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1.
Eur J Nutr ; 62(4): 1599-1610, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36717385

RESUMO

PURPOSE: To test the hypothesis that daily supplementation with low-dose B vitamins plus betaine could significantly reduce plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia and free from background mandatory folic acid fortification. METHODS: One hundred apparently healthy adults aged 18-65 years with hyperhomocysteinemia were recruited in South China from July 2019 to June 2021. They were randomly assigned to either the supplement group (daily supplementation: 400 µg folic acid, 8 mg vitamin B6, 6.4 µg vitamin B12 and 1 g betaine) or the placebo group for 12 weeks. Fasting venous blood was collected at baseline, week 4 and week 12 to determine the concentrations of homocysteine, folate, vitamin B12 and betaine. Generalized estimation equations were used for statistical analysis. RESULTS: Statistically significant increments in blood concentrations of folate, vitamin B12 and betaine after the intervention in the supplement group indicated good participant compliance. At baseline, there were no significant differences in plasma homocysteine concentration between the two groups (P = 0.265). After 12-week supplementation, compared with the placebo group, there was a significant reduction in plasma homocysteine concentrations in the supplement group (mean group difference - 3.87; covariate-adjusted P = 0.012; reduction rate 10.1%; covariate-adjusted P < 0.001). In the supplement group, the decreased concentration of plasma homocysteine was associated with increments of blood concentrations of both folate (ß = -1.680, P = 0.004) and betaine (ß = -1.421, P = 0.020) after 12 weeks of supplementation. CONCLUSIONS: Daily supplementation with low-dose B vitamins plus betaine for 12 weeks effectively decreased plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT03720249 on October 25, 2018. Website: https://clinicaltrials.gov/ct2/show/NCT03720249 .


Assuntos
Hiper-Homocisteinemia , Complexo Vitamínico B , Adulto , Humanos , Betaína , Suplementos Nutricionais , Método Duplo-Cego , População do Leste Asiático , Ácido Fólico , Homocisteína , Vitamina B 12 , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso
2.
Bioorg Chem ; 129: 106161, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36162287

RESUMO

Dual-modal magnetic resonance/fluorescent imaging (MRI/FI) attracts moreandmoreattentions in diagnosis of tumors. A corresponding dual-modal imaging agent with sufficient tumor sensitivity and specificity should be matched to improve imaging quality. Tripeptide (RGD) and pentapeptide (YIGSR) were selected as the tumor-targeting groups and attached to gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) and rhodamine B (RhB), and then make two novel polypeptide-based derivatives (RGD-Gd-DTPA-RhB and YIGSR-Gd-DTPA-RhB), respectively. These derivatives were further characterized and their properties, such as cell uptake, cell cytotoxicity, MRI and FI assay, were measured. YIGSR-Gd-DTPA-RhB and RGD-Gd-DTPA-RhB had high relaxivity, good tumor-targeting property, low cell cytotoxicity and good red FI in B16F10 melanoma cells. Moreover, YIGSR-Gd-DTPA-RhB and RGD-Gd-DTPA-RhB possessed high uptake to B16F10 melanoma, and then achieve highly enhanced FI and MRI of tumors in mice for a prolonged time. Therefore, YIGSR-Gd-DTPA-RhB and RGD-Gd-DTPA-RhB can be applied as the potential agents for tumor targeted MRI/FI in vivo.


Assuntos
Meios de Contraste , Melanoma , Camundongos , Animais , Meios de Contraste/química , Gadolínio DTPA/farmacologia , Gadolínio DTPA/química , Gadolínio/química , Imageamento por Ressonância Magnética/métodos , Oligopeptídeos/farmacologia , Imagem Óptica/métodos , Espectroscopia de Ressonância Magnética
3.
J Dig Dis ; 23(5-6): 248-252, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35561147

RESUMO

Chronic active Epstein-Barr virus (CAEBV) enteritis is a rare disease that has not been well described. Owing to the similarities between CAEBV enteritis and inflammatory bowel diseases such as ulcerative colitis and Crohn's disease, it is easy to be misdiagnosed and mistreated in clinical practice, resulted in complications and even death in severe cases. Through a literature review, this study aimed to summarize the clinical characteristics, pathological features, examinations, and treatment strategies of CAEBV enteritis and its similarities and differences with inflammatory bowel diseases.


