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1.
Sci Rep ; 13(1): 2381, 2023 Feb 10.
Article in English | MEDLINE | ID: mdl-36765191

ABSTRACT

Since the western region of China, which is typical of extraordinary resource endowments, has gradually emerged as the major mining zone in China, the mining of thick coal seams and roadways with coal-rock composite roof have become more and more common in this region. However, it is extremely difficult to realize safe and effective maintenance and control of such roadways due to the differences in natural endowments of coal-rock masses. With the roadway with coal-rock composite roof of Hulusu Coal Mine in western China as the engineering background, experiment research on large-scale similarity model was conducted through comprehensive measures such as the pneumatic loading system, the surrounding rock stress monitoring system, the roadway deformation monitoring system, the bolt load monitoring system, and the displacement field monitoring system in this paper. According to the results of the experiment, the control effects of the three support systems on the roadway with coal-rock composite roof were significantly different. When the single support of short anchor bolts was applied, the comparatively low initial anchor-hold failed to constrain the initial micro deformation of the roof. Consequently, wide-range fractures of the roof were triggered at a loading pressure of 0.8 MPa. In the meanwhile, the deep surrounding rocks witnessed a downward inflection point in stress, accompanied by the possibility of the collapse of the thin-layer anchorage zone at any time. As for the support combining both short anchor bolts and long anchor cables, though a reinforced effect on the bolt anchorage zone could be achieved with the help of the cables, the active reinforcement capacity of the bolt was limited. The bolt anchorage zone was the first to be damaged at a loading pressure of 0.9 MPa, which would subsequently affect the effective bearing capacity of the deep surrounding rocks. In the application of the single support of high-strength long anchor bolts, the long bolts with high pre-tightening force were able to lock multiple groups of coal-rock strata to form a thick-layer anchorage bearing structure capable of withstanding a load as high as 1.0 MPa. The crash and collapse of the coal wall eventually caused the subsidence of the roof. Based on the intense dynamic load experiment and the feedbacks of engineering application outcomes in the field, it was concluded that the high-pretension thick-layer (HPTL) anchoring technology can effectively constrain the deformation of roadways with coal-rock composite roof with favorable application outcomes.

2.
BMC Pharmacol Toxicol ; 22(1): 48, 2021 09 06.
Article in English | MEDLINE | ID: mdl-34488896

ABSTRACT

BACKGROUND: Aidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. However, limited information is available about the herb-drug interactions between ADI and DOX. The study aimed to investigate the pharmacokinetic mechanism of herb-drug interactions between ADI and DOX in a rat model of HCC. METHODS: Experimental HCC was induced in rats by oral administration of diethylnitrosamine. The HCC rats were pretreated with ADI (10 mL/kg, intraperitoneal injection) for 14 consecutive days prior to administration of DOX (7 mg/kg, intravenous injection) to investigate pharmacokinetic interactions. Plasma concentrations of DOX and its major metabolite, doxorubicinol (DOXol), were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: Preadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both DOX and DOXol. The area under the plasma drug concentration-time curve (AUCs) of DOX and DOXol in rats pretreated with ADI were 3.79-fold and 2.92-fold higher, respectively, than those in control rats that did not receive ADI. CONCLUSIONS: Increased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI.


Subject(s)
Antibiotics, Antineoplastic/pharmacokinetics , Carcinoma, Hepatocellular/metabolism , Doxorubicin/pharmacokinetics , Drugs, Chinese Herbal/pharmacology , Herb-Drug Interactions , Liver Neoplasms/metabolism , Animals , Antibiotics, Antineoplastic/blood , Area Under Curve , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/chemically induced , Diethylnitrosamine , Doxorubicin/blood , Liver Neoplasms/blood , Liver Neoplasms/chemically induced , Male , Rats, Sprague-Dawley
3.
Front Microbiol ; 12: 658292, 2021.
Article in English | MEDLINE | ID: mdl-33912150

ABSTRACT

Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography-mass spectrometry (LC-MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested in vitro. The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with Clostridium butyricum-containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.

