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Gliomas tend to have a poor prognosis and are the most common primary malignant tumors of the central nervous system. Compared with patients with other cancers, glioma patients often suffer from increased levels of psychological stress, such as anxiety and fear. Chronic stress (CS) is thought to impact glioma profoundly. However, because of the complex mechanisms underlying CS and variability in individual tolerance, the role of CS in glioma remains unclear. This review suggests a new proposal to redivide the stress system into two parts. Neuronal activity is dominant upstream. Stress-signaling molecules produced by the neuroendocrine system are dominant downstream. We discuss the underlying molecular mechanisms by which CS impacts glioma. Potential pharmacological treatments are also summarized from the therapeutic perspective of CS.
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Humanos , Glioma/patologia , Transdução de Sinais , Fatores de Risco , Ansiedade , Neoplasias Encefálicas/patologiaRESUMO
The present study aimed to explore the main active components and underlying mechanisms of Marsdenia tenacissima in the treatment of ovarian cancer(OC) through network pharmacology, molecular docking, and in vitro cell experiments. The active components of M. tenacissima were obtained from the literature search, and their potential targets were obtained from SwissTargetPrediction. The OC-related targets were retrieved from Therapeutic Target Database(TTD), Online Mendelian Inheritance in Man(OMIM), GeneCards, and PharmGKB. The common targets of the drug and the disease were screened out by Venn diagram. Cytoscape was used to construct an "active component-target-disease" network, and the core components were screened out according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened out according to the node degree. GO and KEGG enrichment analyses of potential therapeutic targets were carried out with DAVID database. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock. Finally, the anti-OC activity of M. tenacissima extract was verified based on SKOV3 cells in vitro. The PI3K/AKT signaling pathway was selected for in vitro experimental verification according to the results of GO function and KEGG pathway analyses. Network pharmacology results showed that 39 active components, such as kaempferol, 11α-O-benzoyl-12β-O-acetyltenacigenin B, and drevogenin Q, were screened out, involving 25 core targets such as AKT1, VEGFA, and EGFR, and the PI3K-AKT signaling pathway was the main pathway of target protein enrichment. The results of molecular docking also showed that the top ten core components showed good binding affinity to the top ten core targets. The results of in vitro experiments showed that M. tenacissima extract could significantly inhibit the proliferation of OC cells, induce apoptosis of OC cells through the mitochondrial pathway, and down-regulate the expression of proteins related to the PI3K/AKT signaling pathway. This study shows that M. tenacissima has the characteristics of multi-component, multi-target, and multi-pathway synergistic effect in the treatment of OC, which provides a theoretical basis for in-depth research on the material basis, mechanism, and clinical application.
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Humanos , Feminino , Marsdenia , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Neoplasias Ovarianas/genética , Bases de Dados Genéticas , Extratos Vegetais , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