Assuntos
Colite Ulcerativa , Enterite , Infecções por Vírus Epstein-Barr , Doenças Inflamatórias Intestinais , Doença Crônica , Colite Ulcerativa/complicações , Enterite/diagnóstico , Enterite/terapia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4 , Humanos , Doenças Inflamatórias Intestinais/complicações
4.
Dig Liver Dis ; 54(6): 763-770, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991975

RESUMO

BACKGROUND: Mucosal healing, the result of endoscopic remission, is associated with prolonged clinical remission and delayed deterioration of Crohn's disease, which is significant and accompanied by reduced hospitalizations and surgeries. Currently, the relationship between ultrasonic parameters and mucosal healing remains controversial. To establish an ultrasonic regression model to evaluate mucosal healing, we conducted this preliminary study using multiple parameters from B-mode ultrasonography, colour Doppler flow imaging and shear wave elastography systematically. METHODS: This study consisted of two single-centre investigations based on development and validation populations who received endoscopies (as the gold standard) and ultrasound. The involved bowel segments were divided into mucosal healing (MH) and nonmucosal healing (NMH) groups according to endoscopic results. Eight ultrasonic parameters were observed, including bowel wall thickness (BWT), mesenteric fat thickness (MFT), median modulus of elasticity (Emean), average shear wave velocity (SWV), Limberg scoring (LG), bowel wall stratification (BWS), ascites (AS) and lymph node enlargement (LN). We developed an ultrasonic regression model in the development phase to evaluate segmental mucosal healing and undertook prospective validation of this model. RESULTS: A total of 124 patients with 380 involved bowel segments from the development and validation cohorts were evaluated. Eight ultrasonic parameters were significantly different between the two groups (P<0.05) in the development phase. Four significant parameters with better AUC performance were selected to establish an ultrasonic regression model to predict mucosal healing. The AUCs of this ultrasonic model were 0.975 and 0.942 in the development and validation cohorts, respectively. CONCLUSION: The multimodal ultrasonic model has the potential to evaluate segmental mucosal healing in Crohn's disease.


Assuntos
Doença de Crohn , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/patologia , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Intestinos/diagnóstico por imagem , Mucosa/patologia , Ultrassonografia/métodos , Cicatrização
5.
World J Clin Cases ; 9(16): 3858-3868, 2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34141742

RESUMO

BACKGROUND: Gastrointestinal involvement in Behçet's disease (GIBD) and Crohn's disease (CD) are inflammatory diseases sharing a considerable number of similarities. However, different from CD, the operative and postoperative management of GIBD remains largely empirical because of the lack of comprehensive treatment guidelines. AIM: To compare surgical patients with GIBD and those with CD in a medical center and identify notable clinical features and effective postoperative treatment for surgical patients with GIBD. METHODS: We searched patients diagnosed with CD and GIBD who underwent operations for gastrointestinal complications from 2009 to 2015 at West China Hospital of Sichuan University. A total of 10 surgical patients with GIBD and 106 surgical patients with CD were recruited. Information including demographic data, medication, and operative and postoperative parameters were collected and analyzed. As the incidence of surgical GIBD is low, their detailed medical records were reviewed and compared to previous studies. Moreover, the prognoses of CD and GIBD were evaluated respectively between groups treated with biological and non-biological agents. RESULTS: Indication for first surgery was often acute intestinal perforation for GIBD patients (7/10 vs 0/106, P < 0.001), whereas intestinal fistulae (0/10 vs 44/106, P = 0.013) and ileus (0/10 vs 40/106, P = 0.015) were the indications for surgical CD patients. Approximately 40% of patients with GIBD and 23.6% of patients with CD developed postoperative complications, 50% of patients with GIBD and 38.7% of patients with CD had recurrence postoperatively, and 40% (4/10) of patients with GIBD and 26.4% (28/106) of patients with CD underwent reoperations. The average period of postoperative recurrence was 7.87 mo in patients with Behçet's disease (BD) and 10.43 mo in patients with CD, whereas the mean duration from first surgery to reoperation was 5.75 mo in BD patients and 18.04 mo in CD patients. Surgical patients with GIBD more often used corticosteroids (6/10 vs 7/106, P < 0.001) and thalidomide (7/10 vs 9/106, P < 0.001) postoperatively, whereas surgical patients with CD often used infliximab (27/106), azathioprine, or 6-mercaptopurine (74/106) for maintenance therapy. CONCLUSION: Patients suffering GIBD require surgery mostly under emergency situations, which may be more susceptible to recurrence and reoperation and need more aggressive postoperative treatment than patients with CD.

