This study was conducted to investigate the paclitaxel loaded by hydrazone bonds in poly(ethylene glycol)-poly(caprolactone) micelles (mPEG-PCL-PTX) on proliferation and apoptosis of human lung cancer A549 cells and its possible mechanisms of anti-tumor activity. The cell proliferation was measured with MTT assay. Flow cytometry were used to analyze the cell cycle. The cell apoptosis was analyzed using Hoechst/P staining. The expression levels of apoptotic genes expression in the mitochondrial apoptosis pathway were detected by RT-PCR and Western blotting, respectively. The mPEG-PCL-PTX could inhibit the proliferation of A549 cells and promote the apoptosis. The Bax, caspase-3 protein expression were increased while Bcl-2 protein expression was decreased in A549 cells. Results showed that the polymer containing hydrazone bond is non-toxic in vitro, the mPEG-PCL-PTX micelles can inhibit the proliferation and induce the apoptosis of A549 cells. Key words: paclitaxel; micelle; A549 cell; proliferation; cell cycle; apoptosis
Apoptosis ; Caspase 3 ; metabolism ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Micelles ; Paclitaxel ; pharmacology ; Polyesters ; Polyethylene Glycols ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo explore the clinical roles of Jiawei Shentong Zhuyu Decoction (JSZD) in preventing the occurrence of failed back surgery syndrome (FBSS), and to observe its effect on serum tumor necrosis factor-alpha (TNF-alpha).

METHODSTotally 100 patients prepared for surgical operation due to lumbar intervertebral disc herniation were randomly assigned to the treatment group and the control group according to random number table, 50 cases in each group. Patients in the treatment group additionally took JSZD, one dose per day, taken in two portions, once in the morning and once in the evening. Those in the control group took Celecoxib Capsule (200 mg each time, once per day) and Mecobalamin Tablet (0.5 mg each time, 3 times per day). They only took Mecobalamin Tablet from the 11th day. All patients were treated for 30 days. Japanese Orthopaedic Association (JOA) score was performed before treatment, at week 1, after treatment, at 6 months of followed-ups, and at 12 months of followed-ups. And the levels of TNF-alpha in the peripheral blood were observed before treatment and at one month after treatment.

RESULTSTotally 93 patients completed the followed-up study. The JOA scores were improved after treatment, at 6 and 12 months of followed-ups (P < 0.05, P < 0.01). The JOA score at 6 months of followed-ups was superior in the treatment group to that of the control group (P < 0.05). Five patients (accounting for 10.6%) suffered from FBSS in the treatment group, while 9 (accounting for 19.6%) suffered from FBSS in the control group. The treatment group was superior to the control group (P < 0.05). The TNFalpha level was improved after treatment in the two groups. Of them, the improvement of TNF-alpha in the treatment group was better than that of the control group (P < 0.05).

CONCLUSIONThe application of JSZD was effective for preventing the occurrence of FBSS, and improved the serum TNF-alpha level.

Adult ; Drugs, Chinese Herbal ; therapeutic use ; Failed Back Surgery Syndrome ; prevention & control ; Female ; Humans ; Intervertebral Disc Displacement ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha ; blood ; Young Adult

This study is to investigate the effect of the effective components group of Xiaoshuantongluo (XECG) on neuronal injury induced by oxygen-glucose deprivation (OGD) in primary cortical cultures isolated from SD rat cortex at day 3 and the possible mechanism. Cells were divided into control group, OGD model group and XECG group (1, 3 and 10 mg x L(-1)). The cell viability was assessed with MTT assay and the LDH release rate was measured by enzyme label kit. The cell apoptosis was analyzed using Hoechst staining. RT-PCR was applied to detect the mRNA levels of JAK2 and STAT3. Western blotting was used to detect the expressions of Bcl-2, Bax, p-JAK2 and p-STAT3 proteins. Results showed that XECG resulted in an obvious resistance to oxygen-glucose deprivation-induced cell apoptosis and decrement of cell viability, decrease the cell LDH release rate. XECG could adjust the expression of Bcl-2 and Bax proteins and increase Bcl-2/Bax ratio, up-regulate the expression of p-JAK2 and p-STAT3. In conclusion, XECG could protect against the neuronal injury cells exposed to OGD, which may be relevant to the promotion of JAK2/STAT3 signaling pathway, and impact the expression of Bax and Bcl-2.
Animals ; Apoptosis ; Cell Survival ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Glucose ; Janus Kinase 2 ; metabolism ; Neurons ; drug effects ; metabolism ; Neuroprotective Agents ; pharmacology ; Oxygen ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; bcl-2-Associated X Protein ; metabolism

