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1.
Medicine (Baltimore) ; 99(9): e19230, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118724

RESUMO

Spermatogenesis associated serine rich 2 (SPATS2) has been reported to be dysregulated in few types of cancer; however, no reports have investigated SPATS2 in liver cancer. The aim of the present study was to investigate SPATS2 expression in liver cancer and to analyze its association with the prognosis of liver cancer patients.We examined the differential expression of SPATS2 in liver cancer by exploring The Cancer Genome Atlas (TCGA) database. The diagnostic efficiency of SPATS2 was obtained by Receiver Operating Characteristic (ROC) curve. The Chi-Squared test was used to assess clinical relevance. Survival analysis and Cox regression model were used to detect the effect of SPATS2 on the survival of liver cancer patients. Gene Set Enrichment Analysis (GSEA) was used to identify signaling pathways related to SPATS2 expression.SPATS2 is highly expressed in liver cancer (P < 2.2e-16) and has the high diagnostic ability (AUC = 0.964). Survival analysis showed that patients with high SPATS2 expression have an apparently shorter overall survival (OS, P < .0001) and relapse-free survival (RFS, P < .0001). Cox regression analysis showed that high SPATS2 expression might be an independent risk factor for liver cancer (OS, HR = 2.41, P = .000; RFS, HR = 1.90, P < .001). GSEA analysis identified 3 signaling pathways (Mitotic spindle, G2 M checkpoint, E2F targets) that were enriched in the presence of high SPATS2 expression.SPATS2 expression could be a novel diagnostic and prognostic biomarker in liver cancer.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Recidiva Local de Neoplasia/genética , Proteínas/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Proteínas/metabolismo , Curva ROC , Análise de Sobrevida
2.
Ann Nutr Metab ; : 1-7, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32172254

RESUMO

INTRODUCTION: Superior mesenteric artery syndrome (SMAS) is a relatively rare cause of chronic duodenal obstruction, owing to the compression of the third portion of the duodenum. OBJECTIVES: This retrospective study aims to discuss the efficacy of enteral nutrition (EN) therapy in nutritional status and symptom improvement at a short-term follow-up for SMAS patients. METHODS: We retrospectively analyzed clinical data of patients diagnosed as SMAS and treated with EN from September 2012 to January 2019. RESULTS: Twenty-six patients were included (16 women; mean age 24.96 ± 11.77 years), none was excluded, and one was lost to follow-up. The patients' mean body weight was 40.94 ± 10.16 kg, mean weight loss 11.73 ± 7.58 kg, and mean body mass index (BMI) 14.82 ± 2.52 kg/m2. The mean duration of EN therapy was 10.10 ± 4.66 months. Serum level of nutritional indicators, BMI and body weight increased after EN therapy. During a median follow-up of 24 months (9-44) after EN therapy, the mean symptom score decreased from 24.28 ± 9.57 to 8.06 ± 8.29 (p < 0.0001), and 65% of patients' symptoms resolved and 15% of patients' symptoms improved. In total, 16 complications occurred, including tube blockage, peristomal wound infections, peristomal leakage, granulomas, and nasopharyngeal pain. CONCLUSION: EN therapy may be an effective option for SMAS patients. While it might not remove all symptoms, it can improve the nutritional status to support subsequent treatments.

3.
Nutr Clin Pract ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32166772

RESUMO

BACKGROUND: Intestinal failure (IF) and its management are associated with an increased likelihood of infectious complications. This study aimed to evaluate the prevalence and potential risk factors for nosocomial infections (NIs) in hospitalized adult patients with IF. METHODS: In total, 259 eligible patients with IF admitted to a single clinical nutrition center in a tertiary referral hospital from January 1, 2012, to January 1, 2019, were retrospectively identified. NIs were defined according to the 2008 Centers for Disease Control and Prevention criteria. Univariate and multivariate analyses were performed to identify independent risk factors for NIs. RESULTS: The mean age of the study population was 47.0 ± 17.7 years, and 158 (61.0%) were men. The mean body mass index was 16.2 ± 2.9 kg/m2 , and 219 (84.6%) were diagnosed with malnutrition. The prevalence of NIs was 25.5% (113 NIs in 66 patients). The most common NIs were pneumonia (14.3%), bacteremia of unknown origin (13.5%), catheter-related bloodstream infection (5.0%), lower respiratory tract infection (5.0%), surgical site infection (3.9%), and urinary tract infection (1.9%). Multivariate analysis revealed that decreased serum albumin level (odds ratio [OR], 0.884; 95% CI, 0.883-0.978, P < .05), presence of gallbladder stones or cholestasis (OR, 3.144; 95% CI, 1.044-9.464; P < .05), and prolonged parenteral nutrition (PN) use (OR, 1.072; 95% CI, 1.039-1.105; P < .001) were independent predictors for NIs. CONCLUSIONS: NIs remain prevalent in hospitalized adult patients with IF. Prolonged PN use was one of the most significant predictors for NIs.