6.
Open Med (Wars) ; 16(1): 532-539, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33851032

RESUMO

BACKGROUND: Good's syndrome (GS) is an immunodeficiency disease, causing thymoma, low or absent B-cells, hypogammaglobulinemia, and defects in cell-mediated immunity. The most common clinical presentation is recurrent infection, followed by refractory diarrhea, due to the immunodeficiency. However, there are only few reports on intestinal endoscopy and pathology. CASE SUMMARY: We report here two typical GS cases with diarrhea as the prominent manifestation. Both cases presented with thymoma combined with immunodeficiency, characterized by hypogammaglobulinemia, low or absent B lymphocytes, and decreased T-cells with inverted CD4+/CD8+ T-cell ratio, while two GS patients were evaluated by endoscopy revealed mucosal edema and fine-granular or nodular appearance changes in the small intestine. Histological examination showed chronic inflammation and villous atrophy. A very interesting finding is that the inflammatory cell infiltration in the two GS cases was different. In one case, predominantly CD138+ plasma cells with only scattered CD3+ T-cells infiltration were revealed, while in another, it showed predominantly T-cells infiltration without plasma cells in the lamina propria. Although GS cases shared various clinical characteristics with common variable immunodeficiency (CVID) cases, they still differed from CVID cases in terms of its late onset, lack of familial clusters, low or absent peripheral blood B lymphocytes, absence of lymphoid hyperplasia, and plasma cells infiltration in the lamina propria in some patients. Although both patients had been diagnosed previously with recurrent diarrhea, respiratory infection, and thymoma, the association between these conditions and the possibility of GS was not recognized. The patients had remained misdiagnosed for 2 and 4 years, respectively, even after receiving the diagnosis of thymoma. The rarity of GS was likely the primary cause for the lack of disease recognition. Reporting of these cases will help to alert clinicians and raise awareness of this disease. CONCLUSION: GS should be considered among the differential diagnoses for patients with unexplained recurrent diarrhea and opportunistic infection. Although it was regarded as a subset of CVID with thymoma, GS had a different clinical-pathological feature from CVID.

7.
Sci Rep ; 10(1): 16243, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004964

RESUMO

Food coloring is often used as a coloring agent in foods, medicines and cosmetics, and it was reported to have certain carcinogenic and mutagenic effects in living organisms. Investigation of physiological parameters using zebrafish is a promising methodology to understand disease biology and drug toxicity for various drug discovery on humans. Zebrafish (Danio rerio) is a well-acknowledged model organism with combining assets such as body transparency, small size, low cost of cultivation, and high genetic homology with humans and is used as a specimen tool for the in-vivo throughput screening approach. In addition, recent advances in microfluidics show a promising alternative for zebrafish manipulation in terms of drug administration and extensive imaging capability. This pilot work highlighted the design and development of a microfluidic detection platform for zebrafish larvae through investigating the effects of food coloring on cardiovascular functionality and pectoral fin swing ability. The zebrafish embryos were exposed to the Cochineal Red and Brilliant Blue FCF pigment solution in a concentration of (0.02‰, 0.2‰) cultured in the laboratory from the embryo stage to hatching and development until 9 days post fertilization (d.p.f.). In addition, zebrafish swimming behaviors in terms of pectoral fin beating towards the toxicity screening were further studied by visualizing the induced flow field. It was evidenced that Cochineal Red pigment at a concentration of 0.2‰ not only significantly affected the zebrafish pectoral fin swing behavior, but also significantly increased the heart rate of juvenile fish. The higher concentration of Brilliant Blue FCF pigment (0.2%) increased heart rate during early embryonic stages of zebrafish. However, zebrafish exposed to food coloring did not show any significant changes in cardiac output. The applications of this proposed platform can be further extended towards observing the neurobiological/hydrodynamic behaviors of zebrafish larvae for practical applications in drug tests.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Aditivos Alimentares/farmacologia , Hemodinâmica/efeitos dos fármacos , Animais , Compostos Azo/efeitos adversos , Compostos Azo/farmacologia , Benzenossulfonatos/efeitos adversos , Benzenossulfonatos/farmacologia , Relação Dose-Resposta a Droga , Aditivos Alimentares/efeitos adversos , Corantes de Alimentos/efeitos adversos , Corantes de Alimentos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Ensaios de Triagem em Larga Escala/métodos , Técnicas Analíticas Microfluídicas , Naftalenossulfonatos/efeitos adversos , Naftalenossulfonatos/farmacologia , Peixe-Zebra
8.
World J Gastroenterol ; 26(17): 2119-2125, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32536779

