Influence of ursodeoxycholic acid on blood glucose, insulin and GLP-1 in rats with liver fibrosis induced by bile duct ligation.

BACKGROUND: The prevalence of impaired glucose tolerance and diabetes is much higher in people with cirrhosis than that in the general population. However, there are inadequate concrete guidelines for the management of diabetes in these patients, particularly in the early stage. Bile aids (BAs) have been found to exert hormone-like functions in the control of lipid and glucose metabolism. We studied the effect of ursodeoxycholic acid (UDCA) on glucose levels in rats with cirrhosis induced by bile duct ligation (BDL). METHODS: SD rats were divided into three groups: sham operation (Group A); BDL (Group B), and UDCA plus BDL (Group C). After 4 weeks, oral glucose tolerance tests were performed. Serum biochemical parameters and the levels of glucose, insulin, and glucagon-like peptide 1 (GLP-1) were measured. Histopathology of the liver and islet was observed. The gene expression of cholesterol 7α-hydroylase (CYP7A1), microsomal oxysterol 7a-hydroxylase (CYP7B1) in the liver, and Takeda G-protein-coupled receptor-5 (TGR5) in the intestine was determined by real-time PCR. RESULTS: Compared with Group A, fasting glucose and 1-h and 2-h postprandial glucose levels increased slightly (all P > 0.05), 2-h postprandial insulin levels increased significantly (P < 0.05), 15 min postprandial GLP-1 levels decreased (P < 0.05) in Group B. Compared with Group B, fasting glucose and 1-h postprandial glucose levels decreased (all P < 0.05), 2-h postprandial insulin levels decreased (P < 0.01), and 15 min postprandial GLP-1 levels increased (P < 0.05) in Group C. After UDCA intervention, liver fibrosis induced by BDL was alleviated, and the islet areas were increased (P < 0.05). Compared with Group A, the mRNA expression of CYP7A1 and CYP7B1 in the liver increased, and the mRNA expression of TGR5 in the intestine decreased in Group B (all P < 0.05). Compared with Group B, the mRNA expression of CYP7A1 and CYP7B1 in the liver decreased, and TGR5 in the intestine increased in Group C (P < 0.05). CONCLUSIONS: After 4 weeks of BDL, the rats developed liver fibrosis and abnormal glucose metabolism. UDCA administration improved liver fibrosis, increased islet area, decreased glucose levels, inhibited genes in BA synthesis, enhanced TGR5 gene expression in the intestine, and further improved islet function.

Molecular mechanisms of Baihedihuang decoction as a treatment for breast cancer related anxiety: A network pharmacology and molecular docking study.

BACKGROUND: The therapeutic effects of a combination of Chinese medicines called Baihedihuang decoction (BD) have been clinically verified, although its molecular targets in breast cancer related anxiety remain unknown. AIM: To explore the molecular mechanisms of BD for breast cancer related anxiety treatment. METHODS: We used the Traditional Chinese Medicine Systems Pharmacology database to screen the active ingredients and potential targets of BD, and constructed the "drug-ingredient-target" network map with the help of Cytoscape 3.8 software. Also, we used the Online Mendelian Inheritance in Man, DrugBank, and Gencards databases to collect the disease targets of breast cancer related anxiety, and used the STRING platform to perform protein interaction analysis and construct the protein-protein interaction network. Metascape platform was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of key targets. Molecular docking technology was used to verify the drug component/target disease network. RESULTS: We screened 16 active ingredients of BD for breast cancer related anxiety, with 113 target proteins. There are 931 disease targets of breast cancer related anxiety, and finally, 43 key targets and 305 Kyoto Encyclopedia of Genes and Genomes pathways were generated. The main active ingredients of BD for breast cancer related anxiety are verbascoside, ß-sitosterol, stigmasterol, catalpol, etc. CDK2, TP53, HTR2A, ESR1, etc. are its key targets, and the main involved signaling pathways may include neuroactive ligand-receptor interaction pathway, 5-hydroxytryptaminergic synapse, P53 signaling pathway, cGMP-PKG signaling pathway, the cAMP signaling pathway, etc. Finally, molecular docking was performed with Vina software to validate the key active ingredients in BD with the selected key action targets. The molecular docking results showed that verbascoside, ß-sitosterol, stigmasterol and CDK2 could stably bind and interact through amino acid residues SER249, ARG260, PRO228, ALA282, SER276, LYS273, ASN272, etc. CONCLUSION: The therapeutic effect of BD for breast cancer related anxiety is multi-level, multi-target, and multi-pathway. The findings of this study provide ideas and basis for further research.

