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1.
Artigo em Inglês | MEDLINE | ID: mdl-31682026

RESUMO

BACKGROUND AND AIM: Clear visualization of the small bowel is a requirement for satisfactory video capsule endoscopy (VCE). The aim of this study was to identify the optimal dose and timing of polyethylene-glycol (PEG) for small-bowel preparation before VCE. METHODS: 410 patients were enrolled in this prospective randomized trial. All patients fasted for 12 h and ingested 320 mg simethicone 30 min before swallowing the capsule. Patients were randomized into 5 groups: Group A (no PEG), Group B (1 L PEG, 12 h before VCE), Group C (2 L PEG, 12 h before VCE), Group D (1 L PEG, 4 h before VCE), and Group E (2 L PEG, 4 h before VCE). The primary endpoint was small bowel visualization quality (SBVQ), and the secondary endpoints were patient acceptability and diagnosis rate of VCE. RESULTS: Excellent SBVQ was achieved in 27 (32.5%) of Group A, 38 (46.3%) of Group B, 40 (48.2%) of Group C, 55 (66.3%) of Group D and 43 (54.4%) of Group E. The percentage of excellent SBVQ in Group D was significantly more than in Group A (66.3% vs. 32.5%, P < 0.001), and diagnostic rate in the distal segment was higher (28.9% vs. 10.8%, P = 0.0035). Patient acceptance of 1 L PEG was better than of 2 L PEG (P < 0.005). CONCLUSIONS: Small bowel cleansing with 1 L PEG given 4 h before VCE was the optimal preparation for visualization of the bowel and patient acceptance. (ClinicalTrials.gov, ID: NCT02486536).

2.
Mediators Inflamm ; 2019: 7634761, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31611735

RESUMO

Objective: Recent researches have demonstrated that inflammation-related diseases are effectively regulated by posttranslational modifications (PTMs) including phosphorylation and acetylation. Our previous study found a new acetyltransferase inhibitor, oridonin, which had a protective effect on acute liver injury (ALI). In the present study, we further investigated its protective mechanism against D-galactosamine (D-Gal) combined with lipopolysaccharide- (LPS-) induced ALI in mice. Methods: Intraperitoneal injections of LPS (40 µg/mouse)/D-Gal (5 mg/mouse) were given to the mice, and the experimental group was pretreated with intraperitoneal injection of oridonin (0.2 mg/mouse). To elucidate the protective mechanism of oridonin, we collected liver specimens and used RNA-sequencing (RNA-Seq) analysis. We focused on the genes that were upregulated by LPS/D-Gal and downregulated after pretreatment with oridonin. The downregulated genes examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were further verified by real-time polymerase chain reaction (PCR) and western blot. Results: GO analysis showed that genes that were downregulated after pretreatment with oridonin were extremely concentrated in immune response, chemotaxis, and inflammatory response. Real-time PCR confirmed that the expression of these genes was upregulated by LPS/D-Gal induction and reduced after treatment with oridonin, which was consistent with RNA-Seq results. KEGG pathway analysis showed a significantly enriched downregulated gene that was present in the Toll-like receptor (TLR) 4 signaling cascade. Our results manifested that phosphorylation levels of upstream signaling molecules in the TLR4 signaling cascade, including extracellular signal-regulated kinase (ERK), P38, and IκB, were significantly inhibited by oridonin. Furthermore, LPS/D-Gal stimulation triggered posttranslational modifications of related gene loci in the TLR4 signaling pathway, including phosphorylation of IL-1 receptor-associated kinase 4 (IRAK4 T345/S346) and acetylation of IRAK4 (K34). However, after treatment with oridonin, the modification pattern of IRAK4 expression stimulated by LPS/D-Gal was suggestively attenuated. Conclusion: Our study revealed that the protective effects of oridonin on LPS/D-Gal-induced ALI mediated by inhibition of the PTMs of IRAK4, including phosphorylation of T345/S346 and acetylation of K34.

