Objective To observe the damage to Langerhans cells induced by UVB irradiation,and to evaluate photoprotective effect of these cells from UVB irradiation by epigallocatechin-3-gallate (EGCG).Methods Biopsy specimens were obtained from normal adult foreskin,and epidermal cells were isolated.Density gradient centrifugation and magnetic cell sorting were used simultaneously to purify Langerhans cells from the cell suspension.These cells were then divided into three groups,control (no ir- radiation or EGCG treatment),UVB (irradiation) and EGCG (irradiation+ECCG treatment) groups. The cells in the UVB and EGCG group were irradiated by UVB (30 mJ/cm~2).After the irradiation,the U- VB group was incubated with RPMI-1640 containing 10% bovine serum for 4 hours,while the EGCG group with the same medium containing 200?g/mL of EGCG for 4 hours.Another four hours after the treatment, the cells were collected for the detection of apoptosis rate by propidium iodide staining and flow cytometry. Results Exposure to UVB (30 mJ/cm~2) significantly increased the apoptotic rate of Langerhans cells.The apoptotic rate in EGCG group was significantly lower than that in the UVB group,but was higher than that in the control group.Conclusion Rate of apoptosis of Langerhans cells could be increased by UVB irradia- tion,while EGCG could prevent the increase of apoptosis.

Objective:To examine the expression of CLC-3 in colorectal tissues and the effect of CLC-3 on the viability and invasion of colorectal cancer (CRC) SW480 and SW620 cells. Methods:The mRNA levels of CLC-3 in CRC cell lines were determined by RT-PCR. CLC-3 expression was inhibited by adding DIDS or NPPB to the CRC cells. Subsequently, cell viability and invasion were assessed by CCK-8 assay and Transwell assay, respectively. In addition, the effects of DIDS and NPPB on the Wnt orβ-catenin signaling pathways were de-termined by Western blot analysis. Results:The mRNA level of CLC-3 was remarkably increased in the CRC tissues compared with that in normal colorectal tissues (P<0.05) and was positively correlated with the T stage of CRC. The blockade of CLC-3 inhibited the viability and invasion of CRC cells (P<0.05). The expression ofβ-catenin, C-myc, cyclin D1, Ki-67, and survivin were evidently reduced by the in-hibition of CLC-3 (P<0.05). Conclusion:The inhibition of CLC-3 decreases the cell viability and invasion of CRC cells by reducing the ex-pression of the proteins related to the Wnt orβ-catenin signaling pathway.

Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Molecular Docking Simulation ; Molecular Structure ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; Quinazolinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

OBJECTIVETo observe the inhibitory effect of gefitineb on the proliferation and its inducing effect on the apoptosis of mouse I-10 Leydig testicular cancer cells in vitro.

METHODSWe treated I-10 Leydig testicular cancer cells of mice with gefitineb at 0, 1.25, 2.5, 5, 10, 20, and 40 µmol/L. Then we determined the inhibitory effect of gefitineb on the growth of the cells by MTT, detected their early and late apoptosis by Annexin V-FITC/propidium iodide double staining and Hoechst 33258 nuclear staining, respectively, and observed the expressions of apoptosis-related proteins Bcl-2, Bax and caspase 3/9 by Western blot.

RESULTSCompared with the blank control group, gefitineb significantly inhibited the proliferation of the I-10 cells at 10 and 20 µmol/L (P < 0.05). The survival rate of the cells was (32.4 ± 2.8)% (P < 0.01) and their early and late apoptosis rates were (26.7 ± 4.2)% and (59.33 ± 10.2)% in the 40 µmol/L group, significantly different from those in the control (P < 0.05 and P <0.01). In comparison with the blank control group, gefitineb at 10, 20, and 40 µmol/L increased the expression of pro-apoptotic protein Bax by (41.9 ± 7.1), (60.1 ± 9.8), and (69.0 ± 11.3)% (all P < 0.05), decreased that of apoptosis-inhibitory protein Bcl-2 by (50.3 ± 8.9), (63.9 ± 6.9), and (88.7 ± 13.9)% (all P < 0.05), and elevated that of the cleft proteins caspase-3 by (69.0 ± 6.9)% (P < 0.05), (71.5 ± 8.1)% (P < 0.05), and (110.9 ± 14.2)% (P < 0.01) and caspase-9 by (51.8 ± 4.9), (54.7 ± 6.7), and (43.8 ± 11.8)% (all P < 0.05).