4.
Arab J Gastroenterol ; 21(3): 162-168, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32451200

ABSTRACT

BACKGROUND AND STUDY AIMS: To identify the roles and interaction of farnesoid X receptor (FXR) and peroxisome proliferator activated receptors (PPARs) in Non-alcoholic fatty liver disease (NAFLD) pathogenesis. MATERIAL AND METHODS: 16 C57/BL male FXR knockout (KO) mice and sex- and age-matched C57/BL wild type mice were received either standard rodent chow or high-fat and sucrose diet (Blank control, NAFLD, FXR KO and FXR KO NAFLD) for 8 weeks. After that, all mice were sacrificed. Liver tissues and blood samples were collected for laboratory and RT-PCR examination. RESULTS: NAFLD, FXR KO and FXR KO NAFLD mouse models were successful established. Compared with blank control, FXR and PPAR-α mRNA expression decreased significantly (P < 0.05), PPAR-ß expression increased slightly (P > 0.05), PPAR-γ expression increased significantly in NAFLD (P < 0.05). Slight increased PPAR-α mRNA expression (P > 0.05) and markedly decreased PPAR-ß and PPAR-γ expression (P < 0.05) were found in FXR KO. Compared with FXR KO group, there was a slight increase in PPAR-αand PPAR-ßmRNA expression (P > 0.05) and significant increase in PPAR-γ expression (P < 0.05) in FXR KO NAFLD group. Comparison with NAFLD, PPAR-α mRNA expression increased slightly (P > 0.05), PPAR-ß and PPAR-γ expression decreased significantly (P < 0.05) in FXR KO NAFLD. CONCLUSION: FXR and PPARs interaction may play important roles in NAFLD pathogenesis.


Subject(s)
Non-alcoholic Fatty Liver Disease , Receptors, Cytoplasmic and Nuclear , Animals , Liver , Male , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/metabolism , PPAR alpha/metabolism
5.
Xenobiotica ; 50(10): 1251-1257, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32375563

ABSTRACT

Hepatocellular carcinoma (HCC) is a malignancy of liver cells. Recent studies have shown that HCC patients often have changes in the activities of transporters and metabolic enzymes, which can considerably affect drug pharmacokinetics and lead to drug toxicity. Doxorubicin (DOX) has been frequently administered in chemotherapy for HCC, but to our knowledge, the effects of HCC on the pharmacokinetics of DOX are unknown.In the present study, following intravenous administration of DOX in diethylnitrosamine-induced HCC rats, the plasma concentration was determined by a UPLC/MS/MS method. The expression of metabolic enzyme and transporters (p-gp, cbr1 and slc22a16) was analyzed by qRT-PCR and western blot.The results showed that the pharmacokinetic parameters AUC, T1/2, K12 and K21 of DOX were markedly increased, the K10 and CL were significantly decreased in HCC rats. The expression of cbr1 and slc22a16 was markedly decreased, while p-gp was significantly upregulated in HCC rats.These findings suggest that HCC could significantly alter the pharmacokinetic profile of DOX, which may be associated with the decreased expression of cbr1 and slc22a16 rather than the upregulation of p-gp expression.


Subject(s)
Doxorubicin/pharmacokinetics , Animals , Carcinoma, Hepatocellular , Diethylnitrosamine , Liver Neoplasms , Rats
6.
Medicine (Baltimore) ; 97(51): e13509, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30572451

ABSTRACT

RATIONALE: Cavernous hemangiomas are benign vascular malformations that usually involve the skin, subcutaneous tissue, and liver. Described herein was multiple masses in the lung and liver mimicking metastasis, which was proved to be cavernous hemangiomas histologically. PATIENT CONCERNS: A 78-year-old man with complaint of dizziness for 3 days was referred to the local hospital for medical attention. DIAGNOSES: Multiple masses in the lung and liver was diagnosed pathologically as cavernous hemangioma. INTERVENTIONS: Because of the benign pathological characteristic and multiple distribution, no treatment except some symptomatic treatment for dizziness was administered. OUTCOME: After more than 2 years of follow-up visits, the patient had no apparent symptoms and was healthy. LESSONS: Proper diagnosis of multiple cavernous hemangiomas is essential. The final diagnosis depends on the pathology results. The most appropriate management is follow-up. Surgical treatment is suitable for large or symptomatic lesions which can result in satisfactory prognoses.