Berberine exerts its antineoplastic effects by reversing the Warburg effect via downregulation of the Akt/mTOR/GLUT1 signaling pathway.

Glucose transporter 1 (GLUT1) plays a primary role in the glucose metabolism of cancer cells. However, to the best of our knowledge, there are currently no anticancer drugs that inhibit GLUT1 function. The present study aimed to investigate the antineoplastic activity of berberine (BBR), the main active ingredient in numerous Traditional Chinese medicinal herbs, on HepG2 and MCF7 cells. The results of Cell Counting Kit­8 assay, colony formation assay and flow cytometry revealed that BBR effectively inhibited the proliferation of tumor cells, and induced G2/M cell cycle arrest and apoptosis. Notably, the results of luminescence ATP detection assay and glucose uptake assay showed that BBR also significantly inhibited ATP synthesis and markedly decreased the glucose uptake ability, which suggested that the antitumor effect of BBR may occur via reversal of the Warburg effect. In addition, the results of reverse transcription­quantitative PCR, western blotting and immunofluorescence staining indicated that BBR downregulated the protein expression levels of GLUT1, maintained the cytoplasmic internalization of GLUT1 and suppressed the Akt/mTOR signaling pathway in both HepG2 and MCF7 cell lines. Augmentation of Akt phosphorylation levels by the Akt activator, SC79, abolished the BBR­induced decrease in ATP synthesis, glucose uptake, GLUT1 expression and cell proliferation, and reversed the proapoptotic effect of BBR. These findings indicated that the antineoplastic effect of BBR may involve the reversal of the Warburg effect by downregulating the Akt/mTOR/GLUT1 signaling pathway. Furthermore, the results of the co­immunoprecipitation assay demonstrated that BBR increased the interaction between ubiquitin conjugating enzyme E2 I (Ubc9) and GLUT1, which suggested that Ubc9 may mediate the proteasomal degradation of GLUT1. On the other hand, BBR decreased the interaction between Gα­interacting protein­interacting protein at the C­terminus (GIPC) and GLUT1, which suggested that the retention of GLUT1 in the cytoplasm may be achieved by inhibiting the interaction between GLUT1 and GIPC, thereby suppressing the glucose transporter function of GLUT1. The results of the present study provided a theoretical basis for the application of the Traditional Chinese medicine component, BBR, for cancer treatment.

Influence of Liver Cirrhosis on Blood Glucose, Insulin Sensitivity and Islet Function in Mice.

BACKGROUND: The relationship between cirrhosis and diabetes is controversial. We studied the influence of cirrhosis on glucose levels and islet function and explored its possible mechanisms. MATERIALS AND METHODS: Cirrhosis was induced in male C57BL/6 mice by bile duct ligation (BDL). Serum biochemical parameters were determined, and oral glucose tolerance tests (OGTT) were performed at 4 and 8 weeks after BDL. Histopathology and phospho-NF-κB-p65/I-kappa B α immunohistochemical staining of the liver and islet were observed. The protein levels of the insulin signaling system and the gene expression of insulin-degrading enzyme (IDE) in the liver and muscle were determined. The activity of glucokinase (GCK) and glucose 6-phosphatase (G6P) and glycogen levels in liver homogenates were measured. RESULTS: After BDL, the mice developed cirrhosis, and fasting glucose decreased significantly, but 2 h postprandial glucose increased, and the insulin areas under the curves increased. At 4 weeks of BDL, the ratios of phospho-NF-κB-p65/I-kappa B α accumulation in the liver and islet increased, the activity of G6P and the glycogen content in liver homogenates decreased, the insulin signaling system and the gene expression of IDE in the liver was downregulated, and the islet areas were decreased. After 8 weeks, these changes were more severe. CONCLUSIONS: In different periods of cirrhosis, the levels of fasting glucose and 2 h postprandial glucose changed in different amplitudes. Glycogen concentrations and the activity of G6P in the liver were decreased. The mice developed insulin resistance and the islet areas were decreased. The NF-κB pathway may play a role in the process.