CONCLUSIONGefitineb can increase the cytotoxicity of I-10 Leydig testicular cancer cells of mice and induce their apoptosis via the mitochondria-mediated apoptosis signaling pathway.

Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; metabolism ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Cell Proliferation ; drug effects ; Cell Survival ; Leydig Cell Tumor ; drug therapy ; metabolism ; pathology ; Male ; Mice ; Neoplasm Proteins ; metabolism ; Neoplasms, Germ Cell and Embryonal ; drug therapy ; metabolism ; pathology ; Quinazolines ; pharmacology ; Testicular Neoplasms ; drug therapy ; metabolism ; pathology ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo explore the correlation of the gene polymorphisms of Toll-like receptor 2 ( TLR2) and TLR4 with the susceptibility and recurrence of condyloma acuminatum (CA).

METHODSUsing Snapshot, we detected the gene polymorphisms of TLR2 597(T/C), 1350(T/C), 15607(A/G), and 2258(G/A) and TLR4 896(A/G) and 1196(C/T) in the peripheral blood of 140 CA patients and 105 HPV-negative controls. We made comparisons between the CA patients and controls as well as between the cases of recurrent CA and those of non-recurrence at 6 months after treatment.

RESULTSThere were 72, 48, and 20 cases of genotype TT, TC, and CC of TLR2 597 (T/C), respectively, in the CA patients, as compared with 71, 31, and 3 cases in the controls. The gene frequency of mutant C was 31. 43% in the patients, significantly higher than 17.62% in the controls (χ2 = 12.04, P < 0.01), and it was 38.68% in the recurrent cases, remarkably higher than 27.01% in the non-recurrent cases (χ2 = 4.16, P < 0.05). There were 74, 49, and 17 cases of genotype TT, TC, and CC of TLR2 1350( T/C), respectively, in the CA patients, as compared with 73, 29, and 3 cases in the controls. The gene frequency of mutant C was 29. 64% in the patients, significantly higher than 16. 67% in the controls (χ2 =11.05, P < 0.01), and it was 36.79% in the recurrent cases, markedly higher than 25. 29% in the non-recurrent cases (χ2 = 4.18, P < 0.05). There were 44, 66, and 30 cases of genotype AA, AG, and GG of TLR2 15607(A/G), respectively, in the CA patients, as compared with 26, 58, and 21 cases in the controls. There was no significant difference in the gene frequencies of mutant G between the two groups (χ2 = 0.33, P > 0.05). No mutant genes of TLR2 2508 (G/A) or TLR4 896(A/G) and 1196(C/ T) were detected in either the CA patients or the controls. Linkage disequilibrium analysis showed a tight linkage between TLR2 597 (T/C) and 1350(T/C) (D' = 1, r2 = 0.93).

CONCLUSIONTLR2 597(T/C) is tightly linked to 1350(T/C), which is correlated with both the susceptibility and the recurrence of condyloma acuminatum.

Aged ; Case-Control Studies ; Condylomata Acuminata ; genetics ; Gene Frequency ; Genetic Linkage ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Genetic ; Recurrence ; Toll-Like Receptor 2 ; genetics ; Toll-Like Receptor 4 ; genetics

