RESUMO
2-isopropyl-N,2,3-trimethylbutyramide (WS-23) is a well-known artificial synthesis cooling agent widely used in foods, medicines, and tobaccos. As a commonly cooling agent in e-cigarette liquids, WS-23 has led to concerns about the inhalation toxicity with the prosperous of e-cigarettes in recent years. Thus, the aim of this study is to assess the acute and subacute inhalation toxicity of WS-23 in Sprague-Dawley (SD) rats according to the Organization for Economic Cooperation and Development (OECD) guidelines. In the acute toxicity study, there was no mortality and behavioral signs of toxicity at the limit test dose level (340.0 mg/m3 ) in the exposure period and the following 14-day observation period. In the subacute inhalation toxicity study, there was no significant difference observed in the body weights, feed consumption, and relative organ weights. Haematological, serum biochemical, urine, and bronchoalveolar lavage fluid (BALF) analysis revealed the non-adverse effects after 28-day repeated WS-23 inhalation (342.85 mg/m3 ), accompanied by slight changes in few parameters which returned to normal during the 28-day recovery period. The histopathologic examination also did not show any differences in vital organs. In conclusion, the maximum tolerated dose for WS-23 acute inhalation is not less than 340.0 mg/m3 , and the No Observed Adverse Effect Level (NOAEL) of WS-23 subacute inhalation was determined to be over 342.85 mg/m3 .
Assuntos
Amidas/toxicidade , Exposição por Inalação , Animais , Feminino , Masculino , Ratos , Ratos Sprague-Dawley , Organismos Livres de Patógenos Específicos , Testes de Toxicidade Aguda , Testes de Toxicidade SubagudaRESUMO
Chronic heart failure(CHF), a serious and end stage of various heart diseases, is a common chronic cardiovascular disease in the 21 st century. Literature data show that the 5-year mortality rate of hospitalized patients with heart failure is as high as 50%. Nowadays, the development of drugs treating heart failure has become a hot spot, meanwhile, traditional Chinese medicine(TCM) has shown the advantages in the treatment of chronic heart failure. In this article, four stages to develop traditional Chinese medicine for chronic heart failure were proposed. Firstly, discuss and screen ideas and methods with regard to the development of TCM and its prescriptions based on clinical needs. Secondly, study the preparation process and quality control method by referring to the existing clinical background of TCM prescriptions and analyzing the chemical compositions and pharmacological action characteristics of each herb in the prescription. Then, design non-clinical evaluation programs and carry out researches on pharmacodynamics and toxicology by combining the experience of clinical use of TCM prescriptions and future clinical positioning, and gradually adjust and improve the programs during implementation. Finally, conduct clinical trial application(IND) by submitting registration application data which are base on the clinical drug experience, preclinical research pharmacy, main pharmacodynamics, safety test results of the prescription, clinical positioning, and reasonable clinical trial plan designed by the theory of TCM. After passing the IND technical review, the clinical trial study shall be officially launched to achieve the desired results and obtain effective Chinese patent medicines for heart failure treatment.
Assuntos
Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Doença Crônica , Humanos , Medicina Tradicional Chinesa , Controle de QualidadeRESUMO
OBJECTIVE: To study the prevention effect of Huoluotongnao tablet on stroke. METHODS: Bilateral common carotid artery ligation and reperfusion injury model and reperfusion injury in focal cerebral ischemia-induced thrombosis line method rat model were used. RESULTS: Huoluotongnao tablet could significantly reduce the pathological injury of rat brain tissue changes of these two models, and increase the activity of SOD and decrease the content of MDA in the brain tissue and plasma of rats. The brain water content of treatment groups were significantly reduced. The behavioral index and cerebral infarction range index were effectively improved in the middle cerebral artery occlusion reperfusion model rats. CONCLUSION: Huoluotongnao tablet has certain prevention effect on stroke.
