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Objective@#Pharmacotherapy including mood stabilizers and antipsychotics are frequently used in bipolar disorder (BD); however, the lack of consensus regarding the definition of polypharmacy hinders conducting comparative studies across different settings and countries. Research on Asian Prescription Pattern (REAP) is the largest and the longest lasting international collaborative research in psychiatry in Asia. The objective of REAP BD was to investigate the prescription patterns of psychotropic medications across Asian countries. The rates of polypharmacy and psychotropic drug load were also analyzed. @*Methods@#The data collection was web-based. Prescription patterns were categorized as (1) mood stabilizer monotherapy: one mood stabilizer; (2) antipsychotic monotherapy: one antipsychotic; (3) simple polypharmacy: one mood stabilizer and one antipsychotic; and (4) complex polypharmacy: ≥ 2 mood stabilizers or/and antipsychotics. The psychotropic drug load in each patient was calculated using the defined daily dose method. @*Results@#Among 2003 patients with BD (52.1% female, 42.4 years) from 12 countries, 1,619 (80.8%) patients received mood stabilizers, 1,644 (82.14%) received antipsychotics, and 424 (21.2%) received antidepressants, with 14.7% mood stabilizer monotherapy, 13.4% antipsychotic monotherapy, 48.9% simple polypharmacy, 20.3% complex polypharmacy, and 2.6% other therapy. The average psychotropic drug load was 2.05 ± 1.40. Results varied widely between countries. @*Conclusion@#Over 70% of psychotropic regimens involved polypharmacy, which accords with the high prevalence of polypharmacy in BD under a permissive criterion (2 or more core psychotropic drugs) worldwide. Notably, ≥ 80% of our sample received antipsychotics, which may indicate an increasing trend in antipsychotic use for BD treatment.
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Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron–glia interaction mediated by the C3–TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3–TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.
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Objective@#Recently, rational polypharmacy approaches have been proposed, regardless of the lower risk and cost of monotherapy. Considering monotherapy as first-line treatment and polypharmacy as rational treatment, a balanced attitude toward polypharmacy is recommended. However, the high prevalence of polypharmacy led the Japanese government to establish a polypharmacy reduction policy. Based on this, the association between the policy and psychiatrists’ attitude toward polypharmacy has been under debate. @*Methods@#We developed an original questionnaire about Psychiatrists’ attitudes toward polypharmacy (PAP). We compared the PAP scores with the treatment decision-making in clinical case vignettes. Multiple regression analyses were performed to quantify associations of explanatory variables including policy factors and PAP scores. The anonymous questionnaires were administered to psychiatrists worldwide. @*Results@#The study included 347 psychiatrists from 34 countries. Decision-making toward polypharmacy was associated with high PAP scores. Multiple regression analysis revealed that low PAP scores were associated with the policy factor (β=-0.20, p=0.004). The culture in Korea was associated with high PAP scores (β=0.34, p<0.001), whereas the culture in India and Nepal were associated with low scores (β=-0.15, p=0.01, and β=-0.17, p=0.006, respectively). @*Conclusion@#Policy on polypharmacy may influence psychiatrists’ decision-making. Thus, policies considering rational polypharmacy should be established.
