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1.
Eur J Pharmacol ; 876: 173052, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32135124

RESUMO

As diabetic macroangiopathy is becoming increasingly prevalent, it is urgent to explore preventive and therapeutic drugs and study the mechanism. Diabetic mice were induced by intraperitoneal injection of streptozotocin (STZ)for five consecutive days. Diabetic mice were divided into diabetic and allicin groups. After sacrifice, frozen aortic root sections were immunohistochemically stained for nuclear factor erythroid 2-related factor 2 (Nrf2) and inflammation cytokine-tumor necrosis factor α (TNF-α), and the remaining aortic tissues were analyzed by Western blot for the expression of proinflammation genes. In vitro, Nrf2 and inflammatory relative protein expression levels in Human Umbilical Vein Endothelial Cells (HUVECs) were examined. HUVECs proliferation and apoptosis were measured. TNF-α expression was increased in diabetic group compared to that in control group; this effect was alleviated in allicin-treated mice. Inflammation relative protein expression of Vascular Cell Adhesion Molecule 1(VCAM-1), Matrix metalloproteinase 2 (MMP-2), Inducible Nitric Oxide Synthase (iNOS), and monocyte chemotactic protein 1 (MCP-1) was higher in the diabetic group than in the control group; however, allicin treatment inhibited these diabetes-induced increase. In vitro, allicin treatment reversed the hyperglycemia-induced reduction in proliferation, and decreased the apoptosis induced by high glucose. Inflammation relative protein expression was consistent with that in vivo. Additionally, the expression of nuclear factor kappa-B (NF-κB)and Nrf2 was increased in both DM mice and HUVECs; allicin treatment induced a significant reduction in NF-κB level and improvement in Nrf2 level. Allicin alleviates inflammation caused by diabetic macroangiopathy, and the mechanism may occur via increasing Nrf2 and decreasing NF-κB.

2.
Inflammation ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32076940

RESUMO

Pyroptosis, a new pro-inflammatory programmed cell death, is linked to atherosclerosis (AS). Our previous studies suggested that salidroside (SAL) can alleviate AS and exert anti-oxidative and anti-inflammatory properties. However, the effect of SAL on atherosclerosis-related pyroptosis has not been studied. Here, we investigated the effect of SAL on pyroptosis to explain the underlying mechanisms of SAL on atherosclerosis-related inflammation. We established an atherosclerosis mouse model via western diet (HFD) to explore the protective effect of SAL. According to our results, administration of SAL for 12 weeks markedly reduced the atherosclerotic plaque in aorta. Meanwhile, SAL also alleviated the pyroptosis, as evidenced by inhibiting caspase-1 activation, interleukin-1ß (IL-1ß) release, and TUNEL-positive staining, and decreasing the expression of Gasdermin D (GSDMD). Furthermore, SAL also decreased the activation of caspase-1 and inhibited the release of IL-1ß induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP) in human umbilical vein endothelial cell (HUVECs). Our data indicate that SAL inhibit NLRP3-related pyroptosis, which might be the underlying mechanism of SAL anti-inflammatory in atherosclerosis.

3.
J Org Chem ; 85(2): 622-632, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31799847

RESUMO

An efficient Pd-catalyzed arylation of alkylpyridine based on the pyridinium activation strategy has been developed for synthesis of mixed aryl alkylpyridines. It was found that (1) the N-methyl group in the pyridinium salts acted as a transient activator and could be automatically departed after the reaction, (2) CuBr was an indispensable additive for achieving the C6-selective arylation, (3) the α-branched alkyl chain on the alkylpyridine greatly increased the yield of the product. Deuterium labelling experiment revealed that in the case of the α-branched alkylpyridine, the presence of CuBr completely inhibited the H/D exchange at the benzylic position and thus enabled the selective arylation at the C6 position. This protocol demonstrates a broad substrate scope, and with respect to both the aryl iodides and the α-branched alkylpyridine, the desired mixed aryl alkylpyridines were obtained in generally good to excellent yields.