yggG, a Era-binding protein gene, was isolated and cloned from the E.coli genomic DNA library. Previous studies indicated that the product of yggG gene, YggG294(amino acids 1-294), strongly inhibited the growth of host bacteria and caused the death of bacteria cells. To elucidate whether Era is related to the death of bacterial cells expressed YggG294,A double promoter expression vector that can express YggG294 and Era proteins controllably in cells was constructed. Using this vector to express YggG294 and Era protein in the same E.coli cells, then analyzed the relation between YggG294 and Era. The results showed that the ratio of Era proteins to total proteins increased with the increase of induction time in E.coli cells without YggG294 expression and with little YggG294 expression;the ratio of Era proteins to total proteins seemed to be a constant level in E.coli cells overexpressing YggG294;but we could not detect any Era hydrolyzate in E.coli cells overexpressed YggG294 could not be detected. The results also showed that pre-expression of Era protein did not produce any effect on the growth inhibition of E.coli cells caused by YggG294. These results indicate that YggG294 can not hydrolyze Era protein in E.coli cells, and that YggG-Era interaction is not associated with the death of bacteria expressed YggG294. It is thus reasonable to draw a conclusion that Era is not associated with the growth inhibition of E.coli cells caused by YggG294. YggG294 inhibits the growth of bacteria by other way.

AIM:To investigate the effects of DL-3-n-butylphthalidle (NBP) on angiogenesis of human um-bilical vein endothelial cells ( HUVECs) and the role of vascular endothelial growth factor ( VEGF)/VEGF receptor 2 (VEGFR2)-Notch1/Delta-like ligand 4 (Dll4) signaling pathway in this process. METHODS:The serum-free medium and anoxic tank were used to simulate the conditions of hypoxia and ischemia ( H/I). HUVECs were divided into control group, H/I group, H/I+NBPhigh group and H/I+NBPlow group. The HUVECs in control group were conventionally cul-tured, and those in H/I group were cultured under H/I intervention. The HUVECs in H/I+NBPhigh group were treated with NBP at 20 μmol/L under H/I intervention. The HUVECs in H/I+NBPlow group were treated with NBP at 5 μmol/L under H/I intervention. The cell viability of each group was measured by CCK-8 assay. The migration ability of the HUVECs in each group was detected by cell scratch test. The vessel formation ability of the HUVECs was examined by in vitro angiogenesis assay. The expression of VEGFR2, Notch1 and Dll4 at mRNA and protein levels was determined by qPCR and Western blot, and the expression of VEGF was determined by qPCR and ELISA. RESULTS:NBP increased the viability of HUVECs, and promoted the migration ability and the formation of blood vessels in vitro under H/I interven-tion. These effects of NBP at high dose were more significant than those at low dose. NBP increased the expression of VEGF, VEGFR2, Notch1 and Dll4 at mRNA and protein levels (P<0.05). CONCLUSION:NBP promotes HUVECs to form blood vessels under H/I intervention. The mechanism may be related to the activation of VEGF/VEGFR2-Notch1/Dll4 signaling pathway.

OBJECTIVETo investigate the association between the level of serum testosterone and atherosclerosis in middle-aged and elderly men.

METHODSWe conducted a population-based study of 413 males aged 40-75 years in a community in Guangzhou. We obtained the sociodemographic characteristics, clinical data, physical measurements, and laboratory results of sex hormones, blood glucose, and blood lipid of the subjects. We also measured the carotid intima media thickness (CIMT) by color Doppler ultrasonography.