Influences of sterol regulatory element binding protein-1c silencing on glucose production in HepG2 cells treated with free fatty acid.

BACKGROUND: Elevation of exogenous free fatty acid (FFA) level leads to insulin resistance (IR) in liver, IR is manifested by elevated hepatic glucose production. We aim to study whether inhibition of endogenous fatty acid synthesis could decrease hepatic glucose production. METHODS: Low-passage HepG2 cells derived from human liver tissue were cultured in medium supplemented with FFA to induce IR, the influences of sterol regulatory element binding protein-1c (SREBP-1c) silencing on glucose production of HepG2 cells were investigated, and genes responsible for fatty acid and glucose metabolism were detected by real-time PCR. RESULTS: Compared with HepG2 cells cultured in normal growth medium, glucose production of HepG2 cells treated by FFA was significantly increased {[(0.28 ± 0.01) vs (0.83 ± 0.02)] umol.ug- 1 protein, n = 6 wells, P < 0.01}; the mRNA expression of phosphoenolpyruvate carboxylase kinase (PEPCK) and glucose-6-phosphatase (G6PC) in HepG2 cells increased by more than 5-fold and 3-fold, respectively; the mRNA expression of fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD1) increased by approximately 4-fold and 1.1-fold, respectively; the mRNA expression of carnitine palmitoyltransferase-1 (CPT-1) changed slightly. Compared with the scrambled siRNA control, glucose production of HepG2 cells treated by FFA significantly increased after SREBP-1c silencing {[(0.018 ± 0.001) vs (0.028 ± 0.002)] umol.ug- 1 protein, n = 6 wells, P < 0.01}; the mRNA expression of PEPCK and G6PC increased by approximately 1.5-fold and 5-fold, respectively, but the mRNA expression of FAS, SCD1 and CPT-1 changed slightly. CONCLUSIONS: SREBP-1c silencing further augmented glucose production of HepG2 cells treated by FFA significantly, genes responsible for fatty acid synthesis and gluconeogenesis played an important role in this process. SREBP-1c functions not only as a lipid regulator but also plays an important role in regulation of glucose metabolism.

Clinical significance of aberrant cyclin-dependent kinase-like 2 methylation in hepatocellular carcinoma.

BACKGROUND AND AIMS: Aberrant DNA methylation of cyclin-dependent kinase-like 2 (CDKL2) had been observed in several types of tumors. Herein, the present study was aimed to explore the epigenetic and expression status of CDKL2 and evaluate the diagnostic potential of CDKL2 methylation in hepatocellular carcinoma (HCC). METHODS: The methylation status of CDKL2 was detected by methylation-sensitive restriction enzyme based quantitative PCR (MSRE-qPCR) and bisulfite genomic sequencing (BGS). The mRNA expression of CDKL2 was measured using real-time quantitative PCR (qPCR). The correlations between the methylation of CDKL2 and mRNA expression, clinicopathological features were evaluated. RESULTS: Compared with normal liver tissues, the methylation levels of CDKL2 were significantly increased in the HCC tissues and cell lines (All p < 0.05). And the receiver operating characteristic (ROC) analysis showed that the hypermethylation of CDKL2 had a high specificity and sensitivity to distinguish adjacent non-tumor tissues from HCC tissues. Additionally, the mRNA expression levels of CDKL2 were decreased both in HCC tissues and cell lines than those in normal liver tissues (All p < 0.05), and the expression could be upregulated by 5-aza-2'-deoxycytidine treatment in HCC cell lines. Furthermore, the methylation of CDKL2 was negatively correlated with its mRNA expression (p < 0.001, rs = -0.513), and was associated with gender (p = 0.023), age (p = 0.001) and tumor size (p = 0.016). CONCLUSIONS: Our results showed that CDKL2 promoter hypermethylation played an important role in hepatocarcinogenesis and might be a valuable biomarker for HCC diagnosis.