RESUMO

BACKGROUND: Fistulas are common complications of Crohn's disease (CD). Gastrocolic fistulas (GFs) are rare, occult and potentially life-threatening complications. Few cases of GFs have been reported. Oral agent contrast-enhanced ultrasound (OA-CEUS) is a novel technique of ultrasound (US) for gut. Contrast agent made by Chinese yam is taken orally to dilate the lumen of the upper gastrointestinal tract. Thus, the impediment of gas inside gastrointestinal tract is removed and a good acoustic window is provided for gastroin-testinal tract scanning. This paper describes a case of GF secondary to CD detected by OA-CEUS when it was missed by endoscopy and computed tomography (CT). To our knowledge, this is the first report of GF secondary to CD detected by OA-CEUS up to date. CASE SUMMARY: A 29-year-old woman with a 6-year history of CD was admitted to our hospital for abdominal pain and diarrhea for 5 months without obvious predisposing causes. Initial gastroscopy failed to show any evidence of lesions. Colonoscopy revealed multiple erosions, mucosal nodularity, linear ulcers and a cobblestone appearance. A CT scan of her abdomen showed a complex multilocular structure adherent to the greater curvature of the stomach in her left lower abdomen, with fluid, gas and significant surrounding inflammation. CT also demonstrated an abdominal abscess, which was later treated with US-guided drainage. Colonoscopy, gastroscopy and CT missed the presence of a GF. OA-CEUS was performed. A contrast agent made from Chinese yam was taken orally to dilate the lumen of the gastrointestinal tract. A good acoustic window was provided for gastrointestinal tract scanning and the impediment of gas inside the gastrointestinal tract was removed. With the aid of the "window", a canal with hypoechoic wall was identified connecting the greater curvature of stomach to the splenic colon flexure in free sections. We also observed the hyperechoic gas flowing dynamically inside the canal. Thus, a GF was suspected. US is the first imaging modality taking GF into account. At the same time, OA-CEUS identified the site of the fistula and its two orifices. Gastroscopy was performed again, revealing a small ulcer approximately 5 mm in diameter, which was considered as an orifice. On the basis of OA-CEUS and other examinations, the patient was diagnosed with a GF secondary to CD. Then, laparoscopic exploration, partial stomach resection, transverse colostomy and abdominal abscess drainage were performed. The patient recovered uneventfully. CONCLUSION: GFs are rare, occult and potentially life-threatening complications in CD. US is one of the first-line modalities to evaluate CD and its complications. OA-CEUS, a novel technique of US for gut, may be helpful in reducing the possibility of a missed diagnosis of GF.


Assuntos
Doenças do Colo/diagnóstico , Meios de Contraste/administração & dosagem , Doença de Crohn/complicações , Fístula Gástrica/diagnóstico , Ultrassonografia Doppler em Cores/métodos , Abscesso Abdominal/diagnóstico , Abscesso Abdominal/etiologia , Abscesso Abdominal/cirurgia , Dor Abdominal/etiologia , Dor Abdominal/cirurgia , Administração Oral , Adulto , Colo/diagnóstico por imagem , Colo/cirurgia , Doenças do Colo/etiologia , Colostomia , Dioscorea/química , Drenagem , Feminino , Gastrectomia , Fístula Gástrica/etiologia , Gastroscopia , Humanos , Diagnóstico Ausente , Estômago/diagnóstico por imagem , Estômago/cirurgia , Tomografia Computadorizada por Raios X
9.
Talanta ; 212: 120718, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32113526

RESUMO

Currently, fluorescent imaging is one of the most promising diagnostic approaches for facile detection of cancers in situ in thanks to a fluorescent probe. Two novel polypeptide-based fluorescent probes for different biomarkers to cancers are reported here. These probes focused on tyrosine-isoleucine-glycine-serine-arginine (YIGSR) and arginine-glycine-aspartic (RGD), which receptors play an important role in the extracellular matrix and are overexpressed in tumor cells and then can be used as tumor-targeting groups in fluorescent imaging. In this work, the pentpeptide-rhodamine B derivative (YIGSR-RhB) and tripeptide-rhodamine B derivative (RGD-RhB) were synthesized respectively by using the solid phase synthesis methods. These derivatives were further characterized by 1HNMR, MS, UV and IR, etc. Their fluorescent and biocompatibility properties, such as the cell cytotoxicity, cell uptake and fluorescent imaging of tumor cells, and fluorescent imaging in BALB/c female mice with 4T1 tumors and C57 mice with B16F10 tumor in vivo, were also measured. Experiment results demonstrated that YIGSR-RhB and RGD-RhB possessed the low cell cytotoxicity, good tumor-targeting property and fluorescent properties similar to rhodamine B. Moreover, YIGSR-RhB and RGD-RhB can be taken up highly by the B16F10 melanoma cells and 4T1 breast cancer cells, and then achieve the good fluorescent imaging in these tumor cells in vitro and tumors of mice in vivo. Therefore, YIGSR-RhB and RGD-RhB can be used as the potential tumor-targeting probes for fluorescent imaging. They can directly attach the cell membrane and specifically target to the tumor cells.


Assuntos
Corantes Fluorescentes/química , Neoplasias/diagnóstico por imagem , Oligopeptídeos/química , Rodaminas/química , Animais , Linhagem Celular Tumoral , Feminino , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Laminina/química , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência , Oligopeptídeos/síntese química , Oligopeptídeos/toxicidade , Imagem Óptica , Receptores de Fibronectina/química , Rodaminas/síntese química , Rodaminas/toxicidade
10.
Cancer Biother Radiopharm ; 34(7): 419-426, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31149837

