonate tend to have higher total saturated fatty acid concentrations but lower docosahexaenoic acid concentrations in their neonate cord serum. Fatty acid concentrations in maternal and cord serum are not associated with maternal dietary pattern.
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Ácidos Grasos/sangre , Sangre Fetal/química , Macrosomía Fetal/sangre , Aumento de Peso , Adulto , Dieta , Ácidos Docosahexaenoicos/sangre , Ácido Eicosapentaenoico/sangre , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Insaturados/sangre , Femenino , Humanos , Recién Nacido , EmbarazoRESUMEN
Sulfamonomethoxine (SMM), a veterinary antibiotic, is widely used in China. However, the impacts of maternal SMM exposure on neurobehavioral development in early life remain little known. In this study, we investigated the effects of maternal SMM exposure during pregnancy on behavioral and physiological responses in offspring mice. Pregnant mice were randomly divided into three SMM-treated groups, namely low-(10mg/kg/day), medium-(50mg/kg/day), and high-dose (200mg/kg/day), and a control group. The pregnant mice in the SMM-treated groups received SMM by gavage daily from gestational day 1-18, whereas those in the control received normal saline. On postnatal day (PND) 50, spatial memory was assessed using the Morris water maze test, and anxiety was measured using the elevated plus-maze and open field tests. The results showed significantly increased blood glucose in pups whose mothers received a high SMM dose. In addition, maternal SMM exposure increased anxiety-related activities among the offspring; spatial learning and memory were impaired more severely in the male offspring. The contents of tetrahydrobiopterin (BH4) and brain-derived neurotrophic factors (BDNF) on PND 22 were significantly reduced in the male offspring of the high-dose group compared with the controls. These findings indicate that SMM may be identified as a risk factor for cognitive and behavioral development on the basis of gender and that it may be associated with diminished BH4 and BDNF levels early in life.
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Antiinfecciosos/toxicidad , Exposición Materna , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Efectos Tardíos de la Exposición Prenatal/psicología , Sulfamonometoxina/toxicidad , Animales , Ansiedad/inducido químicamente , Conducta Animal/efectos de los fármacos , Glucemia , Peso Corporal/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/sangre , Femenino , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Serotonina/sangre , Tiroxina/sangre , Triyodotironina/sangreRESUMEN
The aim of the present study was to investigate the effects of ketamine, imipramine, and ketamine plus imipramine on chronic depression-like behaviors of Wistar Kyoto (WKY) rats and underlying mechanism. Six-week-old Wistar rats were used as normal control. WKY rats, depression model animal, were injected intraperitoneally with ketamine (1 week, replaced with saline in 2(nd) week), imipramine (2 weeks), or ketamine in combination with imipramine. The depression-like behaviors were assessed by sucrose preference and forced swimming tests. Protein expressions of ß form of calcium/calmodulin-dependent protein kinase type II (ßCaMKII) and membrane fraction of glutamate receptor 1 (GluR1) were measured in corresponding brain tissue with Western blot. The results showed that, compared with Wistar rats, WKY rats exhibited decreased sucrose preference and extended immobility time. Ketamine alone did not affect depression-like behaviors of WKY, whereas imipramine or its combination with ketamine could significantly decrease the immobility time. Compared with Wistar rats, WKY rats showed up-regulated levels of ßCaMKII and membrane GluR1 protein expressions in habenula, and down-regulated level of membrane GluR1 protein expressions in the prefrontal cortex. Imipramine or its combination with ketamine could reverse these changes of protein expressions in WKY rats. There was no difference in reversing effect between imipramine and its combination with ketamine. Ketamine alone did not affect the ßCaMKII and membrane GluR1 protein expressions in the habenula, but increased membrane GluR1 protein expression in the prefrontal cortex of WKY rats. These results suggest 2-week imipramine treatment significantly improves depressive behavior in WKY rats; however, the addition of ketamine in the first week fails to enhance the effect of imipramine. The underlying mechanisms of imipramine's anti-depressive effect may be associated with the down-regulation of ßCaMKII and membrane GluR1 in the habenula, as well as the up-regulation of membrane GluR1 in the prefrontal cortex.
