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1.
QJM ; 117(3): 167-176, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-37318994

RESUMEN

Immune homeostasis is a steady immune state that not only protects the host from pathogens but also prevents the emergence of pathological self-reactive immune cells. The disruption of immune homeostasis leads to the development of various diseases, such as cancer and autoimmune diseases. An emerging paradigm for the treatment of these diseases with dysfunctional immune systems is the restoration and maintenance of immune homeostasis. However, currently available drugs exert a unidirectional influence on immunity whereby they either augment or inhibit it. This strategy is associated with the drawback of potential adverse effects arising from uncontrolled activation or suppression of the immune system. Fortunately, evidence suggests that acupuncture can bidirectionally regulate the immune system to maintain immune homeostasis. In cases of immunosuppressive diseases (e.g. cancer), acupuncture has an enhancing effect on immunity. Conversely, in autoimmune diseases (e.g. rheumatoid arthritis), acupuncture has been observed to have an immunosuppressive effect, which helps restore normal immune tolerance. However, there is no publication systematically summarizing the bidirectional regulatory effects of acupuncture on the immune system in the literature. Here, our review provides a comprehensive overview of the various mechanisms through which acupuncture modulates the immune system in a bidirectional manner. These mechanisms include the augmentation of NK and CD8+ T cell function, as well as the restoration of Th1/Th2, Th17/Treg and M1/M2 balance. Thus, we propose the concept that acupuncture has the potential to alleviate illnesses through the facilitation of immune normalization. Moreover, we further highlight the therapeutic potential of acupuncture.


Asunto(s)
Terapia por Acupuntura , Artritis Reumatoide , Enfermedades Autoinmunes , Neoplasias , Humanos , Enfermedades Autoinmunes/terapia , Homeostasis , Neoplasias/patología
2.
Physiol Res ; 72(4): 511-520, 2023 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-37795893

RESUMEN

Farrerol (FA) is a traditional Chinese herbal medicine known for its anti-inflammatory and anti-oxidative properties in various diseases. Ferroptosis is an iron-dependent oxidative stress-induced cell death. It is characterized by lipid peroxidation and glutathione depletion and is involved in neuronal injury. However, the role of FA in inhibiting ferroptosis in hypoxic-ischemic encephalopathy (HIE) and its underlying mechanisms are not yet completely elucidated. This study aimed to investigate whether FA could mediate ferroptosis and explore its function and molecular mechanism in HIE. A neonatal rat model of HIE was used, and rats were treated with FA, ML385 (a specific inhibitor of nuclear factor erythroid 2-related factor 2 [Nrf2]), or a combination of both. Neurological deficits, infarction volume, brain water content, pathological changes, and iron ion accumulation in the brain tissues were measured using the Zea-Longa scoring system and triphenyl tetrazolium chloride (TTC), hematoxylin-eosin (HE), and Perls' staining. The expression levels of GSH-Px, MDA, SOD, and ROS in brain tissues were also evaluated. Western blot analysis was performed to analyze the expression of the Nrf2 pathway and ferroptosis-related proteins. The results showed that FA administration significantly reduced neuronal damage, infarct volume, cerebral edema, and iron ion accumulation and inhibited MDA and ROS levels while promoting GSH-Px and SOD levels. FA also increased the expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), Nrf2, and HO-1. Moreover, the combination of ML385 and FA in HIE abolished the FA protective effects. Therefore, the study concludes that FA exerts a neuroprotective effect after HIE by inhibiting oxidative stress and ferroptosis via the Nrf2 signaling pathway.


Asunto(s)
Ferroptosis , Hipoxia-Isquemia Encefálica , Animales , Ratas , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Animales Recién Nacidos , Factor 2 Relacionado con NF-E2 , Especies Reactivas de Oxígeno , Glutatión , Hierro , Superóxido Dismutasa
3.
Plant Biol (Stuttg) ; 25(6): 902-914, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37641387

RESUMEN

Studies on plant responses to combined abiotic stresses are very limited, especially in major crop plants. The current study evaluated the response of chorismate mutase overexpressor (OxCM) rice line to combined UV light and drought stress. The experiments were conducted in pots in a growth chamber, and data were assessed for gene expression, antioxidant and hormone regulation, flavonoid accumulation, phenotypic variation, and amino acid accumulation. Wild-type (WT) rice had reduced the growth and vigour, while transgenic rice maintained growth and vigour under combined UV light and drought stress. ROS and lipid peroxidation analysis revealed that chorismate mutase (OsCM) reduced oxidative stress mediated by ROS scavenging and reduced lipid peroxidation. The combined stresses reduced biosynthesis of total flavonoids, kaempferol and quercetin in WT plants, but increased significantly in plants with OxCM. Phytohormone analysis showed that SA was reduced by 50% in WT and 73% in transgenic plants, while ABA was reduced by 22% in WT plants but increased to 129% in transgenic plants. Expression of chorismate mutase regulates phenylalanine biosynthesis, UV light and drought stress-responsive genes, e.g., phenylalanine ammonia lyase (OsPAL), dehydrin (OsDHN), dehydration-responsive element-binding (OsDREB), ras-related protein 7 (OsRab7), ultraviolet-B resistance 8 (OsUVR8), WRKY transcription factor 89 (OsWRKY89) and tryptophan synthase alpha chain (OsTSA). Moreover, OsCM also increases accumulation of free amino acids (aspartic acid, glutamic acid, leucine, tyrosine, phenylalanine and proline) and sodium (Na), potassium (K), and calcium (Ca) ions in response to the combined stresses. Together, these results suggest that chorismate mutase expression induces physiological, biochemical and molecular changes that enhance rice tolerance to combined UV light and drought stresses.