Objective To explore the influence of LPS treatment on related molecules in Smads and ERK1/2 signal pathway in pancreatic stellate cell line LTC-14.Methods LTC-14 cells were cultured in vitro, and were treated with LPS at different dose in different time points.Protein expressions of related molecules in Smads pathway and ERK1/2 pathway and α-SMA in LTC-14 Cells were examined by Western blot.Results On Treated LTC-14 cells by 0, 1, 5, 10, 20 and 50 mg/L LPS,protein expressions of Smad3 were 0.15±0.02, 0.37±0.02, 0.44±0.01, 0.46±0.02, 0.372±0.01 and 0.24±0.03;expressions of Smad7 were 0.79±0.05, 0.84±0.02, 0.55±0.03, 0.45±0.03, 0.34±0.02 and 0.92±0.07;p-ERK1/2 levels were 0.48±0.05, 0.74±0.03, 0.72±0.04, 0.89±0.02, 0.81±0.02 and 0.72±0.03;p-cPLA2 levels were 0.15±0.03, 0.30±0.01, 0.31±0.01, 0.30±0.02, 0.28±0.03 and 0.32±0.02;α-SMA levels were 0.56±0.06, 0.62±0.06, 0.54±0.04, 1.03±0.11, 1.39±0.08 and 1.28±0.10.The changes of protein expressions before and after LPS treatment were obvious (all P<0.01).The protein expressions of ERK1/2 were 0.56±0.03, 0.57±0.02, 0.53±0.02, 0.58±0.02, 0.59±0.05 and 0.55±0.04, which did not change obviously along with increased LPS dosages.LTC-14 cells treated with 10 mg/L LPS for 0, 1, 3, 6 and 9 h,the expressions of Smad3 were 0.69±0.05, 0.68±0.07, 1.02±0.14, 1.82±0.0 and 2.04±0.11,those of Smad7 were 2.77±0.10, 1.37±0.08, 1.45±0.14, 0.78±0.09 and 0.63±0.06,those of p-ERK1/2 were 0.16±0.03, 0.32±0.05, 0.79±0.03, 1.50±0.07 and 1.77±0.04,those of p-cPLA2 were 0.15±0.04, 0.32±0.06, 0.63±0.04, 0.95±0.04 and 1.49±0.10,those of α-SMA were 0.84±0.03, 1.26±0.21, 1.81±0.19, 4.28±0.26 and 4.37±0.15, all of which changed obviously as the treatment time increased (P<0.05 or 0.01).The expressions of ERK1/2 were 0.75±0.03, 0.72±0.02, 0.80±0.04, 0.74±0.03 and 0.85±0.09, which did not change obviously as the treatment time increased.Conclusions LPS could upregulate the expression of α-SMA in a time-and dose-dependent way, and activate intracellular Smads and ERK1/2 inflammatory pathways, which may be the potential molecular mechanism of the development of chronic pancreatitis.

AIM To establish an HPLC method for the simultaneous content determination of five constituents in Jiangzhi Granules (Salviae miltiorrhizae Radix et Rhizoma,Polygoni cuspidati Rhizoma et Radix,Artemisiae scopariae Herba,etc.).METHODS The analysis of methanol extract of this drug was performed on a 30 ℃ thermostatic Hanbon-C18 column (4.6 mm × 250 mm,5 μm),with the mobile phase comprising of acetonitrile (A) 0.1％ phosphoric acid (B) flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 286 nm (0-30,40-50 min) and 203 nm (30-40 min).RESULTS Gypenoside A,chlorogenic acid,polydatin,salvianolic acid B and emodin showed good linear relationships within the ranges of 0.176-2.46,0.056-0.84,0.36-5.40,0.192-2.88 and 0.12-1.80 μg (r ＞0.999 0),respectively,whose average recoveries were 97.17％-102.59％ with the RSDs of 1.9％-2.9％.CONCLUSION This accurate and simple method can be used for the quality control of Jiangzhi Granules.