Assuntos
Isquemia Encefálica/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Isquemia Encefálica/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/isolamento & purificação , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/prevenção & controle , Masculino , Malondialdeído/sangue , Malondialdeído/metabolismo , Fármacos Neuroprotetores/isolamento & purificação , Plantas Medicinais/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo , ComprimidosRESUMO
OBJECTIVE: To observe the effect of immunoregulation and anti-oxidation of Zhongyaofangji NO1 (ZYFJ). METHODS: 1. SPF BALB/C mice were randomly divided into control group (distilled water), positive control group (Broken Spore), ZYFJ low dose group (0.35 g/kg), middle dose group (0.70 g/kg) and high dose group (1.40 g/kg), with intragastric administration 1 time/d for 30d; The spleen and thymus index, ability of spleen lymphocyte proliferation, phagocytosing chicken red blood cell (CRBC) of abdominal macrophage cell, carbon clearance were investigated. 2. SPF BALB/C mice were divided into normal control group, model control group (D-galactose induced peroxidation damage), model plus ZYFJ low dose, middle dose and high dose group, model plus positive control group (Broken Spore), with drug administration 1 time/d for 30 d. SOD activity, MDA and LPO content in brain tissue were tested while Nrf2 [Nuclear factor (erythroi D-derived 2)-like 2] protein expression in brain tissue nucleus was tested by western blotting. RESULTS: The thymus index and spleen index in groups of ZYFJ high dose and positive control were higher than those in control group, the ability of lymphocyte proliferation and phagocytosis of macrophages were increased in all the other groups significantly compared with control group; The activity of SOD and Nrf2 protein expression level in brain tissue of model mice was increased, MDA and LPO contents were reduced in ZYFJ middle and high dose as well as positive control significantly, while the MDA content was reduced and Nrf2 protein was increased in low dose group. CONCLUSION: Appropriate dose of ZYFJ1 has good effect of immunoregulation, and plays a role of anti-oxidation probably by regulating Nrf2 protein expression in brain tissue and related signaling pathway.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Baço/efeitos dos fármacos , Baço/imunologia , Animais , Encéfalo , Proliferação de Células , Modelos Animais de Doenças , Galactose , Camundongos , Camundongos Endogâmicos BALB C , Oxirredução , Transdução de SinaisRESUMO
OBJECTIVE: To study the prevention effect of Huoluotongnao tablet on stroke. METHODS: Thrombosis on arteriovenous shunt rats model, platelet aggregation and hypertension combined high cholesterol rats model were used. RESULTS: Huoluotongnao tablet high and low dosage could inhibit the formation of arteriovenous thrombosis and platelet aggregation significantly ,the inhibition rate was 17.71%, 22.69%, 20.34% and 24.43%, respectively. Pretreatment of Huoluotongnao tablet could inhibit the formation of arteriovenous thrombosis significantly; The levels of CHOz in all treatment groups of hypertension combined high cholesterol rats model were decreased significantly,the levels of TGz and LDL-C were decreased in the high dosage group,the blood pressure was decreased in the middle dosage group. eta bL, eta P and eta r (B/P) were decreased in the middle and high dosage groups. eta bM, AI and CY were decreased in the middle and high dosage groups. Huoluotongnao tablet had effect on blood lipid,blood pressure and hemorheology and in a dose-dependence manner. Its minimal effecting dose was the middle dose. g/kg (crude drug) and has certain prevention effect on stroke. CONCLUSION: Huoluotongnao tablet's minimal effecting dose is 1.28
Assuntos
Trombose das Artérias Carótidas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Fibrinolíticos/farmacologia , Arteriosclerose Intracraniana/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Animais , Viscosidade Sanguínea/efeitos dos fármacos , Trombose das Artérias Carótidas/sangue , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Fibrinolíticos/administração & dosagem , Hemorreologia/efeitos dos fármacos , Hipertensão/complicações , Arteriosclerose Intracraniana/etiologia , Masculino , Plantas Medicinais/química , Agregação Plaquetária/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/tratamento farmacológico , ComprimidosRESUMO
OBJECTIVE: To compare the survival outcomes of early-stage oropharyngeal cancer (OPC) patients treated with upfront surgery versus definitive radiotherapy (RT). STUDY DESIGN: Retrospective observational study. SETTING: Publicly available database. METHODS: A total of 1877 patients with T1-2N0-1M0 OPC were retrieved from the Surveillance, Epidemiology, and End Results database. Primary endpoints were cancer-specific and noncancer mortalities, which were estimated using cumulative incidence function and compared by Gray's test. Univariate and multivariate Fine-Gray subdistribution hazard models were used to estimate the effects of treatment modality on mortality. Subgroup analyses were performed in propensity-score-matched cohorts. All the analyses were conducted separately in human papillomavirus (HPV)-negative and HPV-positive cohorts. RESULTS: In the HPV-negative cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted subdistribution hazard ratio [SHR], 2.29; 95% confidence interval [CI], 1.42-3.68; p = .001) and noncancer mortality (adjusted SHR, 2.74; 95% CI, 1.50-5.02; p = .001). In the HPV-positive cohort, definitive RT and upfront surgery could achieve similar cancer-specific and noncancer survival outcomes. CONCLUSION: Upfront surgery is associated with lower cancer-specific and noncancer mortality in HPV-negative early-stage OPC patients. However, in the setting of HPV-positive early-stage OPC with better prognosis, the 2 treatment modalities have similar efficacy in terms of cancer-specific and noncancer survival outcomes. In the future, carefully designed prospective clinical trials are needed to confirm our findings.
Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Infecções por Papillomavirus/complicações , Estudos Prospectivos , Prognóstico , Medição de Risco , Neoplasias de Cabeça e Pescoço/complicaçõesRESUMO
PURPOSE: This study was performed to introduce a modified procedure involving a combination of bilateral vocal fold mucosal flaps and microsurgical sutures for the management of anterior glottic webs and to study its efficacy in decreasing the recurrence rate and improving voice quality. METHODS: We retrospectively reviewed 102 patients with anterior glottic webs who underwent surgical treatment by a carbon dioxide laser incision with or without microsurgical suturing in our hospital from May 2014 to April 2021. We focused on the reoperation rate and the voice outcomes based on the 30-item Voice Handicap Index. RESULTS: This study included 102 patients with anterior glottic webs, which were caused by papilloma excision and endoscopic laryngocarcinoma resection in 97 (95.1%) of the 102 patients; less common causes were infection and traumatic injury. All incisions were performed along the midline with a carbon dioxide laser under microscopy and a self-retaining laryngoscope; 37 (36.3%) patients underwent microsurgical suturing and 65 (63.7%) patients did not. The microsuture group had a lower reoperation rate (χ2= 7.069, P = 0.0078) and higher voice quality (t = 2.054, P = 0.0462) than the non-microsuture group. CONCLUSIONS: We introduced a modified procedure that can both decrease the recurrence rate and improve the voice quality in patients with anterior glottic webs. Hence, this combination therapy involving bilateral vocal fold mucosal flaps and microsurgical sutures is worthy of clinical application and promotion.
RESUMO
Background: PD-1/PD-L1 blockade is a promising immunotherapeutic strategy with the potential to improve the outcomes of various cancers. However, there is a critically unmet need for effective biomarkers of response to PD-1/PD-L1 blockade. Materials and methods: Potential biomarkers of response to PD-1/PD-L1 blockade were obtained from the Cancer Treatment Response gene signature Database (CTR-DB). A comprehensive pan-cancer analysis was done on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Correlations between gene expression and infiltration by immune cells were assessed using TIMER, EPIC, MCPcounter, xCell, CIBERSORT, and quanTIseq. Immunophenoscore (IPS) was used to assess the potential application of the biomarkers to all TCGA tumors. Results: Analysis of CTR-DB data identified CD69 and SBK1 as potential biomarkers of response to PD-1/PD-L1 blockade. Correlation analysis revealed that in various TCGA cancer datasets, CD69 expression level correlated positively with most immune checkpoints and tumor-infiltrating immune cells, while SBK1 expression level correlated negatively with infiltrating immune cells. IPS analysis demonstrated the ability of CD69 and SBK1 to predict PD-1/PD-L1 blockade responses in various cancers. Conclusion: CD69 and SBK1 are potential predictors of response to cancer immunotherapy using PD-1/PD-L1 blockade. These biomarkers may guide treatment decisions, leading to precise treatment and minimizing the waste of medical resources.