Asthma is a heterogeneous disease that affects three hundred million people worldwide. About half of them are not well controlled, new therapeutic approach and more effective medicines are therefore urgently needed. Recent studies have shown that bitter taste receptors (Tas2rs) are expressed in respiratory system, and Tas2rs might be used as new targets for asthma treatment since some bitter compounds show therapeutic potential for asthma therapies. Based on this situation, we studied the effect of bitter compound baicalin (BA) on the apoptosis of inflammatory cells in the respiratory tract of asthmatic mice and its relationship with bitter signal transduction. Male BALB/c mice were selected as the tested animals randomly divided into control group (CK), asthma mouse model group stimulated by intraperitoneal injection and aerosol inhalation of ovalbumin(OVA) and intragastric administration of BA intervention OVA-induced asthma group (OVA + BA). The results showed that inflammatory cells infiltration, alveolar septum thickening and diminished alveolarspaces were observed in the OVA group after HE staining. The above symptoms were significantly alleviated in OVA+BA group. The total number of inflammatory cells and classified cell count in the bronchoalveolar lavage fluid of mice in OVA group were increased, and the number of inflammatory cells in BA intervention group were decreased significantly (P < 0. 05). Analysis of real-time quantitative PCR showed that the expression levels of mucin Muc5ac were significantly increased in the lung in OVA group (P <0. 05), while the expression levels of Muc5ac in OVA+BA group were significantly lower than that in OVA group (P <0. 05). The expression of Tas2r108, Tas2r126, Tas2r135, Tas2r143 and their downstream signal transduction molecules α-gust and Trpm5 were down-regulated in OVA group (P < 0. 05). In OVA group, the transcription of pro-apoptotic factors P53, Bax and Casp3 was inhibited, and decreased activity of caspase3 was detected, whereas the transcription of anti-apoptotic factor Bcl2 was up-regulated (P < 0. 05). In OVA+BA group, the transcription of tested Tas2rs genes and downstream signal transduction molecules (P < 0. 05), as well as pro-apoptotic genes P53, Bax and Casp3 were all up-regulated associated with the decreased Bcl2 expression and increased caspase3 activity (P < 0. 05). Our results suggest that BA might function as a bitter taste receptor agonist to mediate the regulation of respiratory tract inflammatory cells apoptosis by activating the bitter signal transduction system, and thus to reduce the lung inflammation and injury in asthmatic mice.
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Reproductive health is an important issue in the field of population and health. As the most common respiratory disease in the world, asthma is linked with male reproductive dysfunction, but the related study is rarely reported. In this study, we analyzed the interventional effect of baicalin (BA) on male reproductive injury in asthmatic mice and its mechanism. Male BALB/c mice were randomly divided into three groups, namely as control group ( CK group), OVA-induced asthma model group ( OVA group) and baicalin intervention asthma group (OVA+BA group). The results showed that no significant difference was found in body weight among the three groups. In the OVA group, the testicular coefficient and sperm count decreased significantly, with sperm malformation rate increased significantly ( P < 0.05). In the baicalin intervention group, the testicular coefficient was increased significantly and sperm malformation rate decreased significantly ( P < 0. 05) ; Hematoxylin-eosin ( HE) staining showed that damaged basement membrane of seminiferous tubules, decreased the number of spermatogenic cells and reduced Johnson score were observed in OVA group. The seminiferous tubule diameter and seminiferous epithelium height were significantly increased (P < 0. 05), the basement membrane of seminiferous tubules was relatively complete and Johnson score gains in the OVA + BA group. Compared with control group, the contents of hydrogen peroxide ( H
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The UDRS interlocking fault is a common dose interlocking of Varian high-energy linear accelerator. Due to the complexity of the system, this fault has brought challenges to the engineers for a long time. Hence, an effective solution is urgently required. In this article, the circuit and principle for UFRS interlocking fault for Varian CLINAC-IX linear accelerator were explicitly analyzed and the maintenance methods were summarized. The management methods of such rare fault were shared, aiming to provide reference for subsequent management of similar interlocking faults.