4.
Cell Death Dis ; 11(2): 85, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015323

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disease with a strong heritability, but recent evidence suggests that epigenetic dysregulation may also contribute to the pathogenesis of ASD. Especially, increased methylation at the MECP2 promoter and decreased MECP2 expression were observed in the brains of ASD patients. However, the causative relationship of MECP2 promoter methylation and ASD has not been established. In this study, we achieved locus-specific methylation at the transcription start site (TSS) of Mecp2 in Neuro-2a cells and in mice, using nuclease-deactivated Cas9 (dCas9) fused with DNA methyltransferase catalytic domains, together with five locus-targeting sgRNAs. This locus-specific epigenetic modification led to a reduced Mecp2 expression and a series of behavioral alterations in mice, including reduced social interaction, increased grooming, enhanced anxiety/depression, and poor performance in memory tasks. We further found that specifically increasing the Mecp2 promoter methylation in the hippocampus was sufficient to induce most of the behavioral changes. Our finding therefore demonstrated for the first time the casual relationship between locus-specific DNA methylation and diseases symptoms in vivo, warranting potential therapeutic application of epigenetic editing.

6.
Int J Biol Macromol ; 150: 737-745, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32027898

RESUMO

The purpose of present work was to investigate the antioxidant activity of oligosaccharides from mountain-cultivated ginseng (MCG) and cultivated ginseng (CG). The antioxidant activity of total oligosaccharides from MCG and CG were compared preliminary. And then, the total oligosaccharides of MCG, which displayed stronger activity than that of CG, were separated by Carbon-Celite column and eluted with water and ethanol of different concentrations (30%, 50%, 70%, 95%, v/v). Five fractions, MCGOS-H2O, MCGOS-30, MCGOS-50, MCGOS-70, MCGOS-95, were obtained. Seven oligosaccharides were purified from MCGOS-30-MCGOS-95. The structure features of oligosaccharides (MCGO-1-MCGO-7) were characterized using high performance liquid chromatography (HPLC), methylation and gas chromatography-mass (GC-MS), as well as nuclear magnetic resonance spectroscopy. ABTS radical scavenging assay, DPPH radical scavenging assay as well as ferric reducing antioxidant power assay were adopted for antioxidant activity of all the different oligosaccharides sub-fraction. The result showed that the fractions of MCGOS-70 and MCGOS-95 exhibited significant radical scavenging activity with DPPH and ABTS. In conclusion, the oligosaccharides from MCG possessed the significant antioxidant activity. Therefore, we propose that the oligosaccharides from Panax ginseng can be developed as natural antioxidants in food and pharmaceutical fields.

7.
Am J Clin Nutr ; 111(3): 570-579, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31968072

RESUMO

BACKGROUND: Cancer cachexia is characterized by weight loss, especially ongoing skeletal muscle loss, and is associated with poor patient outcomes. However, the molecular mechanism of skeletal muscle wasting is not fully understood. OBJECTIVES: We aimed to investigate muscle fiber morphology and proteolysis system activity changes that may account for cancer cachexia and to relate these changes to patients' clinical phenotypes. METHODS: We divided 39 patients with resectable gastric cancer into 4 groups based on the presence of cachexia (weight loss) and/or sarcopenia (low muscularity), including a noncachexia/nonsarcopenia group (N, n = 10), a cachexia/sarcopenia group (CS, n = 13), a cachexia/nonsarcopenia group (C, n = 9), and a noncachexia/sarcopenia group (S, n = 7). Rectus abdominis muscle biopsy specimens were obtained intraoperatively. Muscle fiber size, ultrastructural architecture, and the expression of autophagic-lysosomal system (ALS) and ubiquitin proteasome system (UPS) markers were assayed. RESULTS: Mean ± SD muscle fiber cross-sectional areas were significantly decreased in the CS (460 ± 120 µm2) and S groups (480 ± 135 µm2) compared with the N (1615 ± 388 µm2, both P < 0.05) and C groups (1219 ± 302 µm2, both P < 0.05). In the C, S, and CS groups, the muscle exhibited tissue disorganization and autophagosome formation to different degrees. The levels of ALS and UPS markers were significantly increased in the CS, C, and S groups compared with the N group. Alterations in muscle fiber morphology and increased ALS and UPS activity were related to severe muscle loss, but not weight loss. CONCLUSIONS: The ALS and UPS are simultaneously activated in cancer cachexia and may play coordinated roles in cachexia-induced muscle loss.