3.
Cancer Lett ; 460: 128-138, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31207319

RESUMO

Alterations in circular RNA (circRNA) expression have a vital impact on the biological processes in cancer. Moreover, the expression pattern and roles of circRNAs in hepatocellular cancer (HCC) remain unclear. This study performed qRT-PCR to determine the regulated circRNAs in HCC tissues and cell lines. CCK8, 5-ethynyl-2'-deoxyuridine (EdU) assay, colony formation, cell cycle assay, apoptotic assay, transwell, and wound healing assay were conducted to assess the function of hsa_circ_0091570 or miR-1307 on cell proliferation, apoptosis, and migration in vitro. Mouse xenograft models were used to measure the functions of hsa_circ_0091570 in vivo. The decreased expression of hsa_circ_0091570 was associated with the pathological staging of HCC patients. Furthermore, inhibition of hsa_circ_0091570 promoted cell proliferation and migration, blocked cell apoptosis in HCC cell lines, and promoted tumor growth in the mouse xenograft model. RNA immunoprecipitation assay verified the interaction of hsa_circ_0091570 and miR-1307. The miR-1307 inhibitor inhibited the function induced by hsa_circ_0091570 siRNA. Overall, hsa_circ_0091570 sponge miR-1307 as a ceRNA and regulate ISM1 expression by exerting functional roles in HCC.

4.
Acta Pharmacol Sin ; 40(8): 1127-1128, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31097762

RESUMO

The authors regretted to find the mis-representative images in Fig. 3a, c and Fig. 4a, c when re-read our previously published article Synergistic suppression of human breast cancer cells by combination of plumbagin and zoledronic acid In vitro (DOI: 10.1038/aps.2015.42) in the journal of Acta Pharmacologica Sinica. This mistake occurred due to the careless compilation when the authors tried to show the synergistic effect against tumor apoptosis during figure presentation process. The right Fig. 3a, c and Fig. 4a, c were provided below. Despite that this correction does not affect the results and conclusions of the aforementioned paper, all the authors still consent on the correction of this negligence. We apologize to the Editor and the readership of the journal for any inconvenience caused. Your thoughtful understanding is highly appreciated.

5.
J Exp Clin Cancer Res ; 38(1): 153, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30971290

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the major histological type of liver cancer with high morbidity and mortality worldwide. Long noncoding RNAs (lncRNA) has been proved to be associated with various cancer types, while its regulation in HCC is largely unknown. METHODS: To figure out the specific role of lncRNA EPB41L4A-AS2 in HCC. Fluorescence in situ hybridization (FISH) was first used to determine the cellular sublocalization of EPB41L4A-AS2 to determine its primary mode of action. QRT-PCR, Western blot and hematoxylin-eosin staining were then used to measure the expression of genes in cells and tissues. Cell proliferation and invasion assays were performed to determine the effects of EPB41L4A-AS2, miR-301a-5p and FOXL1 on the malignant phenotype of tumor cells. With luciferase reporter assay, the direct interaction between target genes were further confirmed for research on molecular mechanism. Finally, the mice hepatocarcinoma model was also established to disclose the tumor suppressor effects of EPB41L4A-AS2 in vivo. RESULTS: Here, we have identified a novel lncRNA EPB41L4A-AS2, which is significantly downregulated both in HCC cells and tissues, and plays a negative regulatory role in HCC proliferation and invasion. Mechanistically, cytoplasmic lncRNA EPB41L4A-AS2 functions as an efficient miR-301a-5p sponge, thereby release the expression inhibition of forkhead box L1 (FOXL1). Indeed, lncRNA EPB41L4A-AS2 inhibits proliferation and migration by upregulating FOXL1 expression and FOXL1 was confirmed as a direct target of miR-301a-5p. MiR-301a-5p shows an inverse correlation with EPB41L4A-AS2 expression and was verified as a direct target of EPB41L4A-AS2 as well. Correspondingly, FOXL1 and miR-301a-5p show opposite biological effects in cell proliferation and migration. Moreover, miR-301a-5p overexpression rescued the EPB41L4A-AS2 upregulation induced depression in proliferation, migration and invasion of HCC cells, as well as promotion effect on FOXL1 expression. Also, in vivo experiments proved that EPB41L4A-AS2 suppress tumor growth and extrahepatic metastasis (lung) via the miR-301a-5p-FOXL1 axis. CONCLUSIONS: Taken together, this research revealed a concrete mechanism of lncRNA EPB41L4A-AS2 in HCC, which may serve as a potential biomarkers and novel therapeutic targets for further clinical application.