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Objective:To investigate the relationship between serum ubiquitin C-terminal hydrolase-L1 (UCH-L1) and neuroglobin levels and the prognosis of neurological function in coma patients after cardiopulmonary resuscitation, and to analyze their value in predicting the prognosis of patients.Methods:From February 2018 to June 2020, 45 comatose patients admitted to the Chengdu Third People′s Hospital of Sichuan Province after successful cardiopulmonary resuscitation were prospectively selected as the coma group, and 62 patients admitted to the emergency intensive care unit during the same period after successful cardiopulmonary resuscitation with consciousness recovered within 24 hours were selected as the control group.Serum UCH-L1 and neuroglobin levels were detected within 24 hours after admission.Glasgow coma Scale (GCS)and cerebral performance category(CPC)were used to evaluate coma severity and neurological prognosis.Spearman rank correlation analyzed the correlation between UCH-L1 and neuroglobin levels and GCS and CPC scores.Logistic regression analyzed the factors affecting the prognosis of neurological function in coma patients after cardiopulmonary resuscitation.Receiver operating characteristic curve (ROC) was used to analyze the value of UCH-L1 and neuroglobin in predicting the prognosis of neurological function in coma patients after successful cardiopulmonary resuscitation.Results:In coma group, serum UCH-L1((0.63±0.21) μg/L) and the concentration of neuroglobin ((89.34±21.35) mg/L) was higher than that in the control group ((0.27±0.08) μg/L, (32.13±9.21) mg/L), the difference was statistically significant( t=12.338, 18.846; all P<0.001). The levels of UCH-L1 and neuroglobin in mild, medium and severe coma groups were increased in turn, and the differences between the groups were statistically significant( F=86.430, 26.958; all P<0.001). The serum levels of UCH-L1((0.72±0.06) μg/L)and neuroglobin ((100.35±5.79) mg/L)in the group with poor neurological prognosis were higher than those in the group with good neurological prognosis((0.52±0.08) μg/L, (75.58±6.91) mg/L), and the differences between the groups were statistically significant( t=9.585, 13.086; all P<0.001). UCH-L1 and neuroglobin were negatively correlated with GCS score(rs=-0.685, -0.669; all P<0.001), and positively correlated with CPC score (rs=0.688, 0.670; all P<0.001). Multivariate Logistic regression analysis showed that low GCS score( OR=0.552, 95% CI: 0.392-0.776, P<0.001), high UCH-L1 ( OR=1.881, 95% CI: 1.276-2.773, P<0.001)and neuroglobin( OR=1.677, 95% CI: 1.206-2.331, P=0.001)were independently associated with poor neurological outcomes in coma patients after cardiopulmonary resuscitation .The AUC of combining UCH-L1 and neuroglobin in predicting poor neurological outcomes in coma patients after cardiopulmonary resuscitation was 0.954, which was higher than that of UCH-L1 and neuroglobin alone (0.821, 0.790) ( Z=2.351, 2.649; all P<0.05). Conclusion:After successful cardiopulmonary resuscitation, the levels of UCH-L1 and neuroglobin in coma patients are increased.High levels of UCH-L1 and neuroglobin are associated with coma severity and neurological dysfunction, which can be used as a potential biological indicator for prognosis evaluation of neurological function.
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Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3-TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.
Subject(s)
Animals , Mice , Astrocytes/metabolism , Complement C3/metabolism , Epilepsy , Neurons/pathology , Status Epilepticus , TRPV Cation Channels/metabolismABSTRACT
In the current clinical medication, there is no method to confirm the sensitivity of patients with different genotypes to corresponding anticancer-drugs and also lack of response to side effects and drug resistance. In recent years, the development of high-throughput technology has made it possible to screen chemotherapeutic drugs on a large scale in cancer cell lines, and generated a large number of omics-data. Currently, based on these data, many predictive models of anticancer-drugs have been established, which will be helpful to predict and optimize the drug targets for cancer patients. This paper reviews the research progress of anticancer-drug prediction models.
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Objective@#To investigate the clinicopathological characteristics and improve the clinical treatment of prostatic small-cell carcinoma (PSCC).@*METHODS@#We reported 2 cases of PSCC derived from prostate cancer after treated by androgen blockade and prostate electrotomy and reviewed the relevant literature.@*RESULTS@#Two patients with PSA elevation were diagnosed with prostate cancer by prostatic puncture biopsy and treated by maximum androgen blockade, which reduced their total PSA to the normal level. Later, due to difficult urination, they both underwent prostate electrotomy, followed by chemotherapy or radiotherapy for PSCC confirmed by postoperative pathology. Nevertheless, they died at 8 to 9 months after the discovery of PSCC.@*CONCLUSIONS@#PSCC can derive from prostate cancer after treatment, which may be attributed to the pathological mutation induced by long-term endocrine therapy. PSCC is more malignant than prostate cancer, and its prognosis is poor.
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With the rapid development of organ transplantation in China,the donation after cardiac death (DCD) donor organs are widely used.However,the quality of these organs is relatively poor,so the way to preserve and maintain organ still remains a severe problem.Among them,ischemic reperfusion injury (IRI) impairs the organs severely.Acetaldehyde dehydrogenase 2 (ALDH2) protects organs from stress conditions,including ischemia-reperfusion injury,and the activation and autophagy inhibition also protects the organs from stress conditions as well.Recent studies showed that ALDH2 can regulate autophagy to inhibit the organ injury during ischemia-reperfusion.Our study aims to discuss the new findings in this mechanism.
