The purpose of this paper is to clarify the structure-activity relationship of anti-tumor activity of diosgenin derivatives in vitro. Study has found that diosgenin can inhibit the reproduction of tumor cells by inducing apoptosis and the main target spot of this effect is Bcl-2. Based on the characteristics of pharmacophoric points' of the three-dimensional pharmacophore for Bcl-2 inhibitors, we have docked lots of diosgenin derivatives with Bcl-2, then synthesized 31 compounds of them, finally assessed the anti-tumor activity of the diosgenin derivatives in vitro against A375, A549, HepG-2 and K562. Preliminary studies of SAR have indicated that the aliphatic esters, and aromatic esters of diosgenin without F ring have no anti-tumor activity in vitro. The triazole bromides of diosgenin all achieve fairly good anti-tumor activity in vitro, and those with larger hydrophobic group have the better activity. The stronger is the hydrogen bonding interaction and dipole-dipole interaction of the heterocyclic of diosgenin and diosgenin without F ring and the acid ester of diosgenin without F ring, the better is the activity of derivatives.
Antineoplastic Agents, Phytogenic ; chemical synthesis ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Diosgenin ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; antagonists & inhibitors ; Structure-Activity Relationship

To investigate the relationship and significance of Wnt/b-catenin signaling pathway with caspase-3, XIAP, HSP27and Grp-78. The HCC cell line HepG2 was transfected with small interfering RNA (siRNA) directed against b-catenin. After 72 and 96 h, protein was extracted and the protein expressions of b-catenin, caspase-3, XIAP, Grp-78 and HSP27 were detected by Western blot. b-catenin protein expression was inhibited at both time points and the expression at 96 h was higher than that at 72 h (F = 160.72, P is less than to 0.01). Interestingly, Caspase-3 protein expression was decreased at 72 h and increased to normal at 96 h (F = 136.10, P is less than to 0.01), while p-caspase-3 protein expression increased at 72 h and decreased to normal at 96 h (F = 98.65, P is less than to 0.01). XIAP protein expression decreased at 72 h (F = 37.29, P is less than to 0.01) and increased at 96 h. Grp-78 protein expression increased at 72 h and decreased to normal at 96 h ( F = 58.72, P is less than to 0.01). HSP27 protein expression showed no change following transfection ( F = 1.91, P is more than to 0.05). Wnt/b-catenin signaling pathway is related to the protein expressions of caspase-3, XIAP and Grp-78, but not related to HSP27 protein expression in HCC. Wnt/b-catenin signaling pathway may participate in the regulation of HCC apoptosis, proliferation and differentiation through affecting these factors.
Carcinoma, Hepatocellular ; Caspase 3 ; Catenins ; Humans ; Liver Neoplasms ; Wnt Signaling Pathway ; beta Catenin ; metabolism

Studies have found that metformin is not only the preferred drug for lowering blood sugar, but also shows lipid-lowering and weight-loss effects. The purpose of this study was to use a hyperlipidemia hamster model to investigate the lipid-lowering effect of metformin and its effect on important metabolic pathways in lipid metabolism disorders. Fifty golden hamsters were divided into a control group, a model group, metformin high- and low-dose groups, and a simvastatin group. A high-fat diet was fed for 1 week to create the model, and then drug was administered for 11 weeks with the high-fat diet. Serum was taken for measurement of blood lipid and blood glucose at 2, 6, and 9 weeks after administration, and at weeks 3, 5, and 9 feces and urine were collected for ¹H NMR metabolomics tests. After 11 weeks of intravenous injection of [U-¹³C₆] glucose, serum was collected for a ¹³C NMR metabolic flux test. The results showed that the administration of metformin can significantly reduce blood lipids and glucose levels and can significantly affect metabolic pathways such as sugar metabolism, lipid metabolism, ketone metabolism, amino acid metabolism, and intestinal flora metabolism. The results of the metabolic flux analysis showed that the high-fat diet reduced the metabolism of tricarboxylic acids by 37.48%. After administration of low and high doses of metformin the metabolism of tricarboxylic acid increased by 98.14% and 143.10%, respectively. After administration of simvastatin tricarboxylic acid metabolism increased by 33.18%. The results indicate that metformin has a significant effect on promoting energy metabolism. This study used a combination of metabolomics and metabolic flow to explore the effect of metformin on lipid metabolism disorders and quantifies changes in the key pathway of energy metabolism-the tricarboxylic acid cycle. This study provides useful information for the study of the efficacy and mechanism of metformin, as well as a practical technical method for the screening of lipid-lowering drugs based on a hamster model.