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Because the large number of people is suffering from asthma, and about half of them are not well controlled, new therapeutic approach and more effective medicines are therefore urgently needed. Recent studies have shown that bitter taste receptors (T2Rs) are expressed in various tissues, and T2Rs might be used as the new targets for asthma treatment since some bitter compounds show therapeutic potential for asthma therapies. In this study, the relationship between the development and exacerbation of asthma and bitter signal transduction was analyzed by establishing the asthma model in the C57BL/6 mice. The present results showed that the total number of white blood cells and the number of eosinophil, neutrophil, lymphocyte and macrophages in the bronchoalveolar lavage fluid (BALF) were significantly increased (P < 0. 05), accompanied with the up-regulation of Muc5ac gene expression (P< 0. 01) and asthma-like pathologically changes in mice lungs in OVA or OVA+SO
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Objective To evaluate the clinical value of thyroid cancer gene detection and its joint diagnos-tic model in early diagnosis of thyroid nodule. Methods Retrospective study was used to analyze 61 cases of thy-roid nodules. These cases were divided into benign nodules and malignant nodules according to the pathology out-comes. We evaluated the AUC,sensitivity and specificity of preoperative fine needle aspiration biopsy(FNAB), thyroid cancer gene detection and color ultrasonography feature in the early diagnosis of thyroid nodule through lo-gistic regression analysis and ROC working curve. Results Among the 61 patients with thyroid nodules,there were 31 cases of benign thyroid nodules and 30 cases of malignant nodules.Diagnostic indexes significantly related with thyroid nodules and their AUC were listed as following:cancer gene detection 0.915(95% CI:0.814-0.971), FNAB 0.813(95% CI:0.691-0.902),low echo 0.657(95% CI:0.523-0.775),size of nodules 0.623(95% CI:0.488-0.745),joint diagnostic model respectively 0.957(95%CI:0.871-0.993). The value of joint diagnosis was the highest,whose sensitivity was 93.1% and the specificity was 90.3%.Conclusion Preoperative cancer gene de-tection joint FNAB and color ultra-sonography will improve the detection rate of thyroid cancer and reduce unneces-sary operation.
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Objective To discuss the efficacy and safety of pre-hospital use of hemagglutinin in patients with craniocerebral trauma and scalp laceration.Methods Totally 100 patients with craniocerebral trauma and scalp laceration who were admitted into our hospital from De -cember 2014 to December 2017 were selected as the object of study.These patients were divided into the hemagglutinin group and the control group with 50 cases in each group according to the random number table method.The control group was given conventional first aid treatment, while the hemagglutinin group was given pre-hospital use of hemagglutinin on the basis of conventional first aid treatment.Then,the efficacy and safety of the two groups were compared.Results The hemoglobin(Hb),hematocrit(HCT),platelet aggregation rate(PAR)of the he-magglutinin group were significantly higher than those of the control group after treatment,and the difference was statistically significant(P<0.05).The prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(FIB)levels and embolism complication rates of the hemagglutinin group and the control group were basically the same after treatment,and the difference was not statistically significant(P>0.05).The hypotension rate and poor prognosis of Glasgow outcome score(GOS)of the hemagglutinin group were significantly lower than those of the control group with statistically significant difference(P<0.05).Conclusion Pre-hospital use of hemagglutinin can effectively improve the hemostatic effect in patients with traumatic brain injury and scalp laceration,and it is beneficial to improve the hypotension and prognosis of patients with high safety.
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<p><b>OBJECTIVE</b>To investigate the inducing effect of down-regulation of MCL-1 by diallyl disulfide(DADS) on the G/M arrest of human leukemia K562 cells and its mechanisms.</p><p><b>METHODS</b>CCK-8 was used to detect the effect of DADS on proliferation of K562 cells, flow cytometry was employed to observe the effect of cycle arrest by DADS and RNAi silencing MCL-1 gene in K562 cells. The expressions of MCL-1, PCNA and CDK1 in K562 cells treated with DADS were detected by Western blot. The amphigamy of MCL-1 with PCNA and CDK1 was detected by Coimmunoprecipitation.