8.
Viruses ; 12(1)2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31963559

RESUMO

Orf is a zoonotic disease that has caused huge economic losses globally. Systematical analysis of dysregulated cellular micro RNAs (miRNAs) in response to Orf virus (ORFV) infection has not been reported. In the current study, miRNA sequencing and RNA sequencing (RNA-seq) were performed in goat skin fibroblast (GSF) cells at 0, 18, and 30 h post infection (h.p.i). We identified 140 and 221 differentially expressed (DE) miRNAs at 18 and 30 h.p.i, respectively. We also identified 729 and 3961 DE genes (DEGs) at 18 and 30 h.p.i, respectively. GO enrichment analysis indicates enrichment of apoptotic regulation, defense response to virus, immune response, and inflammatory response at both time points. DE miRNAs and DEGs with reverse expression were used to construct miRNA-gene networks. Seven DE miRNAs and seven DEGs related to "negative regulation of viral genome replication" were identified. These were validated by RT-qPCR. Cfa-let-7a, a significantly upregulated miRNA, was found to repress Thrombospondin 1 (THBS1) mRNA and protein expression by directly targeting the THBS1 3' untranslated region. THBS1 has been reported to induce apoptosis; therefore, the cfa-let-7a-THBS1 axis may play an important role in cellular apoptosis during ORFV infection. This study provides new insights into ORFV and host cell interaction mechanisms.

9.
J Invest Surg ; : 1-8, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31994947

RESUMO

Background: The purpose of this study was to assess the body composition score (BCS) impact on 3-year survival after radical gastrectomy in patients with gastric cancer.Methods: This retrospective study included patients with gastric cancer from September 2015 to June 2017. The patients were divided into three groups: BCS0 (having normal skeletal muscle or adipose mass), BCS1 (having low skeletal muscle mass only), and BCS2 (having low skeletal muscle and adipose mass) according to their third lumbar vertebra skeletal muscle index and fat index calculated using abdominal computed tomography. The clinicopathological indicators, postoperative complications, 3-year over survival (OS) rate after radical gastrectomy, and cause of death among the three groups were compared.Results: A total of 187 patients were enrolled in the study, in which 102 patients (54.6%) had BCS0, 76 (40.6%) had BCS1 and 9 (4.8%) had BCS2. There was no significant difference in postoperative complications among the groups. 3-year OS was significantly shortened with each 1-score increase in BCS (Log-rank p < 0.001). Multivariate Cox regression analyses showed that no neoadjuvant chemotherapy, tumor stage III, BCS1, and BCS2 were independent prognostic factors for 3-year OS after radical gastrectomy. The main cause of death was cancer-related.Conclusion: We demonstrated that BCS1 and BCS2 were strongly associated with poor 3-year survival for patients with gastric cancer who underwent radical gastrectomy, suggesting that special attention may be required for nutritional support while determining therapeutic strategies.

10.
Cancer Lett ; 469: 173-185, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31629935

RESUMO

Resistance to oxaliplatin is a major obstacle hindering the clinical treatment of colorectal cancer, but the underlying immunological mechanism has not yet been well illustrated. As a pivotal immunosuppressive component in tumor microenvironment, myeloid-derived suppressor cells (MDSCs) and their differentiated tumor-associated macrophages (TAMs) have been considered to be associated with resistance to chemotherapy. The aim of current study was to investigate the role of MDSCs in oxaliplatin-resistance and antitumor activity in colorectal cancer. Here, we found that tumor-bearing mice treated with oxaliplatin performed remarkably decreasing M-MDSCs and M1-type TAMs differentiated from MDSCs in tumor site, which inspired us to combine immunotherapy that activates M1-like TAMs to conquer oxaliplatin resistance. In addition, this study further confirmed a dose-dependent improvement of M1-like macrophage supernatants on enhancing pro-apoptotic effect and inhibiting migration and invasion of cancer cells incubated with oxaliplatin. Administration of oxaliplatin combined with Toll-like receptors agonists R848 reversed the functional orientation of MDSCs towards M1-like macrophages and strengthened antitumor effect of oxaliplatin. In this study, we uncovered novel immunological mechanism of oxaliplatin-resistance and showed the great potential of TLR7/8 agonist as a new immunologic adjuvant in chemotherapy for oxaliplatin-resistant colorectal cancer.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31689711

