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OBJECTIVE: To observe the effects of acupuncture at "umbilical four-acupoints" on chronic insomnia and its comorbid symptoms. METHODS: A total of 120 patients with chronic insomnia were randomly divided into an observation group (60 cases, 8 cases dropped off) and a control group (60 cases, 5 cases dropped off). The patients in the observation group were treated with acupuncture at regular acupoints (Baihui [GV 20] and bilateral Shenmen [HT 7], Neiguan [PC 6], Anmian [Extra]) and "umbilical four-acupoints", while the patients in the control group were treated with acupuncture at regular acupoints. Acupuncture was given once a day, 6 times a week, for a total of 3 weeks in the two groups. The Pittsburgh sleep quality index (PSQI), insomnia severity index (ISI) scores were observed before treatment, after treatment and in follow-up of one month after treatment completion; the Beck anxiety inventory (BAI), Beck depression inventory (BDI), fatigue severity scale (FSS), and Epworth sleepiness scale (ESS) scores were observed before and after treatment; the sleep parameters of polysomnography (PSG), including sleep latency (SL), awake-up time (AT), sleep efficiency (SE) and total sleep time (TST), were observed before and after treatment using polysomnography monitor in the two groups. RESULTS: Compared with those before treatment, the PSQI and ISI scores in both groups were reduced after treatment and in follow-up (P<0.05), and the PSQI and ISI scores in the observation group were lower than those in the control group after treatment and in follow-up (P<0.05). Compared with those before treatment, the BAI, BDI, FSS and ESS scores in both groups were reduced after treatment (P<0.05), and the BAI, BDI, FSS and ESS scores in the observation group were lower than those in the control group after treatment (P<0.05). Compared with those before treatment, the SL and AT in both groups were reduced after treatment (P<0.05), while SE and TST were increased after treatment (P<0.05); after treatment, the SL and AT in the observation group were lower than those in the control group (P<0.05), while SE and TST in the observation group were higher than those in the control group (P<0.05). CONCLUSION: On the basis of regular acupoint selection, acupuncture at "umbilical four-acupoints" could improve sleep quality, alleviate the severity of insomnia, and improve the comorbid symptoms i.e. anxiety, depression, fatigue and lethargy in patients with chronic insomnia.
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Terapia por Acupuntura , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/terapia , Pontos de Acupuntura , Sono , FadigaRESUMO
Deprivation of rapid eye movement sleep (REMSD) reduces the potential for learning and memory. The neuronal foundation of cognitive performance is synapse plasticity. MicroRNA-132 (MiR-132) is an important microRNA related to cognitive and synapse plasticity. Acupuncture is effective at improving cognitive impairment caused by sleep deprivation. Furthermore, its underlying principle is still unclear. Herein, whether electroacupuncture (EA) helps alleviate cognitive impairment in REMSD by targeting miR-132 was assessed. A rat model of REMSD was constructed using the developing multiplatform water environment technique, as well as EA therapy in Baihui (GV20) and Dazhui (GV14) was performed for 15 minutes, once daily for 7 days. Agomir or antagomir of MiR-132 was injected into the hippocampal CA1 areas to assess the EA mechanism in rats with REMSD. Then, the learning and memory abilities were detected by behavioral tests; synapse structure was assessed by transmission electron microscope (TCM); and dendrites branches and length were examined by Golgi staining. MiR-132-3p was assessed by real-time quantitative polymerase chain reaction (qRT-PCR). P250GAP, ras-related C3 botulinum toxin substrate 1 (Rac1), and cell division cycle 42 (Cdc42) expression levels in hippocampal tissues were evaluated by immunohistochemistry and Western blot. According to the research, EA therapy enhanced cognitive in REMSD rats, as evidenced by reduced escape latency; upregulated the performance of platform crossings and prolonged duration in the goal region; and improved spontaneous alternation. EA administration restored synaptic and dendritic structural damage in hippocampal neurons, enhanced miR-132 expression, and reduced p250GAP mRNA and protein levels. Additionally, EA boosted the protein level of Rac1 and Cdc42 associated with synaptic plasticity. MiR-132 agomir enhanced this effect, whereas miR-13 antagomir reversed this action. The current data demonstrate that EA at GV20 and GV14 attenuates cognitive impairment and modulates synaptic plasticity in hippocampal neurons via miR-132 in a sleep-deprived rat model.
