Objective To observe the effects of mizoribine(MZR)on renal tubular epithelial?mesenchymal transition(EMT)of mice which have been performed unilateral ureteral obstruction(UUO),and study the mechanism of its anti?fibrosis of renal interstitial. Methods A total of 24 CD1 mice were randomly divided into sham group,UUO model group and MZR treatment group,with 8 mice in each group. The day before op?eration,mice of MZR treatment group had been given MZR 10 mg/kg/d lavage,those of sham group and UUO model group had been given equal saline lavage. Fourteen days after the operation ,blood was collected and serum creatinine and blood urea nitrogen were measured;the obstruction kidneys were harvested for section,HE staining and Masson staining were employed to observe the changes of kidney pathological;the expression ofα?SMA and E?Cad in kidney with detected by immunohistochemical and Western blot method. Results Compared with sham group,serum creatinine and blood urea nitrogen of mice in UUO model group and MZR treatment group were significantly elevated ,kidney pathological chang?es and the expression ofα?SMA in renal tissue were increased and that of E?Cad was reduced ,the differences were all statistically significant(P<0.05);compared with UUO model group,mice in MZR treatment group had different degree of improvements in serum creatinine,blood urea ni?trogen and kidney pathological changes ,the expression ofα?SMA in renal tissue was inhibited and that of E?Cad was increases ,and the differences were statistically significant(P<0.05). Conclusion MZR may inhibit the development of renal tubular EMT in UUO mice ,thereby reduce the level of renal tubule interstitial fibrosis and improve renal function.

Animals ; Antigens, CD34 ; metabolism ; Cell Culture Techniques ; methods ; Cells, Cultured ; Endothelial Cells ; cytology ; metabolism ; Female ; Kidney Glomerulus ; cytology ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Vimentin ; metabolism

Objective To investigate the therapeutic effects of fluorouracil implants in Stage Ⅲgastric carcinoma patients after radical gastreetomy. Methods The general state of health and cumulative survival of 200 stage Ⅲ gastric carcinoma patients undergone radical gastrectomy from January, 1999 to, December 2002 in the People's Hospital of Zhongshan City were analyzed, in which only 120 patients administrated fluorouracil implants during radical gastreetomy. The therapeutic effects of fluorouracil implants in stage Ⅲ gastric carcinoma patients after radical gastrectomy were observed. Results The differences of weight (P = 0.041), HGB(P =0.024), Plt(P =0.017), CEA(P =0.001), CA19-9(P =0.003) were significant between two groups. The incidence rate of nausea/emesis in group T (28 %) was higher than that in group O(17 %, P = 0.006), and incidence rates of myelosuppression(P =0.81), diarrhea(P =0.72), hepatic function lesion(P =0.97) and renal function lesion(P =0.20) were no significant. The cumulative 5-year survival rate of group T(45 %) was higher than that in group O (15 %, P =0.002). Conclusion Fluorouracil implants can improve the therapeutic effects on gastric carcinoma patients undergone radical gastrectomy.

AIM: To investigate the effect of glomerular intercellular interaction under high glucose concentration on the production of reactive oxygen species (ROS) and transforming growth factor ?_1 (TGF-?_1) in co-cultured human ECV304 cells, and to study the intervention with tea polyphenols (TPs). METHODS: The endothelial cells were cultured alone or co-cultured with mesangial cells in high glucose media with or without TPs for 0 h, 12 h and 36 h, respectively. The activity of SOD and the content of MDA in the media of the system were detected by spectrophotometry. The expression of TGF-?_1 mRNA in the endothelial cells was measured by using semi-quantitative reverse transcription PCR (RT-PCR). RESULTS: High glucose decreased the activity of SOD, increased the content of MDA and up-regulated the expression of TGF-?_1 mRNA in co-cultured ECV304 cells and the effect became more prominent than the single-cultured cells. TPs interrupted it more effectively. CONCLUSION: These data suggest that there is interaction between mesangial cells and ECV304 cells under high glucose concentration. The interaction may markedly up-regulate the production of ROS and the expression of TGF-?_1 in co-cultured ECV304 cells. TPs may protect ECV304 cells by intervening intercellular interaction.