</p><p><b>RESULTS</b>CCK-8 detection showed that the inhibition rates of K562 cells treated with 15, 30, 60, 120, 240 µmol/L DADS were 32.48%, 59.34%, 66.42%, 77.06%, 81.05% respectively (P<0.05). Flow cytometry analysis revealed that the perecentages of G/M cells were increased to 18.6% and 34.4%, 17.5% and 28.5%, respectively at 24 and 48 h after treating K562 cells with 60 and 120 µmol/L DADS (P<0.05). And the perecentage of G/M cells of silencing MCL-1 was significantly increased (P<0.05). Silencing effects of MCL-1+DADS on the cells were enhanced more significantly as compared with DADS or MCL-1 alone (P<0.05). Western blot exhibited that DADS could markedly downregulate the expression of MCL-1, PCNA and CDK1(P<0.05). Coimmunoprecipitation revealed that MCL-1 bound with PCNA and CDK1, then forming heterodimers, which were downregulated respectively more significantly than that in the control group after treating K562 cells with DADS for 8 h (P<0.05).</p><p><b>CONCLUSION</b>DADS can inhibit the K562 cell proliferation and induce them arrest G/M through downregulation of MCL-1, then decreasing the expression of PCNA and CDK1 in hunan leukemia K562 cells. Moreover, silencing MCL-1 can enhance the effect of DADS.</p>
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Humanos , Compostos Alílicos , Apoptose , Linhagem Celular Tumoral , Dissulfetos , Regulação para Baixo , Pontos de Checagem da Fase G2 do Ciclo Celular , Células K562 , Leucemia , Pontos de Checagem da Fase M do Ciclo Celular , Proteína de Sequência 1 de Leucemia de Células MieloidesRESUMO
<p><b>OBJECTIVE</b>To study the clinical efficacy of amphotericin B and voriconazole in the treatment of invasive fungal infection in children with acute lymphoblastic leukemia(ALL) during chemotherapy.</p><p><b>METHODS</b>The clinical data of 214 patients with acute lymphoblastic leukemia admitted in our hospital from March 2014 to February 2017 was retrospectively analyzed. Among them 65 patients had invasive fungal infection (IFI) during the chemotherapy period, out of them 35 patients treated with voriconazole were enrolled in group A; anather 30 patients treated with amphotericin B were enrolled in group B. The clinical factors that affected the incidence of IFI was statistically analyzed. And the efficacy and adverse reactions in children with ALL were compared after treatment for 8 weeks.</p><p><b>RESULTS</b>The incidence of IFI in children with ALL in this study was 30.37%, and was related with the duration of hospitalization and the level of neutrophil deficiency (P<0.05). The total effective rates of group A and group B were 72.28% and 43.33%, respectively, their difference was statistically significant between 2 group (P<0.05). The incidence of renal function impairment, digestive dysfunction and neurotoxicity were 8.57%, 5.71% and 5.71% in children with ALL treated with voriconazole respectively, which were lower than those in children treated with amphotericin B (P<0.05). The score index of Physical health, energy state, emotion control and overall health in group A were significantly higher than those in B group, and the difference was statistically significant (P<0.05).</p><p><b>CONCLUSION</b>The occurrence of IFI in children with ALL relats with the time of hospitalization and the level of neutrophils. The clinical effect of voriconazole is better, and the incidence of adverse reactions can be reduced, suggesting important clinical significance.</p>
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Objective To study the incidence and risk factors ofdefecatory dysfunction in acute minorischemic strokepatientsandexplore the influence of the risk factors onprognosis.Methods Clinical data of 274 patients with acute minor ischemic strokewere reviewed and analyzed retrospectively.According to the presence of poststroke defecatorydysfunction,they were divided into defecatory dysfunction group and non-defecatory dysfunction group.The factors associated withdefecatory dysfunctionwere analyzed by univariate analysis and multivariatelogisticanalysis respectively,followed by investigating their effects on the prognosis.Results 74 patients of them with acute minor ischemic stroke had defecatory dysfunction.The univariate analysis indicated that4 factors including baseline NIHSS scorewere the risk factors.Multivariate logistic analysis showed that female,age,diabetes mellitus and baseline NIHSS score were independent risk factors for defecatory dysfunction.The scores of modified Rankin Scale (mRS) after 3 months in minor stroke patients with defecatory dysfunction wassignificantly higher(P < 0.05).Baseline NIHSS score was a predictive factor for the prognosis of post-stroke defecatorydysfunctionpatients.Conclusions Defecatory dysfunction in acute minor stroke patients may increase the risk of poor prognosis.The female,elderlypatients as well those with diabetes mellitus and serious neurologicalfunction deficits are more likely to suffer post-stroke defecatory dysfunction.