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Objective To compare the efficacy of surgical treatment(ST) and mechanical ventilation treatment(MVT) for flail chest.Methods From March 2013 to May 2017,81 patients with flail chest who underwent ST(28 cases) and MVT(53 cases) were enrolled in ICU.The relevant indicators of efficacy were compared including mechanical ventilation (MV) time,bed rest time,oxygen administration time,catheterization time,antibiotic use time,drug analgesia,drug analgesia patients,proportion of stop/postoperative sputum alone,ICU treatment time,hospital stay,mortality,readmission within two months and long-term pulmonary function after discharge.Results The MV time,bed time,oxygen time,antibiotic use time,ICU treatment time and hospitalization time of MVT were longer than those of ST group,the differences were significant(P ＜ 0.05).MVT had more analgesic times,more analgesic cases,smaller proportion of offline/postoperative sputum along and less hospitalization fees compared with ST group,the differences were significant(P ＜0.05).There was no significant difference in the main indexes of pulmonary function between two groups in 3 months after discharge.Conclusion ST and MVT respectively has advantages and disadvantages for flail chest.There is no significant difference in long-term pulmonary function of ST and MVT.While MVT has less trauma and lower cost.The appropriate treatment could be selected according to the clinical situation.
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<p><b>Objective</b>To explore the inhibitory effect of polyphyllin Ⅰ (PPⅠ) on the proliferation of castration-resistant prostate cancer PC3 cells and its molecular mechanism.</p><p><b>METHODS</b>We cultured human prostate cancer PC3 cells in vitro and treated them with PPⅠ at the concentrations of 0 (blank group), 0.4, 0.8, 1.2, 1.6, 2.0, and 2.4 μmol/L for 24, 48, and 72 hours, respectively. Then we detected the proliferation of the cells by MTT assay, measured their apoptosis by flow cytometry, and determined the expressions of p-ERK1/2, ERK1/2, NF-κB/p65 and DNMT1 proteins as well as the level of NF-κB/p65 in the cells additionally treated with the ERK1/2 inhibitor SP600125 by Western blot.</p><p><b>RESULTS</b>Compared with the blank control group, the PPⅠ-treated PC3 cells showed a concentration- and time-dependent reduction of the survival rate (1.00 ± 0.00 vs 0.85 ± 0.05, P < 0.01) at 0.4 μmol/L after 48 hours of intervention, concentration-dependent early apoptosis at 0.8 μmol/L (4.83 ± 0.95 vs 13.83 ± 2.97, P < 0.01), time-dependent increase of the expressions of p-ERK1/2 (1.00 ± 0.00 vs 1.73 ± 0.17, P < 0.01) and ERK1/2 (1.00 ± 0.00 vs 1.36 ± 0.12, P < 0.01) at 2 hours, and concentration-dependent decrease of the expressions of NF-κB/p65 and DNMT1 at 1.2 μmol/L (1.00 ± 0.00 vs 0.78 ± 0.10 and 0.63 ± 0.06, P < 0.01) and 1.6 μmol/L (1.00 ± 0.00 vs 0.67 ± 0.11 and 0.52 ± 0.09, P<0.01). Inhibition of ERK1/2 phosphorylation with PD98059 markedly reversed PPⅠ-induced decrease of the NF-κB/p65 expression as compared with that in the PPⅠ group (0.86 ± 0.18 vs 0.43 ± 0.09, P < 0.05).</p><p><b>CONCLUSIONS</b>PPⅠ induces the early apoptosis and suppresses the proliferation of PC3 cells, probably by activating the ERK1/2 pathway and inhibiting the expressions of the NF-κB/p65 and DNMT1 proteins.</p>
Subject(s)
Humans , Male , Apoptosis , Cell Proliferation , DNA (Cytosine-5-)-Methyltransferase 1 , Metabolism , Diosgenin , Pharmacology , Flavonoids , Metabolism , MAP Kinase Signaling System , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , NF-kappa B , Metabolism , PC-3 Cells , Phosphorylation , Prostatic Neoplasms, Castration-Resistant , Drug Therapy , Metabolism , Pathology , Signal Transduction , Transcription Factor RelA , MetabolismABSTRACT
Objective To investigate the value of IL-27,IL-29 and miRNA-497 in HER-2 positive radioactive particles combined targeted therapy. Methods Sixty-one elderly inpatients with HER-2 positive gastric cancer ascites in the Gaoming District People's Hospital, Wuchuan Municipal People's Hospital and Zhejiang Provincial Tumor Hospital were divided into the two groups. The treatment group(n= 31) was treated by the radioactive particles+ targeted drug Trastuzumab(initial dose 8 mg/kg, maintenance dose 66 mg/kg, once per 3 weeks) for 6 weeks; the control group(30 cases) was treated by targeted drug Trastuzumab (initial dose 8 mg/kg,maintenance dose 6 mg/kg, once per 3 weeks) for 6 weeks. The levels of ascites IL-27,IL-29 and miRNA-497 in the radioactive partcles combined targeted therapy group and control group were detected. Results The levels of ascites IL-27, IL-29 and miRNA-497 after treatment in the treatment group were significantly decreased compared with those before treatment and in the control group,the effective remission rate in the treatment group was 74. 19%, which was higher than 36.67% in the control group, the average median survival time in the treatment group was 155 d, which washigher than 72 d in the control group, the difference was statistically significant. Conclusion IL-27 ,IL-29 and miRNA-497 has the significance of curative effect evaluation and prognosis judgment in the radioactive particles combined targeted therapy for the patients with HER 2 positive gastric cance.