The relationship between Bcl-2, Bax, Fas, caspase-3 and development of hemangioma and the molecular mechanism was investigated. By using immunohistochemical S-P method, proliferating cell nuclear antigen was detected. According to the classification of Mulliken in combination with PCNA expression, 27 cases were identified as proliferating hemangioma and 22 cases as involutive hemangioma. Five normal skin tissues around the tumor tissue served as controls. By using immunohistochemical technique, the expression of Bcl-2, Bax, Fax and Caspase-3 was detected. The cells expressing Bcl-2, Bax, Fax and cappase-3 were identified as hemangioma endothelia by immunohistochemical staining of VIII factor. The average absorbance (A) and average positive area rate of Bcl-2, Bax, Fas and caspase-3 expression were measured by using HPIAS-2000 imaging analysis system. The results showed that the expression of Bcl-2 in the endothelia of proliferating hemangioma was significantly higher that in involutive degenerative hemangioma endothelia and vascular endothelia of normal skin tissue (P < 0.01). The expression of Bax, Fas and Caspase-3 in the endothelia of involutive hemangioma was obviously higher than in the endothelia of proliferating hemangioma and normal skin tissue (P < 0.01). The expression of BAx and Fas in endothelia of proliferating hemangioma was higher than in those of normal skin tissue (P < 0.05). It was suggested that Bcl-2, Bax, Fas and caspase-3 might be involved in the development and involution of hemangioma. Bcl-2 could promote the growth of hemangioma by inhibiting apoptosis of endothelia. Bax, Fas and caspase-3 promote the switch of hemangioma from proliferation to involution by inducing the apoptosis of hemangioma endothelia.

Objective:To study the enhancing effect of bFGF-targeted antisense phosphorothioate oligonucleotide (APO)on the chemosensitivity of human laryngeal squamous carcinoma cell line Hep2 to Doxorubicin,5-Fluorouracil, and Cisplatin.Methods:bFGF-specific APO was designed,constructed and transfected into Hep2 cells with jetPEI (polyethyleneimine).Expression of bFGF mRNA was evaluated by semi-quantitative RT-PCR after transfection;immuno- cytochemical method was used to examine the expression of bEGF expression before and after transfection of Hep2;the in- duction of cell apoptosis was analyzed by flow cytometry;cell proliferation was then analYzed by MTT assay after treatment with bFGF-specific APO or chemotherapeutic drugs,or a combination of both.Results:bFGF-specific APO inhibited the growth of Hep2 cells in a dose-and time-dependent manner,with the peak inhibitory rate being 25.5%.The expression of bFGF mRNA and protein decreased by 52.0% and 41.1%,respectively.The apoptosis rate of Hep2 cells was 20.5% after transfection,bFGF-specifie APO reduced the 50% inhibitory concentration of Doxorubicin,5-Fluorouracil,and Cis- platin in Hep2 cells by 75.5%,83.5% and 65.4%,respectively.Conclusion:bFGF-specific APO can enhance the chemosensitivity of Hep2 cells,which paves a new way for potential biologic chemotherapy of laryngeal squamous carcino- ma.