PURPOSE: The lack of vascularity in the hyaline cartilage is thought to be the main cause of why the cartilage can not repair itself. Therefore, authors designed the reversed intraarticular periosteal flap which preserves the vascular system to the periosteum and assesses neochondrogenesis. MATERIALS AND METHODS: The subjects used were 90 white New Zealand rabbits. Reversed intraarticular periosteal flap, intraarticular periosteal free flap and inducing articular cartilage defect only were performed in 30 rabbits, respectively. We compared the results of each groups according to gross morphology of regenerated tissue, histology and histochemical findings. RESULTS: Reversed intraarticular periosteal flap group and intraarticular periosteal free flap group resulted in better cartilage formation than in the articular cartilage defect only group and the reversed intraarticular periosteal flap group had better results than intraarticular periosteal free flap group even though the difference was not statistically significant. CONCLUSION: The reversed intraarticular periosteal flap was thought to be one of the methods which preserves the vascular system in the process of cartilage regeneration with periosteum.
Cartilage ; Cartilage, Articular ; Free Tissue Flaps ; Hyaline Cartilage ; Periosteum ; Rabbits* ; Regeneration

Purpose: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. Materials and Methods: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). Results: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokinecytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. Conclusions These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

This study is to investigate the treatment of Jin Chai antiviral capsule for influenza virus FM1/47 (H1N1) infection. The model of pneumonia was established by dropping influenza virus into the nose of normal mice, real-time PCR and Western blot technique were used to detect the virus load and the interferoninducible transmembrane protein3 (IFITM3) in lung of mice at the 1st day, 3rd day, 5th day and 7th day after affected. The results showed that Jin Chai antiviral capsule in large, middle, small dose groups can decrease virus load significantly at each time point, after being affected (P<0.05, P<0.01), Jin Chai antiviral capsule can increase the interferoninducible transmembrane protein3 in lung of mice, large dose groups are significantly higher in expression of IFITM3 compared with model group at each time point (P<0.05, P<0.01). Middle dose groups are significantly higher in expression of IFITM3 compared with model group at the 3th day and the 5th day (P<0.05), small dose groups are significantly higher in expression of IFITM3 compared with model group at the 3th day (P<0.05). It can be concluded that Jin Chai antiviral capsule exerts antiviral effects against influenzavirus by raised expression of IFITM3.
Animals ; Antiviral Agents ; administration & dosage ; pharmacology ; Capsules ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Female ; Influenza A Virus, H1N1 Subtype ; drug effects ; Lung ; metabolism ; Male ; Membrane Proteins ; metabolism ; Mice ; Mice, Inbred ICR ; Orthomyxoviridae Infections ; metabolism ; virology ; Plants, Medicinal ; chemistry ; Pneumonia ; metabolism ; virology ; Viral Load ; drug effects

Allopurinol-induced hypersensitivity syndrome is characterized by an idiosyncratic reaction involving multiple-organs, which usually begins 2 to 6 weeks after starting allopurinol. In rare cases, the adverse reactions to allopurinol are accompanied by a variety of liver injury, such as reactive hepatitis, granulomatous hepatitis, vanishing bile duct syndrome, or fulminant hepatic failure. Here we report a case with granulomatous hepatitis and ductopenia. A 69-year-old man with chronic renal failure, hyperuricemia, and previously normal liver function presented with jaundice, skin rash, and fever 2 weeks after taking allopurinol (200 mg/day). In histopathology, a liver biopsy specimen showed mild spotty necrosis of hepatocytes, marked cholestasis in parenchyma, and some granulomas in the portal area. There were vacuolar degeneration in the interlobular bile ducts and ductopenia in the portal tracts. Pathologic criteria strongly suggested the presence of allopurinol-induced granulomatous hepatitis with ductopenia and cholestasis. The patient fully recovered following the early administration of systemic corticosteroid therapy.
Aged ; Allopurinol/*adverse effects/therapeutic use ; Antimetabolites/*adverse effects/therapeutic use ; Bile Duct Diseases/*chemically induced/diagnosis/pathology ; Bile Ducts, Intrahepatic/*drug effects/pathology ; Cholestasis/*chemically induced/diagnosis/pathology ; Drug Eruptions/pathology ; Granuloma/*chemically induced/pathology ; Hepatitis, Toxic/*pathology ; Humans ; Kidney Failure, Chronic/complications/drug therapy ; Male