4.
Int J Mol Sci ; 20(24)2019 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-31817978

RESUMO

Citrus fruits are mainly consumed as fresh fruit and processed juice products. They serve as nutritional and a tasty diet in our daily life. However, the formidable bitterness and delayed bitterness significantly impact the citrus industry attributable to the two major bitter compounds naringin and limonin. The extremely sour and acidic also negatively affects the sensory quality of citrus products. Citrus breeding programs have developed different strategies to improve citrus quality and a wealth of studies have aimed to uncover the genetic and biochemical basis of citrus flavor. In this minireview, we outline the major genes characterized to be involved in pathways shaping the sweet, bitter, or sour taste in citrus, and discuss briefly about the possible approaches to modify citrus taste by genetic engineering.

5.
Huan Jing Ke Xue ; 40(10): 4440-4449, 2019 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854811

RESUMO

In order to research the impact of continuous extreme rainfall on the water quality of the Dongjiang River, which is a drinking water source, the characteristics of extreme rainfall events in the basin were analyzed for last 38 years. The impacts of these events on water quality are discussed by considering both hydrological data and water quality data. Using SWAT2012 software, a high-precision basin model was established for the flux of major pollutants during extreme rainfall and water quality. The results indicate that there were 173 extreme rainfall events in the Dongjiang River basin over the past 38 years. The annual frequency of extreme rainfall events in high-flow years was higher than in other years. During the year, rainfall was mainly affected by climate, particularly from March to September (80%), with the peak rainfall usually occurring in June. Spatially, the Zengcheng-Bolo-Huizhou-Longmen area had the highest frequency of extreme events. During the study period, rainfall was significantly positively correlated with the concentrations of cyanide, Pb, Fe, Mn, TP, and with turbidity, and the correlation coefficients for the concentrations of TP and turbidity with rainfall were relatively high. Rainfall was significantly negatively correlated with pH, conductivity, the concentration of Zn, as well as some other indicators. These observations show that water quality is affected by rainfall to some extent. Turbidity, TN, ammonia nitrogen, and TP concentrations all showed increasing trends, to different degrees, during rainstorm runoff periods. Turbidity and TP concentrations showed a significant and consistent relationship with flow rate, peaking earlier than the flow rate peak (by approximately 1 d), showing a significant initial flushing effect. The pH curve showed an opposite trend to the flow rate, forming a "V" shape, which may be affected by the rainfall, soil acidity, and confluence conditions in the upstream mountains. Ammonia nitrogen was subject to initial flushing in the early stages of extreme rainfall but was diluted by the clean rainwater; initially, ammonia nitrogen showed high values that declined during the middle and late stages. The variations in pollutant loads were consistent with that of runoff flux, and the peaks in TN, ammonia nitrogen, and TP flux appeared later than the flow peak (by approximately 1 d), thus differing from the pollutant concentration peak. The pollutant load mainly showed a significant increase during storm runoff periods. The proportion of pollutant COD, ammonia nitrogen, and TP transported by 59.48% of the runoff reached 68.42%, 54.68%, and 70.20%, respectively, demonstrating the characteristics of rapid and high-impact pollutant loads. These characteristics have a great influence on the quality of Dongjiang River drinking water and it is suggested that initial rainwater treatment should be strengthened to reduce the negative impact of rainstorm runoff periods on water quality.

7.
Mini Rev Med Chem ; 19(19): 1611-1626, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31481002

RESUMO

Over the past three decades, the knowledge gained about the mechanisms that underpin the potential use of Rhodiola in stress- and ageing-associated disorders has increased, and provided a universal framework for studies that focused on the use of Rhodiola in preventing or curing metabolic diseases. Of particular interest is the emerging role of Rhodiola in the maintenance of energy homeostasis. Moreover, over the last two decades, great efforts have been undertaken to unravel the underlying mechanisms of action of Rhodiola in the treatment of metabolic disorders. Extracts of Rhodiola and salidroside, the most abundant active compound in Rhodiola, are suggested to provide a beneficial effect in mental, behavioral, and metabolic disorders. Both in vivo and ex vivo studies, Rhodiola extracts and salidroside ameliorate metabolic disorders when administered acutely or prior to experimental injury. The mechanism involved includes multi-target effects by modulating various synergistic pathways that control oxidative stress, inflammation, mitochondria, autophagy, and cell death, as well as AMPK signaling that is associated with possible beneficial effects on metabolic disorders. However, evidence-based data supporting the effectiveness of Rhodiola or salidroside in treating metabolic disorders is limited. Therefore, a comprehensive review of available trials showing putative treatment strategies of metabolic disorders that include both clinical effective perspectives and fundamental molecular mechanisms is warranted. This review highlights studies that focus on the potential role of Rhodiola extracts and salidroside in type 2 diabetes and atherosclerosis, the two most common metabolic diseases.