Assuntos
Carcinoma Hepatocelular/genética , Fatores de Transcrição Forkhead/metabolismo , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Fatores de Transcrição Forkhead/genética , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Camundongos , MicroRNAs/genética , RNA Longo não Codificante/genética
6.
J Med Genet ; 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30518547

RESUMO

BACKGROUND: T cell dysfunction occurs in many diseases, especially in chronic virus infection and cancers. However, up to now, little is known on the distinctions in T cell exhaustion between cancer and chronic virus infection. The objective of this study is to explore the transcriptional similarities and differences in exhausted CD8 +T cell between chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). METHODS: RNA sequencing was performed to compare the transcriptome of CD8 +T cells isolated from healthy donors' blood, tumour tissues of patients with HCC and chronic HBV infected HCC patients' paracancerous tissues. DESeq2 algorithm was used to determine differentially expressed genes. Gene ontology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted for in-depth analysis of these differentially expressed genes. RESULTS: A total number of 2109 and 2203 genes were differentially expressed in patients with chronic HBV infection and HCC, respectively. Comparing these two groups of differentially deregulated genes, we found that nearly half of them were shared, and these shared genes were further classified into several functional categories, such as metabolic process, binding and intracellular organelle. KEGG analysis revealed that these shared deregulated genes were involved in many important pathways such as Parkinson's disease, oxidative phosphorylation and messenger RNA surveillance. Interestingly, we reported that chronic HBV infection specific deregulated genes were mainly enriched in graft versus host disease, allograft rejection, phenylalanine, tyrosine and tryptophan biosynthesis pathways. Whereas, HCC-specific deregulated genes were highly enriched in oxidative phosphorylation, thyroid cancer and endometrial cancer pathways. CONCLUSION: Our study demonstrated that T cell dysfunction associated with HCC and chronic HBV infection shares high similarities, however, each possesses its own features in terms of specific genes and signalling pathways. Uncovering the differences of T cells dysfunction would facilitate our understanding the diseases pathogenesis and developing innovative therapies in the future.

7.
Cell Physiol Biochem ; 51(3): 1276-1286, 2018 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-30481793

RESUMO

BACKGROUND/AIMS: This study aimed at investigating the effects of metformin on the growth and metastasis of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. METHODS: Two human ESCC cell lines EC9706 and Eca109 were selected and challenged with metformin in this study. Western blot assay was performed to detect th level of Bcl-2, Bax and Caspase-3. Scratch wound assay, transwell assay and Millicell invasion assay were used to assay the invasion and migration of EC9706 and Eca109 cells. Nude mice tumor models were used to assay the growth and lung metastasis of ESCC cells after metformin treatment. The plasma glucose level was also assayed. RESULTS: We found that metformin significantly inhibited proliferation and induced apoptosis of both ESCC cell lines in a dose- and time-dependent manner, and the expression of Bcl-2 was down-regulated and Bax and Caspase-3 were up-regulated. Metformin significantly inhibited the invasion and migration of EC9706 and Eca109 cells (p < 0.05). mRNA and protein levels of MMP-2 and MMP-9 decreased significantly upon treatment with metformin of 10mM for 12, 24 and 48h in a time-dependent manner (p < 0.05). In line with in vitro results, in vivo experiments demonstrated that metformin inhibited tumorigenicity, inhibited lung metastasis and down-regulated the expression of MMP-2 and MMP-9. Moreover, we showed that metformin treatment did not cause significant alteration in liver and renal functions and plasma glucose level. CONCLUSION: Our study for the first time demonstrated the anti-invasive and anti-metastatic effects of metformin on human ESCC cells both in vitro and in vivo, which might be associated with the down-regulation of MMP-2 and MMP-9. As a whole, our results indicate the potential of metformin to be developed as a chemotherapeutic agent for patients with ESCC and might stimulate future studies on this area.

