The DNA structures could be altered or even damaged by exogeous or endogenous factors during cell proliferation. Failure of effective and timely repair will lead to cell cycle arrest or apoptosis. By taking the advantage of the quick proliferation of cancer cells, DNA damage induction, cell cycle arrest and apoptosis promotion have become important strategies for ant-cancer chemotherapy. Previous reports showed that an array of natural compounds inhibit cancer cell proliferation by inducing DNA damage, which have therapeutic potentials for anti-cancer drug research and development.
Animals ; Biological Products ; pharmacology ; therapeutic use ; DNA Damage ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Neoplasms ; drug therapy

Objective To investigate the relationship between heart rate variability ( HRV) and chronic complications in pa-tients with type 2 diabetes mellitus (T2DM).Methods A total of 96 patients with T2DM was given chronic complication assessment . Demographic data were obtained .Diabetic retinopathy , diabetic kidney disease , diabetic peripheral neuropathy ( DPN) , and peripher-al artery disease ( PAD) were diagnosed according to international clinical classification .The parameters of HRV in the patients with diabetes and non-diabetes were examined with24 h Holter recorder .Results The HRV parameters of type 2 diabetic patients were significantly lower than those of non-diabetes ( P <0.05 ) .HRV time domain parameters [ standard deviation of normal RR intervals (SDNN), standard deviation of 5-minute mean RR intervals (SDANN), root mean square difference among successive RR normal in-tervals ( RMSSD) ] were especially impaired in diabetic patients with retinopathy compared to those without retinopathy .HRV parame-ters except low-to-high frequency ratio ( LF/HF) and MNN were lower in diabetic patients with kidney disease than those without kid-ney disease .HRV parameters were no significant difference between patients with or without PAD .Conclusions HRV of diabetic pa-tient is lower.Diabetic retinopathy and kidney disease impact on the HRV .

Objective To study the safety and efficacy of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in elderly patients with biliary and pancreatic diseases under the concept of enhanced recovery after surgery (ERAS). Methods 320 patients were enrolled in ERCP operation. Both ERAS elderly group (experimental group A, n = 58, above 75 years) and young and middle-aged group (control group B, n=202,below 60 years)underwent enhanced recovery after surgery,meanwhile traditional elderly group(control group C, n = 60, above 75 years) received traditional perioperative management. It had compared multiple clinical indexes between group A with B and group A with C during the preoperative, intraoperative, and postoperative period. Results The incidence rate of cholangiocarcinoma, multiple complications, nutrition screening ≥ 3 points, ASA scored III degree and Child-Pugh scored A-level in preoperative ERAS elderly patients were higher than that of the young and middle-aged group (P < 0.05); And its incidence rate of nausea and vomiting and abdominal pain,nutritional screening < 3 points and ASA scored I degree were lower than that of the middle-aged group (P < 0.05);the fasting and water- deprivation time of the ERAS elderly group was shorter than that of the traditional elderly group (P < 0.05). The intraoperative operation time of the elderly ERAS group was slightly longer than that of the traditional elderly group (P < 0.05). The duration of electrocardiographic monitoring and the first aerofluxus time of the elderly patients with ERAS were longer than that of the young and middle-aged group (P < 0.05). The success, failure rate, and complication rate of the elderly patients with ERAS were 91.38% (53/58) and 8.62% (5 /58), 3.45% (2/58), meanwhile the young and middle-aged group were 96.53% (195/202), 3.47% (7/202), and 4.95% (10/202), and with no statistical difference (P > 0.05). The mild pain in ERAS elderly group was more than that of in traditional elderly group, while the moderate, and severe pain was less than that of traditional elderly group (P < 0.05); The opioid use rate, endoscopic nasobiliary indwelling, first-time ambulation and aerofluxus, total hospitalization, and postoperative hospitalization time of ERAS elderly group was less than the traditional elderly group (P < 0.05). Conclusions With ERAS, the treatment effect of ERCP in elderly patients is similar to that in young and middle-aged people, and it has good safety and effectiveness.

The quality control and evaluation methods of Schizonepeta tenuifolia were established by HPLC fingerprint, multi index component content determination and chemical pattern recognition to provide basis for the quality control of medicinal materials. The chemical components of 25 batches of Schizonepeta tenuifolia panicle medicinal materials and decoction pieces collected were analyzed by high performance liquid chromatography, and the common pattern of fingerprint was established. A total of 22 common chromatographic peaks were calibrated, and their similarity was more than 0.9. The samples were divided into three categories according to different producing areas by cluster analysis. The results of principal component analysis and cluster analysis were consistent. Finally, five differential markers of different batches of Schizonepeta tenuifolia were selected by orthogonal partial least squares discriminant analysis. Through the identification of the reference substance, it was determined that peak 9 was hesperidin, peak 10 was rosmarinic acid, peak 13 was tilianin, peak 14 was quercetin, and peak 20 was pulegone. The quality evaluation method established in this study is stable and reliable, and is suitable for the quality control of Schizonepeta tenuifolia.