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Peptic ulcer disease (PUD) is a common disease and frequently encountered in the clinic. Accumulating evidence suggests that PUD is associated with the gastrointestinal microbiota. Electroacupuncture (EA) is an improved version of acupuncture, which can improve the clinical effect by increasing the stimulation and delivering appropriate electrical pulses to needles. This method has been widely used in the treatment of peptic ulcer disease. However, its effect on gastrointestinal microbiota remains unclear. Therefore, in the present study, the ameliorative effect of EA was evaluated on the gastroduodenal mucosa, and the regulatory effect of the gastroduodenal microbiota was assessed in PUD mice. A total of 48 male Kun Ming mice were randomly divided into the following groups: normal control group (NC), PUD model group (PUD), Shousanli group (LI10), and Zusanli group (ST36) (n=12). The mice in groups LI10 and ST36 were treated with EA at LI10 and ST36, respectively. This intervention was continued for 7 days. Subsequently, we evaluated the morphological changes in the gastric and duodenal mucosa, and specific indices were measured, including the contents of serum dopamine (DA), the trefoil factor (TFF), and the vasoactive intestinal peptide (VIP). In addition, the gastric and duodenal microbiota were assessed via 16S ribosomal DNA sequencing. The results indicated that EA at LI10 or ST36 significantly reduced the injury of the gastroduodenal mucosa in PUD mice. The gastric microbial community structure of the groups LI10 and ST36 was similar to that of the NC group following comparison with the microbial community structure of the PUD model group. Moreover, the abundance of Firmicutes in the stomach was decreased, whereas that of Bacteroidetes was increased, and the abundance of Firmicutes in the duodenum was decreased. Furthermore, the microbial diversity and richness of the gastric microbiota in group LI10 were also significantly increased, and the serum dopamine and trefoil factor levels in group ST36 were significantly increased. Therefore, it is suggested that EA ameliorating PUD is in association with improving the levels of DA and TFF and regulating the relative abundances of Firmicutes and Bacteroidetes in the gastric microbiota.
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Eletroacupuntura , Microbioma Gastrointestinal , Úlcera Péptica , Fatores Trefoil , Animais , Dopamina , Masculino , Camundongos , Úlcera Péptica/terapiaRESUMO
Background: Acute sleep deprivation (ASD) can effect mood, attention, memory, alertness and metabolism. Especially, it is often accompanied by cognitive impairment of the brain. Acupuncture is safe and effective for improving cognitive function, but its underlying mechanism is not fully understood. In this study, an event-related potential (ERP) technique will be employed to measure the behavioral, cognitive, and physiological changes produced by electroacupuncture intervention after ASD. Methods: We will recruit 60 healthy subjects. The participants will be randomly divided into a treatment group, a control group, a sham electroacupuncture group and a blank group, at a 1:1:1:1 ratio. The primary outcome will be determined by the change from baseline to 36 h in the MoCA score. The secondary results include the amplitude and latency of ERP N2 and P3, Go-hit rates, Go-RTs, No-Go-FA rates, the WCST, the Digit Span Subtest of the WAIS, the ESS score and FS-14. The 15 healthy subjects will not receive acupuncture treatment and ASD, but will receive EEG records and cognition functions test at the beginning and end of the experiment. Electroacupuncture intervention will be performed for 30 min once every 12 h, a total of three times. ERP measurements and other tests will be performed after baseline and ASD, and the statistician and outcome evaluator will be blinded to treatment allocation. Discussion: This study is expected to investigate the effectiveness of electroacupuncture in improving cognition for ASD. Trial Registration: ChiCTR2200055999.