Asunto(s)
Oryza , Oryza/genética , Sequías , Especies Reactivas de Oxígeno , Rayos Ultravioleta , Aminoácidos , Corismato Mutasa , Flavonoides
4.
Zhonghua Yi Xue Za Zhi ; 103(34): 2639-2646, 2023 Sep 12.
Artículo en Chino | MEDLINE | ID: mdl-37475568

RESUMEN

Chest tightness variant asthma (CTVA) was first reported and named by Chinese scholars in 2013. It is a new clinical type of asthma characterized by chest tightness as the only or primary symptom, without typical asthma manifestations such as recurrent wheezing and shortness of breath, and without wheezing sounds heard during lung auscultation. The overall epidemiological data on CTVA is currently unavailable. Its pathogenesis is similar to that of typical asthma, involving eosinophilic airway inflammation. Due to the lack of typical clinical manifestations, insufficient knowledge of this disease in some clinicians and some other reasons, CTVA is susceptible to misdiagnosis or missed diagnosis. Currently, the diagnostic criteria for CTVA are: chest tightness as the only or primary symptom, without typical asthma symptoms and signs such as wheezing and shortness of breath, and with any one of the objective indicators of variable airflow limitation. Effective anti-asthma treatment is required, and other diseases that cause chest tightness, such as cardiovascular, digestive, nervous, muscular, and mental diseases should be excluded. CTVA treatment follows that of typical asthma, but the specific treatment duration is uncertain and may require long-term management. Traditional Chinese medicine has shown some therapeutic effects on CTVA. Most CTVA patients have a good prognosis after active anti-asthma treatment. This paper analyzes and summarizes the research of CTVA in China from 2013 and provides new perspectives for further exploration of CTVA.


Asunto(s)
Antiasmáticos , Asma , Humanos , Ruidos Respiratorios , Asma/tratamiento farmacológico , Disnea/tratamiento farmacológico , China
5.
Eur J Neurol ; 27(11): 2233-2241, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32562320

RESUMEN

BACKGROUND AND PURPOSE: Migraine is a complex and disabling neurological disorder, the exact neurological mechanisms of which remain unclear. The thalamus is considered to be the hub of the central processing and integration of nociceptive information, as well as the modulation of these processes. METHODS: A total of 48 migraineurs without aura (MWoAs) during the interictal phase and 48 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. We utilized masked independent component analysis and seed-based functional connectivity (FC) to investigate whether MWoAs exhibited abnormal FC between subregions in the thalamus and the cortex regions. RESULTS: The MWoAs showed significantly weaker FC between the anterior dorsal thalamic nucleus and left precuneus. Additionally, MWoAs exhibited significantly reduced FC between the ventral posterior nucleus (VPN) and left precuneus, right inferior parietal lobule (R-IPL) and right middle frontal gyrus. Furthermore, the FC Z-scores between the VPN and R-IPL were negatively correlated with pain intensity in MWoAs. The disease duration of patients was negatively correlated with the FC Z-scores between the VPN and R-IPL. CONCLUSION: These altered thalamocortical connectivity patterns may contribute to multisensory integration abnormalities, deficits in pain attention, cognitive evaluation and pain modulation. Pain sensitivity and disease duration are closely tied to abnormal FC between the VPN and R-IPL. Remarkably, recurrent headache attacks might contribute to this maladaptive functional plasticity closely related to pain intensity.


Asunto(s)
Migraña sin Aura , Corteza Cerebral/diagnóstico por imagen , Epilepsia , Humanos , Imagen por Resonancia Magnética , Migraña sin Aura/diagnóstico por imagen , Tálamo/diagnóstico por imagen
6.
Zhonghua Yi Xue Za Zhi ; 100(23): 1783-1788, 2020 Jun 16.
Artículo en Chino | MEDLINE | ID: mdl-32536123