Objective To evaluate the efficacy and safety of oral propranolol versus atenolol in the treatment of infantile hemangioma(IH). Methods A total of 75 infants with IH aged 5-24 weeks were randomly divided into two groups: propranolol group(n = 30)orally administrating propranolol 2 mg · kg?1 · d?1 in 3 divided doses daily for 24 consecutive weeks, atenolol group(n=45)orally administrating atenolol 1 mg · kg?1 · d?1 once a day for 24 consecutive weeks. After 1?, 4?, 12?, 24?week treatment, the infants with IH were followed and adverse reactions were recorded. In addition, the activity of IH was assessed by hemangioma activity score(HAS)before and after 24?week treatment, and changes of HAS were compared between the propranolol group and atenolol group. Results There was no significant difference in the proportion of patients experiencing satisfactory regression of hemangioma between the propranolol group and atenolol group(70%[21/30]vs. 75.6%[34/45], P>0.05). Treatment failure occurred in one patient in the propranolol group because of severe airway hyperreactivity, and in another patient in the atenolol group because of drug resistance. The incidence rates of gastrointestinal reactions, central nervous system adverse effects, chills on the extremities and bronchiolitis complicated by airway hyperreactivity were all significantly higher in the propranolol group than in the atenolol group(all P<0.05). None of hypotension, hypoglycemia and bradycardia occurred in the two groups. Conclusion Compared with propranolol, atenolol shows similar efficacy but less adverse effects in the treatment of IH.

Objective To investigate the methods and results of perforator pedicled flaps by anastomosis of superficial veins for reconstructing the extremity defects.Methods From February, 2012 to September, 2012, a total of 14 patients with traumatic skin and soft tissue and artery defects in extremities were repaired by perforator pedicled flaps anastomosed superficial veins with the recipient vessels.Fourteen flaps were based on five kinds of perforator arteries, the posterior interrosseous artery in 5 cases, the ulnar artery in 3 cases, the metacarpal artery in 2 cases, the peroneal artery in 3 cases, the lateral supramalleolar artery in 2 cases, the ulnar artery in 2 cases,and the posterior interrosseous artery in 1 case.After the operation, the blood supplies of flaps were observed severely,postoperative flap swelling were evaluated by edema level classification.After 1 month the blood flow of vein anastomosis were examed by color Doppler ultrasound.Questionnaire of the flap aesthetic satisfactory were performed during fellow-up periods.Results Twelve flaps were all survived well, 2 flaps had partial marginal skin necrosis in the distal, which was managed with surgical debridement, and wound healed in 1 month.Flap swelling were light, edema level classification were one degree in 4 cases,two degree in 10 cases postoperation 7 days, one degree in 11 cases and two degree in 3 cases, after 6 months.Color Doppler ultrasound examinations showed 9 vein anastomosises were all bypassed well.Eleven cases had 6-12 months' fellow-up periods.The flaps had like-like appearance, good contour, high aesthetic satisfactory.Conclusion Perforator pedicledr flaps by anastomosis of superficial veins can reduce the flap venous pressure obviously, avoid transientvenous venous congestion, improve the survival quality of the flap.It's a safe and effective method for soft tissue coverage of traumatic extremity wounds.

Background:Colonoscopy is considered as a standard method for detecting various kinds of colorectal polyps. However,conventional colonoscopy( CC)still has the chance to miss some lesions. Literatures have already reported that transparent hood assisted colonoscopy( THAC)can improve the detection of colorectal polyps. However,the effect of black hood assisted colonoscopy( BHAC)on detection of colorectal polyps is still unclear. Aims:To evaluate the effect of BHAC on detection of colorectal polyps. Methods:A total of 1 076 patients underwent CC and BHAC from Sept. 2014 to April 2015 at Huadong Hospital Affiliated to Fudan University were enrolled in this prospective randomized controlled study. Baseline characteristics,cecal intubation time,withdrawal time,number of polyps,detection rate of polyps,location, size,morphology and pathological diagnosis of polyps between two groups were compared. Results:Compared with CC group,cecal intubation time was significantly shorter in BHAC group than in CC group[(6. 31 ± 3. 51)min vs.(7. 05 ± 4. 15)min,P=0. 002]. No significant differences in withdrawal time and rate of cecal intubation were found between two groups(P>0. 05). Detection rate of polyps was significantly higher in BHAC group than in CC group(65. 4% vs. 48. 7%,P=0. 004). No significant differences in size,morphology of polyps were found between two groups(P>0. 05). Conclusions:Compared with CC,BHAC could significantly improve the detection of colorectal polyps,and shorten cecal intubation time.