8.
J Cell Physiol ; 234(1): 572-580, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30216442

RESUMO

Long non-coding RNAs (lncRNAs) are a class of regulatory noncoding RNAs. Emerging evidence highlights the critical roles of lncRNAs in the progression of hepatocellular carcinoma (HCC). Although many lncRNAs have been identified in the development of HCC, the association between DiGeorge syndrome critical region gene 5 (DGCR5) and HCC remains unclear. In the current study, we focused on the biological role of DGCR5 in HCC. We observed that DGCR5 was decreased in HCC cells, including SMCC7721, Hep3B, HepG2, MHCC-97L, MHCC-97H, and SNU449 hepatocellular carcinoma cells, compared with the normal human liver cell line THLE-3 normal human liver cells. In addition, DGCR5 overexpression could repress HCC cell growth, migration, and invasion considerably. Increasing studies have indicated the interactions between lncRNAs and microRNAs. MicroRNAs are endogenous small noncoding RNAs and they can play important roles in tumorigenesis. MicroRNA 346 (miR-346) has been demonstrated in various human cancer types, including HCC. MiR-346 was found to be increased in HCC cells and DGCR5 can act as a sponge of miR-346 to modulate the progression of HCC. The binding correlation between DGCR5 and miR-346 was validated in our research. Subsequently, Krüppel-like factor 14 (KLF14) was predicted as a downstream target of miR-346 and miR-346 can induce the development of HCC by inhibiting KLF14. Finally, we proved that DGCR5 can rescue the inhibited levels of KLF14 repressed by miR-346 mimics in MHCC-97H and Hep3B cells. Taken together, it was indicated in our study that DGCR5 can restrain the progression of HCC through sponging miR-346 and modulating KLF14 in vitro.

9.
J Cell Biochem ; 119(6): 4711-4716, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29278659

RESUMO

Currently available studies have implicated that exosome-delivered microRNAs (miRNAs) play crucial roles in human cancer. However, the association of serum exosomal miR-638 and hepatocellular carcinoma (HCC) remains largely unknown. We aim to investigate the expression of exosomal miR-638 in serum of HCC patients and its prognostic role in this deadly disease. Kaplan-Meier and Cox regression analyses were used to determine the survival of patients histologically diagnosed with HCC. Reduced levels of exosomal miR-638 in serum samples from patients with HCC were identified by real-time PCR. Negative association of serum exosomal miR-638 with tumor size, vascular infiltration, and TNM stage was observed in HCC patients. Besides, the proliferation of Huh7 and SMCC7721 HCC cells were significantly inhibited when miR-638 was over-expressed in these cells. In addition, HCC patients with lower levels of serum exosomal miR-638 had poor overall survival than those with higher levels of exosomal miR-638 in serum. Our study strongly suggests that serum exosome-delivered miR-638 may serve as a novel circulating biomarker for HCC. Downregulation of miR-638 predicts poor prognosis for patients with HCC.

10.
Sci Rep ; 7(1): 3909, 2017 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-28634394

RESUMO

Pathogen-associated biliary fibrosis (PABF) is a type of liver fibrosis characterized by injuries of cholangiocytes and extra cellular matrix (ECM) deposition around bile ducts caused by various bacteria, fungi, virus and parasites. Recent studies show that TLR4 plays an important role in several other types of liver fibrosis, but the mechanism of TLR4 in PABF is yet really unclear. In the present study, a PABF mouse model was established by a trematode infection-Clonorchis sinensis which dwells in the bile ducts and causes severe biliary fibrosis of mice. The results showed that the levels of collagen depositions, α-SMA and hydroxyproline (Hyp) contents in TLR4 mut mice infected by C. sinensis were significantly lower than in those of TLR4 wild ones. Furthermore, we found that the activation of TGF-ß signaling was impaired in the TLR4 mut mice, compared with wild mice when they were challenged to the same dose of C. sinensis metacercariae. Moreover, the mice with TLR4 mutation showed a decreased activation of hepatic stellate cells indicated by the expression of α-SMA, when compared with TLR4 wild mice. These data demonstrate that TLR4 contributes to PABF caused by C. sinensis and TLR4 signaling may be a potential medical target for treatment of PABF.