RESUMEN

Objective: To determine whether 60 Gy is superior to standard 50 Gy for definitive concurrent chemoradiation(CCRT) in esophageal squamous cell carcinoma (ESCC) using modern radiation technology in a phase Ⅲ prospective randomized trial. Methods: From April 2013 to May 2017, 331 patients from 22 hospitals who were pathologically confirmed with stage ⅢA-ⅣA ESCC were randomized to 60 Gy or 50 Gy with random number table. Total of 305 patients were analyzed, including 152 in 60 Gy group and 153 in 50 Gy group. The median age was 63 years, 242(79.3%) males and 63(20.7%) females. The median length of primary tumor was 5.6 cm. The clinical characteristics between two groups were comparable. All patients were delivered 2 Gy per fraction, 5 fractions per week. Concurrent weekly chemotherapy with docetaxel (25 mg/m(2)) and cisplatin (25 mg/m(2)) and 2 cycles consolidation chemotherapy with docetaxel (70 mg/m(2)) and cisplatin (25 mg/m(2), d1-3) were administrated. The primary endpoint was local/regional progression-free survival (LRPFS). The data were compared with Pearson chi-square test or Fisher's exact test. Results: At a median follow-up of 27.3 months, the disease progression rate was 37.5% (57/152), 43.8% (67/153) in the high and standard-dose group, respectively (χ(2)=1.251, P=0.263). The 1, 2, 3-year LRPFS rate was 75.4%, 56.8%, 52.1% and 74.2%, 58.4%, 50.1%, respectively (HR: 0.95, 95%CI: 0.69-1.31, P=0.761). The 1, 2, 3-year overall survival rate was 84.1%, 64.8%, 54.1% and 85.4%, 62.9%, 54.0%, respectively (HR: 0.98, 95%CI: 0.71-1.38, P=0.927). The 1, 2, 3-year progression-free survival rate was 70.8%, 54.2%, 48.5% and 65.5%, 51.9%, 45.1%, respectively (HR: 0.93, 95%CI: 0.68-1.26, P=0.621). The incidence rates in toxicities between the two groups were similar except for higher rate of severe pneumonitis in high dose group (χ(2)=11.596, P=0.021). Conclusions: The efficacy in disease control is similar between 60 Gy and 50 Gy using modern radiation technology concurrent with chemotherapy for ESCC. The 50 Gy should be recommended as the regular radiation dose with CCRT for ESCC.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioradioterapia , Cisplatino , Terapia Combinada , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/terapia , Femenino , Fluorouracilo , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
7.
Arq. bras. med. vet. zootec. (Online) ; 71(4): 1207-1216, jul.-ago. 2019. tab, graf
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1038614

RESUMEN

Aims to investigate the effects of grape seed proanthocyanidin extract (GSPE) on production performance, metabolism, and anti-oxidative status of Holstein dairy cattle in early lactation. Forty-eight multiparous Holstein dairy cattle were assigned to four groups (CON, G20, G40 and G80) and supplied with 0, 20, 40, and 80mg GSPE/kg of body weight/day. G20 significantly increased milk yield compared with other groups. Milk protein and non-fat-solids were increased in G20, G40 and G80 groups compared with the control group only at the 7th day during the experiment. No significant difference was observed in milk fat and somatic cell count, nor on parameters of energy metabolism in blood, liver function and kidney function between the four groups. There was no significant difference in glutathione peroxidase, superoxide dismutase, total antioxidant capacity, and hydrogen peroxide between the groups; but the malondialdehyde content of G20 significantly increased at day 14 in comparison with CON, and tended to increase at the 28th day. In conclusion, feeding 20mg GSPE/kg of body weight/day was associated with a significant increase in milk yield without detrimental effects on liver or kidney function and with substantial energy metabolism and antioxidant parameters improvement in early lactation dairy cattle.(AU)


O presente trabalho visa investigar os efeitos do extrato de semente de uva Proanthocyanidin (GSPE) sobre o desempenho da produção, o metabolismo e o status antioxidante de gado leiteiro Holstein em lactação precoce. Quarenta e oito vacas leiteiras multíparas Holstein foram divididas em quatro grupos (CON, G20, G40 e G80) e receberam 0, 20, 40 e 80mg de GSPE/kg de peso corporal/dia, respectivamente. O G20 aumentou significativamente o rendimento do leite em comparação com os outros grupos. A proteína e os sólidos não gordurosos do leite foram aumentados nos grupos G20, G40 e G80 somente no sétimo dia durante a experiência. Não foi observada diferença significativa na gordura do leite e na contagem de células somáticas, bem como nos parâmetros de metabolismo energético no sangue, na função hepática e na função renal entre os grupos em relação ao grupo controle. Não houve diferença significativa na glutationa peroxidase, na dimutase de superóxido, na capacidade antioxidante total e no peróxido de hidrogênio entre os grupos, mas o conteúdo malondialdeído do G20 aumentou significativamente no dia 14 em comparação com o CON, e tendia a aumentar no dia 28. Em conclusão, a alimentação de 20mg de GSPE/kg de peso corporal/dia foi associada a um aumento significativo no rendimento do leite, sem efeitos nocivos sobre a função hepática ou a renal, com o metabolismo de energia substancial e a melhoria dos parâmetros antioxidantes de gado leiteiro no início da lactação.(AU)


Asunto(s)
Animales , Femenino , Bovinos , Lactancia/efectos de los fármacos , Proantocianidinas , Leche , Extracto de Semillas de Uva/administración & dosificación , Antioxidantes/análisis
8.
Anim Genet ; 50(4): 407-411, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31094009