RESUMO

Objective: To explore the association between the incidence of acute radiation gastritis attributed to postoperative intensity modulated irradiation therapy (IMRT) and the dose volume of intrathoracic stomach of patients with esophageal squamous cell carcinoma (ESCC) after radical esophagectomy. Methods: The authors retrospectively collected the data of 49 ESCC patients who participated in postoperative IMRT treatment after radical esophagectomy, and analyzed the incidence of acute radiation gastritis during the treatment. Results: Among all the 49 patients, acute grade ≥2 radiation gastritis was observed in 19 patients (39%). Receiver operating characteristic (ROC) curve analysis showed that the physical variables, such as stomach Dmax, Dmean, length of the whole stomach received 5-40 Gy (LSTT5-LSTT40), and V10-V50, were associated with acute radiation gastritis. Patients were grouped according to cutoff values in physical indicators obtained from the ROC curve. Other than V5, the incidence of acute grade ≥2 radiation gastritis was significantly higher in the group with indicators above cutoff values than that below cutoff values, and the between-group difference was statistically significant in terms of physical indicators. Multivariate analysis suggested that LSTT5 and V40 could be acted as indicators to predict the incidence of acute grade ≥2 radiation gastritis. Conclusions: In the postoperative IMRT treatment for ESCC patients, protection of intrathoracic stomach is strongly recommended. Dose-volume histogram is a preferable predictive indicator for the occurrence of acute radiation gastritis, especially for the stomach LSTT5 and V40. Nevertheless, a larger sample size is needed to provide insight into the relevant study.


Assuntos
Carcinoma de Células Escamosas do Esôfago/radioterapia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/métodos , Gastrite/induzido quimicamente , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Gastrite/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Radiometria
11.
J Cell Biochem ; 120(10): 17006-17014, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31131464

RESUMO

An ideal positron emission tomography (PET) tracer should be highly extractable by the tumor tissue or organ that contains low toxicity and can provide high-resolution images in vivo. In this work, the aim was to evaluate the application of Al18 F-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid containing sulfonamide group (18 F-Al-NOTA-SN) as a potential tumor-targeting signal-enhanced radioactive tracer in PET. SN as a tumor-targeting group was incorporated to NOTA to make a ligand. Subsequently, this ligand reacted with Na18 F and AlCl3 to produce a compound 18 F-Al-NOTA-SN. This compound was further characterized and its property in regard to cell cytotoxicity assay, microPET imaging, biodistribution, cell uptake assay, and tumor selectivity in vitro and in vivo, was also investigated. 18 F-Al-NOTA-SN possessed low cell cytotoxicity and uptake to COS-7 and 293T healthy cells and high cell cytotoxicity and uptake to MDA-MB-231, HepG2, and HeLa tumor cells in vitro. Moreover, 18 F-Al-NOTA-SN showed good tumor-targeting property and high PET signal enhancement of HeLa tumors, liver, and kidneys in mice, as well as the uptake ratios of tumor to blood and tumor to muscle, were 4.98 and 3.87, respectively. 18 F-Al-NOTA-SN can be accepted to be kidney and liver eliminated earlier and show a potential tumor-targeting signal-enhanced radioactive tracer in PET.


Assuntos
Radioisótopos de Gálio/química , Compostos Heterocíclicos com 1 Anel/farmacologia , Tomografia por Emissão de Pósitrons/métodos , Sulfonamidas/química , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/tratamento farmacológico , Animais , Células COS , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Feminino , Células HEK293 , Células HeLa , Células Hep G2 , Compostos Heterocíclicos com 1 Anel/síntese química , Compostos Heterocíclicos com 1 Anel/farmacocinética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Distribuição Tecidual , Neoplasias Uterinas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(1): 61-65, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31037906

RESUMO

OBJECTIVE: To analyze the correlation of K-ras gene mutations with the protein expressions of transforming growth factor-ß activating kinase 1 (TAK1) protein and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2) protein in colorectal cancer. METHODS: K-ras gene mutations were detected by DNA sequencing analysis, and the expressions of TAK1 protein and MAP4K2 protein were detected by immunohistochemical method in 76 cases of colorectal cancer tissues. RESULTS: In 76 cases of colorectal cancer tissues, the mutation rate of K-ras gene was 32.89% (25 cases), and K-ras gene mutations were correlated with the degrees of cell differentiation ( P<0.05). The positive rates of TAK1 protein and MAP4K2 protein were 48.68% and 46.05%, respectively. The protein expressions of TAK1 and MAP4K2 were positively correlated with the degrees of cell differentiation and lymph node metastases, respectively ( P<0.05). There was no correlation between K-ras gene mutation and either TAK1 protein or MAP4K2 protein expression ( P>0.05). In 25 cases of colorectal cancer with K-ras mutation, the expression of TAK1 protein was positively correlated with the expression of MAP4K2 protein ( P<0.05). CONCLUSION: K-ras gene mutation, TAK1 and MAP4K2 protein expressions were related to the degree of differentiation of colorectal cancer, but not to the depth of invasion. In colorectal cancer with K-ras gene mutation, the expression of TAK1 protein was positively correlated with the expression of MAP4K2 protein.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Proteínas Proto-Oncogênicas p21(ras)/genética , Genes ras , Quinases do Centro Germinativo , Humanos , Metástase Linfática , MAP Quinase Quinase Quinases , Mutação , Proteínas Serina-Treonina Quinases
13.
Nat Cell Biol ; 20(4): 492-502, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29593331