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Objective · To evaluate the influence of cathepsin S(CatS) on the severity of communicating hydrocephalus in a kaolin injected mouse model.Methods · Kaolin suspension was injected to 8 CatS knock-out (CatS -/-) mice and 12 wild type (WT) C57BL/6 mice through cisterna magna to establish communicating hydrocephalus mouse model. Cerebral magnetic resonance imaging (MRI) was used before and 1 week after kaolin injection to compare lateral ventricular volume. Lateral ventricular index was calculated to analyze the severity of hydrocephalus. Results · One week after kaolin injection,1 in CatS -/- group and 2 in WT group died. The mortality rate was 12.5% each and there was no significant difference (P=1.000). MRI results showed varying degrees of ventriculomegaly in both groups. Lateral ventricular index of CatS -/-group (n=8) and WT group (n=16) before kaolin injection was 0.05±0.01 and 0.04±0.01 respectively (P=0.720). One week after kaolin injection, lateral ventricular index of CatS-/- group (n=7) and WT group (n=14)was 0.13±0.02 and 0.11±0.01 respectively (P=0.950). In each group, in 71.4% of mice, lateral ventricular index enlarged twice or more. Conclusion · One week after kaolin injection into cisterna magna, lateral ventricles enlarges obviously, indicating hydrocephalus occurs, with high success rate. CatS gene deficiency has no significant influence on the development of communicating hydrocephalus.
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Objective · To evaluate the influence of cathepsin S(CatS) on the severity of communicating hydrocephalus in a kaolin injected mouse model.Methods · Kaolin suspension was injected to 8 CatS knock-out (CatS -/-) mice and 12 wild type (WT) C57BL/6 mice through cisterna magna to establish communicating hydrocephalus mouse model. Cerebral magnetic resonance imaging (MRI) was used before and 1 week after kaolin injection to compare lateral ventricular volume. Lateral ventricular index was calculated to analyze the severity of hydrocephalus. Results · One week after kaolin injection,1 in CatS -/- group and 2 in WT group died. The mortality rate was 12.5% each and there was no significant difference (P=1.000). MRI results showed varying degrees of ventriculomegaly in both groups. Lateral ventricular index of CatS -/-group (n=8) and WT group (n=16) before kaolin injection was 0.05±0.01 and 0.04±0.01 respectively (P=0.720). One week after kaolin injection, lateral ventricular index of CatS-/- group (n=7) and WT group (n=14)was 0.13±0.02 and 0.11±0.01 respectively (P=0.950). In each group, in 71.4% of mice, lateral ventricular index enlarged twice or more. Conclusion · One week after kaolin injection into cisterna magna, lateral ventricles enlarges obviously, indicating hydrocephalus occurs, with high success rate. CatS gene deficiency has no significant influence on the development of communicating hydrocephalus.
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Objective:To investigate serum IgG4 levels in different diseases and the changes of serum IgG4 levels in post treatment of IgG4 related disease.Methods:Clinical data of 620 patients who received investigation of serum IgG4 in Peking University People's Hospital from January 1,2015 to March 31,2016 were collected retrospectively.According to the difference of the diseases,they were divided into common group of diseases,autoimmune diseases and IgG4 related diseases;pancreatic disease patients were divided into autoimmune pancreatitis and pancreatic cancer group;According to different treatment stages of the disease,the patients with IgG4 related diseases were divided into pretreatment group and post treatment group.And the expressions of the patients' serum IgG4 levels in different groups were analyzed.Results:The median serum IgG4 level in the group of the patients with common diseases was 0.480 (0.005,50.400) g/L,in the group of autoimmune disease was 0.406 (0.003,18.700) g/L,in the group of IgG4 related diseases was 5.200(0.046,46.000) g/L,which was significantly higher in the group of IgG4 related diseases than the other two groups,and there was obvious statistical significance in serum IgG4 levels between the group of IgG4 related diseases and the other two groups (P <0.01);There was no obvious difference in serum IgG4 levels between the common disease group and the autoimmune disease group,and there was no obvious statistical difference in serum IgG4 levels between the two groups (P > 0.05).In the patients with IgG4 related diseases,the median serum IgG4 level in the group of pretreatment patients was 6.540 (1.330,34.100) g/L,and 3.735 (0.063,46.000) g/L in the post treatment patients.Serum IgG4 levels decreased in post treatment group,significantly lower than in pretreatment,there was obvious statistical difference in serum IgG4 levels between the two groups (P < 0.01).The median serum IgG4 level in the group of patients with autoimmune pancreatitis was 3.735 (0.063,46.000) g/L,and 0.438 (0.056,1.130) g/L in the group of patients with pancreatic cancer,which was significantly higher in the group of patients with autoimmune pancreatitis than the others,and there was obvious statistical difference in serum IgG4 levels between the two groups (P <0.01).Conclusion:Serum IgG4 levels in patients with different diseases were different,and were significantly higher in patients with autoimmune pancreatitis and IgG4 related diseases,so serum IgG4 levels can provide the basis for the differential diagnosis of different diseases;Serum IgG4 levels in patients with IgG4 related diseases decrease significantly after treatment,so it can be used as an important index to evaluate the curative effect of IgG4 related diseases.