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In this study, the following three experimental devices were operated for 70 days for the treatment of ciprofloxacin pollutants in wastewater: constructed wetlands (CW), constructed wetland-microbial fuel cells (EG), and constructed wetland-microbial fuel cells with new iron-carbon fillers (TPFC). The water quality, power generation capacity, microbial community structure, and changes in the resistance gene qnrs were studied. The efficiency of removal of total phosphate in the TPFC (97.1% ± 2.5%) was significantly higher than that in the EG (51.6% ± 4.8%) and the CW (68.1% ± 2.9%). The efficiency of removal of ciprofloxacin was also significantly higher (TPFC: 91.2% ± 3.4%, EG: 82.1% ± 2.3%, and CW: 75.1% ± 5.6%) (P < 0.05). The voltage of TPFC reached 300.16 ± 12.12 mV, which was apparently greater than that of EG (180.36 ± 16.73 mV) (P < 0.05), possibly because of the higher abundance of microorganisms such as Burkholderiaceae, Hydrogenophaga, and Proteobacteria. There were more copies of the resistance gene qnrs (TPFC: 7.74/µL, EG: 5.52/µL, and CW: 2.65/µL), which may be associated with stronger resistance; therefore, the efficiency of removal of ciprofloxacin was higher in the TPFC. TPFCs are a promising way to remove ciprofloxacin in wastewater.
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Fontes de Energia Bioelétrica , Purificação da Água , Carbono , Ciprofloxacina , Eletricidade , Eletrodos , Ferro , Águas Residuárias , Áreas AlagadasRESUMO
Objective: To investigate the intervention effects of curcumin (Curc) on liver injury induced by chronic alcohol addiction in mice. Methods: Thirty Balb/c mice were randomly divided into normal control group (Control), model group (Model), low-dose Curc group (5 mg/kg, Curc-L), medium dose Curc group (10 mg/kg, Curc-M) and high-dose Curc group (15 mg/kg, Curc-H), with 6 mice in each group. The chronic alcohol addiction liver injury model was prepared with 20% liquor. The mice in control group were given 2 ml of normal saline every day. The mice in model group were given 5 ml/kg of 20% liquor every day, and the mice in Curc treatment group were treated with Curc at the doses of 5, 10, 15 mg/kg in 2 ml saline every day for 35 days. The weight of liver was measured and the health status of mice was observed. Serum ALT, AST, ALP and liver TG, TC, HDL-C, LDL-C, MDA, SOD, GSH-Px and NO were measured. The pathological changes of liver tissues stained with hematoxylin and eosin were observed. Results: Compared with the control group, the liver mass and serum levels of ALT, AST, ALP, MDA, NO, TC, TG, HDL-C, LDL-C in the model group were increased significantly (Pï¼0.05, Pï¼0.01), the activities of SOD and GSH-Px were decreased significantly (Pï¼0.05, Pï¼0.01), the liver cells were vacuolated and infiltrated with inflammatory cells, and the expression levels of NF-κB and MAPK protein in liver tissues were increased significantly (Pï¼0.01). Compared with the model group, the levels of ALT, AST, ALP, MDA, NO, TC, TG, HDL-C, LDL-C in Curc group were decreased significantly nd the activities of SOD and GSH-Px were increased significantly (Pï¼0.05, Pï¼0.01). Conclusion: Curc can effectively reduce liver tissue damage by regulating NF-κB/MAPK signal pathway.