RESUMO

The list of long non-coding RNAs (lncRNAs) involved in the p53 pathway of the DNA damage response is rapidly expanding, but whether lncRNAs have a role in maintaining the de novo structure of DNA is unknown. Here, we demonstrate that the p53-responsive lncRNA GUARDIN is important for maintaining genomic integrity under steady-state conditions and after exposure to exogenous genotoxic stress. GUARDIN is necessary for preventing chromosome end-to-end fusion through maintaining the expression of telomeric repeat-binding factor 2 (TRF2) by sequestering microRNA-23a. Moreover, GUARDIN also sustains breast cancer 1 (BRCA1) stability by acting as an RNA scaffold to facilitate the heterodimerization of BRCA1 and BRCA1-associated RING domain protein 1 (BARD1). As such, GUARDIN silencing triggered apoptosis and senescence, enhanced cytotoxicity of additional genotoxic stress and inhibited cancer xenograft growth. Thus, GUARDIN may constitute a target for cancer treatment.


Assuntos
Instabilidade Genômica , Neoplasias/genética , RNA Longo não Codificante/genética , Proteína Supressora de Tumor p53/genética , Células A549 , Animais , Antineoplásicos/farmacologia , Apoptose , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Proliferação de Células , Senescência Celular , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Instabilidade Genômica/efeitos dos fármacos , Células HCT116 , Células HEK293 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Conformação de Ácido Nucleico , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Proteína 2 de Ligação a Repetições Teloméricas/genética , Proteína 2 de Ligação a Repetições Teloméricas/metabolismo , Carga Tumoral , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
14.
J Invest Dermatol ; 138(4): 922-932, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29174371

RESUMO

Although the expression of programmed death-ligand 1 (PD-L1) is an important mechanism by which cancer cells evade the immune system, PD-L1 expression in cancer cells is commonly associated with patients' responses to treatment with anti-programmed death 1/PD-L1 antibodies. However, how PD-L1 expression is regulated in melanoma cells remains to be fully elucidated. Here we report that the class I histone deacetylase (HDAC) HDAC8 controls transcriptional activation of PD-L1 by a transcription complex consisting of transcription factors homeobox A5 and signal transducer and activator of transcription 3. Inhibition of HDAC8 upregulated PD-L1 in melanoma cells. This was due to an increase in the activity of a fragment of the PD-L1 gene promoter that is enriched with binding sites for both homeobox A5 and signal transducer and activator of transcription 3. Indeed, knockdown of homeobox A5 or signal transducer and activator of transcription 3 abolished upregulation of PD-L1 by HDAC8 inhibition. Moreover, homeobox A5 and signal transducer and activator of transcription 3 were physically associated and appeared interdependent in activating PD-L1 transcription. Functional studies showed that HDAC8-mediated regulation of PD-L1 expression participated in modulating anti-melanoma T-cell responses. Collectively, these results identify HDAC8 as an important epigenetic regulator of PD-L1 expression, with implications for better understanding of the interaction between melanoma cells and the immune system.


Assuntos
Antígeno B7-H1/genética , Regulação Neoplásica da Expressão Gênica , Histona Desacetilases/genética , Proteínas de Homeodomínio/genética , Melanoma/genética , Proteínas Repressoras/genética , Fator de Transcrição STAT3/genética , Antígeno B7-H1/biossíntese , Linhagem Celular Tumoral , DNA de Neoplasias/genética , Histona Desacetilases/biossíntese , Proteínas de Homeodomínio/biossíntese , Humanos , Melanoma/metabolismo , Melanoma/patologia , Proteínas Repressoras/biossíntese , Fator de Transcrição STAT3/biossíntese , Transdução de Sinais , Fatores de Transcrição , Ativação Transcricional , Regulação para Cima
15.
J Crohns Colitis ; 11(12): 1440-1448, 2017 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-28961760