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Authors raised that staging based strategies and practice of integrative medicine (IM) by combining syndrome typing and disease identification, and choosing suitable measures in accordance with different persons and seasonal conditions after more than ten years' clinical practice and researches. Radical operation as prior (as evil eliminating) and strengthening vital qi in perioerative period are best strategy for promoting rapid rehabilitation of early stage prostate cancer patients. Strengthening body resistance to eliminate evil was used in treating advanced prostate cancer patients. For example, a comprehensive treatment program for hormone-dependent patients was combined with endocrinotherapy and Chinese herbs for synergisic efficacy-enhancing actions. In this way, these patients' quality of life (QOL) were improved and time to castration resistant prostate cancer (CRPC) was delayed, even some patients were clinically cured. There are lack of effective medicines and methods for CRPC patients. Greatly tonifying original qi is mainly used for improving their clinical symptoms and prolonging survivals. Practice has proved staging based strategies and practice of IM has favorable advantages in treating prostate cancer, especially showing prospect in prolonging survival and postponing progression of advanced prostate cancer patients. Besides, it also could provide beneficial considerations and inspiration for combination of syndrome typing and disease identification.
Subject(s)
Humans , Male , Disease Progression , Medicine, Chinese Traditional , Neoplasm Staging , Prostatic Neoplasms, Castration-Resistant , Diagnosis , Quality of LifeABSTRACT
<p><b>BACKGROUND</b>Optimizing treatment outcomes for depression requires understanding of how evidence-based treatments are utilized in clinical practice. Antipsychotic medications concurrent with antidepressant treatment are frequently used in major depression, but few studies have investigated trends and patterns of their use over time. This study aimed to examine the prescription patterns of antipsychotic medications for major depression in China from 2002 to 2012 and their association with treatment satisfaction and quality of life (QOL).</p><p><b>METHODS</b>A total of 3655 subjects with major depression treated in 45 Chinese psychiatric hospitals/centers nationwide were interviewed between 2002 and 2012. Patients' socio-demographic and clinical characteristics including psychopathology, medication side effects, satisfaction with treatment and QOL were recorded using a standardized protocol and data collection.</p><p><b>RESULTS</b>The frequency of antipsychotic use was 24.9% in the whole sample; the corresponding figures were 17.1%, 20.3%, and 32.8% in 2002, 2006, and 2012, respectively (χ2 = 90.3, df = 2, P < 0.001). Multiple logistic regression analyses revealed that patients on concurrent antipsychotics had significantly more delusions or hallucinations, longer illness duration, greater side effects, and more likely to be treated as inpatients and in major hospitals (i.e., Level-III hospital). Antipsychotic use was associated with lower treatment satisfaction while there was no significant difference with respect to physical and mental QOL between the antipsychotic and nonantipsychotic groups.</p><p><b>CONCLUSIONS</b>Concurrent antipsychotic use was found in about one in four treated depressed patients in China, which has increased over a 10-year period. Considering the association of drug-induced side effects and the lack of patients' and relatives' satisfaction with antipsychotic treatment, further examination of the rationale and appropriateness of the use of antipsychotics in depression is needed.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Antipsychotic Agents , Therapeutic Uses , Depressive Disorder, Major , Drug Therapy , Personal Satisfaction , Psychotropic Drugs , Therapeutic Uses , Quality of LifeABSTRACT