Subject(s)
Hemangioma, Cavernous/diagnosis , Liver Neoplasms/diagnosis , Lung Neoplasms/diagnosis , Aged , Diagnosis, Differential , Dizziness/diagnosis , Dizziness/etiology , Dizziness/therapy , Hemangioma, Cavernous/complications , Hemangioma, Cavernous/pathology , Humans , Liver Neoplasms/complications , Liver Neoplasms/pathology , Lung Neoplasms/complications , Lung Neoplasms/pathology , Male
7.
J Dig Dis ; 19(7): 421-430, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29802754

ABSTRACT

OBJECTIVE: Our studies in vitro and in vivo aimed to investigate the influence of DNA methylation of peroxisome proliferator activated receptor-α (PPAR-α) gene in non-alcoholic fatty liver disease (NAFLD) pathogenesis and to observe whether the DNA methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR) and the herbal medicine curcumin might reverse the effect both in vivo and in vitro. METHODS: Steatotic hepatocyte model of cell lines and NAFLD rat models were established following protocols documented in previous studies. Subsequently, the models received 5-Aza-CdR and curcumin treatment. Morphological, histological and laboratory variables in each group were determined by routine methods, including PPAR-α mRNA expression by polymerase chain reaction (PCR), PPAR-α protein expression by Western blot and DNA methylation by pyrosequencing. RESULTS: The steatotic hepatocyte model and NAFLD rat model were completely established. The expressions of PPAR-α mRNA and protein were significantly lower in the steatotic hepatocyte and NAFLD rat model groups than in the controls (P < 0.05). The mean DNA methylation levels of the PPAR-α gene were significantly higher in the two steatotic model groups than in the controls, especially at several CpG sites (P < 0.05). 5-Aza-CdR and curcumin treatment significantly reversed the DNA methylation levels, increased PPAR-α mRNA and protein expression, and improved lipid accumulation in the two steatotic models (P < 0.05). CONCLUSIONS: DNA methylation at the PPAR-α gene is involved in the pathogenesis of NAFLD and is possibly reversible by 5-Aza-CdR and curcumin. Curcumin may be a promising candidate for NAFLD therapy.


Subject(s)
Curcumin/pharmacology , DNA Methylation/drug effects , Decitabine/pharmacology , Enzyme Inhibitors/pharmacology , Non-alcoholic Fatty Liver Disease/drug therapy , PPAR alpha/genetics , Animals , Cell Line , Disease Models, Animal , Hepatocytes , Humans , Non-alcoholic Fatty Liver Disease/genetics , Rats
8.
Chin Med J (Engl) ; 131(11): 1349-1356, 2018 Jun 05.
Article in English | MEDLINE | ID: mdl-29786050

ABSTRACT

BACKGROUND: Increasing evidence has supported the link of intestinal Fusobacterium nucleatum infection to colorectal cancer (CRC). However, the value of F. nucleatum as a biomarker in CRC detection has not been fully defined. In order to reduce the random error and bias of individual research, this meta-analysis aimed to evaluate the diagnostic performance of intestinal F. nucleatum in CRC patients and provide evidence-based data to clinical practice. METHODS: An article search was performed from PubMed, Embase, Cochrane Library, and Web of Science databases up to December 2017, using the following key words: "Fusobacterium nucleatum", "Fusobacterium spp.", "Fn", "colorectal cancer(s)", "colorectal carcinoma(s)", "colorectal neoplasm(s)", and "colorectal tumor(s)". Articles on relationships between F. nucleatum and CRC were selected according to the preestablished inclusion and exclusion criteria. This meta-analysis was performed using STATA 12.0 software, which included mapping of forest plots, heterogeneity tests, meta-regression, subgroup analysis, sensitivity analysis, and publication bias. The sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and their corresponding 95% confidence interval (CI) of each eligible study were summarized. RESULTS: Finally, data for 1198 participants (629 CRC and 569 healthy controls) in 10 controlled studies from seven articles were included. The summary receiver operator characteristic curve was mapped. The diagnostic performance of intestinal F. nucleatum infection on CRC was as follows: the area under the curve: 0.86 (95% CI: 0.83-0.89), the pooled sensitivity: 0.81 (95% CI: 0.64-0.91), specificity: 0.77 (95% CI: 0.59-0.89), and DOR: 14.00 (95% CI: 9.00-22.00). CONCLUSION: Intestinal F. nucleatum is a valuable marker for CRC diagnosis.


Subject(s)
Colonic Neoplasms/microbiology , Colorectal Neoplasms/microbiology , Fusobacterium nucleatum/physiology , Intestines/microbiology , Humans , Intestines/pathology
9.
Rev. esp. enferm. dig ; 109(12): 818-827, dic. 2017. tab, ilus, graf
Article in English | IBECS | ID: ibc-169189