Study on Colloidal Model of Petroleum Residues through the Attraction Potential between Colloids.

The samples of DaGang atmospheric residue (DG-AR), Middle East atmospheric residue (ME-AR), TaHe atmospheric residue (TH-AR), and their thermal reaction samples were chosen for study. All the samples were fractioned into six components separately, including saturates plus light aromatics, heavy aromatics, light resins, middle resins, heavy resins, and asphaltenes. The dielectric permittivity of the solutions of these components was measured, and the dielectric permittivity values of the components can be determined by extrapolation, which increased steadily from saturates plus light aromatics to asphaltenes. Moreover, the Hamaker constants of the components were calculated from their dielectric permittivity values. The Van der Waals attractive potential energy between colloids corresponding to various models could be calculated from the fractional composition and the Hamaker constants of every component. It was assumed that the cores of colloidal particles were formed by asphaltenes and heavy resins mainly; the other fractions acted as dispersion medium. For the three serials of thermal reaction samples, the Van der Waals attraction potential energy between colloids for this kind of model was calculated. For TH-AR thermal reaction samples, the Van der Waals attraction potential energy presented the maximum as thermal reaction is going on, which was near to the end of coke induction period.

[Relationship between RAD51-G135C and XRCC3-C241T Single Nucleotide Polymorphisms and Onset of Acute Myeloid Leukemia].

OBJECTIVE: To investigate the relationship between RAD51-G135C and XRCC3-C241T single nucleotide polymorphisms and onset of acute myeloid leukemia (AML). METHODS: The study was performed in 2 groups: AML patient group and normal person group as control group. Genomic DNA was extracted from peripheral blood cells of 545 AML patients and 1 034 normal persons. Genotypes of RAD51-G135C and XRCC3-C241T were analyzed by TaqMan probe technology and the ralatienship between RAD51-G135C/XRCC3-C241T polymorphisms and onset of acute myeloid leukemia was investigated. RESULTS: Compared with the control group, RAD51-G135C homozygous mutant (CC) could significantly increase the risk of AML patients (OR=3.07), and there was no statistical relationship between heterozygous mutant (GC) of RAD51-G135C and onset of AML. There was no statistical relationship between homozygous mutant (TT) of XRCC3-C241T and onset of AML, and the XRCC3-C241T heterozygous mutation type (CT) increased the risk of AML patients (OR=0.66). CONCLUSION: RAD51-G135C homozygous mutant and XRCC3-C241T heterozygous mutation significantly increase the risk of the AML onset, which can provide more predictive value for incidence of AML.

[Polymorphisms of FcγRIIA, FcγRIIIA and FcγRIIB in patients with immune thrombocytopenia and their clinical significance].

This study was aimed to investigate the correlation of FcγR polymorphisms with the susceptibility, severity and efficacy of immunotherapy for patients with immune thrombocytopenia (ITP). PCR and DNA sequencing were used to determine the polymorphisms of FcγRIIA, FcγRIIIA and FcγRIIB in 44 ITP patients, and in 97 healthy control subjects. The results indicated that FcγRIIIA-158V/F polymorphisms between patients and controls were statistically significantly different (P = 0.015); among FcγRIIIA genotypes, the frequency of 158V/V homotype was higher in ITP (P = 0.005). However, the FcγRIIA-131H/R or FcγRIIB-232T/I polymorphisms were not significantly different between patients and controls; there were no correlation of FcγRIIA, FcγRIIIA and FcγRIIB genotype frequencies with the platelet counts or the courses of ITP; among the 38 ITP patients who received treatments, the complete response (CR) rate was 42% (16/38), and partial response (PR) rate was 34% (13/38). The therapeutic response was significantly different between FcγRIIIA-158V/V homotype and 158F/V heterotype (P = 0.034). The CR of patients with 158V/V homotype was obviously lower than that of patients with 158F/V, but the frequencies of FcγRIIA and FcγRIIB genotypes not correlated with the responsiveness to treatment. The CR rate of 6 patients treated with rituximab was 67%, and PR rate was 17%. The overall response rate was as high as 84%, the adverse reactions were not observed. It is concluded that the polymorphism of FcγRIIIA-158V/F, but not FcγRIIA-131H/R or FcγRIIB-232T/I, correlates with the patient susceptibility and therapeutic response of ITP.