<p><b>OBJECTIVE</b>To systematically evaluate the efficacy and safety of kidney-tonifying traditional Chinese medicine in the treatment of male infertility.</p><p><b>METHODS</b>Based on the principles and methods of Cochrane systematic reviews, we searched CNKI, VIP, and Wanfang databases from inception to December 2012 for randomized controlled clinical trials addressing the treatment of male infertility with kidney-tonifying traditional Chinese medicine. According to the inclusion and exclusion criteria and retrieval strategies, we extracted the data, evaluated the quality of the included literature, and conducted meta-analysis using the RevMan 5. 2 software.</p><p><b>RESULTS</b>Twenty trials involving 2,272 patients were included, and the sample size of each study was from 60 to 270 cases. All the studies were graded as of poor quality, with Jadad scores of no more than 3 points. The results of meta-analysis showed that the total effectiveness rate of traditional Chinese medicine versus Western medicine on male infertility was RR = 1.71, 95% CI 1.19-2.47, and that of Chinese-Western combined therapy versus Western medicine was RR = 1.15, 95% CI 1.01-1.30. Both traditional Chinese medicine and Chinese-Western combined therapy showed a significantly better total effectiveness than Western medicine alone in improving the pregnancy rate without serious adverse reactions.</p><p><b>CONCLUSION</b>Due to the poor methodological quality and high heterogeneity of the included studies, the evidence for the efficacy and safety of kidney-tonifying traditional Chinese drugs in the treatment of male infertility is of but limited value, and further validation is needed by more high-quality studies.</p>
Subject(s)
Female , Humans , Male , Pregnancy , Drugs, Chinese Herbal , Therapeutic Uses , Infertility, Male , Drug Therapy , Kidney , Medicine, Chinese Traditional , Randomized Controlled Trials as TopicABSTRACT
<p><b>BACKGROUND</b>Depression is often comorbid with chronic somatic diseases. Few previous studies have investigated the prevalence of somatic diseases in depression or the prescription pattern of antidepressants in comorbidly depressed patients in Asia. This study aimed to investigate the prevalence of somatic comorbidity (SC) in depression and compared the prescriptions of antidepressants in depressed patients with and without SC.</p><p><b>METHODS</b>A total of 2320 patients treated with antidepressants in 8 Asian countries were examined, and a diagnosis was based on the International Classification of Disease, 10 th revision. We listed 17 common chronic somatic diseases. Patients' socio-demographic and clinical characteristics and psychotropic drug prescriptions were recorded using a standardized protocol and data collection procedure.</p><p><b>RESULTS</b>Of the patients examined, 1240 were diagnosed with depression and 30% of them (n = 375) had SC. The most common comorbid condition was diabetes (23.7%). The patients with SC were more likely to seek help at a general hospital (74.7% vs. 47.2%), and had a higher incidence of symptoms involving sadness, disturbed sleep, and poor appetite. Noradrenergic and specific serotonergic antidepressant was prescribed more for patients with SC than for those without SC (30.4% vs. 22.9%).</p><p><b>CONCLUSIONS</b>SC is common in depressed Asian patients. It is important to strengthen the recognition of depression, especially in general hospitals and when patients report some somatic discomfort. It is also a matter of urgency to establish evidence-based guidelines for the use of new antidepressants in depressed patients with SC.</p>
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Adult , Female , Humans , Male , Middle Aged , Antidepressive Agents , Therapeutic Uses , Asia , Asian People , Depression , Drug Therapy , Epidemiology , Drug Prescriptions , PrevalenceABSTRACT
To explore the effect of quercetin on the proliferation and apoptosis of HeLa cells, HeLa cells were incubated with quercetin at different concentrations. Cell viability was evaluated by MTT assay, cell apoptosis was detected by Annexin-V/PI double labeled cytometry and DNA ladder assay. Cell cycle was flow cytometrically determined and the morphological changes of the cells were observed under a fluorescence microscope after Hoechst 33258 staining and the apoptosis-related proteins in the HeLa cells were assessed by Western blotting. The results showed that quercetin significantly inhibited the growth of HeLa cells and induced obvious apoptosis in vitro in a time- and dose-dependent manner. Moreover, quercetin induced apoptosis of HeLa cells in cell cycle-dependent manner because quercetin could induce arrest of HeLa cells at G0/G1 phase. Quercetin treatment down-regulated the expression of the PI3K and p-Akt. In addition, quercetin could down-regulate expression of bcl-2, up-regulate Bax, but exerted no effect on the overall expression of Akt. We are led to conclude that quercetin induces apoptosis via PI3k/Akt pathways, and quercetin has potential to be used as an anti-tumor agent against human cervix cancer.