ABSTRACT

Background: Acute-on-chronic hepatitis B liver failure (ACHBLF) is an acute deteriorating liver disease and rapidly progresses to multiple organ failure. There is currently no adequate accurate predictive models of ACHBLF prognosis. Aims: To identify the methylation frequency of the estrogen receptor 1 (ESR1) promoter in ACHBLF and analyze the associated prognostic significance. Methods: Methylation-specific PCR (MSP) was used to determine the methylation frequency of the ESR1 promoter in peripheral blood mononuclear cells from a training and validation cohort of patients. The training cohort included 113 patients with ACHBLF, 73 with chronic hepatitis B (CHB) and 40 healthy controls (HCs). The validation cohort consisted of 37 patients with ACHBLF. Another 18 patients with pre-ACHBLF who progressed to ACHBLF were used to dynamically evaluate ESR1 promoter methylation changes associated with a severe clinical condition. Results: Death from ACHBLF was associated with hyperbilirubinemia, a higher score in the model for end-stage liver disease (MELD), a higher incidence of hepatic encephalopathy (HE) and an increased frequency of ESR1 promoter methylation during the 28 day follow-up. HE, MELD score and ESR1 promoter methylation were the independent risk factors associated with 28-day mortality from ACHBLF. The frequency of ESR1 promoter methylation was significantly higher than in patients with CHB and HCs. Albumin and the MELD score were significantly associated with ESR1 promoter methylation. Moreover, ESR1 promoter methylation frequency increased with ACHBLF progression. More importantly, ESR1 promoter methylation was an independent risk factor and had a high value to predict 28-day mortality from ACHBLF. Conclusions: Abnormal ESR1 methylation could be a prognostic biomarker for ACHBLF (AU)


No disponible


Subject(s)
Humans , Hepatitis B, Chronic/complications , Hepatic Insufficiency/etiology , Receptors, Estrogen/genetics , Biomarkers/analysis , DNA Methylation , Prognosis
10.
Oncol Lett ; 14(5): 5197-5202, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29113155

ABSTRACT

Polyneuropathy, organomegaly, endocrinopathy, M proteins, and skin changes (POEMS) syndrome is a rare variant of plasma cell disorders with multiple systemic manifestations. A 50-year-old female patient presented with progressive weakness in her upper and lower limbs; tingling, numbness and burning in her feet; polyneuropathy (demyelinating in the majority of cases of POEMS syndrome); monoclonal plasma cell disorder (typicallyλ-restricted in cases of POEMS syndrome); sclerotic lesions on the spine and pelvis; organomegaly, including hepatomegaly, splenomegaly and lymphadenopathy; edema; pleural effusion; adrenal, thyroidal, pituitary, gonadal and pancreatic endocrinopathy; skin changes, including hyperpigmentation, dry skin and hypertrichosis; thrombocytosis; pulmonary hypertension; low vitamin B12 and weight loss. Following the diagnosis of POEMS syndrome, the patient was treated only with pain-alleviating corticosteroids. Respiratory failure-induced mortality occurred 24 months after the patient first experienced difficulty walking and numbness in her lower extremities. The present study suggests that abnormal symptoms in cases of POEMS syndrome should be further evaluated during the diagnosis and treatment.

11.
Rev Esp Enferm Dig ; 109(12): 818-827, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29082740

ABSTRACT

BACKGROUND: Acute-on-chronic hepatitis B liver failure (ACHBLF) is an acute deteriorating liver disease and rapidly progresses to multiple organ failure. There is currently no adequate accurate predictive models of ACHBLF prognosis. AIMS: To identify the methylation frequency of the estrogen receptor 1 (ESR1) promoter in ACHBLF and analyze the associated prognostic significance. METHODS: Methylation-specific PCR (MSP) was used to determine the methylation frequency of the ESR1 promoter in peripheral blood mononuclear cells from a training and validation cohort of patients. The training cohort included 113 patients with ACHBLF, 73 with chronic hepatitis B (CHB) and 40 healthy controls (HCs). The validation cohort consisted of 37 patients with ACHBLF. Another 18 patients with pre-ACHBLF who progressed to ACHBLF were used to dynamically evaluate ESR1 promoter methylation changes associated with a severe clinical condition. RESULTS: Death from ACHBLF was associated with hyperbilirubinemia, a higher score in the model for end-stage liver disease (MELD), a higher incidence of hepatic encephalopathy (HE) and an increased frequency of ESR1 promoter methylation during the 28 day follow-up. HE, MELD score and ESR1 promoter methylation were the independent risk factors associated with 28-day mortality from ACHBLF. The frequency of ESR1 promoter methylation was significantly higher than in patients with CHB and HCs. Albumin and the MELD score were significantly associated with ESR1 promoter methylation. Moreover, ESR1 promoter methylation frequency increased with ACHBLF progression. More importantly, ESR1 promoter methylation was an independent risk factor and had a high value to predict 28-day mortality from ACHBLF. CONCLUSIONS: Abnormal ESR1 methylation could be a prognostic biomarker for ACHBLF.