[Research advances on correlation of ARID5B gene with childhood acute lymphoblastic leukemia - review].

Childhood acute lymphoblastic leukemia (C-ALL) is the most common pediatric cancer. Although its etiology remains poorly understood, the hypothesis of ALL correlated with a genetic basis was examined through association studies based on candidate genes. Recently, two independent large-scale genome-wide association studies reported that the five single nucleotide polymorphisms (rs7073837; rs10821936; rs10994982; rs7089424; rs10740055) in the gene AT rich interactive domain 5B (ARID5B) at 10q21.2, were associated with the high incidence risk of C-ALL, especially with hyperdiploid lymphoblastic leukemia. Variations in these single nucleotide polymorphisms influence the risk of specific disease subtypes, and also possess race- and sex-differences in leukemia incidence. Further elucidation of the mechanisms through which ARID5B variants are involved in C-ALL not only has a great diagnostic value, but also a guidance for the clinical therapy, ultimately improving the prognosis of disease. Therefore, the related studies of ARID5B with C-ALL were summarized briefly in this review.

JAK2 V617F, MPL W515L and JAK2 Exon 12 Mutations in Chinese Patients with Primary Myelofibrosis.

OBJECTIVE: JAK2 V617F, MPL W515L and JAK2 exon 12 mutations are novel acquired mutations that induce constitutive cytokine-independent activation of the JAK-STAT pathway in myeloproliferative disorders (MPD). The discovery of these mutations provides novel mechanism for activation of signal transduction in hematopoietic malignancies. This research was to investigate their prevalence in Chinese patients with primary myelofibrosis (PMF). METHODS: We introduced allele-specific PCR (AS-PCR) combined with sequence analysis to simultaneously screen JAK2 V617F, MPL W515L and JAK2 exon 12 mutations in 30 patients with PMF. RESULTS: Fifteen PMF patients (50.0%) carried JAK2 V617F mutation, and only two JAK2 V617F-negative patients (6.7%) harbored MPL W515L mutation. None had JAK2 exon 12 mutations. Furthermore, these three mutations were not detected in 50 healthy controls. CONCLUSION: MPL W515L and JAK2 V617F mutations existed in PMF patients but JAK2 exon 12 mutations not. JAK2 V617F and MPL W515L and mutations might contribute to the primary molecular pathogenesis in patients with PMF.

[Role of CD44(+)/ESA(+) in sorting colonic cancer stem cells].

OBJECTIVE: To isolate CD133(+)/CD44(+)/ESA(+) subsets cells from SW480 colon cancer cells, and to observe the tumor formation. METHOD: CD133(+)/CD44(+)/ESA(+) subsets cells, CD133(-)/CD44(+)/ESA(+) subsets cells and CD133(-)/CD44(-)/ESA(-) subsets cell were sorted by flow cytometry from SW480 colon cancer cells, then three subsets were separately inoculated in five NOD/SCID mice and the growth rates were calculated. RESULT: The proportion of CD133(-)/CD44(-)/ESA(-), CD133(-)/CD44(+)/ESA(+) and CD133(+)/CD44(+)/ESA(+) subsets cells in SW480 cells were (86.38±10.23)%,(1.26±0.28)% and(0.38±0.07)%. After inoculation, tumor nodules could be formed three days later in CD133(+)/CD44(+)/ESA(+) group, and they could be formed 9 days later in CD133(-)/CD44(+)/ESA(+) group, while they could be formed 15 days later in CD133(-)/CD44(-)/ESA(-) group. Eighteen days later, tumor sizes in three groups were(13.82±5.04) mm(3), (9.25±4.57) mm(3) and (4.76±3.92) mm(3) respectively, and the differences were statistically significant(P<0.05). CONCLUSION: ESA(+)-CD44(+) is one of the surface markers for colonic cancer stem cells, and CD133(+)-CD44(+)-ESA(+) cells are SW480-like cancer stem cells.

Association between four adipokines and insulin sensitivity in patients with obesity, type 1 or type 2 diabetes mellitus, and in the general Chinese population.