Assuntos
Neoplasias Pulmonares , Melanoma , Antígeno B7-H1/genética , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Pulmonares/patologia , Melanoma/tratamento farmacológico , Receptor de Morte Celular Programada 1RESUMO
Ferritin is the most important iron storage form and is known to influence tumor immunity. We previously showed that expression of ferritin light chain (FTL) and ferritin heavy chain (FTH1) subunits is increased in head and neck squamous cell carcinoma (HNSC). Here, we analyzed solid tumor datasets from The Cancer Genome Atlas and Genotype-Tissue Expression databases to investigate correlations between FTL and FTH1 expressions and (i) patient survival, using univariate, multivariate, Kaplan-Meier and Receiver Operator Characteristic analysis; and (ii) tumor-infiltrating immune cell subsets, using the bioinformatics tools Estimation of Stomal and Immune cells in Malignant Tumor tissues, Microenvironment Cell Population-counter, Tumor Immune Estimation Resource, and Tumor Immunology Miner. We found that FTL and FTH1 are upregulated and downregulated, respectively, in most of the human cancers analyzed. Tumor FTL levels were associated with prognosis in patients with lower grade glioma (LGG), whereas FTH1 levels were associated with prognosis in patients with liver hepatocellular carcinoma, HNSC, LGG, and kidney renal papillary cell carcinoma. In many cancers, FTL and FTH1 levels was significantly positively correlated with tumor infiltration by tumor-associated macrophages and T regulatory cells. These results suggest an important role for FTL and FTH1 in regulating tumor immunity to solid cancers.
Assuntos
Apoferritinas/genética , Biomarcadores Tumorais/genética , Ferritinas/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias/imunologia , Oxirredutases/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Conjuntos de Dados como Assunto , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias/patologia , Prognóstico , Linfócitos T Reguladores/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/imunologia , Adulto JovemRESUMO
OBJECTIVE: To investigate the role of ferroptosis, an iron-dependent form of non-apoptotic cell death, in the head and neck squamous cell carcinoma (HNSCC) immune microenvironment. MATERIALS AND METHODS: A list of ferroptosis-related genes was obtained from the FerrDb database. Gene expression data were acquired from the cancer genome atlas (TCGA) and analyzed using the R language. Protein-protein interaction analysis was conducted using STRING and GeneMANIA. The correlations between gene expression levels and a patient's survival were analyzed using GEPIA, the Kaplan-Meier estimate, and a multivariate Cox proportional hazards model. The expression results were verified using Oncomine and Human Protein Atlas data. We used the TIMER, GEPIA2, GEPIA2021, and TIMER2 databases to investigate the relationships between gene expression and infiltrating immune cells. RESULTS: Analysis of differentially expressed genes (DEGs) identified nine each ferroptosis drivers and ferroptosis suppressors, among which four genes correlated with survival as follows: two drivers (SOCS1, CDKN2A) associated with better survival and two suppressors (FTH1, CAV1) associated with poorer survival. Multivariate Cox survival analysis identified SOCS1 and FTH1 as independent prognostic factors for HNSCC, and their higher expression levels were verified using Oncomine and HPA data. The results acquired using TIMER, GEPIA2, GEPIA2021, and TIMER2 data revealed that the driver SOCS1 and the suppressor FTH1 independently correlated with M1 and M2 macrophage infiltration. CONCLUSIONS: The ferroptosis driver SOCS1 and suppressor FTH1 are independent prognostic factors and that correlate with M1 and M2 macrophage infiltration in HNSCC. Targeting ferroptosis-immunomodulation may serve as a strategy to enhance the activity of immunotherapy.
RESUMO
BACKGROUND: The prognostic role of the interval between disease onset and hospital admission (O-A interval) was undetermined in patients with the coronavirus disease 2019 (COVID-19). METHODS: A total of 205 laboratory-confirmed inpatients admitted to Hankou hospital of Wuhan from January 11 to March 8, 2020 were consecutively included in this retrospective observational study. Demographic data, medical history, laboratory testing results were collected from medical records. Univariate and multivariate logistic regression models were used to evaluate the prognostic effect of the O-A interval (≤7 versus >7 days) on disease progression in mild-to-moderate patients. For severe-to-critical patients, the in-hospital mortality and the length of hospital stay were compared between the O-A interval subgroups using log-rank test and Mann-Whitney U test, respectively. RESULTS: Mild-to-moderate patients with a short O-A interval (≤7 days) are more likely to deteriorate to severe-to-critical stage compared to those with a long O-A interval (>7 days) [unadjusted odds ratio =2.93, 95% confidence interval (CI), 1.32-6.55; adjusted odds ratio =3.44, 95% CI, 1.20-9.83]. No association was identified between the O-A interval and the mortality or the length of hospital stay of severe-to-critical patients. CONCLUSIONS: The O-A interval has predictive values for the disease progression in mild-to-moderate COVID-19 patients. Under circumstances of the specific health system in Wuhan, China, the spontaneous healthcare-seeking behavior is usually determined by patients' own heath conditions. Hence, the O-A interval can be reflective of the natural course of COVID-19 to some extent. However, our findings should be validated further in other cohorts and in other health systems.