Subject(s)
Acute-On-Chronic Liver Failure/genetics , Estrogen Receptor alpha/genetics , Hepatitis B, Chronic/genetics , Acute-On-Chronic Liver Failure/therapy , Adult , Cohort Studies , DNA Methylation , Female , Hepatitis B, Chronic/therapy , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis
12.
Int J Oncol ; 51(3): 812-822, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28731152

ABSTRACT

Astrocyte elevated gene-1 (AEG-1), known as an oncogene, is overexpressed in various cancers and implicated in tumor progression and metastasis. However, its functional significance and underlying molecular mechanisms in thyroid cancer remain to be elucidated. In the present study, we detected the potential function of AEG-1 in papillary thyroid cancer (PTC). We also investigated the relation between AEG-1 and matrix metalloproteases (MMP)2 and 9 through immunohistochemistry, western blotting, real-time PCR, immunofluorescence staining, zymography and co-immunoprecipitation (Co-IP). We found that overexpression of AEG-1 in PTC was positively correlated with lymph node metastasis and MMP2/9 expression. Knockdown of AEG-1 reduced the capacity of migration and invasion through downregulation of MMP2/9 in thyroid cancer cells. Furthermore, we firstly found that AEG-1 interacted with MMP9 in thyroid cancer cells. AEG-1 was associated with the activation of the nuclear factor κB (NF-κB) signaling pathways in thyroid cancer cells. Overall, our results for the first time showed that AEG-1 interacted with MMP9 in thyroid cancer cells and AEG-1 expression was closely associated with progression and metastasis of papillary thyroid cancer. AEG-1 might be a potential therapeutic target in papillary thyroid cancer.


Subject(s)
Carcinoma, Papillary/genetics , Cell Adhesion Molecules/genetics , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , Thyroid Neoplasms/genetics , Adolescent , Adult , Aged , Carcinoma, Papillary/pathology , Cell Line, Tumor , Cell Movement/genetics , Child , Female , Gene Expression Regulation, Neoplastic , Humans , Lymphatic Metastasis , Male , Membrane Proteins , Middle Aged , NF-kappa B/genetics , RNA-Binding Proteins , Signal Transduction/genetics , Thyroid Cancer, Papillary , Thyroid Neoplasms/pathology , Transcriptional Activation , Young Adult
13.
Oncol Lett ; 13(3): 1587-1594, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28454295

ABSTRACT

NIMA-related kinase 2 (Nek2) is often upregulated in human cancer and is important in regulating the cell cycle and gene expression, and maintaining centrosomal structure and function. The present study aimed to investigate the expression pattern, clinical significance, and biological function of Nek2 in hepatocellular carcinoma (HCC). mRNA and protein levels of Nek2 were examined in HCC and corresponding normal liver tissues. The MTT and soft agar colony formation assays, and flow cytometry were employed to assess the roles of Nek2 in cell proliferation and growth. In addition, western blot analysis was performed to assess the expression of cell cycle- and proliferation-related proteins. The results revealed that Nek2 was upregulated in HCC tissues and cell lines. The clinical significance of Nek2 expression was also analyzed. Inhibiting Nek2 expression by siRNA suppressed cell proliferation, growth, and colony formation in hepatocellular carcinoma cell line HepG2 cells, induced cell cycle arrest in the G2/M phase by retarding the S-phase, and promoted apoptosis. Furthermore, Nek2 depletion downregulated ß-catenin expression in HepG2 cells and diminished expression of Myc proto-oncogene protein (c-Myc), cyclins D1, B1, and E and cyclin-dependent kinase 1, whilst increasing protein levels of p27. This demonstrates that overexpression of Nek2 is associated with the malignant evolution of HCC. Targeting Nek2 may inhibit HCC cell growth and proliferation through the regulation of ß-catenin by the Wnt/ß-catenin pathway and therefore may be developed as a novel therapeutic strategy to treat HCC.