RESUMO

PURPOSE: Idiopathic hypogonadotropic hypogonadism (IHH) and CHARGE syndrome are two distinct developmental disorders sharing features of hypogonadism and/or impaired olfaction. CHD7 variants contribute to >60% CHARGE syndrome and ~10% IHH patients. A variety of extended CHARGE-like features are frequently reported in CHARGE patients harboring CHD7 variants. In this study, we aimed to systematically analyze the diagnostic CHARGE features and the extended CHARGE-like features in IHH patients with CHD7 variants. METHODS: Rare sequencing variants (RSVs) in CHD7 were identified through exome sequencing in 177 IHH probands. Detailed phenotyping was performed in the IHH patients harboring CHD7 variants and their available family members. RESULTS: CHD7 RSVs were identified in 10.2% (18/177) of the IHH probands. Two diagnostic CHARGE features, hearing loss and ear deformities, were significantly enriched in patients with CHD7 variants. Furthermore, CHD7 variants were significantly associated with a panel of extended CHARGE-like phenotypes, including mild ocular defects, dyspepsia/gastroesophageal reflux disease and skeletal defects. We also developed a predictive model for prioritizing CHD7 genetic testing in IHH patients. CONCLUSION: CHD7 variants rarely cause isolated IHH. Surveillance of symptoms in CHARGE syndrome-affected organs will facilitate the proper treatment for these patients. Certain clinical features can be useful for prioritizing CHD7 genetic screening.

12.
Eur J Pharmacol ; 861: 172587, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31377155

RESUMO

Oridonin is a diterpenoid isolated from Rabdosia rubescens (Hemsl.) Hara, a well-known herbal tea in China with many health benefits. To provide a better understanding of the potential cardioprotective effect of Oridonin, we investigated the metabolic alterations in heart tissue and serum of rat subjected to myocardial ischemia/reperfusion (MI/R) injury with or without pretreatment of Oridonin by UPLC-MS/MS metabolomics approach. Rats were randomly divided into groups as follows: Control, Sham, MI/R and pretreated with Oridonin (10 mg/kg)+MI/R. After 24 h of reperfusion, heart tissue and serum were collected for biochemical and metabolomic analysis. Pretreatment with Oridonin significantly decreased infarct size and reversed the abnormal elevated myocardial zymogram in serum. Moreover, Oridonin regulated several metabolic pathways, including glycolysis, branched chain amino acid, kynurenine, arginine, glutamine and bile acid metabolism. Our results suggest that Oridonin indeed displays outstanding cardioprotective effect mainly by regulating energy and amino acid metabolism.


Assuntos
Diterpenos de Caurano/farmacologia , Metabolômica , Traumatismo por Reperfusão Miocárdica/metabolismo , Animais , Diterpenos de Caurano/uso terapêutico , Masculino , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley
13.
Ann Nutr Metab ; 75(1): 47-54, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31434099

RESUMO

INTRODUCTION: Patients with short bowel syndrome (SBS) commonly develop nephrolithiasis. However, the risk factors for nephrolithiasis in patients with SBS remain unclarified. The present study aimed to identify the risk factors for nephrolithiasis in adults with SBS. METHODS: All eligible adults diagnosed with SBS and admitted to a tertiary referral center from December 2008 to 2018 were retrospectively identified from a prospectively maintained database. Patients' demographic and clinical characteristics were analyzed using univariate and multivariate analyses to identify the risk factors for nephrolithiasis. RESULTS: Of 231 adults with SBS, 42 (18.2%) developed nephrolithiasis. The mean age was 46.4 ± 17.8 years, the mean body mass index was 18.2 ± 3.8 kg/m2, and median duration of SBS was 11 months (range 2-324 months). Multivariate binary logistic regression analysis revealed that the independent risk factors for nephrolithiasis in adults with SBS were jejuno-ileal anastomosis and colon-in-continuity (OR 4.335; 95% CI 1.175-16.002; p = 0.028), prolonged duration of SBS (OR 1.008; 95% CI 1.002-1.014; p = 0.010), and increased serum creatinine concentration (OR 1.005; 95% CI 1.001-1.009; p = 0.012). CONCLUSIONS: Nephrolithiasis is common in adults with SBS. As nephrolithiasis can have adverse clinical consequences, patients with SBS should be closely monitored, and prophylactic interventions should be considered.