RESUMEN

In sheep, increased expression of the follicle-stimulating hormone receptor (FSHR) in the ovary is a common feature of ewes that carry the prolific allele. In this study, we demonstrated that polymorphisms in the core promoter of the FSHR gene are associated with the reproductive performance of Hu sheep and are involved in the transcriptional activity of FSHR. An approximately 1.5-kb region of the 5' flanking sequence of the Hu sheep FSHR gene was isolated and characterized, and its core promoter was located in the 5' regulatory region, from nucleotides -580 to -342. Four variants (c.-518T>C, c.-466C>T, c.-414A>G and c.-365C>T) were detected in this region, and six genotypes and three haplotypes were found in the Hu sheep population (n = 245). An association analysis revealed that these polymorphisms are associated with the litter size of Hu ewes. Furthermore, a luciferase assay showed that the T-C-A-C- and C-T-G-T-type core promoters have higher transcriptional activity than does the T-C-G-C type. Notably, the putative binding site for the transcription factor Yin Yang 1 (YY1) was present at the A allele of nucleotide -414, but YY1 can significantly increase the transcriptional activity of the FSHR core promoter, which contains three different haplotypes. Taken together, our results establish that these variants might be involved in regulating the transcriptional activity of FSHR and litter size in Hu ewes and may provide a novel candidate marker for marker-assisted selection in sheep breeding.


Asunto(s)
Tamaño de la Camada , Regiones Promotoras Genéticas , Receptores de HFE/genética , Oveja Doméstica/genética , Animales , Cruzamiento , Femenino , Haplotipos , Secuencias Reguladoras de Ácidos Nucleicos , Oveja Doméstica/fisiología , Transcripción Genética , Factor de Transcripción YY1/genética
9.
Osteoarthritis Cartilage ; 26(12): 1733-1743, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30201491

RESUMEN

OBJECTIVE: We previously reported that genetic ablation of (Fibroblast Growth Factors Receptors) FGFR1 in knee cartilage attenuates the degeneration of articular cartilage in adult mice, which suggests that FGFR1 is a potential targeting molecule for osteoarthritis (OA). Here, we identified R1-P1, an inhibitory peptide for FGFR1 and investigated its effect on the pathogenesis of OA in mice induced by destabilization of medial meniscus (DMM). DESIGN: Binding ability between R1-P1 and FGFR1 protein was evaluated by enzyme-linked immuno sorbent assay (ELISA) and molecular docking. Alterations in cartilage were evaluated histologically. The expression levels of molecules associated with articular cartilage homeostasis and FGFR1 signaling were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC). The chondrocyte apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay. RESULTS: R1-P1 had highly binding affinities to human FGFR1 protein, and efficiently inhibited extracellular signal-regulated kinase (ERK)1/2 pathway in mouse primary chondrocytes. In addition, R1-P1 attenuated the IL-1ß induced significant loss of proteoglycan in full-thickness cartilage tissue from human femur head. Moreover, this peptide can significantly restore the IL-1ß mediated loss of proteoglycan and type II collagen (Col II) and attenuate the expression of matrix metalloproteinase-13 (MMP13) in mouse primary chondrocytes. Finally, intra-articular injection of R1-P1 remarkably attenuated the loss of proteoglycan and the destruction of articular cartilage and decreased the expressions of extracellular matrix (ECM) degrading enzymes and apoptosis in articular chondrocytes of mice underwent DMM surgery. CONCLUSIONS: R1-P1, a novel inhibitory peptide for FGFR1, attenuates the degeneration of articular cartilage in adult mice, which is a potential leading molecule for the treatment of OA.


Asunto(s)
Artritis Experimental/prevención & control , Cartílago Articular/metabolismo , Oligopéptidos/uso terapéutico , Osteoartritis/prevención & control , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Animales , Apoptosis/efectos de los fármacos , Artritis Experimental/metabolismo , Artritis Experimental/patología , Cartílago Articular/efectos de los fármacos , Cartílago Articular/patología , Células Cultivadas , Condrocitos/efectos de los fármacos , Condrocitos/patología , Evaluación Preclínica de Medicamentos/métodos , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/patología , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Oligopéptidos/farmacología , Osteoartritis/metabolismo , Osteoartritis/patología , Proteoglicanos/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Técnicas de Cultivo de Tejidos
10.
Anim Genet ; 47(5): 606-9, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27329478

RESUMEN

Residual feed intake (RFI) is now considered a more reasonable metric to evaluate animal feed efficiency. In this study, the correlation between RFI and other feed efficiency traits was investigated and gene expression within the hypothalamus was determined in low RFI (LRFI) and high RFI (HRFI) ducks. Further, several hypothalamic neuropeptide genes were measured using quantitative real-time PCR. The mean feed intake value was 160 g/day, whereas the egg mass laid (EML) and body weight were approximately 62.4 g/day and 1.46 kg respectively. Estimates for heritability of RFI, feed conversion ratio (FCR) and feed intake were 0.26, 0.18 and 0.23 respectively. RFI is phenotypically positively correlated with feed intake and FCR (P < 0.01). The expression of neuropeptide Y (NPY) and neuropeptide Y receptor Y5 (NPY5R) mRNA was higher in HRFI ducks compared with LRFI ducks (P < 0.05), whereas that of proopiomelanocortin (POMC), melanocortin 4 receptor (MC4R) and cholecystokinin (CCK) was lower (P < 0.05). The mRNA expression of gonadotropin-releasing hormone 1 (luteinizing-releasing hormone) (GNRH1) and prolactin receptor (PRLR) was unchanged between LRFI and HRFI ducks. The results indicate that selection for LRFI could reduce feed intake without significant changes in EML, whereas selection on FCR will increase EML.


Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales/genética , Patos/genética , Ingestión de Alimentos/genética , Hipotálamo/fisiología , Neuropéptidos/genética , Alimentación Animal , Animales , Patos/fisiología , Hormona Liberadora de Gonadotropina/genética , Neuropéptido Y/genética , Óvulo , Proopiomelanocortina/genética , Precursores de Proteínas/genética , Receptor de Melanocortina Tipo 4/genética , Receptores de Neuropéptido Y/genética , Receptores de Prolactina/genética
11.
Zhonghua Xue Ye Xue Za Zhi ; 37(5): 360-5, 2016 May 14.
Artículo en Chino | MEDLINE | ID: mdl-27210868

RESUMEN

OBJECTIVE: To investigate the clinical features and outcomes of high-risk acute promyelocytic leukemia (APL) patients. METHODS: A retrospective analysis was conducted to compare the clinical characteristics and prognosis of 118 high-risk APL patients (WBC≥10 × 10(9)/L) and 234 low and intermedia-risk patients (WBC <10×10(9)/L) from January 2003 to April 2015, who were treated in the First Affiliated Hospital of Zhejiang University and Yinzhou People's Hospital affiliated to Medical College of Ningbo University. RESULTS: The initial platelet counts of high-risk APL were significantly lower than that of low and intermediate-risk groups (P=0.003); the major type of PML-RARα isoforms in high-risk patients was short-form (51.8% vs 28.2%, P <0.001); the early death (ED) rate of high-risk patients was higher than low and intermedia-risk patients (20.3% vs 2.6%, P<0.001); in contrast, the complete remission (CR) rate and 5 years estimated overall survival (OS) rate of the former were lower than the latter (76.3% vs 94.9%, P <0.001; 74.2% vs 93.7%, P <0.001). However, the CR rate (P=0.682) and 5 years estimated OS rate (P=0.481) did not have difference when the ED patients were excluded. The 5 years estimated relapse-free survival (RFS) and central nervous system (CNS) relapse were 82.7%, 9.4%, respectively, which were lower than low and intermediate-risk groups (87.8%, 1.4% ) with statistic difference (P=0.048, 0.002). High-dose cytarabine and intrathecal chemotherapy may reduce the risk of CNS relapse. CONCLUSION: The outcomes of high-risk APL patients were worse than low and intermediate-risk group owing to the high ED rate and CNS relapse, it was important to decrease the ED rate and emphasis the CNS prophylaxis for high-risk APL patients.


Asunto(s)
Leucemia Promielocítica Aguda/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica , Citarabina/uso terapéutico , Humanos , Recuento de Leucocitos , Proteínas de Fusión Oncogénica/metabolismo , Recuento de Plaquetas , Pronóstico , Isoformas de Proteínas/metabolismo , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Tasa de Supervivencia
12.
Transl Psychiatry ; 5: e548, 2015 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-25871973

RESUMEN

We investigated in vivo neurochemical markers reflective of neuronal health and glial activation to determine if these could yield clues regarding the reduced fractional anisotropy (FA) of white matter and accelerated decline of FA with age in schizophrenia. Participants with schizophrenia and healthy controls completed diffusion tensor imaging to assess FA and proton magnetic resonance spectroscopy to assess neurochemical metabolites in the same frontal region. Frontal FA was significantly lower in the schizophrenia and declined more rapidly with age compared with the healthy control group. In both groups, N-acetylaspartate (NAA), a putative marker of neuronal integrity, and glutamate declined with age, and this decline was stronger in patients. Myo-inositol, a marker of glial cells, was negatively related to FA in both groups. The relationship between FA and age remained significant in schizophrenia even when controlling for all metabolites. The relationships of FA, NAA and myo-inositol to age appear to be independent of one another. The relationship between FA and myo-inositol was independently present in both patients and controls, even after controlling for age, indicating a potential general effect of neuroinflammation on white matter microstructure. Further studies are warranted to determine the underlying mechanism driving the accelerated FA decline with age in schizophrenia.


Asunto(s)
Lóbulo Frontal/patología , Esquizofrenia/patología , Sustancia Blanca/patología , Adulto , Factores de Edad , Anisotropía , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Estudios de Casos y Controles , Colina/metabolismo , Creatina/metabolismo , Imagen de Difusión Tensora , Femenino , Lóbulo Frontal/metabolismo , Ácido Glutámico/metabolismo , Humanos , Inflamación , Inositol/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroglía/metabolismo , Esquizofrenia/metabolismo , Sustancia Blanca/metabolismo , Adulto Joven
13.
Genet Mol Res ; 14(4): 19349-59, 2015 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-26782588