This study is to investigate the treatment of YinQiaojiedu soft capsule for influenza virus A/PR8/34 (H1N1) infection. The model of pneumonia was established by dropping influenza virus into the nose of normal mice, and the lung index and death rate were observed. Real time RT-PCR and Western blotting technique were used to detect the virus load and the relative expression of M1 protein in lungs of mice on the 1st, 3rd, 5th and 7th day after infection. The results showed that YinQiaojiedu soft capsule in 1 g x kg(-1) and 0.5 g x kg(-1) dose groups can decrease the lung index significantly on the 3rd, 5th and 7th day after being infected (P < 0.05, P < 0.01), and the number of death in the two groups of animals decreased significantly. YinQiaojiedu soft capsule in 1 g x kg(-1) dose group can decreased virus load at each time point, and lower it in 0.5 g x kg(-1) dose group at the 3rd, 5th and 7th day (P < 0.05, P < 0.01). YinQiaojiedu soft capsule can decrease the relative expression of M1 protein in lungs of mice, 1 g x kg(-1) and 0.5 g x kg(-1) dose groups are significantly lower in expression of M1 protein compared with model group at the 3rd and 7th day (P < 0.05, P < 0.01). It can be concluded that YinQiaojiedu soft capsule exerts antiviral effects against influenza virus by downregulating expression of virus load and M1 protein.
Animals ; Antiviral Agents ; administration & dosage ; pharmacology ; Capsules ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Female ; Influenza A Virus, H1N1 Subtype ; Lung ; metabolism ; virology ; Male ; Mice ; Mice, Inbred ICR ; Orthomyxoviridae Infections ; drug therapy ; metabolism ; virology ; Pneumonia ; metabolism ; virology ; Viral Load ; drug effects ; Viral Matrix Proteins ; metabolism

This study was aimed to investigate the expression levels of CXCR4 and VEGF in serum of patients with DLBCL and their clinical significances. The peripheral blood of 44 patients with newly diagnosed DLBCL and 20 healthy adults as a control group were chosen for study. And the expression levels of CXCR4 and VEGF in serum were detected by ELISA. The results showed that the expressions of VEGF and CXCR4 in DLBCL patients were higher than those in the control group (P < 0.05). The expression of VEGF was positively correlated with the expression of CXCR4 in DLBCL patients, and the correlation coefficient was 0.743 (P < 0.05). The VEGF expression in DLBCL patients was correlated with LDH, immunotyping, the number of extranodal involvements, Ann Arbor staging and ECOG performance score; while the expression of CXCR4 was correlated with LDH, immunotyping, the number of extranodal involvements and Ann Arbor staging. Univariate analysis showed that LDH, extranodal involvements, immunotyping, Ann Arbor staging, CXCR4 and VEGF were associated with OS. Multivariate analysis showed that the immunotyping and CXCR4 expression independently associated with OS. It is concluded that both expression levels of VEGF and CXCR4 are significant higher than those in the control group. CXCR4 expression positively correlates with VEGF expression and displays a prognostic significance for OS. This study suggests that combined targeting VEGF and CXCR4 may become a novel therapeutic strategy for diffuse large B cell lymphoma.
Adolescent ; Adult ; Aged ; Case-Control Studies ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; Male ; Middle Aged ; Prognosis ; Receptors, CXCR4 ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Young Adult

To analyze the genomic sequence characteristics of a human Echovirus 9(ECHO-9) strain isolated from a child with Hand-foot-mouth disease (HFMD) in Kunming, Yunnan Province, in 2010. The complete genome sequence of a human echovirus 9 strain, MSH-KM812-2010 was determined. As other human enterovirus, its genome was 7,424 nucleotides (nts) in length and encoded for 2,203 amino acids (aas). In comparison to other human enteroviruses, MSH-KM812-2010 strain had the highest homology with other strains of human echovirus 9 in structural genomic regions and more homologous to other serotypes of B specie than to human echovirus 9 in non-structural genomic regions. Phylogenetic analysis based on complete VP1 gene revealed that the sequences of human echovirus 9 segregated into three distinct clades A, B and C with more than 15. 0% diversity between clades. All Chinese isolates belonged to the same clade. RDP3 and Blast revealed evident recombination in non-structural genomic regions. This report is the first to, describe the complete genome of the human echovirus 9 in China and provide an overview of the diversity of genetic characteristics of a circulating human echovirus 9.
Base Sequence ; China ; Echovirus 9 ; classification ; genetics ; isolation & purification ; Female ; Genome, Viral ; Humans ; Infant ; Molecular Sequence Data ; Phylogeny ; Viral Proteins ; genetics