Assuntos
Glucosídeos/química , Doenças Metabólicas/tratamento farmacológico , Fenóis/química , Extratos Vegetais/química , Rhodiola/química , Proteínas Quinases Ativadas por AMP/metabolismo , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Antioxidantes/química , Antioxidantes/uso terapêutico , Autofagia/efeitos dos fármacos , Glucosídeos/uso terapêutico , Humanos , Doenças Metabólicas/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fenóis/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Rhodiola/metabolismo
8.
Res Microbiol ; 170(6-7): 272-279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31449848

RESUMO

Candida albicans has the ability to switch reversibly between budding yeast, filamentous, pseudohypha, and hyphal forms, a process in which the transcription factor Flo8 plays an important role. This ability is important for the virulence and pathogenicity of C. albicans. To determine whether Flo8 plays a role in the regulation of drug sensitivity, we constructed a FLO8 null mutant flo8/flo8 from the parental strain SN152 and a Flo8-overexpressing strain, flo8/flo8::FLO8. The susceptibility of the isolates to antifungal agents was then evaluated using the agar dilution and broth microdilution methods. Expression of drug resistance-related genes by the isolates was investigated by real-time PCR. The flo8/flo8 mutation isolates exhibited increased resistance to fluconazole, voriconazole, and itraconazole compared with the wild-type and drug sensitivity was restored by FLO8 overexpression (flo8/flo8∷FLO8). Of seven drug resistance-related genes, the FLO8 null mutation resulted in increased CDR1 and CDR2 expression (1.60-fold and 5.27-fold, respectively) compared with SN152, while FLO8 overexpression resulted in decreased CDR1 expression (0.63-fold). These results suggest that Flo8 is involved in the susceptibility of C. albicans to antifungal azoles, with FLO8 deletion leading to constitutive overexpression of CDR1 and CDR2 and resistance to antifungal azoles.


Assuntos
Antifúngicos/farmacologia , Azóis/farmacologia , Candida albicans/genética , Farmacorresistência Fúngica/genética , Transativadores/genética , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Proteínas Fúngicas/genética , Deleção de Genes , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade Microbiana , Proteínas Serina-Treonina Quinases/genética
9.
Environ Sci Pollut Res Int ; 26(35): 35482-35496, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31327140

RESUMO

Microfluidics has great potential as an efficient tool for a large range of applications in industry. The ability of such devices to deal with an extremely small amount of fluid has additional benefits, including superlatively fast and efficient mass and heat transfer. These characteristics of microfluidics have attracted an enormous amount of interest in their use as a novel tool for lipid production and modification. In addition, lipid resources have a close relationship with energy resources, and lipids are an alternative renewable energy source. Here, recent advances in the application of microfluidics for lipid production and modification, especially in the discovery, culturing, harvesting, separating, and monitoring of lipid-producing microorganisms, will be reviewed. Other applications of microfluidics, such as the modification of lipids from microorganisms, will also be discussed. The novel microfluidic tools in this review will be useful in applications to improve lipid production and modification in the future.

10.
Zool Res ; 40(5): 427-438, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31111694

RESUMO

Small populations with low genetic diversity are prone to extinction. Knowledge on the genetic diversity and structure of small populations and their genetic response to anthropogenic effects are of critical importance for conservation management. In this study, samples of Ancherythroculter nigrocauda, an endemic cyprinid fish from the upper reaches of Yangtze River, were collected from five sites to analyze their genetic diversity and population structure using mitochondrial cytochrome b gene and 14 microsatellite loci. Haplotype diversity, nucleotide diversity, and expected heterozygosity indicated that the A. nigrocauda populations had low genetic diversity, and decreased heavily from 2001 to 2016. Significant genetic differentiation was found among different populations in the cyt b gene and SSR markers based on the genetic differentiation index (F ST), whereas no differentiation was found in 2001. Haplotype genealogy showed that eight out of 15 haplotypes were private to one population. The SSR STRUCTURE analysis showed that there were four genetic clusters in the A. nigrocauda samples, with each population forming a single cluster, except for the Chishui River (CSR) and Mudong River (MDR) populations, which formed a common cluster. Therefore, loss of genetic diversity and increased genetic differentiation were found in the A. nigrocauda populations, which could be attributed to dam construction, overfishing, and water pollution in the upper Yangtze River. It is therefore recommended that the government should ban fishing, control water pollution, increase river connectivity, and establish artificial breeding and stocking.