Objective To evaluate tension-free hernia Onlay repair with premuscular positioning of the prosthesis for the treatment of ineisional henia of the abdominal wall.Methods In this study 126 patients with incisional henia were treated with a tension-free manner of hernia repair by using synthetic material ONLAY between September 1999 and June 2007.Results All operations were successful.There was no hospital death or severe postoperative complications.The average age was 58.5 years old ranging from 28 to 89.There were 67 patients in which the abdominal defect ranged from 5～10 cm,and 59 patients with abdominal defect≥10 cm.The mean operating time was 95(70～120)min,and the average intraoperative blood loss was 80 ml(60～250 ml).The mean postoperative hospitalization was 14.5 days(10～28 d). Patients were followed-up from 3 to 96 months,and 3 patients suffered from hernia recurrence(2.38%). Conclusions The ONLAY repair of ineisional hernia of the abdominal wall with synthetic material mesh was a safe procedure,especially for those with large abdominal wall defects.

Objective To observe the relationship between apoptosis of K562 cell induced by iron-deprivation and activation of Caspase-3.Methods K562 cells were treated with desferrioxamine(DFO) in different dosages were collected at different time points.K562 cells were labelled with Annexin V/PI,and then the rate of apoptosis was measured by flow cytometry;The activation of Caspase-3 were detected by colorimetric method with pAN labelled substrate;The active protein of Caspase-3 were analyzed by Western blot.Results When K562 cells were treated with different concentrations of DFO,the apoptosis rate and the activity of Caspase-3 increases gradually.When K562 cells were incubated with DFO(50 ?mol/L and 100 ?mol/L) 24 h later,the enzymatic activity of Caspase-3 increases dramatically more than that of control group,and the difference was significantly(P0.05).All those effect above can be counteracted by equal mole concentration of FeCl_3.Conclusion Iron-deprivation maybe induce the apoptosis of K562 cell by chelating intracellular iron and activing Caspase-3.

OBJECTIVETo investigate the effect of advanced glycosylation end products (AGE) on cell cycle of epidermal keratinocyte and its possible signal pathway.

METHODS150 mg/L AGE-human serum albumin (AGE-HSA) was prepared in vitro. Primary cultured keratinocytes in logarithmic growth phase were harvested and divided randomly into: A group [with treatment of defined keratinocyte-SFM (DK-SFM) serum-free medium], B group (with treatment of DK-SFM medium including 150 mg/L AGE-HSA), C group (with DK-SFM medium after treatment of U0126) and group D (with D K-SFM medium including 150 mg/L AGE-HSA after treatment of U0126). Cell cycle distributions were analyzed by flow cytometer. The protein levels of cyclin D1, cyclin B1, CDK4 and p44/42 MAPK were measured by Western blot.

RESULTSCompared with those of A group, the percentage of S-phase and G2/M-phase keratinocytes were decreased obviously in B group, the percentages of G2/M -phase keratinocytes showed the same tendency in C and D groups [(9.7 +/- 1.1)% , (9.8 +/- 0.7)%, respectively, P <0.05]. Compared with that of A group, the expression of cyclin D1 were decreased significantly in other groups, among which a weak expression was showed in D group. There was no obvious difference between A and B groups in CDK4, or cyclin B1 and p44/42 MAPK protein levels ,which were significantly higher than those in C and D groups.

CONCLUSIONAGEs inhibit the progress of cell cycle of keratinocytes by downregulation of cyclin D1 expression.

Animals ; Cell Cycle ; Cyclin D1 ; metabolism ; Epidermis ; cytology ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Glycation End Products, Advanced ; metabolism ; pharmacology ; Keratinocytes ; cytology ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Signal Transduction

OBJECTIVETo investigate the expression of the Pim-1 gene in the LNCaP cells of the animal model of orthotopically implanted prostate cancer by surgical castration simulating androgen-deprivation therapy.

METHODSWe equally allocated 32 male BALBc-nu mice into 4 groups, androgen-dependent prostate cancer (ADPC), androgen-deprivation therapy (ADT) , castration-resistant prostate cancer (CRPC) and blank control, and established the models of orthotopically implanted tumor using human prostate cancer LNCaP cells. We detected and ,compared the expressions of Pim-1, PSA, and androgen receptor (AR) in the tumor tissues of different groups by RT-PCR. qRT-PCR, ELSIA and immunohistochemistry.