RESUMEN

Hailey-Hailey disease (HHD) is an autosomal dominant disorder in which the ATP2C1 gene has been implicated. Many mutations of this gene have been detected in HHD patients. To analyze such mutations in HHD and summarize all those identified in Chinese patients with this disease, we examined four familial and two sporadic cases and searched for case reports and papers by using the Chinese Biological Medicine Database and PubMed. HHD diagnoses were made based on clinical features and histopathological findings. Polymerase chain reaction and direct sequencing of the ATP2C1 gene were performed using blood samples from HHD patients, unaffected family members, and 120 healthy individuals. Three mutations were identified, including the recurrent mutation c.2126C>T (p.Thr709Met), and two novel missense mutations, c.2235_2236insC (p.Pro745fs*756) and c.689G>A (p.Gly230Asp). Considering our data, 81 different mutations have now been reported in Chinese patients with HHD. In cases of misannotation or duplication, previously published mutations were renamed according to a complementary DNA reference sequence. These mutations are scattered throughout the ATP2C1 gene, with no evident hotspots or clustering. It is of note that some reported "novel" mutations were in fact found to be recurrent. Our findings expand the range of known ATP2C1 sequence variants in this disease.


Asunto(s)
ATPasas Transportadoras de Calcio/genética , Predisposición Genética a la Enfermedad , Mutación , Pénfigo Familiar Benigno/genética , Adulto , Pueblo Asiatico , Secuencia de Bases , Estudios de Casos y Controles , Niño , Femenino , Expresión Génica , Genes Dominantes , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Pénfigo Familiar Benigno/diagnóstico , Pénfigo Familiar Benigno/etnología , Pénfigo Familiar Benigno/patología , Análisis de Secuencia de ADN , Terminología como Asunto
14.
Genet Mol Res ; 13(4): 10545-55, 2014 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-25511039

RESUMEN

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a key signaling adaptor molecule for tumor necrosis factor receptor superfamily and Toll-like receptor/interleukin-1 receptor family members. It signals the upstream receptors and is involved in a wide range of biological functions, such as immunity and bone metabolism. In this report, the TRAF6 gene from the pearl oyster Pinctada martensii (designated as PmTRAF6) was identified and characterized. The obtained full-length PmTRAF6 cDNA was 2273 bp, containing a 5'-untranslated region (UTR) of 297 bp, a 3'-UTR of 128 bp with a 42-bp poly (A) tail, and an open reading frame of 1848 bp that encoded 616-amino acid residues. The deduced protein sequence of PmTRAF6 contained a conserved TRAF family motif including a RING-type zinc finger, two TRAF-type zinc fingers, and a coiled-coil region followed by one meprin and TRAF homology domain. Multiple-sequence alignment indicated that TRAF6 was highly conserved among species, and PmTRAF6 showed 53% sequence identity to Azumapecten farreri and Mizuhopecten yessoensis. Furthermore, an amino acid sequence containing a low-complexity region was inserted in the TRAF6s from mollusk. Quantitative real-time polymerase chain reaction analysis demonstrated that PmTRAF6 was constitutively expressed in all tissues studied, with the most abundant mRNA expression in hepatopancreas and gill in P. martensii. After lipopolysaccharide stimulation, the expression of PmTRAF6 mRNA was dramatically upregulated. These results suggested that the obtained PmTRAF6 was a member of the TRAF6 family and perhaps involved in the innate immune response of pearl oyster.


Asunto(s)
Pinctada/genética , Factor 6 Asociado a Receptor de TNF/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , ADN Complementario/genética , Humanos , Filogenia , Alineación de Secuencia , Factor 6 Asociado a Receptor de TNF/aislamiento & purificación
15.
Genet Mol Res ; 13(3): 6995-7005, 2014 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-24737515

RESUMEN

In this paper, interspecific crosses among Crambe abyssinica, Crambe hispanica, and Crambe kralikii were reported. In the C. hispanica x C. abyssinica (H x A) cross, 118 F1 hybrids were produced without embryo rescue, while 5 F1 hybrids were obtained with embryo rescue, when C. hispanica was used as the female parent. In the reciprocal cross (A x H), 232 hybrids were obtained without embryo rescue. From more than 1000 C. kralikii flowers pollinated with pollen grains of C. abyssinica (K x A), only 2 F1 hybrids were obtained with embryo rescue, whereas the reciprocal cross produced no hybrids, even with embryo rescue. The hybrids were confirmed at the morphological, cytological, and molecular levels. In the combinations of A x H and H x A, many BC1 hybrids were obtained without embryo rescue. In contrast, in the K x A cross, only 7 BC1 plants were obtained with embryo rescue, while no seed set was achieved under self-pollination or in backcrosses without embryo rescue. In the H x A F1 hybrids, the pollen stainability was 65.4-86.0%, with an average of 76.9%. In comparison, the pollen viability of hybrids in the reciprocal cross (A x H) ranged from 66.2 to 81.1%, with an average of 75.4%. Fertile pollen grains were not found in the K x A F1 hybrids. All F1 hybrids of the 3 crosses (H x A, A x H, and K x A) had the expected 2n = 75 chromosomes. AFLP analyses indicated that all F1 hybrids and their progenies had typical bands of the parents. These hybrids and progenies are anticipated to be valuable for future C. abyssinica improvement in breeding programs.