Assuntos
Distribuição Animal , Cyprinidae/genética , Variação Genética , Rios , Animais , China , Citocromos b/genética , Marcadores Genéticos , Haplótipos , Filogenia , Fatores de Tempo
11.
Zhongguo Zhong Yao Za Zhi ; 44(5): 935-941, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30989852

RESUMO

1-deoxy-D-xylulose-5-phosphate synthase2(DXS2) is the first key enzyme of the MEP pathway,which plays an important role in terpene biosynthesis of plants. According to the data of Swertia mussotii transcriptome, DXS2 gene(Gen Bank number MH535905) was cloned and named as Sm DXS2. The bioinformatics results showed that Sm DXS2 has no intron,with a 2 145 bp open reading frame encoding a polypeptide of 714 amino acids. They are belonging to 20 kinds of amino acids,and the most abundant amino acids include Ala,Gly and Trp. The predicted protein molecular weight was 76. 91 k Da and its theoretical isoelectric point(p I) was6. 5,which belonging to a hydrophilic protein. α-Helix and loop were the major motifs of predicted secondary structure of DXS2. The three function domains are TPP_superfamily,Transket_pyr_ superfamily and Transketolase_C superfamily,respectively. The Sm DXS2 protein shared high identity with other DXS2 proteins of plants. Phylogenetic analysis showed that Sm DXS2 protein is grouped with the gentian DXS2 protein. The recombinant protein of Sm DXS2 gene in Escherichia coli was approximately 92. 00 k Da(containing sumo-His tag protein 13 k Da),which was consistent with the anticipated size.This work will provide a foundation for further functional research of Sm DXS2 protein and increasing the product of iridoid compound by genetic engineering in S. mussotii.


Assuntos
Proteínas de Plantas/genética , Swertia/genética , Transferases/genética , Sequência de Aminoácidos , Clonagem Molecular , DNA Complementar/genética , Genes de Plantas , Iridoides , Filogenia , Swertia/enzimologia , Transcriptoma
12.
J Pediatr Endocrinol Metab ; 32(4): 375-382, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30849045

RESUMO

Background Cystinosis is a rare autosomal-recessive disorder caused by a defective transport of cystine across the lysosomal membrane. Previous studies have mapped cystinosis to the CTNS gene which is located on chromosome 17p13, and various CTNS mutations have been identified to correlate them with this disease. Methods We analyzed six patients from five unrelated families who were diagnosed with cystinosis in our hospital. We described the diagnostic procedures for all the patients and proposed alternative therapies for cystinosis patients instead of using cysteamine, an orphan drug which was commercially unavailable in China. Moreover, genetic analysis of all patients' samples was carried out to identify novel CTNS gene mutations. Results and conclusions The patients in this study were followed up from 1 to more than 10 years to monitor their growth and development, which indicated that the alternative therapies we used were helpful to ameliorate the complications of the cystinosis patients without cysteamine. Furthermore, by sequencing the patients' genome, we identified novel mutations in the CTNS gene including: c.477C > G (p.S159R), c.274C > T (p.Q92X) and c.680A > T (p.E227V); these mutations were only observed in cystinosis patients and had never been reported in any other populations, suggesting they might be specific to Chinese cystinosis patients.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/genética , Cistinose/diagnóstico , Genética Populacional , Mutação , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Cistinose/tratamento farmacológico , Cistinose/epidemiologia , Cistinose/genética , Feminino , Seguimentos , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Lactente , Masculino , Linhagem , Prognóstico
13.
World J Gastroenterol ; 25(5): 584-599, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30774273