11.
Oncotarget ; 8(27): 44195-44202, 2017 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-28496001

RESUMO

Hepatocellular Carcinoma (HCC) is one of the most fatal cancers, whose incidence and death rates are still rising. Here, we report the identification of long non-coding RNAs (IncRNAs) that associated with HCC progression and metabolism based on the systematically analysis of large scale RNA-seq data from HCC patients. We identified seven lncRNAs with high confidence which were highly related with prognostic of HCC. Of note, three of them had quite different expression patterns between the control samples and the patients, and their critical roles in cancer progression were validated. We proposed that DDX11-AS1 play important role during HCC oncogenesis and may serve as potential therapy target for HCC.


Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , Biomarcadores Tumorais , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , RNA Helicases DEAD-box/genética , DNA Helicases/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Reprodutibilidade dos Testes
12.
Chin J Nat Med ; 15(3): 178-191, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28411686

RESUMO

Heat stress can stimulate an increase in body temperature, which is correlated with increased expression of heat shock protein 70 (HSP70) and tumor necrosis factor α (TNFα). The exact mechanism underlying the HSP70 and TNFα induction is unclear. Berberine (BBR) can significantly inhibit the temperature rise caused by heat stress, but the mechanism responsible for the BBR effect on HSP70 and TNFα signaling has not been investigated. The aim of the present study was to explore the relationship between the expression of HSP70 and TNFα and the effects of BBR under heat conditions, using in vivo and in vitro models. The expression levels of HSP70 and TNFα were determined using RT-PCR and Western blotting analyses. The results showed that the levels of HSP70 and TNFα were up-regulated under heat conditions (40 °C). HSP70 acted as a chaperone to maintain TNFα homeostasis with rising the temperature, but knockdown of HSP70 could not down-regulate the level of TNFα. Furthermore, TNFα could not influence the expression of HSP70 under normal and heat conditions. BBR targeted both HSP70 and TNFα by suppressing their gene transcription, thereby decreasing body temperature under heat conditions. In conclusion, BBR has a potential to be developed as a therapeutic strategy for suppressing the thermal effects in hot environments.


Assuntos
Berberina/farmacologia , Proteínas de Choque Térmico HSP70/genética , Transtornos de Estresse por Calor/tratamento farmacológico , TATA Box/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Animais , Proteínas de Choque Térmico HSP70/metabolismo , Transtornos de Estresse por Calor/genética , Transtornos de Estresse por Calor/metabolismo , Temperatura Alta , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fator de Necrose Tumoral alfa/metabolismo
13.
J Orthop Translat ; 8: 49-61, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30035094

RESUMO

Background/Objective: As a widely used absorbable suture with antibacterial property, triclosan- coated polyglactin suture (Vicryl Plus) has been extensively utilized to reduce the occurrence rate of surgical site infections (SSIs) in orthopaedic surgery. However, the potential toxicity and side-effects of triclosan raised increasing concerns about its biological safety. This study aimed to investigate the antimicrobial activity and biocompatibility of quaternised chitosan-coated Vicryl suture (HV) both in vitro and in vivo. Methods: In this study, a modified chitosan derivate, (hydroxypropyltrimethyl ammonium chloride chitosan, HACC), was coated over the surface of the absorbable Vicryl suture. Two standard bacteria strains, Staphylococcus epidermidis (ATCC35984) and methicillin-resistant Staphylococcus aureus (ATCC43300), were selected to evaluate bacterial adhesion and biofilm formation on the sutures at 6, 24 and 48 h in vitro. Additionally, human skin-derived fibroblasts cells were used to test the cytocompatibility of the sutures. Furtherly, sutures contaminated with methicillin-resistant S. aureus were implanted subcutaneously in SD rats in order to confirm the in vivo antibacterial performance and biocompatibility. Results: We found that HACC-coated Vicryl suture (HV) exhibited significant anti-bacterial effects on the two tested strains. The bacterial attachment and biofilm formation on the surface of the HV sutures were found to be comparable to that of Vicryl Plus sutures (VP). Moreover, all the four tested sutures presented good cytocompatibility with human skin-derived fibroblasts cells. Histology and immunohistochemistry results indicated that the infections and inflammations were significantly inhibited around the HV and VP sutures. Conclusion: In general, the present study demonstrated that the quaternised chitosan coating is a flexible and cost-effective alternative strategy to prevent the suture related surgical site infections in orthopaedic practices.