Asunto(s)
Brassicaceae/genética , Crambe (Planta)/genética , Cruzamientos Genéticos , Hibridación Genética , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Brassicaceae/clasificación , Brassicaceae/fisiología , Cruzamiento/métodos , Cromosomas de las Plantas/genética , Crambe (Planta)/fisiología , Análisis Citogenético/métodos , ADN de Plantas/análisis , ADN de Plantas/genética , Fertilidad/genética , Flores/genética , Flores/fisiología , Polen/genética , Polen/fisiología , Polinización/genética , Polinización/fisiología , Reacción en Cadena de la Polimerasa , Reproducibilidad de los Resultados
16.
Genet Mol Res ; 12(4): 5945-57, 2013 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-24338388

RESUMEN

This study investigated the alteration of gene expression profiles in order to gain a deeper understanding into the molecular mechanism involved in different processes of vascular calcification (VC). Sprague Dawley (SD) rats were injected with 300,000 µg/kg vitamin D3 and gavaged with 25 mg/kg nicotine for 8 or 16 weeks to create 8- and 16-week VC calcification groups. Histological analysis and quantification of aortic calcium content were used to determine the severity of vascular calcification. The suppression subtractive hybridization (SSH) method was employed to screen for up and downregulated genes in early and later phases of vascular calcification. Changes in calcium and phosphorus levels in tissue were used as markers of vascular calcification. Quantification of aortic calcium content revealed that vascular calcification might regress over time. In the early phase of vascular calcification, many calcification-promoting genes were upregulated, including ossification, oxidation, and inflammatory genes. In contrast, in later phase of vascular calcification, various calcification-inhibitor genes were highly expressed, including pyrophosphoric acid synthesis genes, glutamate signal peptide-related, reduction activity, and apoptosis regulation genes. The relatively higher expression of calcification-inhibitor genes compared to that of calcification-promoting genes might explain the genetic mechanism leading to the regression of vascular calcification. Therefore, this study provides a genomic basis to facilitate understanding of the molecular mechanism underlying vascular calcification regression.


Asunto(s)
Transcriptoma , Calcificación Vascular/metabolismo , Fosfatasa Alcalina , Animales , Aorta/metabolismo , Aorta/patología , Calcio/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Masculino , Redes y Vías Metabólicas , Fósforo/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Calcificación Vascular/genética , Calcificación Vascular/patología
17.
Chemosphere ; 90(4): 1419-26, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23021385

RESUMEN

Air sparging (AS) was explored for remediation of a petroleum contaminated semi-confined groundwater system in NE China. Physical, hydro-chemical and hydraulic behaviors in subsurface environment during AS were investigated with support of modeling to understand the hydrogeo-chemical impacts of AS on the aquifer. The responses of groundwater, dissolved oxygen and temperature indicated that the radius of influence of AS was up to 8-9 m, and a 3D boundary of the zone of influence (ZOI) was accordingly obtained with volume of 362 m(3). Water mounding unlike normal observations was featured by continuous up-lift and blocked dissipation. AS induced water displacement was calculated showing no obvious spreading of contaminant plume under this AS condition. Slug tests were employed before and after AS to reveal that the physical perturbation led to sharp increase in permeability and porosity. Modeling indicated that the regional groundwater flow field was not affected by AS except the physical perturbation in ZOI. Hydro-chemically increase of pH and Eh, and reduction of TDS, electrical conductivity and bicarbonate were observed in ZOI during AS. PHREEQC modeling inferred that these chemical phenomena were induced by the inorganic carbon transfer during air mixing.


Asunto(s)
Restauración y Remediación Ambiental/métodos , Agua Subterránea/química , Yacimiento de Petróleo y Gas , Petróleo/análisis , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , Industria Procesadora y de Extracción , Modelos Químicos , Purificación del Agua/métodos
18.
Diabetologia ; 55(5): 1544-53, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22374176

RESUMEN

AIMS/HYPOTHESIS: An increase in the production of reactive oxygen species is commonly thought to contribute to the development of diabetic cardiomyopathy. This study aimed to assess whether administration of the antioxidant coenzyme Q(10) would protect the diabetic heart against dysfunction and remodelling, using the db/db mouse model of type 2 diabetes. Furthermore, we aimed to compare the efficacy of coenzyme Q(10) to that of the ACE inhibitor ramipril. METHODS: Six-week-old non-diabetic db/+ mice and diabetic db/db mice received either normal drinking water or water supplemented with coenzyme Q(10) for 10 weeks. Endpoint cardiac function was assessed by echocardiography and catheterisation. Ventricular tissue was collected for histology, gene expression and protein analysis. RESULTS: Untreated db/db diabetic mice exhibited hyperglycaemia, accompanied by diastolic dysfunction and adverse structural remodelling, including cardiomyocyte hypertrophy, myocardial fibrosis and increased apoptosis. Systemic lipid peroxidation and myocardial superoxide generation were also elevated in db/db mice. Coenzyme Q(10) and ramipril treatment reduced superoxide generation, ameliorated diastolic dysfunction and reduced cardiomyocyte hypertrophy and fibrosis in db/db mice. Phosphorylation of Akt, although depressed in untreated db/db mice, was restored with coenzyme Q(10) administration. We postulate that preservation of cardioprotective Akt signalling may be a mechanism by which coenzyme Q(10)-treated db/db mice are protected from pathological cardiac hypertrophy. CONCLUSIONS/INTERPRETATION: These data demonstrate that coenzyme Q(10) attenuates oxidative stress and left ventricular diastolic dysfunction and remodelling in the diabetic heart. Addition of coenzyme Q(10) to the current therapy used in diabetic patients with diastolic dysfunction warrants further investigation.