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Depresión , Animales , Encéfalo , Trastorno Depresivo , Modelos Animales de Enfermedad , Regulación hacia Abajo , Imipramina , Ketamina , Masculino , Ratas , Ratas Endogámicas WKY , Natación , Regulación hacia ArribaRESUMEN
OBJECTIVE: Association of Signal transducers and activators of transcription-4 (STAT4) gene polymorphism with susceptibility to inflammatory bowel disease have been investigated in a number of epidemiological studies, but the results are inclusive. The aim of this meta-analysis was to more precisely estimate the relationship. METHODS: The databases of Pubmed and CBM updated to October, 2014 were retrieved. Random- or fixed-effect model was used to estimate odd radio (OR) and corresponding 95% confidence interval (95%CI) on the basis of heterogeneity. RESULTS: Seven articles containing 2196 Crohn's disease (CD) cases, 1588 ulcerative colitis (UC) cases and 4126 controls were identified. We detected a significant association between STAT4 rs7574865 polymorphism and IBD susceptibility in overall population (GG vs. GT+TT, OR=0.855, 95% CI=0.760-0.962, P=0.009), but not in Caucasian and Asian population, respectively. No association was detected between rs7574865 polymorphism and CD susceptibility in overall, Asian and Caucasian population, respectively. Interestingly, a significant association was detected between rs7574865 with UC susceptibility in overall population (G vs. T, OR=0.881, 95% CI=0.798-0.972, P=0.012; GG vs. GT+TT, OR=0.788, 95% CI=0.679-0.914, P=0.002; GG vs. TT, OR=0.683, 95% CI=0.498-0.937, P=0.018) and Caucasians (GG vs. GT+TT, OR=0.833, 95% CI=0.701-0.990, P=0.038; GG+GT vs. TT, OR=0.667, 95% CI=0.456-0.975, P=0.037; GG vs. TT, OR=0.636, 95% CI=0.433-0.934, P=0.021), respectively, and a possible association was found in Asian population (GG vs. GT+TT, OR=0.709, 95% CI=0.503-0.998, P=0.049). CONCLUSIONS: STAT4 rs7574865 gene is IBD risk factor, and this gene polymorphism is associated with UC susceptibility, especially in Caucasians. To confirm these findings, further studies with more sample size are required for a definitive conclusion.
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Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad , Enfermedades Inflamatorias del Intestino/genética , Polimorfismo de Nucleótido Simple/genética , Factor de Transcripción STAT4/genética , Población Blanca/genética , Biomarcadores/sangre , China/epidemiología , Colitis Ulcerosa/genética , Enfermedad de Crohn/genética , Medicina Basada en la Evidencia , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/etnología , Valor Predictivo de las Pruebas , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
To investigate the possible risk factors related to macrosomia. Pregnant women and their newborns (n = 1041) were recruited from a cohort study in Maternal and Child Care Center of Hefei from January 2011 to July 2012. Questionnaires were applied to collect the demographic data besides the medical records. Detailed health records of the entire pregnancy were obtained using retrospective study. Meanwhile the data of neonatal outcomes was prospectively tracked. Associations between exposure risk factors and macrosomia were analyzed using Pearson's chi squared test. Logistic regression models were used to assess the independent association between these potential predictors and macrosomia. The incidence of macrosomia of this cohort was 11.24% of which male: female = 2.55:1. Male incidence (8.07%) of macrosomia was higher than female (3.17%), p < 0.001. Body mass index (BMI) before pregnancy (pre-BMI), maternal height, parity were not independently associated with macrosomia; multiple logistic regression analysis indicated that macrosomia was mainly independently associated with weight gain in pregnancy (OR=1.14, 95% CI [1.10-1.19]), maternal age (OR = 1.09, 95% CI [1.03-1.15]) and gestational age (OR = 1.62, 95% CI [1.31-1.99]), respectively. Our findings indicate that weight gain in pregnancy, maternal age and gestational age should be considered as independent risk factors for macrosomia.
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BACKGROUND: The etiology and pathogenesis of neurodegenerative disorders has yet to be elucidated, so their differential diagnosis is a challenge. This is especially true in differentiating Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Parkinson disease (PD), and multiple system atrophy (MSA). METHODS: A total of 11 eligible articles were identified by search of electronic databases including PubMed, Springer Link, Elsevier, and the Cochrane Library, up to June 2014. In meta-analyses, standardized mean differences (SMD), with 95% confidence intervals (CI), comparing cerebrospinal fluid (CSF) measures of α-synuclein between the above conditions were calculated using random-effects models. RESULTS: CSF α-synuclein concentrations were significantly higher in AD compared to DLB [SMD: 0.32, 95% CI: (0.02, 0.62), z = 2.07, P = 0.038]; PD [SMD: 0.87, 95% CI: (0.15, 1.58), z = 2.38, P = 0.017]; or MSA [SMD: 1.14, 95% CI: (0.15, 2.14), z = 2.25, P = 0.025]. However, no significant difference was found between patients with AD and neurological cognitively normal controls [SMD: 0.02, 95% CI: (-0.21, 0.24), z = 0.13, P = 0.894]. CONCLUSIONS: Results of these meta-analysis suggest that quantification of CSF α-synuclein could help distinguish AD from other neurodegenerative disorders such as DLB, PD, or MSA.