RESUMO

BACKGROUND: Claudin-7, one of the important components of cellular tight junctions, is currently considered to be expressed abnormally in colorectal inflammation and colorectal cancer. However, there is currently no effective animal model to study its specific mechanism. Therefore, we constructed three lines of Claudin-7 knockout mice using the Cre/LoxP system. AIM: To determine the function of the tumor suppressor gene Claudin-7 by generating three lines of Claudin-7 gene knockout mice. METHODS: We crossed Claudin-7-floxed mice with CMV-Cre, vil1-Cre, and villin-CreERT2 transgenic mice, and the offspring were self-crossed to obtain conventional Claudin-7 knockout mice, conditional (intestinal specific) Claudin-7 knockout mice, and inducible conditional Claudin-7 knockout mice. Intraperitoneal injection of tamoxifen into the inducible conditional Claudin-7 knockout mice can induce the knockout of Claudin-7. PCR and agarose gel electrophoresis were used to identify mouse genotypes, and Western blot was used to confirm the knockout of Claudin-7. The mental state, body length, and survival time of these mice were observed. The dying mice were sacrificed, and hematoxylin-eosin (HE) staining and immunohistochemical staining were performed to observe changes in intestinal structure and proliferation markers. RESULTS: We generated Claudin-7-floxed mice and three lines of Claudin-7 gene knockout mice using the Cre/LoxP system successfully. Conventional and intestinal specific Claudin-7 knockout mice were stunted and died during the perinatal period, and intestinal HE staining in these mice revealed mucosal gland structure disappearance and connective tissue hyperplasia with extensive inflammatory cell infiltration. The inducible conditional Claudin-7 knockout mice had a normal phenotype at birth, but after the induction with tamoxifen, they exhibited a dying state. Intestinal HE staining showed significant inflammatory cell infiltration, and atypical hyperplasia and adenoma were also observed. Intestinal immunohistochemistry analysis showed abnormal expression and distribution of Ki67, and the normal intestinal proliferation balance was disrupted. The intestinal crypt size in inducible conditional Claudin-7 knockout mice was increased compared with control mice (small intestine: 54.1 ± 2.96 vs 38.4 ± 1.63; large intestine: 44.7 ± 1.93 vs 27.4 ± 0.60; P < 0.001). CONCLUSION: The knockout of Claudin-7 in vivo causes extensive inflammation, atypical hyperplasia, and adenoma in intestinal tissue as well as animal death in mice. Claudin-7 may act as a tumor suppressor gene in the development of colorectal cancer.


Assuntos
Adenoma/genética , Claudinas/genética , Neoplasias Colorretais/genética , Hiperplasia/genética , Intestino Delgado/patologia , Adenoma/patologia , Animais , Proliferação de Células/genética , Claudinas/metabolismo , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Células Epiteliais/patologia , Feminino , Técnicas de Inativação de Genes , Genes Supressores de Tumor , Humanos , Hiperplasia/patologia , Mucosa Intestinal/patologia , Antígeno Ki-67/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
14.
J Diabetes Res ; 2018: 2802540, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30306091

RESUMO

Objective: To characterize the genotype and phenotype of Chinese patients with congenital hyperinsulinism (CHI) caused by activating mutations in GLUD1, the gene that encodes mitochondrial enzyme glutamate dehydrogenase (GDH). Methods: The clinical data of glutamate dehydrogenase hyperinsulinism (GDH-HI) patients were reviewed, and gene mutations were confirmed by whole exome sequencing (WES) and Sanger DNA sequencing. Results: Twenty-six patients with GDH-HI heterozygous missense mutations were identified from 240 patients diagnosed as congenital hyperinsulinism over past 15 years. The median age at onset was 8 months (range: 1 day of life to 3 years). Seizure disorder was common in our cohort of patients (23/26). Four patients had normal serum ammonia levels; the median serum concentration was 101 µmol/L (range: 37-190 µmol/L). Hypoglycemic symptoms could be triggered by fasting or protein meals in all patients while blood glucose could be well controlled in all patients with diazoxide. Dosage of diazoxide could be reduced by protein restriction. Attempts to lower ammonia levels failed with different therapies such as protein restriction, benzoate, or N-carbamoyl glutamate. In follow-up, 15 of 26 patients had normal intelligence. Eleven patients developed epilepsy at the age of 6 months to 11 years. De novo mutations in GLUD1 were found in 24 cases, and dominant inheritance was observed in the other two; all were heterozygous. A total of 35% (9/26) patients carried c.1493C>T (p.S445L) mutation. Conclusions: Phenotypic heterogeneity of GDH-HI patients was observed within the Chinese cohort in the present study. The fact that most patients had a GLUD1 p. S445L mutation implies that this site could be a hotspot in Chinese patients. A high frequency of GDH-HI with normal ammonia has been reported in this study. Hence, GLUD1 mutational analysis may be an important method to differential diagnosis of GDH-HI from other diazoxide-responsive CHI in Chinese patients.