Asunto(s)
Cardiomegalia/tratamiento farmacológico , Cardiomiopatías Diabéticas/tratamiento farmacológico , Ubiquinona/análogos & derivados , Vitaminas/uso terapéutico , Animales , Antihipertensivos/uso terapéutico , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Cardiomegalia/diagnóstico por imagen , Cardiomegalia/metabolismo , Cardiomegalia/fisiopatología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Cardiomiopatías Diabéticas/diagnóstico por imagen , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/fisiopatología , Modelos Animales de Enfermedad , Fibrosis Endomiocárdica/tratamiento farmacológico , Fibrosis Endomiocárdica/etiología , Fibrosis Endomiocárdica/metabolismo , Femenino , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/fisiología , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ramipril/uso terapéutico , Superóxidos/antagonistas & inhibidores , Superóxidos/metabolismo , Ubiquinona/uso terapéutico , Ultrasonografía , Remodelación Ventricular/efectos de los fármacos , Remodelación Ventricular/fisiología
19.
Neural Netw ; 24(6): 568-74, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21421295

RESUMEN

The ability of the brain to attenuate the response to irrelevant sensory stimulation is referred to as sensory gating. A gating deficiency has been reported in schizophrenia. To study the neural mechanisms underlying sensory gating, a neuroanatomically inspired model of auditory information processing has been developed. The mathematical model consists of lumped parameter modules representing the thalamus (TH), the thalamic reticular nucleus (TRN), auditory cortex (AC), and prefrontal cortex (PC). It was found that the membrane potential of the pyramidal cells in the PC module replicated auditory evoked potentials, recorded from the scalp of healthy individuals, in response to pure tones. Also, the model produced substantial attenuation of the response to the second of a pair of identical stimuli, just as seen in actual human experiments. We also tested the viewpoint that schizophrenia is associated with a deficit in prefrontal dopamine (DA) activity, which would lower the excitatory and inhibitory feedback gains in the AC and PC modules. Lowering these gains by less than 10% resulted in model behavior resembling the brain activity seen in schizophrenia patients, and replicated the reported gating deficits. The model suggests that the TRN plays a critical role in sensory gating, with the smaller response to a second tone arising from a reduction in inhibition of TH by the TRN.


Asunto(s)
Vías Auditivas/fisiología , Redes Neurales de la Computación , Neuronas/fisiología , Estimulación Acústica , Animales , Encéfalo/citología , Procesamiento Automatizado de Datos , Trastornos de la Audición/etiología , Trastornos de la Audición/patología , Humanos , Esquizofrenia/complicaciones , Tálamo/citología , Tálamo/fisiología
20.
J Appl Microbiol ; 110(1): 333-40, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21070517

RESUMEN

AIM: To determine the antimicrobial activity of costus (Saussurea lappa) oil against Staphylococcus aureus, and to evaluate the influence of subinhibitory concentrations of costus oil on virulence-related exoprotein production in staph. aureus. METHODS AND RESULTS: Minimal inhibitory concentrations (MICs) were determined using a broth microdilution method, and the MICs of costus oil against 32 Staph. aureus strains ranged from 0.15 to 0.6 µl ml(-1) . The MIC(50) and MIC(90) were 0.3 and 0.6 µl ml(-1) , respectively. Western blot, haemolytic, tumour necrosis factor (TNF) release and real-time RT-PCR assays were performed to evaluate the effects of subinhibitory concentrations of costus oil on virulence-associated exoprotein production in Staph. aureus. The data presented here show that costus oil dose dependently decreased the production of α-toxin, toxic shock syndrome toxin 1 (TSST-1) and enterotoxins A and B in both methicillin-sensitive Staph. aureus (MSSA) and methicillin-resistant Staph. aureus (MRSA). CONCLUSION: Costus oil has potent antimicrobial activity against Staph. aureus, and the production of α-toxin, TSST-1 and enterotoxins A and B in Staph. aureus was decreased by costus oil. SIGNIFICANCE AND IMPACT OF THE STUDY: The data suggest that costus oil may deserve further investigation for its potential therapeutic value in treating Staph. aureus infections. Furthermore, costus oil could be rationally applied in food products as a novel food preservative both to inhibit the growth of Staph. aureus and to repress the production of exotoxins, particularly staphylococcal enterotoxins.


Asunto(s)
Antibacterianos/farmacología , Aceites de Plantas/farmacología , Saussurea , Staphylococcus aureus/efectos de los fármacos , Factores de Virulencia/biosíntesis , Toxinas Bacterianas/biosíntesis , Enterotoxinas/biosíntesis , Exotoxinas/biosíntesis , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/metabolismo , Staphylococcus aureus/patogenicidad , Superantígenos/biosíntesis , Transcripción Genética/efectos de los fármacos , Factores de Necrosis Tumoral/biosíntesis
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