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The study aimed to determine the relationships between the basal metabolic rate (BMR) and body composition of overweight and obese Chinese adults with type 2 diabetes mellitus (DM). This cross-sectional clinical study enrolled 193 Chinese adults with type 2 DM who were overweight (24 kg/m(2)=BMI≤28 kg/m(2), n=99), or obese (BMI ≥28 kg/m(2), n=94). Ninety-seven adults with normal BMIs, including 50 DM patients and 47 healthy adults, were recruited as a control group. BMR was measured by indirect calorimetry; predicted BMR was calculated according to the Schofield equation; and the relationships between BMR, body composition, and biochemical results were determined by the Pearson correlation. The results showed that obese DM patients had significantly higher BMRs than both overweight patients (P<0.05) and patients with normal BMI did (P<0.05). The measured BMR was significantly lower than the predicted BMR (P<0.05) in all groups. Obese and overweight DM patients had significantly greater weight, waist circumference, hip circumference, BMI, body surface area, body fat percentage, fat mass, and fat-free mass than patients with normal BMI. Except for waist circumference, these body composition measurements were significantly increased in obese DM patients when compared with those in overweight DM patients (P<0.05). Fat-free mass was closely correlated with BMR in both DM patients (r=0.874, P<0.01) and in healthy controls (r=0.902, P<0.01). It was concluded that overweight and obese Chinese adults with type 2 DM had increased BMRs compared with normal-weight controls, which may result from the difference in fat-free mass.
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metabolismo Basal , Distribuição da Gordura Corporal , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2 , Metabolismo , Obesidade , MetabolismoRESUMO
Ellagitannins is a kind of phenolic compounds with many biological activities. Recent studies have found that the effective ingredients of these compounds have close relationship with their colon-derived bacteria metabolites, that is urolithins. The objective of this study was to review the structure characteristics, types and distribution of urolithins, improvement in diseases related to prostate, breast and colon, as well as anti-cancer, anti-oxidation, anti-inflammation and other biological activities. The present review will lay the foundation for development and utilization of urolithins.
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The study aimed to determine the relationships between the basal metabolic rate (BMR) and body composition of overweight and obese Chinese adults with type 2 diabetes mellitus (DM). This cross-sectional clinical study enrolled 193 Chinese adults with type 2 DM who were overweight (24 kg/m(2)=BMI≤28 kg/m(2), n=99), or obese (BMI ≥28 kg/m(2), n=94). Ninety-seven adults with normal BMIs, including 50 DM patients and 47 healthy adults, were recruited as a control group. BMR was measured by indirect calorimetry; predicted BMR was calculated according to the Schofield equation; and the relationships between BMR, body composition, and biochemical results were determined by the Pearson correlation. The results showed that obese DM patients had significantly higher BMRs than both overweight patients (P<0.05) and patients with normal BMI did (P<0.05). The measured BMR was significantly lower than the predicted BMR (P<0.05) in all groups. Obese and overweight DM patients had significantly greater weight, waist circumference, hip circumference, BMI, body surface area, body fat percentage, fat mass, and fat-free mass than patients with normal BMI. Except for waist circumference, these body composition measurements were significantly increased in obese DM patients when compared with those in overweight DM patients (P<0.05). Fat-free mass was closely correlated with BMR in both DM patients (r=0.874, P<0.01) and in healthy controls (r=0.902, P<0.01). It was concluded that overweight and obese Chinese adults with type 2 DM had increased BMRs compared with normal-weight controls, which may result from the difference in fat-free mass.