BACKGROUND: Hyperinsulinemic euglycemic clamp is the gold standard to evaluate the insulin sensitivity, but it is too complicated and expensive to use in clinic. We tried to find an alternative indicator to reflect insulin sensitivity. To evaluate the association between the four adipokines, adiponectin, leptin, resistin and tumor necrosis factor-alpha (TNF-alpha) with insulin sensitivity, we used a hyperinsulinemic euglycemic clamp to test insulin sensitivity in Chinese patients with obesity and type 1 or type 2 diabetes mellitus versus controls. METHODS: In this parallel control study, we tested insulin sensitivity using a hyperinsulinemic euglycemic clamp in different groups, then examined levels of adiponectin, leptin, resistin and TNF-alpha in serum, and the relationship between the different adipokines and glucose disposal rate (M value), as well as insulin sensitivity index (M value/insulin, M/I), which are the "gold standard" indices of insulin sensitivity. RESULTS: There were significant differences in mean leptin values in the four adipokines from the four different groups (P < 0.001; comparison of the variation between different groups was analyzed by variance analysis). Compared to controls (using multiple comparison two-way Dunnett t test), only the leptin level showed significant differences in the four adipokines from the four different groups at the same time (P < 0.001). The association analysis between the different adipokines and M or M/I values also showed that only leptin negatively correlated with M (r = -0.64, P < 0.001) or M/I values (r = -0.56, P < 0.001); there was no relationship between the other three adipokines and M or M/I values. CONCLUSION: Only leptin was associated with M or M/I values. Therefore, leptin might be one of the predictive factors of the degree of insulin resistance and risk of the accompanying disease.

Toxoplasma gondii: expression of GRA1 gene in endoplasmic reticulum promotes both growth and adherence and modulates intracellular calcium release in macrophages.

In this study, effects of GRA1 organelle-targeted expression on macrophage functions were investigated. The recombinant plasmid pCMV/myc/ER-GRA1 was constructed and then was transfected into murine macrophage RAW264.7 by Lipofectamine, selected by resistance of G418. The selected mono-clone cell line was named ER-GRA1-RAW264.7. The expression of GRA1 was localized in ER of ER-GRA1-RAW264.7 cells by indirect immunofluorescence detection. GRA1 mRNA expression level in ER-GRA1-RAW264.7 cell was significantly enhanced with a concomitant increase in its growth and adherence activity. Fluorescence intensity of intracellular calcium in ER-GRA1-RAW264.7, ER-ctrl-RAW264.7 and RAW264.7 cells in the presence of 1 mmol/l arachidonic acid (AA) were assayed by confocal microscopy using calcium-sensitive dye, Fluo-3 AM. Cytoplasm [Ca2+]i peaked at about 18 s after AA treatment, and cytoplasm [Ca2+]i of RAW264.7 cell almost instantly stepped up after AA was added, and peaked in 3 s, with a minor cytoplasm [Ca2+]i vibration subsequently. These results demonstrated that the expression of GRA1 in ER of macrophages promotes both growth and adherence of macrophages and modulates the intracellular calcium release stimulated by AA.

Inhibitory effect of modified citrus pectin on liver metastases in a mouse colon cancer model.

AIM: To discuss the expression of glactin-3 in liver metastasis of colon cancer and its inhibition by modified citrus pectin (MCP) in mice. METHODS: Seventy-five Balb/c mice were randomly divided into negative control group (n = 15), positive control group (n = 15), low MCP concentration group (n = 15), middle MCP concentration group (n = 15) and high MCP concentration group (n = 15). CT26 colon cancer cells were injected into the subcapsule of mouse spleen in positive control group, low, middle and high MCP concentrations groups, except in negative control, to set up a colon cancer liver metastasis model. The concentration of MCP in drinking water was 0.0%, 0.0%, 1.0%, 2.5% and 5.0% (wt/vol), respectively. Liver metastasis of colon cancer was observed after 3 wk. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of galectin-3 in serum. Expression of galectin-3 in liver metastasis was detected by immunohistochemistry. RESULTS: Except for the negative group, the percentage of liver metastasis in the other 4 groups was 100%, 80%, 73.3% and 60%, respectively. The number of liver metastases in high MCP concentration group was significantly less than that in positive control group (P = 0.008). Except for the negative group, the median volume of implanted spleen tumor in the other 4 groups was 1.51 cm(3), 0.93 cm(3), 0.77 cm(3) and 0.70 cm(3), respectively. The volume of implanted tumor in middle and high MCP concentration groups was significantly smaller than that in positive control group (P = 0.019; P = 0.003). The concentration of serum galectin-3 in positive control and MCP treatment groups was significantly higher than that in the negative control group. However, there was no significant difference between them. Except for the negative control group, the expression of galectin-3 in liver metastases of the other 4 groups showed no significant difference. CONCLUSION: Expression of galetin-3 increases significantly in liver metastasis of colon cancer, which can be effectively inhibited by MCP.