RESULTSThe subjects were divided into a carotid atherosclerosis (CAS) group (CIMT ≥ 0.9 mm) and a non-CAS group (CIMT < 0.9 mm). The medians of free testosterone (FT) were 57.41 and 59.72 pmol/L in the CAS and non-CAS groups, respectively (P = 0.005), and no significant difference was found between the two groups in total testosterone (TT). The levels of serum FT and TT were negatively correlated to CIMT, with Spearman's rank correlation coefficients of -0.126 (P = 0.011) and -0.188 (P < 0.001), respectively. The incidence rates of CAS were 23.30, 13.46, 17.48, and 7.77% in the Q1, Q2, Q3, and Q4 groups, respectively according to the quartile of FT (P for trend = 0.008) and 17.48, 18.27, 16.50, and 9.71% respectively according to the quartile of TT (P for trend = 0.116). Based on the quartile of FT and after adjustment for age, waist circumference, systolic blood pressure, and HbAlc, the risk of CAS was significantly increased in the Q1 group as compared with Q4 (OR = 2.491, 95% CI 1.01-6.149), but no statistically significant differences were observed according to the quartile of TT.

CONCLUSIONA low serum FT level may be a risk factor of atherosclerosis in Chinese men aged 40 years or older.

Adult ; Age Factors ; Aged ; Blood Glucose ; analysis ; Blood Pressure ; Carotid Artery Diseases ; blood ; epidemiology ; etiology ; Carotid Intima-Media Thickness ; Gonadal Steroid Hormones ; blood ; Humans ; Incidence ; Lipids ; blood ; Male ; Middle Aged ; Risk Factors ; Statistics, Nonparametric ; Testosterone ; blood

OBJECTIVETo evaluate the impact of neoadjuvant chemoradiation on perineal wound healing following abdominoperineal resection(APR) for lower rectal cancer.

METHODSData of 93 patients who underwent APR for low rectal cancer between January 2005 and January 2009 in Peking Union Medical College Hospital were reviewed, including patients who received neoadjuvant chemoradiation (n=29) and those undergoing surgery alone(n=64). Perineal wound healing was the primary outcome measurement. Condition of wound healing was classified as good, moderate, and poor and was compared between the two groups.

RESULTSTwenty nine patients in the neoadjuvant group received preoperative regional radiation(50 Gy, 25 fractions/5 weeks) with synchronous FOLFOX4 chemotherapy(fluorouracil and oxaliplatin). In the neoadjuvant group, wound healing after APR was good in 18 patients(62.1%), moderate in 6(20.7%), and poor in 5(17.2%). In patients who had surgery alone, wound healing after APR was good in 41 patients(64.1%), moderate in 15(23.4%), and poor in 8(12.5%). There was no significant difference in the incidence of wound infection(poor wound healing)between the two groups(P=0.773).

CONCLUSIONNeoadjuvant chemoradiation therapy is not associated with increased perineal wound infection following abdominoperineal resection for low rectal cancer.

Aged ; Combined Modality Therapy ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Perineum ; surgery ; Rectal Neoplasms ; surgery ; therapy ; Rectum ; surgery ; Wound Healing

OBJECTIVETo evaluate the efficacy and safety of using Jiangzhi Tongluo Soft Capsule (JTSC) combined with Atorvastatin Calcium Tablet (ACT) or ACT alone in treatment of combined hyperlipidemia.

METHODSA randomized, double blinded, parallel control, and multi-center clinical research design was adopted. Totally 138 combined hyperlipidemia patients were randomly assigned to the combined treatment group (A) and the atorvastatin treatment group (B) by random digit table, 69 in each group. All patients took ACT 20 mg per day. Patients in the A group took JTSC 100 mg each time, 3 times per day. Those in the B group took JTSC simulated agent, 100 mg each time, 3 times per day. The treatment period for all was 8 weeks. Serum levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were observed before treatment, at week 4 and 8 after treatment; and safety was assessed as well.