14.
BMC Gastroenterol ; 19(1): 97, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221086

RESUMO

BACKGROUND: Currently, WeChat is widely used in disease education for patients with Crohn's disease (CD) in China. It is beneficial for the patients to actively engage in their disease management. METHODS: In this study, we examined the source and expectations of disease information for Chinese CD patients, analysing the content of popular WeChat public accounts and their potential association with medication adherence. RESULTS: Between November 24th, 2017 and April 10th, 2018, online questionnaires were sent to CD patients from eight different large urban hospitals in China. In all, 436 patients with CD were surveyed, and 342 patients responded. Patients most frequently visited Baidu (65%), WeChat (61%) and medical websites such as Haodaifu (35%) when searching for IBD-related information. Among ten WeChat IBD public accounts, the China Crohn's and Colitis Foundation (CCCF) (73%), "IBD Academic Officer" (21%) and "IBD in love" (21%) were the most popular. CD patients were most interested in information from the internet about diet and day-to-day health-related living with IBD (83%), an introduction to the disease (80%), and medication advances and side effects (80%). The correlation between the information provided by the top five WeChat public accounts and patients' expectations was low. Additionally, most patients (64%) had greater confidence in overcoming the disease after learning about CD through their internet searches. Medical adherence was also related to internet access and income (p < 0.05). CONCLUSIONS: WeChat has become a major source of information for IBD education in China, but the content of WeChat didn't fully meet patients' expectations. Therefore, future initiatives should aim to provide high-quality information that based on patients' demands.


Assuntos
Doença de Crohn/psicologia , Internet , Adesão à Medicação/psicologia , Participação do Paciente/psicologia , Mídias Sociais/estatística & dados numéricos , Adulto , Grupo com Ancestrais do Continente Asiático/psicologia , China , Gerenciamento Clínico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/métodos , Inquéritos e Questionários
15.
Genes (Basel) ; 10(6)2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234346

RESUMO

Malaria is one of the three major global health threats. Drug development for malaria, especially for its most dangerous form caused by Plasmodium falciparum, remains an urgent task due to the emerging drug-resistant parasites. Exploration of novel antimalarial drug targets identified a trifunctional enzyme, malate quinone oxidoreductase (MQO), located in the mitochondrial inner membrane of P. falciparum (PfMQO). PfMQO is involved in the pathways of mitochondrial electron transport chain, tricarboxylic acid cycle, and fumarate cycle. Recent studies have shown that MQO is essential for P. falciparum survival in asexual stage and for the development of experiment cerebral malaria in the murine parasite P. berghei, providing genetic validation of MQO as a drug target. However, chemical validation of MQO, as a target, remains unexplored. In this study, we used active recombinant protein rPfMQO overexpressed in bacterial membrane fractions to screen a total of 400 compounds from the Pathogen Box, released by Medicines for Malaria Venture. The screening identified seven hit compounds targeting rPfMQO with an IC50 of under 5 µM. We tested the activity of hit compounds against the growth of 3D7 wildtype strain of P. falciparum, among which four compounds showed an IC50 from low to sub-micromolar concentrations, suggesting that PfMQO is indeed a potential antimalarial drug target.