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Alcoolismo , Curcumina , Animais , Camundongos , LDL-Colesterol , NF-kappa B , Fígado , Camundongos Endogâmicos BALB C , Solução Salina , Superóxido DismutaseRESUMO
BACKGROUND: Cerebral vasospasm still results in high morbidity and mortality rates in patients after aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to establish a protocol for the management of vasospasm and demonstrate our experience of angioplasty using the Scepter XC balloon catheter. METHODS: In this retrospective study, a computed tomography angiography and perfusion image was arranged if early symptoms occurred or on the 7th day following aneurysmal SAH. In patients with clear consciousness, balloon angioplasties were performed for symptomatic vasospasms, which were not improved within 6-12 h after maximal medical treatments. In unconscious patients, balloon angioplasties were performed for all patients with angiographic vasospasms. RESULTS: Fifty patients underwent Scepter XC balloon angioplasty among 396 consecutive patients who accepted endovascular or surgical treatments for ruptured aneurysms. All angioplasty procedures were successful without complications. 100% angiographic improvement and 94% clinical improvement were reached immediately after the angioplasties. A favorable functional outcome (modified Rankin Score of ≤2) could be achieved in 82% of patients. Even in patients with poor clinical grading (Hunt-Hess grade 4-5), a clinical improvement rate of 87.5% and favorable outcome rate was 70.8% could be achieved. CONCLUSION: Balloon angioplasty with Scepter XC balloon catheter is safe and effective for post-SAH vasospasm. This device's extra-compliant characteristics could considerably improve the quality of angioplasty procedures. For all patients, even those with poor neurological status, early treatment with combined protocol of nimodipine and angioplasty can have good clinical outcomes.
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Aneurisma Roto/complicações , Aneurisma Intracraniano/complicações , Nimodipina/uso terapêutico , Vasoespasmo Intracraniano/etiologia , Adulto , Idoso , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/métodos , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Hemorragia Subaracnóidea/complicações , Resultado do TratamentoRESUMO
Corneal neovascularization (CNV) is one of the main factors that induce blindness worldwide. However, current medical treatments cannot achieve non-invasive and safe inhibition of CNV. A noninvasive photoacoustic imaging (PAI)-guided method is purposed for the regression of CNV. PAI can monitor the oxygen saturation of cornea blood vessels through the endogenous contrast of hemoglobin and trace administrated drugs by themselves as exogenous contrast agents. An indocyanine green (ICG)-based nanocomposite (R-s-ICG) is prepared for CNV treatment via eye drops and subconjunctival injections. It is demonstrated that R-s-ICG can enrich corneal tissues and pathological blood vessels rapidly with minor residua in normal eyeball tissues. Anti-CNV treatment-driven changes in the blood vessels are assessed by real-time multimodal PAI in vivo, and then a safe laser irradiation strategy through the canthus is developed for phototherapy and gene therapy synergistic treatment. The treatment leads to the efficient inhibition of CNV with faint damages to normal tissues.
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Oral factor XIa (FXIa) inhibitors may provide a promising new antithrombotic therapy with an improved benefit to bleeding risk profile over existing antithrombotic agents. Herein, we report application of a previously disclosed cyclic carbamate P1 linker which provided improved oral bioavailability in the imidazole-based 13-membered macrocycle to the 12-membered macrocycle. This resulted in identification of compound 4 with desired FXIa inhibitory potency and good oral bioavailability but high in vivo clearance. Further structure-activity relationship (SAR) studies of heterocyclic core modifications to replace the imidazole core as well as various linkers to the P1 group led to the discovery of compound 6f, a potent FXIa inhibitor with selectivity against most of the relevant serine proteases. Compound 6f also demonstrated excellent pharmacokinetics (PK) profile (high oral bioavailability and low clearance) in multiple preclinical species. Compound 6f achieved robust antithrombotic efficacy in a rabbit efficacy model at doses which preserved hemostasis.