[Influence of short-term high-fat diet on glucose and lipid metabolism in male Han Chinese with type 2 diabetes mellitus].

OBJECTIVE: To investigate the influence of short-term high-fat diet (HFD) on glucose and lipid metabolism in male Han Chinese with type 2 diabetes mellitus (T2DM). METHODS: Middle-aged T2DM men supported with solely diet or diet and metformin were enrolled into the study. The design was an unblinded crossover design. Each of the subjects randomly received one from two types of isocalorie (8786.4 kJ/d) standard diet for three consecutive days on two occasions, with a 6-week wash-out period in between. The component ratios of fat, carbohydrate, and protein were 50%, 35%, and 15% vs. 25%, 60%, and 15% in patients administered with HFD or high carbohydrate diet (HCD). The 24-hour blood samples during the third day were collected. On the morning of the forth day an intravenous glucose tolerance test (IVGTT) was conducted with 25g of glucose. RESULTS: According to the determination results of 24-hour profile samples, HFD resulted in a markedly increased circulating level of non-esterified fatty acid (NEFA) as compared to HCD (P < 0.001). Nearly significant higher (P = 0.056) FPG was observed 72 hours after the administration of HFD. Circulating insulin levels were comparable between the two diets. A significantly higher HDL-C was also observed after HFD administration (P < 0.05). As assessed by the IVGTT, acute insulin response of glucose (AIRg) tended to increase after the HFD administration (P = 0.06). Fasting plasma glucagons (GLG) level and AUC(Glucagon) during breakfast period (8:00-12:00) were significantly higher after HFD administration than that of after HCD administration. CONCLUSIONS: Short-term HFD induced the increase of NEFA with lower glucose exposure to the patietns. Fasting plasma glucose increased at the fourth day without remarkable changes of insulin levels which may be due to the increase of hepatic glucose output after HFD administration. The short-term HFD in our study induced early stage of insulin resistance. GLG seemed to play a role in this procedure. beta-cell dysfunction may need a longer high NEFA exposure.

Effects of glucagon on islet beta cell function in patients with diabetes mellitus.

OBJECTIVE: To evaluate islet beta cell response to intravenous glucagon (a non-glucose secretagogue) stimulation in diabetes mellitus. METHODS: Nineteen patients with type 1 diabetes (T1D) and 131 patients with type 2 diabetes (T2D) were recruited in this study. T2D patients were divided into two groups according to therapy: 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intravenous injection of 1 mg of glucagon. RESULTS: Both fasting and 6-minute post-glucagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients (0.76 +/- 0.36 ng/mL vs. 1.81 +/- 0.78 ng/mL, P < 0.05; 0.88 +/- 0.42 ng/mL vs. 3.68 +/- 0.98 ng/mL, P < 0.05). In T1D patients, the C-peptide level after injection of glucagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy (2.45 +/- 0.93 ng/mL vs. 1.61 +/- 0.68 ng/mL, P < 0.05; 5.26 +/- 1.24 ng/mL vs. 2.15 +/- 0.76 ng/mL, P < 0.05). The serum C-peptide level after glucagon stimulation was positively correlated with C-peptide levels at fasting in all three groups (r = 0.76, P < 0.05). CONCLUSIONS: The 6-minute glucagon test is valuable in assessing the function of islet beta cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus.

[Association between A1168C polymorphism in PAX4 gene and type 1 diabetes in Han Chinese].

