OBJECTIVETo investigate whether bortezomib can enhance the sensitivity of human prostate cancer (PCa) cells to natural killer (NK) cell-mediated cytotoxicity, and whether it produces the same effect on different PCa cell lines.

METHODSWe treated androgen-dependent PCa LNCaP cells and androgen-independent PCa DU145 cells with bortezomib at the concentrations of 0, 5, 10, 15, 20 and 25 nmol/L for 24, 48 and 72 hours, and then detected the proliferation and apoptosis of the tumor cells by CCK-8 and Annexin V/PI, respectively.

RESULTSThe proliferation rates of the DU145 cells treated with 15, 20 and 25 nmol/L bortezomib were (82.79 +/-2.04)%, (73.59+/- 2.95)% and (74.16+/- 6. 16)% at 48 hours and (71.24+/- 5.30)%, (51.20+/- 2.91)% and (38.02+/- 2.67)% at 72 hours, and those of the LNCaP cells were (77.04+/- 7.74)% , (42.61 +/- 6.62)% and (23.85 +/-6.04)% at 48 hours and (36.45 +/-7.02)%, (14.94 +/-5.76)% and (11.65 +/-5. 87)% at 72 hours, both significantly inhibited as compared with the control group (P <0.05). At 24 hours, the apoptosis rates of the DU145 cells treated with 15, 20 and 25 nmol/L bortezomib were (14.41 +/- 1.32)% , (16.13 +/- 1.55)% and (14.48 +/- 1.42)% , and those of the LNCaP cells treated with 20 and 25 nmol/L bortezomib were (12.77 +/- 1.28)% and (14. 84 +/- 1.65)% , significantly higher than those of the control group (P <0.05) , and the DU145 cells showed an even higher sensitivity to bortezomib than the LNCaP cells. Bortezomib failed to sensitize these two cell lines to NK cell-mediated cytotoxicity in short-term assay, while long-term assay manifested that the apoptosis rates of DU145 and LNCaP cells after treated with 20 nmol/L bortezomib + NK cells were (41.83 +/- 5.06)% and (30.31 +/- 3.62)% , respectively, significantly higher

CONCLUSIONBortezomib enhances the sensitivity of than those after treated with either bortezomib or NK cells alone (P <0.05). PCa cells to NK cell-mediated cytotoxicity and adds to the effect of current cancer therapies, and it is more efficacious for androgen-independent prostate cancer.

Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; drug effects ; Humans ; Killer Cells, Natural ; drug effects ; Male ; Prostatic Neoplasms ; pathology ; Pyrazines ; pharmacology

Objective To explore the clinical efficacy and the influence of one-port,three-port and four-port laparoscopic cholecystectomy on quality of life in patients with laparoscopic cholecystectomy.Methods The clinical data of 60 patients with laparoscopic cholecystectomy were reviewed,and to compare the general condition,the influence of postoperative recovery and complications,disease of digestive system and the quality of life index in patients treated by one-port laparoscopic cholecystectomy(one-port group),three-port laparoscopic cholecystectomy(three-port group) and four-port laparoscopic cholecystectomy(four-port group).Results Although the time of operation in oneport group was longer than the other two groups (t =3.82,P ＜ 0.05 ; t =4.04,P ＜ 0.05),there were significant differ ences in the volume of the inoperative blood loss,hospital stay time,hospital costs in one-port group compared with the other two groups (P ＜ 0.05).There was no difference among the three groups in the incidence of postoperative complications (P ＞ 0.05).And when leaving hospital,the score of all dimensionalitis in the scale of Gastrointestinal quality of life index (CIQLI),containing the state of physiological function,state of daily life and social activities,psychological emotional state and quality of life of the total score were all higher than those in the other two groups (t =2.22,1.87,2.31,2.43,all P ＜ 0.05),and there was no difference between three-port group and four-port group(P ＞ 0.05).Conclusion Compared with the three-port laparoscopic cholecystectomy and four-port laparoscopic cholecystectomy,one-port laparoscopic cholecystectomy can reduce the inoperative blood loss,shorten hospitalization time and reduce their fee in hospital,and it also can effectively improve patients'quality of life,restore the patients'normal work and life in the shortest possible time.