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Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad por Cuerpos de Lewy/líquido cefalorraquídeo , Atrofia de Múltiples Sistemas/líquido cefalorraquídeo , Enfermedad de Parkinson/líquido cefalorraquídeo , alfa-Sinucleína/líquido cefalorraquídeo , Enfermedad de Alzheimer/diagnóstico , Diagnóstico Diferencial , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico , Atrofia de Múltiples Sistemas/diagnóstico , Enfermedad de Parkinson/diagnósticoRESUMEN
OBJECTIVE: The aim of this study was to determine the predictive value of maternal serum lipid levels during late pregnancy for neonatal body size. METHODS: This study was conducted from January 1, 2011 to July 31, 2012 at a Maternal and Child Health Hospital. Fasting blood glucose, serum triglyceride, total cholesterol, HDL and LDL were estimated in maternal collected before delivery. Detailed anthropometry of the neonates was performed. RESULTS: Women who delivered a large for gestational age baby were older, taller, had a higher pre-pregnancy weight, higher pre-pregnancy BMI, and higher weight gain during pregnancy than women who delivered an appropriate for gestational age infant. After adjusting for maternal age, pre-pregnancy BMI, weight gain during pregnancy, parity, neonatal sex and gestational age at delivery, we found that only maternal HDL level was inverse associated with birth weight, length and head circumference (p<0.05). On logistic regression analysis, the significant metabolic predictors of large for gestational age was HDL (OR 0.57, 95%CI: 0.38-0.84, per 1 mmol/L increase) after adjusting for the confounders. CONCLUSIONS: Maternal serum HDL level determined in maternal blood taken close to delivery was independently associated with neonatal size and was the independent predictor for large for gestational age.
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Peso al Nacer , Tamaño Corporal , Lípidos/sangre , Adulto , Estatura , Índice de Masa Corporal , Femenino , Edad Gestacional , Humanos , Recién Nacido , Lipoproteínas HDL/sangre , Edad Materna , Embarazo , Aumento de PesoRESUMEN
To investigate the effect of γ-terpineol on cell proliferation and apoptosis of human hepatoma BEL-7402 cells to elucidate its molecular mechanism. Here, BEL-7402 cells were treated with various concentrations (40, 80, 160, 320 and 640 µg/ml) of γ-terpineol for 48 h, cell proliferation was determined by 3-(4,5-dimethyl-thiazolyl-2)-2,5-diphenyl tetrazolium bromides (MTT) assay. Cell colony inhibition was determined by soft agar assay. Apoptosis and possible molecular mechanisms were evaluated by morphological observation, flow cytometry analysis, and DNA fragmentation assay. The γ-terpineol significantly suppressed BEL-7402 cell proliferation in a dose-dependent manner. Characteristic morphological and biochemical changes associated with apoptosis such as cells shrinkage, deformation and vacuolization of mitochondria, nuclear chromatin condensation and fragmentation, formation of apoptotic bodies were observed after BEL-7402 cells treated with γ-terpineol for 24 h and 48 h. Cell cycle were displayed by flow cytometry analysis, the γ-terpineol treatment resulted in accumulation of cells at G1 or S phase and a blockade of cell proliferation compared to control group. Treating BEL-7402 cells with 320 µg/ml of γ-terpineol for 36 h and 48 h, a typical apoptotic "DNA ladder" was observed using DNA fragmentation assay. The present study demonstrated that possible anti-cancer mechanism of γ-terpineol on human hematomas cells is through inducing cell apoptosis to suppress tumor cell growth.
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Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Neoplasias Hepáticas/patología , Monoterpenos/farmacología , Carcinoma Hepatocelular/ultraestructura , Línea Celular Tumoral , Forma de la Célula/efectos de los fármacos , Fragmentación del ADN , Relación Dosis-Respuesta a Droga , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , Neoplasias Hepáticas/ultraestructura , Factores de TiempoRESUMEN
OBJECTIVE: To examine how early life exposure to famine would impact on liver and kidney functions and related chronic metabolic diseases during adulthood. METHODS: A random cluster sampling method was adopted in Anhui province, 2011 from a physical examination center, in a first-class hospital. 4 252 study subjects were born between 1957 and 1963. According to the time of birth:the study subjects were divided into three groups, respectively: 1957-1958 (983 persons as pre-famine), 1959-1961 (1 247 persons as exposed to famine) or 1962-1963(2 022 persons as controls, also the post-famine). Variances between groups AST, ALT, r-GGT, differences in the levels of SCr, UA, UREA and the change trend were compared. RESULTS: ALT,IBIL, TBIL, SCr, UREA were statistically different (P < 0.05) among subjects born in the different years. r-GGT, ALT, AST, ALB, SCr were statistically different (P < 0.05) among males born in different years so as the r-GGT, AST, ALB, GLB, TP, SCr, UA, UREA in females (P < 0.05). r-GGT, ALT, ALB, SCr differences statistically significant (P < 0.05) and r-GGT, AST, ALB, GLB, TP, SCr, UA, UREA in females were statistically significantly different (P < 0.05). CONCLUSION: Early life poor nutrition could lead to developmental disorders, organ function damage in liver and kidney function during adulthood. Women appeared to have balanced diet nutrition during pregnancy which was far important in the prevention on adulthood chronic metabolic diseases.