OBJECTIVE: To explore whether A1168C polymorphisms in paired box gene 4 (PAX4) are associated with type 1 diabetes mellitus (T1DM) in Chinese Han population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to genotype A1168C polymorphisms in PAX4 gene. Totally 109 patients with T1DM and 251 control subjects were recruited. The frequency distributions of genotypes between two groups were analyzed by SPSS software. RESULTS: The genotype distributions were in Hardy-Weinberg equilibrium both among T1DM cases and control subjects. No difference was observed in the genotype frequencies and allele frequencies between T1DM cases and control subjects (P > 0.05), nor was any disease association detected when patients were stratified according to age at diagnosis or sex (P > 0.05). CONCLUSION: The A1168C single nucleotide polymorphism in PAX4 gene may not play an essential role in genetic T1DM susceptibility in Chinese Han population.

[The effects of lipiodol-hydroxyapatite nanoparticle on apoptosis, proliferation, and angiogenesis in hepatic tumor: experiment with rabbits].

OBJECTIVE: To investigate the effects of lipiodol-hydroxyapatite nanoparticle (lipi-nHAP) on the growth, necrosis, apoptosis, proliferation, and angiogenesis of hepatic tumor. METHODS: Ultrasound-emulsification was used to make lipi-nHAP Eighty New Zealand white rabbits underwent implantation of carcinoma cells of the line VX2 into the left lobe of liver. Two weeks later the rabbits underwent catheterization into the gastroduodenal artery so that, and then the rabbits were randomly divided into four equal groups to receive infusion via the hepatic artery of different drugs: physiological saline (Group A), lipiodol (Group B), adriamycin + lipiodol (Group C), and lipi-nHAP (Group D). Seven and 14 days after the treatment the size of tumor was observed by spiral CT scan, and the volume and growth rate of tumor were calculated. Two weeks after the treatment 8 rabbits from each group were killed and their liver tumors were taken out and the survival rates of remaining rabbits were observed. The necrosis rate of the liver tumor was assessed by measuring the area of the tumor and the necrosis. The apoptotic rate was examined by TUNEL method. Mcrovessel density (MVD) was examined by immunohistochemistry anti-CD31 antibody. Anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody was used to detect the expression of PCNA so as to calculate the proliferation index of the cells. RESULTS: The tumor volume and growth rate of Group D 7 and 14 days after treatment were both significantly lower than those of other groups (all P < 0.05) and the necrosis rate and apoptotic index of Group D were both significantly higher than those of other groups (all P < 0.05). The values of MVD were higher in Groups C and D compared with those of Group A. Compared with those in other groups, the values of MVD and expression level of PCNA were significantly lower in group D (all P < 0.05). The survival time of Group D was longer than those of other groups (all P < 0.05). CONCLUSION: lipi-nHAP can suppress the growth of tumor, increase the tumor's necrosis rate and apoptotic index, inhibit the development of neovascularization, decrease the expression level of PCNA of residual tumor, and prolong the surviving time of the animals with hepatic tumor. It may become an effective embolization material to treat liver cancer.

Relationship between hemoglobin A1c and blood glucose throughout the day in well-glycemic-controlled medical nutrition therapy alone type 2 diabetic patients.

OBJECTIVE: To investigate the relationship between glycosylated hemoglobin A1c (HbA1c) and blood glucose levels of eight different points throughout the day in well-glycemic-controlled medical nutrition therapy (MNT) alone type 2 diabetic patients. METHODS: Data were collected as' capillary blood glucose value of eight different sample points among sixteen observing days in thirty MNT alone type 2 diabetic patients. The correlation between HbA1c and capillary blood glucose value was evaluated by Pearson's correlation method. RESULTS: The r-values between HbA1c and capillary blood glucose of 3:00, 6:00, and bedtime (22:00-23:00) were 0.81, 0.79, and 0.78, respectively (P < 0.001). The best correlation was found between the mean value of 8-point blood glucose value throughout the day and HbA1c (r = 0.84, P < 0.001). CONCLUSION: Fasting blood glucose and postabsorptive blood glucose have better correlations with HbA1c compared with other points in this group of well-glycemic-controlled MNT alone type 2 diabetic patients.