14.
J Cancer Res Clin Oncol ; 143(4): 619-629, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28035468

RESUMO

PURPOSE: Gastric cancer (GC) is a major tumor throughout the world with remaining high morbidity and mortality. The aim is to generate a gene model to assess the prognoses risk of patients with GC. METHODS: Gene expression profiling of gastric cancer patients, GSE62254 (300 samples) and GSE26253 (432 samples), was downloaded from Gene Expression Omnibus (GEO) database. Univariate survival analysis and LASSO (Least Absolute Shrinkage and Selectionator operator) (1000 iterations) of differentially expressed genes in GSE62254 was assessed using survival and glmnet in R package, respectively. Kaplan-Meier analysis on the clustering algorithm from each regression model was performed to calculate the influence to the prognosis. Random samples in GSE26253 were analyzed in multivariate and univariate survival analysis for one thousand times to calculate statistical stability of each regression model. RESULTS: A total of 854 Genes were identified differentially expressed in GSE62254, among which 367 Genes were found influencing the prognoses. Six gene clusters were selected with good stability. Hereinto, five or more genes in 11-Gene model, TRPC1, SGCE, TNFRSF11A, LRRN1, HLF, CYS1, PPP1R14A, NOV, NBEA, CES1 and RGN, was available to evaluate the prognostic risk of GC patients in GSE26253 (P = 0.00445). The validity and reliability was validated. CONCLUSION: In conclusion, we successfully generated a stable 5-Gene model, which could be utilized to predict prognosis of GC patients and would contribute to postoperational treatment and follow-up strategies.


Assuntos
Perfilação da Expressão Gênica , Neoplasias Gástricas/genética , Humanos , Prognóstico , Fatores de Risco , Análise de Sobrevida
15.
Exp Ther Med ; 12(3): 1618-1624, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27602079

RESUMO

The current study investigated the effects of phased joint intervention on clinical efficacy and Rho/Rho-associated coil protein kinase (ROCK) expression in patients with portal hypertension complicated by esophageal variceal bleeding (EVB) and hypersplenism. Patients with portal hypertension (n=53) caused by liver cirrhosis complicated by EVB and hypersplenism treated with phased joint intervention were assessed, and portal hemodynamics, blood, liver function, complications, and rebleeding incidence were analyzed. Reverse transcription-quantitative polymerase chain reaction was used to measure Rho, ROCK1 and ROCK2 mRNA expression levels in peripheral blood mononuclear cells prior to and following phased joint intervention, and western blotting was employed to determine the protein expression levels of Rho, ROCK1, ROCK2, phosphorylated (p) myosin phosphatase target subunit 1 (MYPT1) and total-MYPT1. All patients underwent an emergency assessment of hemostasis with a 100% success rate. Varicose veins were alleviated, and portal hemodynamics and liver function improved following intervention. Furthermore, preoperative and postoperative expression levels of Rho, ROCK1 and ROCK2 mRNA were higher compared with the control group. Notably, the mRNA expression levels of Rho, ROCK1 and ROCK2 in the postoperative group were significantly lower when compared with the preoperative group. Protein expression levels of Rho, ROCK1, ROCK2 and pMYPT1 in the postoperative group were lower, as compared with the preoperative group. Concentration levels of transforming growth factor-ß1, connective tissue growth factor and platelet-derived growth factor in peripheral blood were significantly reduced following phased joint intervention. Therefore, the present findings demonstrated that phased joint intervention is able to effectively treat EVB and hypersplenism, and improve liver function. The efficacy of phased joint intervention may be associated with its role in the regulation of the Rho-ROCK signaling pathway.

