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1.
Stem Cell Res Ther ; 11(1): 124, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183875

RESUMO

BACKGROUND: Crohn's fistula-in-ano is a refractory disease in colorectal and anal surgery. Although autologous adipose-derived stem cell (ADSC) has been used in the treatment of Crohn's fistula-in-ano because of its convenience, non-incision of normal tissue, good tolerance, repeatability, quick recovery, less pain, less damage to anal function, and high quality of life during the perioperative period, there are no reports of its use in China. This is the first clinical trial in China on the treatment of Crohn's fistula-in-ano with ADSC to evaluate its efficacy and safety. METHODS: A total of 22 patients with Crohn's fistula-in-ano were enrolled in this study from January 2018 to October 2018 in the Colorectal Disease Center of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. Patients were divided (1:1) into an observation group (ADSC) and a control group (incision-thread-drawing procedure). Primary efficacy endpoint evaluated at months 3, 6, and 12 was the closure of fistulas (closure of all treated fistulas at baseline, confirmed by doctor's clinical assessment and magnetic resonance imaging or transrectal ultrasonography). The patients additionally completed some scoring scales at each follow-up including simplified Crohn's Disease Activity Index (CDAI), Perianal Disease Activity Index (PDAI), Inflammatory Bowel Disease Questionnaire (IBDQ), pain scores with visual analog score (VAS), and Wexner score. The data of inflammatory indexes were also collected. RESULTS: The healing rates of the observation group and the control group at months 3, 6, and 12 were as follows: 10/11(90.9%) vs 5/11(45.5%), 8/11(72.7%) vs 6/11(54.5%), and 7/11(63.6%) vs 6/11(54.5%), respectively. There was no statistical difference between the two groups. In addition, the improvement in simplified CDAI, PDAI, IBDQ, VAS, and Wexner score of the observation group were better than that of the control group at each follow-up. The inflammatory indexes decreased in both the observation group and the control group at 3 months follow-up. And there were no significant differences in the changes of inflammatory indexes between two groups at month 3 compared with the baseline. Safety was maintained throughout month 12, and adverse events occurred in 63.6% of patients in the observation group and 100% patients in the control group. And no adverse event associated with ADSC injection was observed in the study. CONCLUSION: ADSC is a feasible and effective treatment for Crohn's fistula-in-ano, compared with traditional incision and thread-drawing. It can protect anal function of patients, relieve pain, allow quick recovery, be well-tolerated, and improve the quality of life during perioperative period. TRIAL REGISTRATION: China Clinical Trials Registry, No. ChiCTR1800014599. Registered 23 January 2018.

2.
J Cell Biochem ; 120(4): 5687-5694, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30548286

RESUMO

In this article, we aim to examine the novel effects of ß-sitosterol on murine experimental colitis. ß-Sitosterol significantly reduces the weight loss, colon length, and alleviated microscopic appearances of colitis induced by dextran sulfate sodium. This compound also decreases the levels of TNF-α, IL-6, and IL-1ß in intestinal tissue of mice with experimental colitis in a concentration-dependent manner. ß-Sitosterol treatment to intestinal epithelial cells significantly increases expression of antimicrobial peptides and reduces survival of intracellular Salmonella typhimurium. These results showed the multiple effects of ß-sitosterol against pathogenic bacteria for a novel approach to the treatment of colonic inflammation.


Assuntos
Colite/prevenção & controle , Sulfato de Dextrana/toxicidade , Hipolipemiantes/farmacologia , Inflamação/prevenção & controle , Salmonella typhimurium/efeitos dos fármacos , Sitosteroides/farmacologia , Febre Tifoide/complicações , Animais , Colite/etiologia , Colite/patologia , Modelos Animais de Doenças , Inflamação/etiologia , Inflamação/patologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Febre Tifoide/tratamento farmacológico , Febre Tifoide/patologia
3.
BMC Plant Biol ; 18(1): 353, 2018 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-30545290