Assuntos
Inibidores Enzimáticos/farmacologia , Malária Cerebral/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Oxirredutases/antagonistas & inibidores , Animais , Antimaláricos/metabolismo , Antimaláricos/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Malária Cerebral/enzimologia , Malária Cerebral/parasitologia , Malária Falciparum/enzimologia , Malária Falciparum/parasitologia , Malatos/metabolismo , Camundongos , Mitocôndrias/enzimologia , Oxirredutases/genética , Plasmodium berghei/efeitos dos fármacos , Plasmodium berghei/patogenicidade , Plasmodium falciparum/enzimologia , Plasmodium falciparum/patogenicidade , Quinonas/metabolismo
16.
Mol Med Rep ; 20(1): 539-548, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180548

RESUMO

CD24 can regulate angiogenesis, drug sensitivity and the progression of colorectal cancer (CRC). However, whether CD24 regulates autophagy and apoptosis in CRC cells remains to be fully elucidated. The present study investigated the functional role of the altered expression of CD24 in the autophagy and apoptosis of HCT116 and HT29 human CRC cells. The results revealed lower expression levels of CD24 in HCT116 cells but higher levels in HT29 cells. Inducing the overexpression or the knockdown of CD24 did not affect the viability or spontaneous apoptosis of HCT116 and HT29 cells, respectively. Induction of the overexpression of CD24 significantly decreased the relative expression levels of Beclin­1, autophagy­related (Atg)3 and Atg5, and the numbers of microtubule­associated protein­1 light chain­3 (LC3)­positive puncta, but increased the expression of p62 in HCT116 cells. By contrast, CD24 silencing increased the expression of Beclin­1, Atg3 and Atg5, and the numbers of LC3­positive puncta, but decreased the expression of p62 in HT29 cells. Treatment with 3­methyladenine, or the knockdown of Atg5 by specific small interfering RNA to attenuate autophagy significantly enhanced the viability of CD24­overexpressing HCT116 cells, but reduced the viability of CD24­silenced HT29 cells, relative to their controls. As a result, the attenuation of autophagy significantly decreased the frequency of apoptotic CD24­overexpressing HCT116 cells, but increased the percentages of apoptotic CD24­silenced HT29 cells. The overexpression of CD24 promoted the activation of nuclear factor (NF)­κBp65, whereas CD24 silencing attenuated its activation in CRC cells. Inhibition of the activation of NF­κB enhanced the CD24 overexpression­induced decrease in autophagy, but attenuated the CD24 silencing­induced increase in autophagy in CRC cells. Therefore, CD24 inhibited the autophagy of CRC cells, and the combination of targeting CD24 and inhibiting autophagy promoted the apoptosis of CRC cells. Conceivably, these findings may aid in the design of novel therapies for the intervention of CRC.


Assuntos
Apoptose , Autofagia , Antígeno CD24/genética , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células HCT116 , Células HT29 , Humanos , Regulação para Cima
17.
Gastrointest Endosc Clin N Am ; 29(3): 515-530, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31078250

RESUMO

Perianal diseases, common complications of Crohn's disease, are difficult to diagnose/manage. Patients with perianal Crohn's disease suffer from persistent pain and drainage, recurrent perianal sepsis, impaired quality of life, and financial burden. Conventional medical and surgical therapies carry risk of infection, myelosuppression, incontinence, disease recurrence. Although the phenotype of Crohn's disease has been extensively studied, reported outcomes are inconsistent. Endoanal ultrasonography is also becoming popular because of low cost and ability to acquire images in real time. Emerging management strategies for treatment including laser therapy, local injection of agents, use of hyperbaric oxygen, and stem cell therapy, have demonstrated efficacy.


Assuntos
Doenças do Ânus/diagnóstico , Doença de Crohn/complicações , Doenças do Ânus/etiologia , Doenças do Ânus/terapia , Efeitos Psicossociais da Doença , Doença de Crohn/diagnóstico por imagem , Endossonografia/métodos , Humanos , Recidiva
18.
Artif Cells Nanomed Biotechnol ; 47(1): 1722-1729, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31032663

RESUMO

Mir-10b has been reported as a key regulator of metastasis in many human tumours. Moreover, it has also been regarded as a prognostic marker and therapeutic target of colorectal cancer (CRC). Whether miR-10b could affect the metastasis and proliferation of CRC is unclear. MiR-10b expression was detected by qPCR in human CRC tissues and cell line, Luciferase activity was employed for miR-10b binding to the 3`UTR of KLF4, Genes expression were examined by western blot, and mRNA by qPCR. PI and Annexin V staining were used to evaluate the cell cycle and apoptosis. Cell proliferation was detected with MTT, and cell migration and invasion were performed with Transwell assay. We found that miR-10b expression was up-regulated in metastatic CRC tissues and cell lines. Inhibition of miR-10b prevented cancer cell metastasis and growth by inducing cell-cycle arrest and apoptosis in vitro. Moreover, we found that KLF4 was a direct target of miR-10b. MiR-10b inhibitor led to the up-regulation of E-cadherin expression and the down-regulation of cyclin D1, which were partly abrogated after silencing KLF4.