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Fator XIa/antagonistas & inibidores , Fibrinolíticos/administração & dosagem , Fibrinolíticos/farmacologia , Administração Oral , Animais , Disponibilidade Biológica , Cristalografia por Raios X , Cães , Avaliação Pré-Clínica de Medicamentos , Fator XIa/química , Fator XIa/metabolismo , Fibrinolíticos/química , Fibrinolíticos/farmacocinética , Humanos , Interações Hidrofóbicas e Hidrofílicas , Compostos Macrocíclicos/administração & dosagem , Compostos Macrocíclicos/química , Compostos Macrocíclicos/farmacocinética , Compostos Macrocíclicos/farmacologia , Modelos Moleculares , Coelhos , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: To explore whether yiqi huoxue tongluo jiedu fang (YHTJF, Traditional Chinese Medicine) alleviates the injury during lung ischemia/reperfusion (I/R) in mice through inhibiting oxidative stress or not. METHODS: C57BL/6J male mice (n=70) were randomly divided into 7 groups:control (C), carboxyl methyl cellulose-Na(CMC·Na) + normal control (CC), carboxyl methyl cellulose-Na + sham (CS), carboxyl methyl cellulose-Na + I/R (CIR), carboxyl methyl cellulose-Na + YHTJF-Low, CMC-Na + YHTJF-Middle, CMC-Na + YHTJF-High (CYL, CYM, CYH). The mice in CYL, CYM and CYH group were treated with YHTJF by intraperitoneal injection every day, while the carboxyl methyl cellulose-Na was administered with the same volume of CYL in CC, CS and CIR group. After 3 h-reperfusion, the left lung tissues were harvested to determine the lung wet/dry weight (W/D), the total lung water content (TLW), and the index of quantita-tive evaluation for alveolar damage (IQA). Morphological observation and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) were applied to evaluate the structural changes and the apoptosis index (AI) of the lung tissues. The expressions superoxide of dis-mutase(SOD), malondialdehyde(MDA) and myeloperoxidase(MPO) in the lung tissues were detected by kits. RESULTS: Compared with group C, the W/D, TLW, IQA, AI, lung tissue structural changes, and the expressions of MDA and MPO in group I/R were increased obviously (P < 0.01), and the expression of SOD was decreased, while there was no significant difference between group CC and CS. Compared with group I/R, the parameters of these experiments in group CYL, CYM, CYH were all decreased, and the expression of SOD was increased, while the reduction in group CYM was the most remarkable among them (P < 0.01). CONCLUSIONS: YHTJF may attenuate the I/R injury of the lung by the inhibition of apoptosis via ROS pathway.
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Medicamentos de Ervas Chinesas/farmacologia , Lesão Pulmonar/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Apoptose , Pulmão/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Radioimmunotherapy (RIT) delivers radioisotopes to antigen-expressing cells via monoantibodies for the imaging of lesions or medical therapy. The chelates are typically conjugated to the antibody through cysteine or lysine residues, resulting in heterogeneous chelate-to-antibody ratios and various conjugation sites. To overcome this heterogeneity, we have developed an approach for site-specific radiolabeling of antibodies by combination of genetic code expansion and click chemistry. As a proof-of-concept study, model systems including anti-CD20 antibody rituximab, positron-emitting isotope 64Cu, and a newly synthesized bifunctional linker (4-dibenzocyclooctynol-1,4,7,10-tetraazacyclotetradecane-1,4,7,10-tetraacetic acid, DIBO-DOTA) were used. The approach consists of three steps: (1) site-specific incorporation of an azido group-bearing amino acid (NEAK) via the genetic code expansion technique at the defined sites of the antibody as a "chemical handle"; (2) site-specific and quantitative conjugation of bifunctional linkers with the antibodies under a mild condition; and (3) radiolabeling of the chelate-modified antibodies with the appropriate isotope. We used heavy-chain A122NEAK rituximab as proof-of-concept and obtained a homogeneous radioconjugate with precisely two chelates per antibody, incorporated only at the chosen sites. The conjugation did not alter the binding and pharmacokinetics of the rituximab, as indicated by in vitro assays and in vivo PET imaging. We believe our research is a good supplement to the genetic code expansion technique for the development of novel radioimmunoconjugates.