14.
J Dig Dis ; 17(12): 829-836, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27860427

ABSTRACT

OBJECTIVE: To investigate the role of adiponectin precursor (ADIPOQ) DNA methylation in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the effect of curcumin on the development of NAFLD using rat models. METHODS: Male Sprague-Dawley rats were divided into the control, NAFLD and curcumin-treated groups. The genetic and epigenetic features of each rat were measured and recorded. Real-time polymerase chain reaction (PCR), Western blot and bisulfite sequencing PCR (BSP) were used to quantify the ADIPOQ mRNA and protein expressions, and DNA methylation status, respectively. RESULTS: Serum levels of alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC) and fasting blood glucose in the NAFLD group were significantly increased compared with the control group. The genetic and epigenetic features were reversed after curcumin treatment. The ADIPOQ mRNA and protein expressions in the livers of the NAFLD rats was lower compared with the control and the curcumin-treated groups. ADIPOQ methylation rate in the NAFLD group was significantly higher than in the control group, which was declined slightly following curcumin treatment. A negative correlation was found between the degrees of DNA methylation and ADIPOQ mRNA expression. ALT, TC, TG and homeostatic model assessment insulin resistance index had a positive correlation with ADIPOQ DNA methylation, showing that curcumin might affect the gene expression involved in lipid and glucose metabolism by influencing ADIPOQ DNA methylation modifications, which contributed to alleviation of NAFLD. CONCLUSION: Altering the DNA methylation of ADIPOQ is one of the mechanisms by which curcumin executes its hepatoprotective function in NAFLD.


Subject(s)
Adiponectin/genetics , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Curcumin/pharmacology , DNA Methylation , Non-alcoholic Fatty Liver Disease/genetics , RNA, Messenger/metabolism , Adiponectin/metabolism , Animals , DNA Methylation/drug effects , Gene Expression/drug effects , Male , Non-alcoholic Fatty Liver Disease/metabolism , Rats , Rats, Sprague-Dawley
15.
Oncol Rep ; 35(6): 3489-95, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27108677

ABSTRACT

The role of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) inhibiting migration in hepatocellular carcinoma (HCC) remains unknown. Expression of EFEMP1 in HCC cell lines were quantified by western blotting and real-time PCR. The role of EFEMP1 in HCC cell migration was explored in vitro via siRNA and adding purified EFEMP1 protein. The associated molecule expression was detected by western blotting after downregulation of EFEMP1 and also tested by immunohistochemistry. Eight pairs of HCC non-HCC liver samples and 215 HCC samples were subjected to immunohistochemistry. EFEMP1 was highly expressed in 7,721 and HepG2 HCC cell lines while HuH7 HCC cell line expressed the lowest level of EFEMP1 compared with the others. Downregulating EFEMP1 by siRNA markedly increased the migration ability of HCC cells while adding purified EFEMP1 protein inhibited HCC cell migration. Downregulation of EFEMP1 increased the expression of ERK1/2, MMP2 and MMP9. Furthermore, U0126 (a highly selective and potent inhibitor of pERK1/2) could abrogate the migration ability enhanced by siRNA. Accordingly, MMP2 and MMP9 were inversely expressed with EFEMP1 expression by immunohistochemistry. EFEMP1 downregulated in HCC tissues, and lower EFEMP1 expression was significantly associated with HCC patients with ascites (P=0.050), vascular invasion (P=0.044), poorer differentiation (P=0.002) and higher clinical stage (P=0.003).


Subject(s)
Carcinoma, Hepatocellular/pathology , Cell Movement/genetics , Extracellular Matrix Proteins/genetics , Extracellular Signal-Regulated MAP Kinases/metabolism , Liver Neoplasms/pathology , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Butadienes/pharmacology , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Down-Regulation/genetics , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Gene Expression Regulation, Neoplastic , Hep G2 Cells , Humans , Immunohistochemistry , Liver Neoplasms/genetics , Nitriles/pharmacology , RNA Interference , RNA, Small Interfering/genetics , Real-Time Polymerase Chain Reaction , Signal Transduction
16.
Dig Dis Sci ; 61(4): 1130-8, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26660680

ABSTRACT

BACKGROUND: DNA methylation mainly affects tumor suppressor genes in the development of hepatocellular carcinoma (HCC). However, sera methylation of specific genes in hepatitis B virus (HBV)-related HCC remains unknown. AIMS: The purpose of this study was to identify methylation frequencies of sera E-cadherin (CDH1), DNA methyltransferase 3b (DNMT3b) and estrogen receptor 1 (ESR1) promoter in HBV-related HCC and analyze the associated clinical significance. METHODS: Methylation-specific PCR was used to determine the frequencies of DNA methylation for CDH1, DNMT3b and ESR1 genes in sera from 183 patients with HCC, 47 liver cirrhosis (LC), 126 chronic hepatitis B (CHB), and 50 normal controls (NCs). RESULTS: Significantly higher frequencies of methylation of CDH1, DNMT3b and ESR1 were found in HBV-related HCC compared with LC, CHB and NCs. Nodule numbers, tumor size and the presence of liver cirrhosis were significantly associated with gene methylation status in HBV-related HCC. Moreover, HBV may have a strong and enhanced effect on the concurrent methylation of CDH1, DNMT3b and ESR1 in HBV-related HCC. More importantly, combined methylation as a biomarker displayed significantly higher diagnostic value than AFP to discriminate HCC from CHB and LC. CONCLUSIONS: Aberrant sera DNA methylation of CDH1, DNMT3b and ESR1 gene promoters could be a biomarker in the early diagnosis of HBV-related HCC.