This study started from the effect of baicalin (BC), the main active component of the labiaceae plant Scutellaria baicalensis, on collagen-induced arthritis (CIA) in rats, to explore the mechanism of glucose metabolism reprogramming in fibroblast like synoviocytes (FLSs), a key effector cell of synovial inflammation in rheumatoid arthritis (RA). First of all, CIA rats and tumor necrosis factor-α (TNF-α)-induced RASFs in vitro and in vivo models were established, the arthritis index (AI) score and histopathological changes of CIA rats after BC administration were observed, and the levels of inflammatory factors in serum and cell supernatant were quantified by ELISA, immunocytochemistry and Western blot were used to detect the expression of G-protein-coupled receptor 81 (GPR81) and pyruvate dehydrogenase kinase 1 (PDK1) proteins. In addition, the kit was used to measure the levels of key products and enzyme activities in glucose metabolism reprogramming. The results showed that BC (50, 100 and 200 mg·kg^-1) could alleviate the symptoms of arthritis in CIA rats in a dose-dependent manner, inhibit synovial hyperplasia, alleviate the infiltration of inflammatory cells, down-regulate the levels of pro-inflammatory factors TNF-α and interleukin (IL)-1β, and up-regulate the levels of anti-inflammatory factor IL-10 in CIA rats. At the same time, the secretion levels of lactate, pyruvate, acetyl-CoA, citrate and the activity of lactate dehydrogenase B (LDH-B) were decreased, and the expressions of GRP81 and PDK1 were down-regulated, suggesting that BC mediated the reprogramming process of glucose metabolism. However, when GPR81 inhibitor 3-OBA inhibited lactate uptake, the activity of LDH-B was significantly increased, suggesting that BC inhibited the expression of PDK1, a key enzyme in the reprogramming metabolism from glycolysis to oxidative phosphorylation. All animal experiments in this study were conducted in accordance with the ethical standards of the Laboratory Animal Care Center of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). These studies revealed that baicalin mediated metabolic reprogramming of RASFs from glycolysis to oxidative phosphorylation by inhibiting PDK1 protein expression, and alleviated joint inflammation in CIA rats.

Animals ; Behavior, Animal ; Reproduction ; physiology ; Social Behavior ; Tupaiidae ; physiology

12E7 Antigen ; Antigens, CD ; metabolism ; Cell Adhesion Molecules ; metabolism ; Child, Preschool ; Chondrosarcoma, Mesenchymal ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Male ; Neuroblastoma ; metabolism ; pathology ; Sarcoma, Ewing ; metabolism ; pathology ; Spinal Cord Neoplasms ; metabolism ; pathology ; surgery ; Spinal Neoplasms ; metabolism ; pathology ; Thoracic Vertebrae ; Vimentin ; metabolism

Objective To develop a probe for photoacoustic imaging and fluorescence imaging targeting integrin αvβ6 . Methods The probe was separated by RP‐HPLC .Molecular weight and the maximum absorption wavelength of the probe were detected by mass spectrum instrument and optical spectrum instrument . Various concentrations of the probe were detected by photoacoustic imaging and fluorescence imaging . The stability of the probe was evaluated when exposed under laser . Targeting of the probe on integrinαvβ6 was evaluated in cell uptake assay with integrinαvβ6 positive and negative cells . The minimum number of cells that could be detected by photoacoustic imaging and fluorescence imaging was also evaluated . Results The probe ICG‐peptide was separated from reaction mixture by RP‐HPLC .The probe had a retention time of 21 .4 minutes and m/z of 4 727 . The labeling ratio of the probe was 1∶1 . The maximum absorption wavelength of the probe was 790 nm . The photoacoustic signal was linearly dependent on the concentration of the probe . The fluorescence signal was linearly dependent on the concentration of the probe when the concentration was smaller than 1 .5 × 10 -5 mol/L . The lowest concentration of the probe that could be detected above the background by photoacoustic imaging and fluorescence imaging was 0 .09 × 10-5 mol/L and 0 .05 × 10-5 mol/L ,respectively . No obvious decrease of the photoacoustic signal was observed after the probe was scanned 20 times ( each time lasted for 1 min) by laser . There existed differences ( P <0 .001) in cell uptake of the probe with various concentrations and reaction time between A431 cells (αvβ6 positive) and 293T cells (αvβ6 negative) . Cell uptake was inhibited by the addition of 5μmol/L unlabeled peptide in A431 cells ( P = 0 .001 ) . The lowest number of the labeled A431 cells detected by photoacoustic imaging and fluorescence imaging was 0 .4 × 106 and 0 .05 × 106 ,respectively . Conclusions The dual functional photoacoustic and fluorescence probe targeting integrin αvβ6 was successfully developed . The targeting and sensitivity of the probe makes it potentially useful in early detection of αvβ6 positive tumors .