RESUMO

BACKGROUND: Nitrogen is one basic element of amino acids and grain protein in wheat. In field experiments, wheat plants were subjected to different timing of nitrogen topdressing treatments: at the stages of emergence of the top fifth leaf (TL5), top third leaf (TL3) and top first leaf (TL1) to test the regulatory effects of nitrogen topdressing timing on grain protein quality. The underlying mechanisms were elucidated by clarifying the relationship between proteolysis in vegetative organs and accumulation of amino acids in the endosperm cavity, conversion of amino acids, and storage protein synthesis in endosperm of wheat grain. RESULTS: Delayed nitrogen topdressing up-regulated gene expression related to nitrogen metabolism and protease synthesis in the flag leaf, followed by more free amino acids being transported to both the cavity and the endosperm from 7 days after anthesis (DAA) to 13 DAA in TL1. TL1 enhanced the conversion between free amino acids in endosperm and upregulated the expression of genes encoding high molecular weight (HMW) and low molecular weight (LMW) subunits and protein disulfide isomerases-like (PDIL) proteins, indicating that the synthesis and folding of glutenin were enhanched by delayed nitrogen topdressing. As a consequense, the content of glutenin macropolymers (GMP) and glutenin increased with delaying nitrogen topdressing. CONCLUSIONS: The results highlight the relationship between nitrogen remobilization and final grain protein production and suggest that the nitrogen remobilization processes could be a potential target for improving the quality of wheat grain. Additionally, specific gene expression related to nitrogen topdressing was identified, which conferred more detailed insights into underlying mechanism on the modification protein quality.


Assuntos
Aminoácidos/metabolismo , Grão Comestível/metabolismo , Nitrogênio/metabolismo , Proteínas de Plantas/metabolismo , Triticum/metabolismo , Aminoácidos/análise , Grão Comestível/química , Endosperma/química , Endosperma/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Nitrogênio/administração & dosagem , Folhas de Planta/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
4.
Cell Discov ; 4: 55, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30345072

RESUMO

DNA methylation is a conserved epigenetic mark that is critical for many biological processes in plants and mammals. In Arabidopsis, the antagonistic activities of RNA-directed DNA methylation (RdDM) and ROS1-dependent active DNA demethylation are key for the dynamic regulation of locus-specific DNA methylation. However, the molecular factors that coordinate RdDM and active demethylation are largely unknown. Here we report that CLSY4 and its three paralogous SWI2/SNF2-type chromatin-remodeling proteins function in both RdDM and DNA demethylation in Arabidopsis. We initially identified CLSY4 in a genetic screen for DNA demethylation factors and subsequently demonstrated that it also is important in RdDM. Comprehensive genetic analyses using single and high order mutants of CLSY family proteins revealed their roles as double agents in the balance between methylation and demethylation reactions. The four CLSY proteins collectively are necessary for the canonical RdDM pathway; at the same time, each CLSY likely mediates DNA demethylation at specific loci where DNA methylation depends on RdDM. These results indicate that the four chromatin-remodeling proteins have dual functions in regulating genomic DNA methylation, and thus provide new insights into the dynamic regulation of DNA methylation in a model multicellular eukaryotic organism.

5.
Proc Natl Acad Sci U S A ; 115(42): E9962-E9970, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30266793

RESUMO

Genomic imprinting is a form of epigenetic regulation resulting in differential gene expression that reflects the parent of origin. In plants, imprinted gene expression predominantly occurs in the seed endosperm. Maternal-specific DNA demethylation by the DNA demethylase DME frequently underlies genomic imprinting in endosperm. Whether other more ubiquitously expressed DNA demethylases regulate imprinting is unknown. Here, we found that the DNA demethylase ROS1 regulates the imprinting of DOGL4 DOGL4 is expressed from the maternal allele in endosperm and displays preferential methylation and suppression of the paternal allele. We found that ROS1 negatively regulates imprinting by demethylating the paternal allele, preventing its hypermethylation and complete silencing. Furthermore, we found that DOGL4 negatively affects seed dormancy and response to the phytohormone abscisic acid and that ROS1 controls these processes by regulating DOGL4 Our results reveal roles for ROS1 in mitigating imprinted gene expression and regulating seed dormancy.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Metilação de DNA , Proteínas de Ligação a DNA/metabolismo , Impressão Genômica , Proteínas Nucleares/metabolismo , Dormência de Plantas , Sementes/fisiologia , Fatores de Transcrição/metabolismo , Proteínas de Arabidopsis/genética , DNA de Plantas/genética , Proteínas de Ligação a DNA/genética , Epigênese Genética , Regulação da Expressão Gênica de Plantas , Proteínas Nucleares/genética , Fatores de Transcrição/genética
6.
Plant Physiol ; 175(1): 424-437, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28701352