Assuntos
Glicemia , Glutamato Desidrogenase/genética , Hiperinsulinismo/genética , Mutação , Pré-Escolar , China , Análise Mutacional de DNA , Feminino , Frequência do Gene , Genótipo , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/congênito , Lactente , Recém-Nascido , Masculino , Fenótipo
15.
J Pharmacol Sci ; 138(1): 38-45, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30241784

RESUMO

Icariside II (ICA II), a flavonoid derived from Epimediumbrevicormum Maxin in, has multiple biological activities in Chinese traditional medicine. Our study aimed to investigate the potential activity of ICA II against cardiac remodeling and the underlying mechanism. Mice received aorta banding (AB) or sham surgery, and then were randomly divided into ICA II or vehicle (veh) group for 6 weeks. After echocardiography and pressure-volume loop examination, hearts were harvested for histopathological analysis and molecular mechanism investigation. Additionally, neonatal rat cardiomyocytes (NRCM) were used for in vitro experiments. ICA II attenuated the systolic and diastolic cardiac dysfunction, and protected mouse heart from hypertrophy and fibrosis. The underlying mechanism might involve in the regulation of Akt, AMPKα and mTORC. In in vitro experiment, ICA II prevented phenylephrine (PE) induced NRCM hypertrophy by regulating AMPKα/mTORC pathway. This protective effect was disappeared after treatment with Compound C (CpC), an AMPKα inhibitor. Moreover, ICA II activated AMPK at baseline. ICAII was superior to resveratrol in activating AMPKα and similar to AICAR. ICA II protected against cardiac remodeling and NRCM hypertrophy by regulating AMPK/mTORC pathway. ICA II may be a candidate for the treatment of malignant cardiac remodeling.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Flavonoides/farmacologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Miócitos Cardíacos/patologia , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/genética , Animais , Cardiomegalia/prevenção & controle , Epimedium/química , Flavonoides/isolamento & purificação , Hipertrofia/prevenção & controle , Fenilefrina/efeitos adversos , Ratos Sprague-Dawley , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
17.
Orthopade ; 47(12): 986-992, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29881916

RESUMO

BACKGROUND: The aim of this study was to evaluate the early clinical safety and efficacy of transforaminal thoracic interbody fusion (TTIF) with interbody cage application for thoracic myelopathy caused by anterior compression (TMAC). METHODS: A total of 10 patients who underwent TTIF for TMAC from July 2009 to July 2014 were retrospectively reviewed. Thoracic spinal lesions included thoracic disc herniation, thoracic ossification of posterior longitudinal ligament, thoracic vertebral compression fracture, and thoracic spine fracture dislocation. Demographic data, radiological findings as well as operative information were collected. Postoperative functional outcomes evaluated by the modified Japanese Orthopedic Association (mJOA) score and complications were analyzed. RESULTS: The mean operation time was 186.5 min (range 110-315 min), the mean operative blood loss was 845.0 ml (range 400-2000 ml), and the mean recumbent period was 2.7 days (range 1-8 days). During the follow-up period all patients exhibited significant improvements in neurological deficits. The mJOA score improved from a mean of 6.1 ± 1.7 preoperatively to 7.4 ± 1.6 postoperatively and to 9.3 ± 1.6 at final follow-up (P <0.01), with an overall recovery rate of 69.0 ± 26.1%. Solid fusion was observed in all cases. A wound infection was found in one case, in which the patient recovered with no residual neurological deficits after surgical debridement and administration of intravenous antibiotics. No cage-related complications were found in this study. CONCLUSION: The use of TTIF with cage application can be an effective treatment method of thoracic myelopathy caused by anterior compression, with favorable efficacy and safety.