16.
Sci Rep ; 6: 32771, 2016 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-27600021

RESUMO

The endocrine role of the skeleton-which is impaired in human diseases including osteoporosis, obesity and diabetes-has been highlighted previously. In these diseases, the role of AMPK, a sensor and regulator of energy metabolism, is of biological and clinical importance. Since AMPK's main catalytic subunit α has two isoforms, it is unclear whether functional differences between them exist in the skeletal system. The current study overexpressed AMPKα1 and α2 in MC3T3-E1 cells, primary osteoblasts and mouse BMSCs by lentiviral transduction. Cells overexpressing AMPKα2 showed higher osteogenesis potential than AMPKα1, wherein androgen receptor (AR) and osteoactivin played important roles. RANKL and M-CSF were secreted at lower levels from cells overexpressing α2 than α1, resulting in decreased osteoblast-associated osteoclastogenesis. Adipogenesis was inhibited to a greater degree in 3T3-L1 cells overexpressing α2 than α1, which was modulated by AR. An abnormal downregulation of AMPKα2 was observed in human BMSCs exhibiting the fibrous dysplasia (FD) phenotype. Overexpression of AMPKα2 in these cells rescued the defect in osteogenesis, suggesting that AMPKα2 plays a role in FD pathogenesis. These findings highlight functional differences between AMPKα1 and α2, and provide a basis for investigating the molecular mechanisms of diseases associated with impaired functioning of the skeletal system.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Adipogenia , Osteoblastos/citologia , Osteoclastos/citologia , Osteogênese , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Células Cultivadas , Proteínas do Olho/metabolismo , Humanos , Glicoproteínas de Membrana/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Receptores Androgênicos/metabolismo
17.
Drug Des Devel Ther ; 10: 2739-44, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27621595

RESUMO

PURPOSE: To further observe and verify the effect of nonalcoholic fatty liver disease (NAFLD) on the response to antiviral therapy in patients with chronic hepatitis B (CHB) and investigate the relationship between the virologic response and insulin resistance. PATIENTS AND METHODS: A retrospective study was adopted and 61 NAFLD patients with HBeAg-positive CHB were included as the observation group (group A), and 64 patients with simple CHB were included as the control group (group B). RESULTS: After 12 weeks of treatment with entecavir, the total virologic response rate in group A was statistically significantly lower than that in group B (P<0.05). During weeks 24-96, the difference was not statistically significant (P>0.05). In weeks 48 and 96, there was no significant difference in the HBeAg seroconversion rates between the two groups (P>0.05). In weeks 12 and 24, there was also no significant difference in the alanine transaminase (ALT) normalization rate between the two groups (P>0.05). Then, in weeks 48 and 96, the ALT normalization rate of group A was obviously lower than that of group B (P<0.05). Group A patients were divided into group A1 (≤M) and group A2 (>M) according to the median value (M=2.79) of the baseline homeostatic model assessment method insulin resistance levels. In weeks 48 and 96, the ALT normalization rate of group A1 was significantly higher than that of group A2 (P<0.05). The correlation coefficient (r) of the baseline homeostatic model assessment method insulin resistance level and the severity of fatty liver in group A was 0.426 (P=0.001). CONCLUSION: NAFLD cannot affect the long-term total virologic response rate and HBeAg seroconversion rate in CHB patients treated with entecavir but can reduce the long-term biochemical response rate, which has a positive correlation with the severity of fatty liver and the insulin resistance index.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Antígenos E da Hepatite B/metabolismo , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/metabolismo , Resistência à Insulina/fisiologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Adolescente , Adulto , Feminino , Guanina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
18.
World J Gastroenterol ; 22(27): 6235-45, 2016 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-27468213