RESUMO

BACKGROUND AND AIMS: Mucosal healing is associated with improved long-term clinical outcomes in patients with ulcerative colitis. This population-based study assessed endoscopic and histological mucosal healing within the first year of diagnosis. METHODS: Consecutive patients diagnosed with ulcerative colitis from six countries in Asia were prospectively enrolled. Clinical demographics, blood markers and inflammatory activity were assessed at baseline. Mayo score and Nancy index were used to assess endoscopic and histological activities, respectively. Clinical, endoscopic and histological evaluations were repeated at 1 year. Logistic regression was performed to identify predictors of mucosal healing. RESULTS: Of 433 ulcerative colitis patients, 202 [46.7%] underwent colonoscopy at 1 year. In total, 68 [38.2%] achieved endoscopic mucosal healing and 35 [23.1%] achieved histological mucosal healing. On multivariate analysis, an elevated erythrocyte sedimentation rate [ESR] at diagnosis (odds ratio [OR], 0.332; 95% confidence interval (CI), 0.133-0.830; p = 0.018) was a significant negative predictor of endoscopic mucosal healing at 1 year, while histological features of ulceration [OR, 0.156; 95% CI, 0.028-0.862; p = 0.033] and being an ex-smoker [OR, 0.067; 95% CI, 0.005-0.965; p = 0.047] were significant negative predictors of histological healing at 1 year. Both endoscopic and histological mucosal healing were associated with less steroid use [p < 0.001 and p = 0.001, respectively] and hospitalization [p = 0.002 and p = 0.01, respectively]. CONCLUSIONS: Mucosal healing was achieved in fewer than half of patients with ulcerative colitis in the first year of diagnosis. An elevated ESR predicted less likelihood of endoscopic mucosal healing, while histological features of ulceration and being an ex-smoker at diagnosis predicted less likelihood of histological healing.


Assuntos
Colite Ulcerativa/diagnóstico por imagem , Colite Ulcerativa/patologia , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Cicatrização , Adulto , Ásia , Sedimentação Sanguínea , Colite Ulcerativa/fisiopatologia , Colonoscopia , Feminino , Hospitalização , Humanos , Mucosa Intestinal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Índice de Gravidade de Doença , Fumar , Esteroides/uso terapêutico , Fatores de Tempo , Úlcera/patologia
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(4): 1221-5, 2016 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-27531804

RESUMO

OBJECTIVE: To study the influence of leukodeplated blood transfusion on cellular immunity of patients with acute leuemia, so as to provide support for application of leuko-deplated blood transfusion in clinic. METHODS: A total of 100 AL patients from January 2012 to December 2015 were chosen, and were divided into 2 groups: leukodeplated blood transfusion group(50 cases) and routine blood transfusion group(RBT) as control (50 cases). The effective rate, side effects, peripheral blood T cells and expression level of TLR2 and TLR4 were compared between 2 groups. RESULTS: The expression levels CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+) of TLR2 and TLR4 in control group were (52.18±2.14)%, (27.28±1.19)%,(24.21±1.65)%,1.22±0.18,0.62±0.04 and 0.57±0.05, respectively, after treatment; while these indicators in LdBT group were (52.18±2.14)%,(30.97±2.01)%,(27.08±1.55)%,1.39±0.24,0.91±0.06 and 0.87±0.07, respectively, and above-mentioned indicators in LdBT group were significantly higher than those in control group(P<0.05). Compared with these indicators before treatment, CD3(+), CD4(+), CD8(+) and CD4(+)/CD8(+) in the patients increased significantly(P<0.05). The efficiency was 92.00% (46/50) in LdBT group, and 84.00% (42/50) in control group, without statistically significant difference(P>0.05). The rate of side effects in study group was 6% (3/50), 18% (9/50) in control group, with statistically significance difference (P<0.05). CONCLUSION: Leukodeplated blood transfusion can improve the cellular immunity of AL patients, and reduce the rate of side effects.


Assuntos
Transfusão de Sangue , Imunidade Celular , Leucemia , Doença Aguda , Humanos , Linfócitos T
18.
J Cancer Res Ther ; 12(1): 259-66, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27072248

RESUMO

BACKGROUND: The objective of the current meta.analysis was to assess the arterial spin labeling. (ASL) perfusion imaging measurement of cerebral blood flow. (CBF) in patients with brain tumors, and assessing preoperative tumor grade in brain. MATERIALS AND METHODS: PubMed, Web of Science, Embase, China BioMedicine (CBM), CINAHL, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases were chosen to evaluate the associations between ASL and brain cancer. Two reviewers separately evaluated the quality of the included trials. Standardized mean difference (SMD) at 95% confidence interval (95% CI) was also calculated. RESULTS: Finally, 475 patients were enrolled into this meta-analysis from 12 eligible studies and were selected for statistical analysis. Results showed that relative tumor blood flow (rTBF) and relative cerebral blood flow (rCBF) in high-grade brain cancer patients were faster than those in low-grade brain cancer patients. Subgroup analysis stratified by country implied that ASL may be the main prediction of increased rTBF in high-grade brain cancer patients among USA, Korea and China; and rCBF was faster in high-grade brain cancer using ASL in USA and China. Further reference by tissue-stratified analysis revealed a positive association of rTBF with high-grade brain cancer by utilization of ASL in all the experimental subgroups, while rCBF was only correlated in white subgroups. CONCLUSION: These results showed that rTBF and rCBF were faster in high-grade brain cancer patients, suggesting that ASL may provide suitable measurement for the differential diagnosis of tumor grade in brain.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Circulação Cerebrovascular , Diagnóstico Diferencial , Gradação de Tumores , Artérias/diagnóstico por imagem , Artérias/patologia , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/patologia , China , Meios de Contraste/uso terapêutico , Humanos , Imagem de Perfusão , República da Coreia , Marcadores de Spin , Estados Unidos
19.
Mol Genet Genomics ; 291(3): 1193-203, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26847828