RESULTSAt week 4 and 8 after treatment serum TG decreased by 26.69% and 33.29% respectively in the A group (both P < 0.01), while it was decreased by 25.7% and 22.98% respectively in the B group (both P < 0.01). At week 8 decreased serum TG was obviously higher in the A group than in the B group (P < 0.05). Compared with before treatment, serum levels of LDL-C and TC levels decreased significantly in the two groups (all P < 0.01). There was no statistical difference in the drop-out value and the drop-out rate of serum LDL-C and TC levels (P > 0.05). At week 8 the serum HDL-C level showed an increasing tendency in the two groups. No obvious increase in peptase or creatase occurred in the two groups after treatment.

CONCLUSIONJTSC combined with ACT could lower the serum TG level of combined hyperlipidemia patients with safety.

Adult ; Atorvastatin Calcium ; Double-Blind Method ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heptanoic Acids ; therapeutic use ; Humans ; Hyperlipidemias ; drug therapy ; Male ; Middle Aged ; Pyrroles ; therapeutic use ; Treatment Outcome ; Triglycerides ; blood

OBJECTIVETo investigate the effect of PTEN tumor suppressor gene combined with doxycycline on telomerase activity in human mucoepidermoid carcinoma cell line.

METHODSThe wild-type PTEN tumor suppressor gene or empty vector was introduced into mucoepidermoid carcinoma cell line in vitro, then the cancer cells were treated with doxycycline. Cancer cell survival was determined by MTT assay. Telomerase activity was determined using telomerase repeat amplification protocol-enzyme-linked immunosorbent assay (TRAP-ELISA).

RESULTSCompared to the control cells, cancer cells transfected with the wild-type PTEN gene showed growth inhibition and increased sensitivity to doxycycyline, and the ratio of augment of drug sensitivity was 1.65-4.75. The telomerase activity in cancer cells treared with PTEN gene transfection or doxycycline alone decreased, however, telomerase activity in combined group decreased more remarkably.

CONCLUSIONPTEN gene in combination with doxycycline has significant inhibitory effect on telomerase activity in cancer cells.

Carcinoma, Mucoepidermoid ; Cell Line ; Cell Line, Tumor ; Doxycycline ; Genes, Tumor Suppressor ; Genetic Vectors ; Humans ; PTEN Phosphohydrolase ; Telomerase ; Transfection

OBJECTIVE: To explore the effect of vinyl chloride on the blood sex hormones and liver function of male workers. METHODS: A total of 129 male vinyl chloride workers(exposure group) and 128 male office workers who were not exposed to occupational hazards(control group) were selected as study subjects by judgment sampling method. The time weighted average concentration(C_(TWA)) of vinyl chloride in the workplace air was measured. The level of urine thiodiglycolic acid(TDGA), blood routine, electrocardiogram and liver B-ultrasound were performed on the subjects. The serum levels of liver function and sex hormones were measured. RESULTS: The median of C_(TWA) of vinyl chloride in the workplace was 0.90 mg/m~3, and the geometric mean was 1.40 mg/m~3. The level of urine TDGA in the exposed group was higher than that of the control group(median: 0.68 vs 0.02 mg/g Cr, P<0.01). The abnormal rate of hemoglobin level, erythrocyte count, leukocyte count, hematocrit, mean platelet volume, aspartate transaminase, total bilirubin, indirect bilirubin and liver B-ultrasound increased in the exposure group than that of the control group(P<0.05). The levels of serum prolactin, leuteinizing hormone(LH), follicle-stimulating hormone and estradiol in the exposure group increased, the abnormal rates of prolactin, LH and estradiol increased, and the level of testosterone decreased compared with the control group(P<0.05). The levels of prolactin in the low-, medium-and high-TDGA subgroups in the exposure group increased(P<0.05), and the abnormal rates increased compared with the control group(P<0.017). CONCLUSION: Vinyl chloride can cause liver function damage in male workers and have reproductive toxicity. Prolactin can be used as a biomarker of reproductive toxicity of vinyl chloride.