RESULTSThe relative gray scales in the ADPC and CRPC groups were 0.59 ± 0.01 and 1.14 ± 0.02, with statistically significant differences from 0.62 ± 0.03 in the ADT group (P < 0.05), and the Δ Ct values of Pim-1 were 6.15 ± 0.34 and 4.56 ± 0.23 in the former two groups, also with significant differences from 5.11 ± 0.21 in the latter (P < 0.05). The results of 2-ΔΔ Ct relative quantification analysis showed that the amplification products of Pim-1 in the ADT and CRPC groups increased 2.05 and 3.01 times respectively that of the ADPC group. The concentration of PSA was significantly higher in the ADPC ([480 ± 25] pg/ml) and CRPC ([870 ± 23] pg/ml) than in the ADT ([170 ± 32] pg/ml) and blank control groups (0 µg/L) (P < 0.01). The mean optical densities of Pim-1 and AR proteins were 0.017 ± 0.002 and 0.032 ± 0.009 in the ADPC group and 0.024 ± 0.002 and 0.040 ± 0.011 in the CRPC group, both with significant differences from those in the ADT group (0.018 ± 0.001 and 0.019 ± 0.006) (P < 0.01).

CONCLUSIONPim-1 is highly expressed in nude mice with prostate cancer receiving androgen-deprivation therapy and plays an important role in the progression and metastasis of prostate cancer.

Androgen Antagonists ; therapeutic use ; Animals ; Disease Progression ; Gene Expression ; Heterografts ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasms, Hormone-Dependent ; metabolism ; Prostate-Specific Antigen ; metabolism ; Prostatic Neoplasms, Castration-Resistant ; genetics ; metabolism ; therapy ; Proto-Oncogene Proteins c-pim-1 ; metabolism ; Receptors, Androgen ; metabolism

Objective To investigate the effects of advanced glycation end-products(AGEPs)on the function of normal keratinocytes in vitro so as to explore the role of AGEPs in impaired wound healing. Methods Normal rat keratinocytes were incubated with different concentrations of AGEPs.After 48 hours of culturing,the cell proliferation rates were measured by MTT colorimetric determination.The cell cycle distributions and apoptosis were analyzed with flow cytometry,and the migration was investigated by 24-well fluorimetric cell migration assay kit by exposing to 100?g/ml AGEPs.Nuclear extracts from these cells were examined for binding of nucleotides containing NF-?B consensus by immunocytochemistry and EMSA in vitro.Results The proliferations of normal keratinocytes were significantly arrested and many cells were induced to early apoptosis compared with control ones(P＜0.05)by exposing to AGEPs for 48 hours. Meanwhile AGEPs also irritated keratinocytes migration compared with control ones(P＜0.05).Inhibiting the activation of NF-?B could partly recover the proliferation of keratinocytes,reverse apoptosis and attenu- ate migration.Conclusion AGEPs are correlated with the migration,proliferation and apoptosis of kera- tinocytes by NF-?B.

OBJECTIVETo investigate of the regulatory effect of Rho-kinase pathway activation on angiotensin II (Ang II)-induced contraction of human airway smooth muscle cells (HASMCs) in vitro.

METHODSCultured primary HASMCs were divided into control group, AngII group, AngII + irbesartan group and AngII + Y-27632 group with corresponding treatment. AngII-induced contraction of HASMCs was evaluated using collagen gel lattices and observed morphologically using immunofluorescence assay. Western Blotting was significantly performed to examine the protein expression of Rho-kinase signal pathway.

RESULTSAngII-induced HASMC contraction was inhibited by treatments with irbesartan and Y-27632 as shown by gel contraction assay (P<0.001). Y-27632 treatment produced a stronger inhibitory effect than irbesartan on the expression of phosphorylated moesin, a substrate of Rho kinase (P<0.05).

CONCLUSIONAngII induces the contraction of HASMCs partially as a result of activation of Rho-kinase pathway.

Amides ; pharmacology ; Angiotensin II ; pharmacology ; Asthma ; physiopathology ; Biphenyl Compounds ; pharmacology ; Bronchi ; cytology ; Humans ; Muscle Contraction ; drug effects ; Muscle, Smooth ; cytology ; Primary Cell Culture ; Pyridines ; pharmacology ; Signal Transduction ; drug effects ; Tetrazoles ; pharmacology ; rho-Associated Kinases ; metabolism