RESUMO

AIM: To investigate the role of activating transcription factor 4 (ATF4) in glucose deprivation (GD) induced colorectal cancer (CRC) drug resistance and the mechanism involved. METHODS: Chemosensitivity and apoptosis were measured under the GD condition. Inhibition of ATF4 using short hairpin RNA in CRC cells under the GD condition and in ATF4-overexpressing CRC cells was performed to identify the role of ATF4 in the GD induced chemoresistance. Quantitative real-time RT-PCR and Western blot were used to detect the mRNA and protein expression of drug resistance gene 1 (MDR1), respectively. RESULTS: GD protected CRC cells from drug-induced apoptosis (oxaliplatin and 5-fluorouracil) and induced the expression of ATF4, a key gene of the unfolded protein response. Depletion of ATF4 in CRC cells under the GD condition can induce apoptosis and drug re-sensitization. Similarly, inhibition of ATF4 in the ATF4-overexpressing CRC cells reintroduced therapeutic sensitivity and apoptosis. In addition, increased MDR1 expression was observed in GD-treated CRC cells. CONCLUSION: These data indicate that GD promotes chemoresistance in CRC cells through up-regulating ATF4 expression.


Assuntos
Fator 4 Ativador da Transcrição/genética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Glucose/deficiência , Microambiente Tumoral , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Fator 4 Ativador da Transcrição/metabolismo , Apoptose/genética , Western Blotting , Linhagem Celular Tumoral , Fluoruracila/administração & dosagem , Técnicas de Silenciamento de Genes , Glucose/metabolismo , Células HCT116 , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismo
19.
Chin J Nat Med ; 14(6): 441-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27473962

RESUMO

Brazilein is an active small molecular compound extracted from Caesalpinia sappan L. with favorable pharmacological properties on immune system, cardiovascular system, and nervous system. C. sappan has been used as a traditional medicine in China for hundreds of years for various diseases. However, the general reproductive toxicity of brazilein is still unknown. The purpose of the present study was to thoroughly evaluate the general reproductive toxicity of brazilein in ICR mice to support the future drug development and modernization of this potent traditional Chinese medicine. The results showed that, although no apparent toxicity on the reproducibility of the male was observed, brazilein might cause considerable risks to the fetuses and females as indicated by the ratios of dead fetuses and reabsorptions. In conclusion, our results from the present study provided some useful insights about the safety profile of brazilein, suggesting that brazilein should be used with caution in pregnant women.


Assuntos
Benzopiranos/toxicidade , Caesalpinia/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Indenos/toxicidade , Reprodução/efeitos dos fármacos , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Gravidez
20.
Tumour Biol ; 37(10): 13323-13331, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27460080

RESUMO

Liver cancer is one of the most common malignant tumors, and most of which is hepatocellular carcinoma (HCC). We aim to study the characteristic changes of numerous genes and their roles in HCC through systematical analysis of the characteristics of expression spectrum of HCC. Firstly, we made systematic clustering of the HCC samples according to the RNAseq data from TCGA (The Cancer Genome Atlas) and newly classified HCC. Then the characteristic genes in different molecular subtypes were found out and further analyzed combing with methylation and SNP 6.0 chip. Finally, these genes were subjected to do functional annotation and abnormal signaling pathways of HCC in various molecular subtypes and were screened out. There were 3843 differential genes screened; among which, 689 genes were enriched into 13 KEGG-related pathways, and the expression of 27 and 924 genes showed positive and negative correlation to methylation level, respectively, while the expression of 43 genes showed positive correlation to variation level of copy number. The methylation degree of ZSCAN18 may be considered as a marker for prognosis evaluation, and ABHD6 could be a potential anti-oncogene.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular/genética , Perfilação da Expressão Gênica , Neoplasias Hepáticas/genética , Transcriptoma , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Tumoral , Análise por Conglomerados , Biologia Computacional/métodos , Metilação de DNA , Epigênese Genética , Dosagem de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/mortalidade , Anotação de Sequência Molecular , Prognóstico
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