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To analyze the complications and nursing countermeasures of PICC [Peripherally Inserted Central Catheter] catheters. using children PICC catheter technique 40 cases, complications were observed, and analyze the original causes, in order to propose a solution. There were 10 cases of catheter blockage, 5 cases of catheter infection, 6 cases of phlebitis, 5 cases of puncture difficulties, 2 cases of poor feeding tube, 2 cases of bleeding puncture site. with the continuous exploration and research of nursing intervention, the production of clinical complications from PICC has been used in children were greatly reduced
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Humanos , Feminino , Masculino , Criança , Pré-Escolar , Enfermagem , PediatriaRESUMO
Aim To study the effects of cycle arrest and molecular mechanism in human leukemia HL-60 cells induced by diallyl disulfide ( DADS ) . Methods Cell count, colony formation in soft agar experiments and flow cytometry analysis were employed to observe the DADS-induced cell growth inhibition and the effect of cycle arrest in HL-60 cells. The expressions of Chk1/2 and its downstream element in HL-60 cells were detected by Western blot. Results Cell count revealed that population doubling time increased to 35. 03 h and 71. 82 h, respectively, from 19. 14 h in HL-60 cells treated with 60 and 120 μmol·L-1 DADS ( P0. 05). The expression of Cdc25C, CyclinB1 and CDK1 decreased after treated with 60 μmol·L-1 DADS in a time-dependent manner ( P0. 05 ) . Conclusion DADS can in-hibit the proliferation of HL-60 cells, and induce G2/M arrest through Chk1/Cdc25 C/CyclinB1/CDK1 path-way.
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Aim Toresearchthemolecularmecha-nisms of DADS-induced apoptosis in human leukemia K562cells.Methods Cellviabilitywasmeasuredby MTT. Levels of DADS-induced ROS were measured by 2ˊ, 7ˊ-dichlorofluorescein diacetate ( DCFH-DA) fluo-rescence. DADS-induced mRNA levels of components of the NADPH oxidase were detected by Real-time PCR. The combination of protein Rac2 and p67phox was measured by immunoprecipitation assays. Flow cy-tometry methods were used to determine the percentage of apoptosis cells. DADS-induced Rac2 levels were measuredbyWesternblot.Results TheDADS-trea-ted K562 cells showed a dose-and time-dependent de-crease in cell viability and proliferation. There was sig-nificant up-regulation of the mRNA level of components of the NADPH oxidase complex in K562 cells after treatment with 6 mg·L-1 DADS for 6 h. Western blot results revealed that, compared with the control group, there was a significant up-regulation of Rac2 protein in K562 cells treated with 5. 0 and 10. 0 mg·L-1 DADS for 24h. And Rac2 combined with p67phox in DADS-induced apoptosis in K562 cells. PMA markedly in-creased the percentage of apoptotic cells, and DPI re-duced the percentage of apoptotic cells in DADS-in-duced K562 cells. Levels of DADS-induced ROS, also showed enhancement when exposed in PMA, but there was no DADS-induced ROS production evident when exposed in DPI in DADS induced K562 cells. Conclu-sions TheseresultsindicatethatNADPHoxidaseis the main source of DADS-induced ROS production. Diallyl disulfide induces apoptosis in human leukemia K562 cells through activation of NADPH oxidase.