Assuntos
Neoplasias Colorretais/patologia , Fatores de Transcrição Kruppel-Like/genética , MicroRNAs/genética , Apoptose/genética , Sequência de Bases , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Metástase Neoplásica
19.
Prog Mol Biol Transl Sci ; 161: 149-179, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30711026

RESUMO

Prokineticins are two conserved small proteins (~8kDa), prokineticin 1 (PROK1; also called EG-VEGF) and prokineticin 2 (PROK2; also called Bv8), with an N-terminal AVITGA sequence and 10 cysteines forming 5 disulfide bridges. PROK1 and PROK2 bind to two highly related G protein-coupled receptors (GPCRs), prokineticin receptor 1 (PROKR1) and prokineticin receptor 2 (PROKR2). Prokineticins and their receptors are widely expressed. PROK1 is predominantly expressed in peripheral tissues, especially steroidogenic organs, whereas PROK2 is mainly expressed in the central nervous system and nonsteroidogenic cells of the testes. Prokineticins signaling has been implicated in several important physiological functions, including gastrointestinal smooth muscle contraction, circadian rhythm regulation, neurogenesis, angiogenesis, pain perception, mood regulation, and reproduction. Dysregulation of prokineticins signaling has been observed in a variety of diseases, such as cancer, ischemia, and neurodegeneration, in which prokineticins signaling seems to be a promising therapeutic target. Based on the phenotypes of knockout mice, PROKR2 and PROK2 have recently been identified as causative genes for idiopathic hypogonadotropic hypogonadism, a developmental disorder characterized by impaired development of gonadotropin-releasing hormone neurons and infertility. In vitro functional studies with these disease-associated PROKR2 mutations uncovered some novel features for this receptor, such as biased signaling, which may be used to understand GPCR signaling regulation in general.


Assuntos
Doença , Saúde , Receptores Acoplados a Proteínas-G/metabolismo , Fator de Crescimento do Endotélio Vascular Derivado de Glândula Endócrina/metabolismo , Sequência de Aminoácidos , Animais , Humanos , Mutação/genética , Nociceptividade , Receptores Acoplados a Proteínas-G/química , Receptores Acoplados a Proteínas-G/genética , Fator de Crescimento do Endotélio Vascular Derivado de Glândula Endócrina/química , Fator de Crescimento do Endotélio Vascular Derivado de Glândula Endócrina/genética
20.
Clin Nutr ; 38(4): 1737-1744, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30126709

RESUMO

BACKGROUND & AIMS: Nutritional monitoring plays an important role in optimizing nutritional support in patients with chronic intestinal failure (CIF) receiving long-term supplementation. Unlike initial nutritional assessment, however, there are no recommended guidelines for establishing a nutritional monitoring index. This study is to evaluate the suitability of insulin-like growth factor-1 (IGF-1) as a nutritional monitoring factor in CIF patients. METHODS: We retrospectively analyzed the correlation between serum nutritional indicators, including IGF-1 levels, and nutritional assessment, nutritional monitoring, and lean body mass in 197 patients with CIF. RESULTS: The mean age of the 197 enrolled patients was 47.22 ± 18.87 years old and; the mean BMI was 16.83 ± 3.31. The mean NRS-2002 score was 3.49 ± 0.83; and moreover, 76.3% of the patients were malnourished. The median length of hospital stay in hospital (LOS) was 18.5 days. IGF-1 was positively correlated with body mass index, hemoglobin, albumin, pre-albumin, retinol-binding protein (RBP), transferrin, serum creatinine (Scr) and cholesterol (p < 0.05 for all). Testing performed over 3 weeks post-admission showed that significantly different weekly changes were observed only in IGF-1, RBP, and Scr during the period of nutritional support (p < 0.05 for each). Multivariate linear regression analysis showed that IGF-1 and body mass index were independent factors influencing fat-free mass, skeletal muscle mass, and body protein mass (p < 0.05 for each). CONCLUSIONS: IGF-1 is suitable for monitoring short-term changes in the nutritional status in CIF patients. This may be attributed to its shorter half-life, greater sensitivity, and better correlation with lean body mass. ClinicalTrials.gov number, NCT03277014.

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