RESUMO
OBJECTIVE: Studies on factors affecting pharyngocutaneous fistulas (PCFs) and PCF repair methods have been widely reported. However, the healing phases of PCF are unclear, and their elucidation could guide clinical treatment. METHODS: Clinical stages of the PCF healing process were identified by a retrospective study of 39 patients with head and neck cancer who developed a PCF. RESULTS: Different conservative treatments were performed in turn according to three defined stages of the PCF healing process: stage I (drainage and debriding period), stage II (pressure dressing period), and stage III (healing period). A 7-day course of antibiotic therapy was only performed in stage I in 23 patients. The PCF was cured in 30 (76.9%) of 39 patients; the remaining 9 patients underwent subsequent surgical interventions for PCF healing. CONCLUSION: The three stages of PCF healing have a certain reference value in guiding clinical treatments. Moreover, antibiotics should be used in stage I when signs of infection are present, but they should not be used in all three phases of conservative treatment.
RESUMO
OBJECTIVE: To observe the preventive effect of xinmaikang capsule against acute myocardial ischemia in coronary artery occlusion dogs. METHODS: 25 healthy hybrids dogs, male and female, were randomly divided into control group (physiological saline solution), 40 mg/kg Di'aoxinxuekang Group, xinmaikang low doses (1.55 g/kg), median doses (3.10 g/kg) and high doses (6.20 g/kg) group, 5 dogs a group. The left downwards coronary arteries of dogs were ligated to establish the acute myocardial ischemia model. The blood gas analysis, myocardial enzyme detection, blood pressure,heart rate and epicardial electrogram recorded were detected before and after the stomach lavage. 240 min later, the myocardial tissues were stained with NBT technology to examine the sizes of infarction areas. RESULTS: (1) Each dose of xinmaikang capsule could increase coronary artery blood flow (CBF) and reduce the coronary resistance (CVR) (P < 0.05 or P < 0.01). (2) The median and high doses of xinmaikang capsule could decrease myocardial oxygen consumption significantly (P < 0.05 or P < 0.01); (3) In the median and high doses of the xinmaikang capsule groups, the infarction areas decreased significantly (P < 0.01). (4) Serum lactate dehydrogenase (LDH) and Creatine phosphokinase (CPK) levels decreased significantly (P < 0.05 or P < 0.01) in all xinmaikang groups. CONCLUSION: Xinmaikang capsule has the effect of anti-myocardial ischemia and can protect myocardial cells, which is a potential drug and precaution treatment for myocardial ischemia.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Fitoterapia , Plantas Medicinais/química , Doença Aguda , Animais , Cápsulas , Circulação Coronária/efeitos dos fármacos , Creatina Quinase/sangue , Modelos Animais de Doenças , Cães , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/uso terapêutico , Eletrocardiografia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Lactato Desidrogenases/sangue , Masculino , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Isquemia Miocárdica/sangue , Isquemia Miocárdica/fisiopatologia , Miocárdio/enzimologia , Miocárdio/patologia , Consumo de Oxigênio/efeitos dos fármacos , Distribuição AleatóriaRESUMO
BACKGROUND: Foreign bodies within the sinuses, orbit, and skull base (FBSOS) are rare; hence, diagnosis and management guidelines are lacking. Endoscopic sinus surgery (ESS) removal is preferred because of the less invasiveness and minimal morbidity. This study was designed to summarize clinical experience with ESS management of FBSOS. METHODS: We retrospectively reviewed clinical manifestations, imaging findings, treatment, and outcomes in consecutive patients with ESS removal of FBSOS between 2004 and 2015 at a tertiary academic medical center. The Chi-square test was performed to compare the infection rate between wooden and nonwooden FBSOS. RESULTS: There were 23 male and five female patients, with median age of 11 years. FBSOS were located within the sinuses (86%), orbit (75%), and skull base/intracranial region (46%). Wooden FBSOS had a significantly higher risk of infection (78%) compared with nonwooden FBSOS (5%, P < 0.05). Contrast-enhanced computed tomography (CT) plus three-dimensional reconstruction was sensitive in all cases. Twenty-seven (96%) FBSOS were removed by ESS alone, while 1 (4%) FBSOS was removed using the combined ESS and lateral cervical approach. Four of the nine intracranial penetrating FBSOS patients had intraoperative cerebrospinal fluid (CSF) leak and received endoscopic CSF leak repair. Twelve (43%) patients suffered complications (meningitis, diplopia, and vision loss). CONCLUSIONS: ESS is a minimally invasive, safe, and promising surgical approach for FBSOS removal. Contrast-enhanced CT is effective in preoperative diagnosis and intraoperative guidance. Wooden FBSOS had higher risk of infection, thus antibiotics are recommended.