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Radioisótopos de Cobre/química , Imunoconjugados/química , Tomografia por Emissão de Pósitrons/métodos , Radioimunoterapia/métodos , Rituximab/química , Animais , Benzoxazinas/química , Quelantes/química , Técnicas de Química Sintética , Estabilidade de Medicamentos , Compostos Heterocíclicos com 1 Anel/química , Humanos , Marcação por Isótopo/métodos , Lutécio/química , Camundongos SCID , Radioisótopos/química , Rituximab/genética , Rituximab/farmacocinéticaRESUMO
The effect of puerarin (Pur) on expressions of Fas/FasL mRNAs in pulmonary ischemia and reperfusion injury (PIRI) in rabbit was investigated. The sole side lung ischemia and reperfusion model was used. Rabbits were randomly divided into three groups, a sham operated group (sham, n = 10), PIR group (IR, n = 30) and PIR + Pur group (Pur, n = 30). Changes of several parameters including apoptotic index (AI), wet to dry ratio of lung tissue weight (W/D) and index of quantitative assessment of histologic lung injury (IQA) were measured after 60, 180 and 300 minutes of reperfusion. Meanwhile, the location and expression of Fas/FasL mRNA were investigated. Lung tissue was prepared for light microscopic and electron microscopic observation after 60, 180 and 300 minutes of reperfusion. Compared with group IR, Fas/FasL mRNAs were slightly expressed in intima and extima of small pulmonary artery, alveoli, and bronchiole epithelia in group Pur. The values of AI, W/D and IQA were significantly lower than those in group IR after 60, 180, and 300 minutes of reperfusion in lung tissue (P <0.01 or P <0.05). Meanwhile, the abnormal changes in lung tissue morphology were markedly less in group Pur. Puerarin notably protects lung from PIRI by inhibiting Fas/FasL mRNA expression and decreasing lung cell apoptosis in rabbits.
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Proteína Ligante Fas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Isoflavonas/uso terapêutico , RNA Mensageiro/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Traumatismo por Reperfusão/complicações , Animais , Proteína Ligante Fas/genética , Feminino , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/metabolismo , Masculino , RNA Mensageiro/genética , Coelhos , Receptores do Fator de Necrose Tumoral/genética , Vasodilatadores/uso terapêuticoRESUMO
OBJECTIVE: To investigate the risk factors for early miscarriage among Chinese women. DESIGN: Hospital-based matched case-control study. SETTING: Academic medical center and maternal health hospital. PATIENT(S): 620 women with early miscarriage (less than 13 weeks of gestation) and 1,240 normal pregnant women. INTERVENTION(S): Face-to-face questionnaire. MAIN OUTCOME MEASURE(S): Multivariable conditional odds ratio (OR) and 95% confidence interval (CI) to measure risk factors. RESULT(S): After adjustment for confounding factors, the following were independently associated with increased risk: history of miscarriage, repeated induced abortion, working night shifts, and frequent staying up late. Vitamin supplementation and regular physical activity reduced the risk of miscarriage. We did not find paternal age, alcohol consumption, or smoking status to be linked with early miscarriage. CONCLUSION(S): Our findings suggest that a healthy diet, regular physical activity, and planned pregnancy may be advantageous for women in pre-pregnancy or early pregnancy. Induced abortion, working night shifts, and frequent staying up late were associated with an increased risk of miscarriage. Further work in larger populations is warranted.