RESUMO

A number of studies assessed the association of ring finger protein 213 (RNF213) gene polymorphisms with moyamoya disease (MMD), but the results were not entirely consistent. This meta-analysis was performed to explore the relationship between RNF213 polymorphisms and moyamoya disease in Asian population. A systematic search from the PubMed, MEDLINE, EMBASE, ISI web of science, CNKI, China CBM and WANFANG DATA databases was conducted to retrieve published studies until March 2015. Statistical analyses were performed using the STATA12.0 software. Fixed or random effects model, subgroup analysis, sensitivity analysis, and publication bias were used to improve the comprehensive analysis. Eight papers including 904 MMD patients and 2258 controls were recruited in the meta-analysis. rs112735431 was closely associated with the risk of MMD among Asian population in all genetic models (dominant model: OR 103.39, 95 % CI 52.25-204.55, P = 1.69e-40; recessive model: OR 16.45, 95 % CI 6.00-45.10, P = 5.33e-08; additive model: OR 61.49, 95 % CI 22.07-171.33, P = 3.32e-15), especially in the Japanese population. Subgroup analysis revealed highly statistically significant higher risk in the patients with family histories. Although another polymorphism rs148731719 showed no significant association with the MMD, rs138130613 was found to be related to the higher risk in Chinese population (dominant model: OR 8.34, 95 % CI 1.72-40.47, P = 0.008). Our meta-analysis strengthens RNF213 rs112735431 is closely associated with the increased risk of MMD in Japanese, and the screening combined with rs112735431 and rs138130613may improve the detection rate for MMD in China.


Assuntos
Adenosina Trifosfatases/genética , Povo Asiático/genética , Estudos de Associação Genética/métodos , Doença de Moyamoya/genética , Polimorfismo de Nucleotídeo Único , Ubiquitina-Proteína Ligases/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Feminino , Predisposição Genética para Doença , Humanos , Japão , Masculino , Pessoa de Meia-Idade , República da Coreia , Adulto Jovem
20.
Gastroenterology ; 150(1): 86-95.e3; quiz e13-4, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26385074

RESUMO

BACKGROUND & AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in Asia, but little is known about disease progression in this region. The Asia-Pacific Crohn's and Colitis Epidemiology Study was initiated in 2011, enrolling subjects from 8 countries in Asia (China, Hong Kong, Indonesia, Sri Lanka, Macau, Malaysia, Singapore, and Thailand) and Australia. We present data from this ongoing study. METHODS: We collected data on 413 patients diagnosed with IBD (222 with ulcerative colitis [UC], 181 with Crohn's disease [CD], 10 with IBD unclassified; median age, 37 y) from 2011 through 2013. We analyzed the disease course and severity and mortality. Risks for medical and surgical therapies were assessed using Kaplan-Meier analysis. RESULTS: The cumulative probability that CD would change from inflammatory to stricturing or penetrating disease was 19.6%. The cumulative probabilities for use of immunosuppressants or anti-tumor necrosis factor agents were 58.9% and 12.0% for patients with CD, and 12.7% and 0.9% for patients with UC, respectively. Perianal CD was associated with an increased risk of anti-tumor necrosis factor therapy within 1 year of its diagnosis (hazard ratio, 2.97; 95% confidence interval, 1.09-8.09). The cumulative probabilities for surgery 1 year after diagnosis were 9.1% for patients with CD and 0.9% for patients with UC. Patients with CD and penetrating disease had a 7-fold increase for risk of surgery, compared with patients with inflammatory disease (hazard ratio, 7.67; 95% confidence interval, 3.93-14.96). The overall mortality for patients with IBD was 0.7%. CONCLUSIONS: In a prospective population-based study, we found that the early course of disease in patients with IBD in Asia was comparable with that of the West. Patients with CD frequently progress to complicated disease and have accelerated use of immunosuppressants. Few patients with early stage UC undergo surgery in Asia. Increasing our understanding of IBD progression in different populations can help optimize therapy and improve outcomes.


Assuntos
Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Adulto , Análise de Variância , Ásia/epidemiologia , Austrália/epidemiologia , Estudos de Coortes , Colectomia/métodos , Estudos Transversais , Diagnóstico Precoce , Educação Médica Continuada , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Incidência , Doenças Inflamatórias Intestinais/diagnóstico , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
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