Assuntos
Corpos Estranhos/cirurgia , Órbita/cirurgia , Base do Crânio/cirurgia , Adolescente , Adulto , Pré-Escolar , Endoscópios , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: To study the protective effects of the total paeony glycoside (TPG) against global cerebral ischemia-reperfusion injury in gerbils. METHODS: Gerbils models of global cerebral ischemia-reperfusion injury were prepared by bilateral common carotid artery ligation for 12 min followed by 24-hour reperfusion. The effects of TGP on brain edema index, superoxide dismatase (SOD) activity and malonaldehyde (MDA) concentration of the cerebral tissue homogenate and pathology of the brain were examined 24 h after model establishment. RESULTS: Compared with the model group, TPG at the doses of 200 and 400 mg/kg could significantly relieve brain edema, enhance SOD activity and lower MDA concentration in the gerbils. Pathological examination showed that the gerbils with TPG treatment had milder injury of the cells in the hippocampal CA1 region. CONCLUSIONS: TPG has obvious protective effects against global cerebral ischemia-reperfusion injury.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Glicosídeos/uso terapêutico , Paeonia/química , Fitoterapia , Traumatismo por Reperfusão/prevenção & controle , Animais , Gerbillinae , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Malondialdeído/metabolismo , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Superóxido Dismutase/metabolismoRESUMO
OBJECTIVE: To observe the cytotoxic effects in vitro and antitumor effects in vivo of total alkaloid of Macleaya cordata. METHODS: MTT assay was used to assess the proliferation of Hep3B and H22 cells in vitro treated with the alkloid, and the inhibitory effects of the alkaloid on H22 and S180 tumors were observed in mice with subcutaneous inoculation of the tumor cells. RESULTS: The total alkaloid significantly inhibited the proliferation of human Hep3B cells and murine H22 cells in a dose-dependent in vitro. IC(50) of the alkloid in 3 repeated experiments was 3.04, 3.98 and 2.98 mug/ml respectively in Hep3B cells, and was 2.89, 2.21 and 2.34 mug/ml in H22 cells. In the tumor-bearing mice, the alkaloid inhibited the development of H22 tumor and prolonged the survival of S180 tumor-bearing mice. At the daily dose of 1, 2, and 4 mg/kg.b.w (i.p.) and 4 mg/kg.b.w. (i.g.) for 10 days, the inhibition rates of the alkaloid on H22 tumor in 3 repeated experiments were 18.6%, 35.1%, 44.9% and 7.9% respectively, and the rates of survival prolongation of the tumor-bearing mice were 24.8%, 48.9%, and 52.7%, respectively. CONCLUSION: The alkloid possesses antitumor effects both in vitro and in vivo.