RESUMO

Calcium signaling is essential for environmental responses including immune responses. Here, we provide evidence that the evolutionarily conserved protein BONZAI1 (BON1) functions together with autoinhibited calcium ATPase10 (ACA10) and ACA8 to regulate calcium signals in Arabidopsis. BON1 is a plasma membrane localized protein that negatively regulates the expression of immune receptor genes and positively regulates stomatal closure. We found that BON1 interacts with the autoinhibitory domains of ACA10 and ACA8, and the aca10 loss-of-function (LOF) mutants have an autoimmune phenotype similar to that of the bon1 LOF mutants. Genetic evidences indicate that BON1 positively regulates the activities of ACA10 and ACA8. Consistent with this idea, the steady level of calcium concentration is increased in both aca10 and bon1 mutants. Most strikingly, cytosolic calcium oscillation imposed by external calcium treatment was altered in aca10, aca8, and bon1 mutants in guard cells. In addition, calcium- and pathogen-induced stomatal closure was compromised in the aca10 and bon1 mutants. Taken together, this study indicates that ACA10/8 and BON1 physically interact on plasma membrane and function in the generation of cytosol calcium signatures that are critical for stomatal movement and impact plant immunity.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Sinalização do Cálcio , ATPases Transportadoras de Cálcio/metabolismo , Cálcio/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Arabidopsis/imunologia , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Ligação ao Cálcio , ATPases Transportadoras de Cálcio/genética , Proteínas de Transporte/genética , Membrana Celular/metabolismo , Citosol/metabolismo , Genes Reporter , Homeostase , Mutação com Perda de Função , Proteínas de Membrana/genética , Imunidade Vegetal , Estômatos de Plantas/genética , Estômatos de Plantas/imunologia , Estômatos de Plantas/fisiologia
7.
Zhonghua Wei Chang Wai Ke Za Zhi ; 16(12): 1169-73, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24369399

RESUMO

OBJECTIVE: To explore the value of dynamic three-dimensional ultrasound in detecting the levator ani muscle fissures morphological changes of female pelvic floor relaxation syndrome after biofeedback and acupuncture treatments. METHODS: Forty female constipation patients with pelvic floor relaxation syndrome were screened from the Constipation Designed Disease Clinic in our hospital between October 2011 and September 2012. Cleveland Constipation Score (CCS) scale was used. Anteroposterior and transverse diameters of the levator ani muscle fissures were measured by dynamic three-dimensional ultrasound in Valsalva maneuver. After a course (10 days) of biofeedback and acupuncture treatments, CCS scale was filled, and dynamic three-dimensional ultrasound was performed in Valsalva maneuver as well. Associated data before and after treatment were compared. RESULTS: Twenty-five patients completed the trial. As compared to pre-treatment, the longitudinal axes of levator ani muscle fissure [(4.89±0.89) cm vs. (5.13±0.82) cm, P<0.01], the horizontal axes of the levator ani muscle fissure [(4.62±0.75) cm vs. (4.86±0.74) cm, P<0.01], and the area of the levator ani muscle fissure [(18.16±6.42) cm(2) vs. (19.92±6.33) cm(2), P<0.01] decreased significantly after treatment, while CCS scale (9.52±2.50 vs. 15.80±3.42, P<0.01) declined significantly as well. CONCLUSIONS: The dynamic three-dimensional ultrasound is an effective, simple and non-invasive method for the determination of levator ani muscle fissure in female patients with pelvic floor relaxation syndrome.


Assuntos
Imageamento Tridimensional , Distúrbios do Assoalho Pélvico/diagnóstico por imagem , Diafragma da Pelve/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Ultrassonografia
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