Objective To examine the circulating glucose and body weight in the transgenic MKR mouse model who expressed dominant-negative IGF-1 receptor and insulin receptor in skeletal muscle leading to systemic insulin resistance and diabetes. Methods MKR mice were genotyped by PCR analysis of tail DNA.And in these mice we examined the circulating glucose and body weight once a week from 1 to 16 weeks of age, and the circulating insulin and glucose tolerance at age of two-month-old by using C57 mice as controls. Results The descendents of MKR mice kept hereditary feature. And these mice had hyperglycaemia from 3 weeks of age,and an increasing body weight slowly(P

[Objective] To study the inhibitory effect of bcl-2 antisense oligonucleotide(ASODN)combined with radiation on lung carcinoma cells NCI-H446.[Method]The cultured NCI-H446 lung carcinoma cells were divided into 5 groups:control,pure radiation,nonsense+radiation,lipofectin+radiation,ASODN+radiation.Every group except for control were assayed by MTT on the inhibition rates,24h,48h,72h after 10Gy irradiation respectively.[Results]The inhibitions of lung carcinoma cells NCI-H446 were observed in ASODN+radiation,lipofectin+radiation,nonsense+radiation and pure radiation groups.The differences between the ASODN+radiation group and the other three groups were significant(P

The significance and method of green chemistry teaching are expounded in detail during the course of medical chemistry experiment,and a new experiment system of green chemistry suiting with medicine is designed in the paper.

Autophagy is an important homeostatic cellular recycling mechanism responsible for degrading injured or dysfunctional cellular organelles and proteins in all living cells. Aging is a universal phenomenon characterized by progressive deterioration of cells and organs due to accumulation of macromolecular and organelle damage. Growing evidences indicate that the rate of autophagosome formation and maturation and the efficiency of autophagosome/lysosome fusion decline with age. Dysfunctional autophagy has also been observed in age-related diseases. Autophagy disruption resulted accumulation of mutated or misfolded proteins is the essential feature of neurodegenerative disorders. However, in cancers, fibroproliferative diseases or cardiovascular diseases, autophagy can play either a protective or destructive role in different types of disease, and even in different stages of the same disease. The review will discuss the cellular and molecular mechanisms of autophagy and its important role in the pathogenesis of aging and age-related diseases, and the ongoing drug discovery strategies for therapeutic intervention.
Aging ; Autophagy ; Drug Discovery ; Humans ; Lysosomes ; metabolism ; Neurodegenerative Diseases ; Phagosomes ; metabolism ; Protein Folding

BACKGROUND: Mesenchymal stem cells are few in human bone marrow, and their number will decrease with aging or body weakening, so a large amount of amplification is necessary. However, the biological characteristics of human mesenchymal stem cells of each passage remain poorly understood.OBJECTIVE: To analyze and compare the biological characteristics of each passage of bone marrow-derived mesenchymal stem cells (MSCs) so as to provide a basis for clinical demands of tissue engineering.DESIGN,TIME AND SETTING: Cytological observation in vitro. The experiment was performed at the Department of Orthopedics and Central Laboratory, Dongzhimen Hospital, Beijing University of Chinese Medicine from March to October 2008.MATERIALS: From bone marrow of patients with non-hematopoietic disease, MSCs were provided by Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine.METHODS: Bone marrow was collected form posterior superior iliac spine of patient, MSCs were isolated and cultured by Percoll method. When the cells were confluent at 90%, they were trypsinized and observed by inverted miscroscopy. The second passage of cells were collected for index detection.MAIN OUTCOME MEASURES: Cell morphological characteristics and immunophenotype; cell activity was detected by MTT; cell division and apoptosis in the proportion of necrosis were analyzed by flow cytometry analysis.RESULTS: The passaged MSCs exhibited uniform appearance in fusiform shape, and their growth was slowed down after 9 passages, exhibiting cytoplasm vacuolization and body enlarging. The second passage of MSCs was positive for CD44, CD106,and CD105, but negative for CD34 and CD45. MTT values peaked at passage 9, and gradually decreased since passage 10. At passage 11, the number of MSCs at division stage was increased, but from the sixth passage, the number of apoptotic cells increased significantly, reaching more than 60% at passage 8.CONCLUSION: According to biological characteristics analysis of MSCs at each passage, the third to the sixth passage cells are recommend for clinical therapy.

Objective To study the preventive effects of erythropoietin (EPO) on acute tubular necrosis of kidney in rats. Method The rat models of acute renal tubular necrosis were established with injecting glycerol in dose of 10 mL/kg. Thirty Wistar rats were randomly (random number) divided into control group, model group and EPO treatment group. EPO was administered intravenously into rats of treatment group in a dose of 1000IU/kg. Levels of blood urea nitrogen (BUN) and serum creatinine (Scr), urine osmolality, urine N-acetyl-D-glucosaminidase (NAG), urine β2-microglobulin (β2-MG), tissue MDA and SOD of rats in the three groups were assayed after the experiment. Renal histological examination was also performed. Results Compared with model group, the levels of BUN and Scr, urine osmolality, NAG,β2-MG and tissue MDA in EPO treament group were significantly lower, but urine osmolality and tissue SOD of rats remarkably increased in comparison with model group. EPO also lessened the histological changes in treatment group. Conclusions EPO has some protective effects on acute renal tubular necrosis in rats, which is probably through preventing oxygen free radical damage and elevating endogenous antioxidation potential.