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Over-expression of Fas ligand (FasL) on tumor cell surface can induce the apoptosis of specific activated tumor infiltrating lymphocytes (TILs) via the Fas/FasL pathway, leading to the formation of a site of immune privilege surrounding the tumor mass for escaping immune surveillance and promoting tumor proliferation, invasion and metastasis. The blocking effect of miR-21 on FasL-mediated apoptosis in breast cancers was investigated in this study. The expression levels of miR-21 and FasL in human breast carcinoma cell lines were detected by using RT-PCR and Western blotting. FasL as a target gene of miR-21 was identified by Luciferase assay. The apoptosis of Jurkat T lymphocytes induced by MCF-7 cells was determined by flow cytometry. It was found that in four human breast cancer cell lines, FasL expression level in MCF-7 cells was the highest, while miR-21 was down-regulated the most notably. After miR-21 expression in MCF-7 cells was up-regulated, FasL was identified as a target gene of miR-21. When the effector/target (E/T) ratio of MCF-7 cells and Jurkat cells was 10:1, 5:1 and 1:1, the inhibitory rate of apoptosis of Jurkat T lymphocytes induced by MCF-7 cells was 95.81%, 93.16% and 91.94%, respectively. It is suggested that in breast cancers miR-21 expression is negatively associated with FasL expression, and FasL is a target gene of miR-21. miR-21 targeting and regulating FasL-mediated apoptosis will bring us the possibility of a new tumor immunotherapy via breaking tumor immune privilege.
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To explore the effect of quercetin on the proliferation and apoptosis of HeLa cells, HeLa cells were incubated with quercetin at different concentrations. Cell viability was evaluated by MTT assay, cell apoptosis was detected by Annexin-V/PI double labeled cytometry and DNA ladder assay. Cell cycle was flow cytometrically determined and the morphological changes of the cells were observed under a fluorescence microscope after Hoechst 33258 staining and the apoptosis-related proteins in the HeLa cells were assessed by Western blotting. The results showed that quercetin significantly inhibited the growth of HeLa cells and induced obvious apoptosis in vitro in a time- and dose-dependent manner. Moreover, quercetin induced apoptosis of HeLa cells in cell cycle-dependent manner because quercetin could induce arrest of HeLa cells at G0/G1 phase. Quercetin treatment down-regulated the expression of the PI3K and p-Akt. In addition, quercetin could down-regulate expression of bcl-2, up-regulate Bax, but exerted no effect on the overall expression of Akt. We are led to conclude that quercetin induces apoptosis via PI3k/Akt pathways, and quercetin has potential to be used as an anti-tumor agent against human cervix cancer.