Subject(s)
Biomarkers/blood , Carcinoma, Hepatocellular/blood , DNA Methylation , Hepatitis B, Chronic/blood , Liver Neoplasms/blood , Adult , Aged , Antigens, CD , Cadherins/genetics , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/virology , Case-Control Studies , DNA (Cytosine-5-)-Methyltransferases/genetics , Early Diagnosis , Estrogen Receptor alpha/genetics , Female , Hepatitis B, Chronic/complications , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/virology , Male , Middle Aged , Promoter Regions, Genetic , Prospective Studies , alpha-Fetoproteins/metabolism , DNA Methyltransferase 3B
17.
J Dig Dis ; 16(10): 601-9, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26334200

ABSTRACT

OBJECTIVE: To explore the role of tagging single nucleotide polymorphisms (tagSNPs) in the adiponectin gene in the natural course of nonalcoholic fatty liver disease (NAFLD). METHODS: The participants were chosen from our previous survey containing 3543 individuals. Finally, a total of 696 participants who had been followed up for a median of 4 years were included. Each participant was administered with an interview, physical examination, blood tests and ultrasonic examination at both baseline and end-point. Polymerase chain reaction-restriction fragment length polymorphism was applied to determine seven tagSNPs in the adiponectin gene, namely, rs182052, rs16861205, rs822396, rs7627128, rs1501299, rs2241767 and rs3774261. Ordinal logistic regression was used to screen risk factors of NAFLD progression as well as the susceptibility to the disease. Haplotypes analyses were performed to confirm the results. RESULTS: After adjusting for age and gender, rs1501299 (G276T), rs2241767 (A45G) and rs3774261 (A712G) were found to be risk factors of both susceptibility (OR 5.040, 7.471 and 3.546, respectively) and progression (OR 3.83, 3.51 and 3.30, respectively) to NAFLD. Nevertheless, rs182052, rs16861205, rs822396 and rs7627128 had no impact on them. These findings were confirmed by haplotype analysis. CONCLUSION: The tagSNPs rs2241767, rs1501299 and rs3774261 in the adiponectin gene are risk factors for the individuals' susceptibility to and progression of NAFLD.


Subject(s)
Adiponectin/genetics , Disease Progression , Non-alcoholic Fatty Liver Disease/genetics , Polymorphism, Single Nucleotide , Aged , Case-Control Studies , China , Female , Follow-Up Studies , Genetic Predisposition to Disease , Haplotypes , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Polymerase Chain Reaction , Risk Factors , Sequence Tagged Sites , Ultrasonography
18.
Oncotarget ; 6(16): 14191-208, 2015 Jun 10.
Article in English | MEDLINE | ID: mdl-25987128

ABSTRACT

The role of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) in osteosarcoma remains unknown. Then applying EFEMP1 siRNA, plasmids transfection and adding purified EFEMP1 protein in human osteosarcoma cell lines, and using immunohistochemistry on 113 osteosarcoma tissues, demonstrated that EFEMP1 was a poor prognostic indicator of osteosarcoma; EFEMP1 was specifically upregulated in osteosarcoma and associated with invasion and metastasis in vitro and in vivo. At the same time, we found a direct regulatory effect of EFEMP1 on MMP-2. Moreover, we firstly found the marked induction of EFEMP1 by oncogenic AEG-1. And EFEMP1 expression was inhibited by the selective inhibitor of NF-κB (PDTC) in osteosarcoma cells. Then we thought that NF-κB pathways might be one of the effective ways which EFEMP1 was induced by AEG-1. Thus, we suggested that EFEMP1 played a part as the mediator between AEG-1 and MMP-2. And NF-κB signaling pathway played an important role in this process. In summary, EFEMP1 was associated with invasion, metastasis and poor prognosis of osteosarcoma patients. EFEMP1 might indirectly enhance the expression of MMP-2, providing a potential explanation for the role of AEG-1 in metastasis. NF-κB pathways might be one of the effective ways which EFEMP1 was induced by AEG-1.