Assuntos
Descompressão Cirúrgica/métodos , Fraturas por Compressão , Doenças da Medula Espinal/cirurgia , Fraturas da Coluna Vertebral , Fusão Vertebral/métodos , Adulto , Idoso , Descompressão Cirúrgica/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças da Medula Espinal/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Resultado do Tratamento , Adulto Jovem
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(3): 922-927, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29950244

RESUMO

In tumor patients, programmed cell death-1 (PD-1) can inhibit T-cell activation and proliferation by binding to its ligand, thereby promote tumor immune escape. A large number of experiments showed that PD-L1 molecule highly expressed on lymphoma cells, while PD-1 expression was up-regulated in tumor-infiltrating lymphocytes, suggesting its role in the development of lymphoma, which may be an important therapeutic target for lymphoma. PD-1 and PD-L1 monoclonal antibodies can block the PD-1 / PD-Ls signaling pathway, restore T cell function, thus inhibit the tumor growth. At present, a number of early clinical trials have demonstrated the significant efficacy and less side effects in various subtypes of recurrent lymphoma, which will be promising therapeutic agents. In this review, the mechanism of PD-1/PD-L1 signal pathway, the expression of PD-1 / PD-L1 in lymphoma and the anti-tumor effect of its antibody in lymphoma are summarized.


Assuntos
Linfoma , Antígeno B7-H1 , Humanos , Linfócitos do Interstício Tumoral , Receptor de Morte Celular Programada 1 , Transdução de Sinais , Linfócitos T
20.
Dig Dis Sci ; 63(5): 1200-1209, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29488037

RESUMO

BACKGROUND: As a potential tumor suppressor gene, Claudin-7 (Cldn7), which is a component of tight junctions, may play an important role in colorectal cancer occurrence and development. AIMS: To generate a knockout mouse model of inducible conditional Cldn7 in the intestine and analyze the phenotype of the mice after induction with tamoxifen. METHODS: We constructed Cldn7-flox transgenic mice and crossed them with Villin-CreERT2 mice. The Cldn7 inducible conditional knockout mice appeared normal and were well developed at birth. We induced Cldn7 gene deletion by injecting different dosages of tamoxifen into the mice and then conducted a further phenotypic analysis. RESULTS: After induction for 5 days in succession at a dose of 200 µl tamoxifen in sunflower oil at 10 mg/ml per mouse every time, the mice appeared dehydrated, had a lower temperature, and displayed inactivity or death. The results of hematoxylin-eosin staining showed that the intestines of the Cldn7 inducible conditional knockout mice had severe intestinal defects that included epithelial cell sloughing, necrosis, inflammation and hyperplasia. Owing to the death of ICKO mice, we adjusted the dose of tamoxifen to a dose of 100 µl in sunflower oil at 10 mg/ml per mouse (aged more than 8 weeks old) every 4 days. And we could induce atypical hyperplasia and adenoma in the intestine. Immunofluorescent staining indicated that the intestinal epithelial structure was destroyed. Electron microscopy experimental analysis indicated that the intercellular gap along the basolateral membrane of Cldn7 inducible conditional knockout mice in the intestine was increased and that contact between the cells and matrix was loosened. CONCLUSIONS: We generated a model of intestinal Cldn7 inducible conditional knockout mice. Intestinal Cldn7 deletion induced by tamoxifen initiated inflammation and hyperplasia in mice.


Assuntos
Claudinas/genética , Modelos Animais de Doenças , Enterite/genética , Deleção de Genes , Intestino Delgado/patologia , Camundongos Knockout/genética , Adenoma/induzido quimicamente , Adenoma/diagnóstico por imagem , Adenoma/genética , Adenoma/patologia , Animais , Western Blotting , Enterite/induzido quimicamente , Enterite/diagnóstico por imagem , Enterite/patologia , Feminino , Hiperplasia/induzido quimicamente , Hiperplasia/diagnóstico por imagem , Hiperplasia/genética , Hiperplasia/patologia , Imuno-Histoquímica , Neoplasias Intestinais/induzido quimicamente , Neoplasias Intestinais/diagnóstico por imagem , Neoplasias Intestinais/genética , Neoplasias Intestinais/patologia , Intestino Delgado/diagnóstico por imagem , Masculino , Camundongos , Microscopia Eletrônica de Varredura , Fenótipo , Tamoxifeno/administração & dosagem , Junções Íntimas/patologia
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