Melanin is a kind of biopolymer, composed of a complex quinine/indole-quinone derived mixture which is produced in melanocytes from tyrosine. More than 100 genes related to melanin deposition have been found in mouse. Slc24a5 (solute carrier family 24, member 5) is a novel gene first cloned in zebrafish. And it has been confirmed that the Slc24a5 is involved in controlling the melanin deposition in zebrafish. Here the full length of the chicken slc24a5 mRNA sequence, its expression profile and a discussion of its relationship to melanin deposition in chicken were reported. Chicken Slc254a5 has a CDS of 1 269bp, predicting a protein of 423 amino acids which is about 80 amino acids shorter than in human and mouse. It has 9 exons and 8 introns and spans more than 1lkb of genome sequence. The quantitative real-time PCR confirmed that the chicken Slc24a5 was highly expressed in the eye of White Leghorn and Beijing Fatty Chickens, and in the eye, skin and muscle of Silky. The relative expression in Silky eye is more than two times that of White Leghorn. The relative expression in Silky skin is about 70 times that of White Leghorn and about 15 times that of Beijing Fatty Chickens. The relative expression in Silky muscle is about 15 times that of White Leghorn and about 3 times that of Beijing Fatty Chickens. And the expression result is in accordance with the melanocyte and melanin deposition in these tissues.

BACKGROUND: Delirium is an acute organic brain syndrome caused by various reasons, and it is common in elderly patients. Antipsychotics treatment is an important method to control delirium.OBJECTIVE: To observe the efficacy of new antipsychotic agent of olanzapine and the traditional antipsychotic agent of haloperidol in treating senile delirium.DESIGN: A randomized controlled observation. SETTING: Mental Health Center, the First Affiliated Hospital of Chongqing University of Medical Sciences.PARTICIPANTS: Totally 175 inpatients with senile delirium were selected from the First Affiliated Hospital of Chongqing University of Medical Sciences from September 2001 to September 2003, they were randomly divided into olanzapine treatment group (n=74), haloperidol treatment group (n=72) and a control group(n=29). There were 111 males (63.4%) and 64 females (36.6%). Delirium had occurred for a duration of 30 minutes to 17 days, with an average of (3.02±2.71) days. The enrolled patients were classified according to the etiological factors of delirium: metabolic (n=68), toxic (n=47), structural (n=25) and infectious (n=35).METHODS: Different treatments were used in different groups. Control group (n=29): The patients were only given somatic treatment aiming at delirium, and not any drug for central nervous system was used. Olanzapine group (n=74): Besides the somatic treatment aiming at delirium, the patients were given olanzapine (Zyprexa, produced by Eli Lilly and Company,5 mg/tablet) taken orally or sublingually (fasted patients), the initial dosage was 1.25-2.5 mg per day, and then adjusted to 1.25-20 mg per day. Haloperidol group (n=72): Besides the somatic treatment aiming at delirium, they were treated with intramuscular injection of haloperidol (2.5-10 mg per day). The effects were prospectively observed for 1 week.The scores were observed before enrollment and at 1-7 days respectively,the severity of mental disorder and amelioration were evaluated by the clinical global impression scale-severity of illness (CGI-SI) and global improvement item of clinical global impression scale (CGI-GI). The dosage and time of administration was taken as the dosage and time to take effect when the CGI-SI baseline scores decreased by more than 1 point.MAIN OUTCOME MEASURES: The severity of mental disorder and amelioration were observed.RESULTS: ① The scores of CGI-SI after treatment were significantly decreased in the olanzapine group, haloperidol group and control group, and there were significant differences (P ＜ 0.01). ② The rates of marked effect in the three groups were 82.4%, 87.5% and 31.0%, respectively, and those in the two treatment groups were significantly different from that in the control group (P ＜ 0.01). ③ Both olanzapine and haloperidol began to take effect at small dosages, and it was the fasted in the olanzapine group, followed by the haloperidol group, and slowest in the control group.CONCLUSION: Olanzapine and haloperidol have similar effects in treating senile delirium. However, olanzapine is faster to take effect than haloperidol.