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Aborto Espontâneo/etnologia , Povo Asiático , Estilo de Vida/etnologia , Aborto Induzido/efeitos adversos , Aborto Espontâneo/prevenção & controle , Centros Médicos Acadêmicos , Adolescente , Adulto , Estudos de Casos e Controles , China/epidemiologia , Dieta/etnologia , Feminino , Idade Gestacional , Maternidades , Humanos , Descrição de Cargo , Modelos Logísticos , Atividade Motora , Análise Multivariada , Razão de Chances , Admissão e Escalonamento de Pessoal , Gravidez , Fatores de Risco , Sono , Inquéritos e Questionários , Fatores de Tempo , Adulto JovemRESUMO
Mechanisms of synergistic effect of thermotherapy and chemotherapy on human lung adenocarcinoma cell growth are unclear. The purpose of this study was to investigate these effects and explore the function of ROS, Akt and caspase-3 in relation to these. A549 cells were subjected to different thermochemotherapy treatments: 43ËC heat+50 µg/l paclitaxel (thermochemotherapy group), 43ËC heat+50 µg/l paclitaxel+1 µmol/l wortmannin (wortmannin group), 43ËC heat+50 µg/l paclitaxel+30 µmol/l NAC (NAC group) and 50 µg/l paclitaxel (chemotherapy group). The cells without any treatment were regarded as controls. Cell proliferation rates were measured with MTT assay and intracellular ROS levels were detected with fluorescence labeling technologies. Phosphorylation of Akt and caspase-3 expression were determined by western blotting and the cell apoptosis rates were examined by flow cytometry. Tests in vivo were carried out at the same time. It was found that the cell proliferation rates of the thermochemotherapy group were significantly lower compared to those of the controls or the chemotherapy group (P<0.05). The intracellular ROS levels of the thermochemotherapy group were elevated significantly compared with those of other groups, and these changes could be reversed using the ROS inhibitor NAC but not a PI3K inhibitor (wortmannin). Phosphorylation of Akt was significantly decreased in the thermochemotherapy group (P<0.05), which could be blocked by wortmannin, but increased by NAC (P<0.05). The caspase-3 expression levels and cell apoptosis rates of the thermochemotherapy group were higher compared to those of the other groups (P<0.05). All results have been confirmed by in vivo tests. Thus, the combination of thermotherapy with chemotherapy showed a stronger inhibitory effect on A549 cell growth compared to chemotherapy alone, which may be able to cause additional cell apoptosis through inhibition of Akt phosphorylation and activation of caspases by increased intracellular ROS production.
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Adenocarcinoma/terapia , Neoplasias Pulmonares/terapia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Androstadienos/farmacologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Inibidores Enzimáticos/farmacologia , Humanos , Hipertermia Induzida , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Paclitaxel/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação , Wortmanina , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To study the synergistic effect of thermo-chemo therapy on lung cancer cells and its possible mechanisms. METHODS: Refer the normal clinic dose, and use the untreated H446 cells as the control group. H446 cells were treated by different thermo-chemo therapy strategies: 43 degrees C + Paclitaxel (120 microg/L) (thermo-chemotherapy group), 43 degrees C + Paclitaxel (120 microg/L) + NAC (30 micromol/L, specific reactive oxygen species (ROS) inhibitor) (NAC group), and Paclitaxel (120 microg/L) alone (only chemotherapy group). Cell apoptosis was analyzed by FCM and fluorescence was used to measure ROS inside the cells. The expressions of Caspase-3 was determined by Westerm Blotting. Use SPSS 13.0 to perform the statistical analysis on the data. RESULTS: The rate of cell apoptosis in the thermo-chemo therapy group was significantly higher than those in the other groups (P < 0.05). The ROS in the thermo-chemo therapy group increased (P < 0.05), but NAC inhibited its expression. The expression of Caspase-3 in the thermo-chemo therapy group increased significantly (P < 0.05), but can be inhibited by NAC (P < 0.05). CONCLUSION: Thermo-chemo therapy can significantly seduce the apotosis of H446 cells, probably through seducing ROS forming, realised by the caspase channel.
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Apoptose/fisiologia , Hipertermia Induzida , Neoplasias Pulmonares/patologia , Paclitaxel/farmacologia , Carcinoma de Pequenas Células do Pulmão/patologia , Antineoplásicos Fitogênicos/farmacologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Terapia Combinada , Humanos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Flow injection chemiluminescence analysis was used to determine the antioxidation activity of extract from Morinda officinalis How. The determination was based on the inhibition effect of Morinda officinalis How extraction in the chemiluminescence reaction of luminol - H2O2-CuSO4 system, and vitamin C was used as positive control. It was showed that Morinda officinalis How original liquid has obvious anti-radical activity. Spectroscopy was applied to determine the inhibition ratio of Morinda officinalis How extraction for the superoxide anion and hydroxy radicals in the special system. It was shown that the extraction from Morinda officinalis How could obviously scavenge superoxide anion and hydroxy radicals. It is suggested that the Chinese Medicine Morinda Officinalis How is a potential antioxidation activity medicine.