Assuntos
Alcaloides/farmacologia , Citotoxicidade Imunológica/imunologia , Neoplasias Hepáticas/tratamento farmacológico , Papaveraceae/química , Fitoterapia , Alcaloides/isolamento & purificação , Animais , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Transplante de Neoplasias , Células Tumorais CultivadasRESUMO
OBJECTIVE: To investigate the effect of Danhong injection on the cardiovascular, the respiratory, and the nervous systems in animals. METHODS: Using the pressure transducer, tension transducer and subcutaneous electrodes connected to a multifunctional signal processor, the femoral artery pressure, respiratory curve and electrocardiogram were recorded, respectively, in dogs before and after administration of Danhong injection. The effect of the injection on spontaneous activities was observed in mice using a multifunctional mouse activity recorder. The effects were also observed on coordinated movements by recording tilt-board falling times of the mice and on hypnosis induced by subthreshold dose of pentobarbital sodium by observing the disappearance of righting reflex. RESULTS: Danhong injection caused slight decrease in systolic blood pressure without obviously affecting the heart rate, diastolic blood pressure and respiratory system of anesthetized dogs 30 min after intravenous Danhong injection at the dose of 2.4 g/kg, but at the doses of 1.2 and 0.6 g/kg.b.w, the injection did not produce any significant impact. The coordinated movement and spontaneous activity and pentobarbital sodium-induced hypnosis in mice were not obviously affected by the 3 doses of Danhong injection. CONCLUSION: Danhong injection does not affect the respiratory functions of the dogs and nervous system of mouse with the exception of the systolic pressure at the 3 doses.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Salvia miltiorrhiza , Animais , Cães , Feminino , Injeções , Masculino , Camundongos , Distribuição AleatóriaRESUMO
OBJECTIVE: To investigate the effects of down-regulated miR-9 expression on ultraviolet rays (UV)-induced reactive oxygen species (ROS) damage in nasopharyngeal carcinoma (NPC) cells. METHODS: The NPC cells were transfected with inhibitors of miR-9 by lipofectamine to decrease the expression of miR-9, and the cells transfected with inhibitor control as the control. ROS levels following UV exposure were examined with DCF-DA method and the concentration of glutathione was analyzed via the benzoic acid method; DNA damage and apoptosis also were evaluated. RESULTS: There was significant difference in ROS levels between miR-9 expression-inhibited cells and control cells (26 895 ± 218 vs 15 765 ± 927, t = 39.754, P < 0.001), and also there were significant differences in DNA damage rates (28.0% ± 10.0% vs 23.6% ± 9.2%) and in apoptosis rates (8.0% ± 0.9% vs 4.5% ± 0.8%) following UV exposure between two groups of cells. The miR-9 expression-inhibited cells showed lower level (1.87 ± 0.15) µmol/L of glutathione compared with the control cells (9.85 ± 0.15) µmol/L (t = -48.832, P < 0.001). CONCLUSION: Inhibition of miR-9 expression promoted UV-induced ROS damage in nasopharyngeal carcinoma cells.
Assuntos
MicroRNAs/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Carcinoma , Linhagem Celular Tumoral , Dano ao DNA , Humanos , Carcinoma Nasofaríngeo , TransfecçãoRESUMO
OBJECTIVE: To identify the differentially expressed microRNAs (miRNAs) between esophageal squamous carcinoma (ESC) and adjacent non-tumorous tissue (NT). METHODS: The expression levels of the miRNAs were detected in 3 fresh ESC and NT samples by hybridization with miRNAs microarray chip. Real-time quantitative RT-PCR was performed to confirm the results of the microarray analysis. The expressions of hsa-miR-126 and hsa-miR-518b in ESC were validated by real-time quantitative RT-PCR in another independent 15 matched samples. RESULTS: A total of 11 miRNAs exhibited differential expressions in ESC samples as compared to their expressions in the NT samples, including a 1 up-regulated miRNA and 10 down-regulated miRNAs. Compared with normal esophageal samples, the ESC tissues showed up-regulated hsa-miR-126 and down-regulated hsa-miR-518b expression. CONCLUSION: hsa-miR-126 and hsa-miR-518b are differentially expressed in ESC, and they might play important roles in the carcinogenesis and progression of ESC.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Perfilação da Expressão Gênica/métodos , Humanos , Células Tumorais CultivadasRESUMO
AIM: The aim of this study was to investigate the expression and the distribution of Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) in several human hepatocellular cancer cell lines (HepG2, Hep3B, SMMC-7721). METHODS: Flow cytometry was used to figure out the percentages of Nrf2-positive cells in these three cell lines. The localization of Nrf2 was estimated by the laser confocal microsopy and the expression levels of Nrf2 in hepatocellular cancer cell lines were detected by Western blot analysis. RESULTS: The percentages of Nrf2 positive cells in HepG2, Hep3B, and SMMC-7721 were 99.39%, 99.94%, and 99.98% through the flow cytometry. The laser confocal microsopy showed that Nrf2 mainly localized in the cytoplasm of HepG2 cells, distributed evenly in the cytoplasm and nucleus of Hep3B cells, and mainly localized in the nucleus of SMMC-7721 cells. Western blot analysis confirmed the result by the laser confocal microsopy. CONCLUSION: The data on the expression and localization of Nrf2 will be helpful for the following research on the role of Nrf2 in the drug resistance of hepatocellular carcinoma to chemotherapy.