Subject(s)
Humans , Antioxidants , Pharmacology , Apoptosis , Blotting, Western , Cell Cycle , Cell Proliferation , Cell Survival , Dose-Response Relationship, Drug , Flow Cytometry , HeLa Cells , Phosphatidylinositol 3-Kinases , Metabolism , Proto-Oncogene Proteins c-akt , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Quercetin , Pharmacology , Signal Transduction , Time Factors , bcl-2-Associated X Protein , MetabolismABSTRACT
Over-expression of Fas ligand (FasL) on tumor cell surface can induce the apoptosis of specific activated tumor infiltrating lymphocytes (TILs) via the Fas/FasL pathway, leading to the formation of a site of immune privilege surrounding the tumor mass for escaping immune surveillance and promoting tumor proliferation, invasion and metastasis. The blocking effect of miR-21 on FasL-mediated apoptosis in breast cancers was investigated in this study. The expression levels of miR-21 and FasL in human breast carcinoma cell lines were detected by using RT-PCR and Western blotting. FasL as a target gene of miR-21 was identified by Luciferase assay. The apoptosis of Jurkat T lymphocytes induced by MCF-7 cells was determined by flow cytometry. It was found that in four human breast cancer cell lines, FasL expression level in MCF-7 cells was the highest, while miR-21 was down-regulated the most notably. After miR-21 expression in MCF-7 cells was up-regulated, FasL was identified as a target gene of miR-21. When the effector/target (E/T) ratio of MCF-7 cells and Jurkat cells was 10:1, 5:1 and 1:1, the inhibitory rate of apoptosis of Jurkat T lymphocytes induced by MCF-7 cells was 95.81%, 93.16% and 91.94%, respectively. It is suggested that in breast cancers miR-21 expression is negatively associated with FasL expression, and FasL is a target gene of miR-21. miR-21 targeting and regulating FasL-mediated apoptosis will bring us the possibility of a new tumor immunotherapy via breaking tumor immune privilege.
Subject(s)
Female , Humans , Apoptosis , Genetics , Breast Neoplasms , Genetics , Fas Ligand Protein , Metabolism , Flow Cytometry , Gene Expression Regulation, Neoplastic , MCF-7 Cells , MicroRNAs , Genetics , Signal TransductionABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect of short-course kidney-invigorating therapy on near-term semen quality in asthenozoospermic men with kidney deficiency.</p><p><b>METHODS</b>Based on the differential types in traditional Chinese medicine, 121 asthenozoospermia patients received at our clinic of andrology were divided into groups A (kidney-yin deficiency), B (kidney-yang deficiency) and C (spleen and kidney deficiency), and treated with Yougui Decoction plus Wuziyanzong Pills, Jinkuishenqi Pills plus Wuziyanzong Pills, and Shizi Decoction plus Liujunzi Decoction, respectively, all given once daily for 4 weeks. Sperm parameters of the patients were analyzed with the computer-assisted sperm analysis system before and after treatment and compared among the three groups.</p><p><b>RESULTS</b>The baseline sperm concentrations in groups A, B and C ([70.4 +/- 38.6], [73.5 +/- 40.2] and [56.0 +/-34.4] x 10(6)/ml) showed no significant differences from those after medication ([74.4 +/- 32.6], [67.0 +/- 30.8] and [58.6 +/- 24.6] x 10(6)/ml) (P > 0.05). The percentages of grade a sperm in the three groups were (12.9 +/- 5.3)%, (13.7 +/- 7.7)% and (12.9 +/- 6.4)% respectively after treatment, significantly higher than (9.9 +/- 6.7)%, (9.3 +/- 5.4)% and (9.0 +/- 6.8)% before treatment (P < 0.05), and so were the percentages of grade a + b sperm ([37.4 +/- 10.2 ]%, [35.7 +/- 13.7]% and [35.9 +/- 12.3]% after treatment versus [29.6 +/- 13.2]%, [27.5 +/- 10.4]% and [28.3 +/- 12.1]% before treatment, P < 0.05). All the three groups showed significantly increased sperm motility after treatment ([53.8 +/- 10.5]%, [52.6 +/- 15.2]% and [51.1 +/- 13.1]%) as compared with the baseline levels ([44.3 +/- 14.0]%, [43.5 +/- 15.0]% and [42.4 +/- 14.9]%) (P < 0.05). The cure rate and total effectiveness rate were significantly higher in group B than in A (P < 0.05), but had no significant differences between either A and C or B and C (P > 0.05).</p><p><b>CONCLUSION</b>Short-course kidney-invigorating therapy can significantly improve near-term semen quality in asthenozoospermic men with kidney asthenia, especially in those with kidney-yang deficiency, and it has no obvious adverse effects.</p>