Subject(s)
Bone Neoplasms/metabolism , Cell Adhesion Molecules/metabolism , Extracellular Matrix Proteins/metabolism , Matrix Metalloproteinase 2/metabolism , NF-kappa B/metabolism , Osteosarcoma/metabolism , Adult , Animals , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Cell Adhesion Molecules/genetics , Cell Line, Tumor , Cell Movement/physiology , Extracellular Matrix Proteins/genetics , Female , Humans , Male , Membrane Proteins , Mice , Mice, Inbred BALB C , Osteosarcoma/genetics , Osteosarcoma/pathology , Prognosis , RNA-Binding Proteins , Signal Transduction , Transfection , Up-Regulation , Young Adult
19.
Exp Ther Med ; 6(1): 77-84, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23935723

ABSTRACT

The aim of this study was to examine the effects of metabolic syndrome (MS) and the number of MS components on the development of non-alcoholic fatty liver disease (NAFLD). A total of 1,343 males and 574 females aged ≥50 years without NAFLD at baseline were included. Information on lifestyle, including alcohol use and personal history, was collected by face-to-face interviews. Biochemical parameters were assayed using fasting blood samples. NAFLD was diagnosed by abdominal ultrasonography. During follow-up at an average of 4.8 years, 223 patients developed NAFLD. Following adjustment for multiple covariates, age was an independent protective predictor [hazard ratio (HR), 0.96; 95% confidence interval (CI), 0.95-0.98], while the independent risk predictors were obesity (HR, 2.81; 95% CI, 2.14-3.69), higher triglycerides (HR, 2.56; 95% CI, 1.95-3.32) and alanine aminotransferase (HR, 1.004; 95% CI, 1.000-1.008). Participants with a diagnosis of MS had a significantly increased risk of developing NAFLD (HR, 3.17; 95% CI, 2.42-4.14). A greater number of MS components was significantly associated with a higher risk of NAFLD (all adjusted P for trend <0.001). Compared with those without any components of MS, participants with only one component of MS had a 3.6-fold higher risk of developing NAFLD (adjusted HR, 3.64; 95% CI, 1.50-8.88). The diagnosis and the number of components of MS were prospectively associated with the risk of developing NAFLD. Even in those with only one component of MS, the risk increased by 2.6-fold compared with that for the individuals without any components, suggesting a beneficial effect of intervention at the very early stage of MS on the prevention of NAFLD.

20.
Tohoku J Exp Med ; 227(4): 253-62, 2012 08.
Article in English | MEDLINE | ID: mdl-22820754

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is defined as excessive accumulation of fatty acid in the liver, a common disease in the world. The research of single nucleotide polymorphisms (SNPs) provides a new approach for managing NAFLD. SNPs may increase or decrease the functions of the target genes and their encoding proteins. Peroxisome proliferator-activated receptor (PPAR) plays a key role in modulating metabolism of hepatic triglycerides and consequently magnitude of NAFLD. In this study, we investigated the effect of three SNPs in the PPAR-γ gene i.e. rs10865710 (C-681G), rs7649970 (C-689T) and rs1801282 (C34G, also termed Pro12Ala) on susceptibility to NAFLD. The participants were selected from our epidemiological survey. Totally 169 participants were enrolled in NAFLD group, and 699 healthy subjects were included as controls. PCR-RFLP was applied to detect the SNPs. The G allele frequency of rs10865710 in NAFLD group (41.1%) was significantly higher than that (34.8%) in controls (p = 0.03). Differences in other two loci (rs7649970 and rs1801282) were not statistically significant between the two groups (p > 0.05). This result was confirmed by haplotype analysis. The GCC haplotype (a set of 3 adjacent SNPs in linkage disequilibrium, corresponding to the three alleles of above polymorphisms in order) was a risk factor for the susceptibility to NAFLD (p = 0.03). This study has revealed that the G allele of rs10865710 in the PPAR-γ gene is associated with the increased susceptibility to NAFLD. Our findings may provide novel diagnostic biomarkers and therapeutic targets for NAFLD.


Subject(s)
Fatty Liver/genetics , Genetic Predisposition to Disease , PPAR gamma/genetics , Polymorphism, Single Nucleotide/genetics , Aged , Case-Control Studies , Demography , Female , Genetic Loci/genetics , Haplotypes/genetics , Humans , Male , Middle Aged , Multivariate Analysis , Non-alcoholic Fatty Liver Disease , Regression Analysis , Risk Factors
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