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AIM: Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is a novel non-invasive therapy that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. An assessor-blinded, randomized, non-inferiority trial was designed to compare the efficacy of TECAS and escitalopram in mild-to-moderate major depressive disorder. METHODS: 468 participants received two TECAS sessions per day at home (n = 233) or approximately 10-13 mg/day escitalopram (n = 235) for 8 weeks plus 4-week follow-up. The primary outcome was clinical response, defined as a baseline-to-endpoint ≥50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score. Secondary outcomes included remission rate, changes in the severity of depression, anxiety, sleep and life quality. RESULTS: The response rate was 66.4% on TECAS and 63.2% on escitalopram with a 3.2% difference (95% confidence interval [CI], -5.9% to 12.9%) in intention-to-treat analysis, and 68.5% versus 66.2% with a 2.3% difference (95% CI, -6.9% to 11.4%) in per-protocol analysis. The lower limit of 95% CI of the differences fell within the prespecified non-inferiority margin of -10% (P ≤ 0.004 for non-inferiority). Most secondary outcomes did not differ between the two groups. TECAS-treated participants who experienced psychological trauma displayed a markedly greater response than those without traumatic experience (81.3% vs 62.1%, P = 0.013). TECAS caused much fewer adverse events than escitalopram. CONCLUSIONS: TECAS was comparable to escitalopram in improving depression and related symptoms, with high acceptability, better safety profile, and particular efficacy in reducing trauma-associated depression. It could serve an effective portable therapy for mild-to-moderate depression.
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Transtorno Depressivo Maior , Escitalopram , Humanos , Pontos de Acupuntura , Citalopram , Depressão/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Método Duplo-Cego , Resultado do TratamentoRESUMO
BACKGROUND: Hepatic arterial infusion chemotherapy and camrelizumab plus apatinib (TRIPLET protocol) is promising for advanced hepatocellular carcinoma (Ad-HCC). However, the usefulness of microwave ablation (MWA) after TRIPLET is still controversial. AIM: To compare the efficacy and safety of TRIPLET alone (T-A) vs TRIPLET-MWA (T-M) for Ad-HCC. METHODS: From January 2018 to March 2022, 217 Ad-HCC patients were retrospectively enrolled. Among them, 122 were included in the T-A group, and 95 were included in the T-M group. A propensity score matching (PSM) was applied to balance bias. Overall survival (OS) was compared using the Kaplan-Meier curve with the log-rank test. The overall objective response rate (ORR) and major complications were also assessed. RESULTS: After PSM, 82 patients were included both the T-A group and the T-M group. The ORR (85.4%) in the T-M group was significantly higher than that (65.9%) in the T-A group (P < 0.001). The cumulative 1-, 2-, and 3-year OS rates were 98.7%, 93.4%, and 82.0% in the T-M group and 85.1%, 63.1%, and 55.0% in the T-A group (hazard ratio = 0.22; 95% confidence interval: 0.10-0.49; P < 0.001). The incidence of major complications was 4.9% (6/122) in the T-A group and 5.3% (5/95) in the T-M group, which were not significantly different (P = 1.000). CONCLUSION: T-M can provide better survival outcomes and comparable safety for Ad-HCC than T-A.
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ABSTRACT: Aim: The purpose of this study was to investigate the effect of esmolol (ES) on LPS-induced cardiac injury and the possible mechanism. Methods: Sepsis was induced by i.p. injection of LPS (10 mg/kg) in male Sprague-Dawley rats pretreated with ES, 3-methyladenine or rapamycin. The severity of myocardial damage was analyzed by hematoxylin-eosin staining, and myocardial damage scores were calculated. The concentration of cardiac troponin was measured by enzyme-linked immunosorbent assay. The expression of autophagy-related proteins (beclin-1, LC3-II, p-AMPK, p-ULK1, p-mTOR) in myocardial tissue was detected by Western blotting. Autophagosome formation and the ultrastructural damage of mitochondria were assessed using transmission electron microscopy. Results: LPS induced an increase in myocardial damage score in a time-dependent manner, accompanied with an increase in autophagy at 3 h and decrease in autophagy at 6, 12, and 24 h. Pretreatment of LPS-treated rats with ES or rapamycin reduced myocardial injury (release of cardiac troponin, myocardial damage score) and increased autophagy (LC3-II, beclin-1, p-AMPK, and p-ULK1 levels and autophagosome numbers) at 12 and 24 h. In contrast, 3-methyladenine showed no effect. Conclusion: Esmolol alleviates LPS-induced myocardial damage through activating the AMPK/mTOR/ULK1 signal pathway-regulated autophagy.
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Proteínas Quinases Ativadas por AMP , Traumatismos Cardíacos , Animais , Ratos , Masculino , Proteínas Quinases Ativadas por AMP/metabolismo , Lipopolissacarídeos/farmacologia , Proteína Beclina-1/farmacologia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Ratos Sprague-Dawley , Serina-Treonina Quinases TOR/metabolismo , Autofagia , Sirolimo/farmacologia , Troponina/farmacologiaRESUMO
Background: The highly heterogeneous pathogenesis of depression and limited response to current antidepressants call for more objective evidence for depression subtypes. Reactive and endogenous depression are two etiologically distinct subtypes associated with different treatment responses. This study aims to explore the potential biomarkers that differentiate reactive and endogenous depressions. Methods: The clinical manifestations and biological indicators of 64 unmedicated mild-to-moderate depression patients (32 reactive depression patients and 32 endogenous depression patients) and 21 healthy subjects were observed. The 24-item Hamilton rating scale for depression (HAMD-24) was used to evaluate the severity of depression. Serum levels of depression-related biological indicators were measured by using the enzyme-linked immunosorbent assay. Results: The NLRP3 level of reactive depression was significantly lower than those of endogenous depression and healthy controls. There was a significant negative correlation between the BDNF level and the HAMD-24 total scores for patients with reactive depression. Conclusion: Our findings suggested the serum NLRP3 and BDNF levels could be potential biomarkers for detecting and evaluating the severity of reactive depression.
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CONTEXT: Postembolization syndrome (PES) is the most common complication in patients with hepatocellular carcinoma (HCC) who had undergone transcatheter arterial chemoembolization (TACE). PES was defined as fever, nausea and/or vomiting, and abdominal pain and these symptoms develop within 1-3 days after TACE. However, few studies have explored the factors influencing PES in patients with TACE for the first time. AIMS: We explored the factors influencing PES in patients with HCC undergoing TACE for the first time. SETTINGS AND DESIGN: The present study was a hospital-based study conducted in the tertiary care hospital of Guangzhou with a retrospective study design. SUBJECTS AND METHODS: In this single-center retrospective study, a total of 242 patients with HCC were included in the first TACE program between November 1, 2018 and November 31, 2019. STATISTICAL ANALYSIS USED: T-test and Chi-square test revealed the factors affecting the occurrence of PES. Correlation analysis (Spearman) explored the relationship between these factors and PES. Binary logistics analyzed the predictive factors of PES. RESULTS: The probability of PES in patients with HCC undergoing TACE for the first time was 55.45%. Types of embolic agents (r = 0.296), types of microspheres (r = 0.510), number of microspheres (r = 0.130), maximum diameter of microspheres used (r = 0.429), type of drug (r = 0.406), and drug loading (r = 0.433) were positively correlated with PES (P < 0.05). Serum albumin was negatively correlated with PES (P = 0.008, r = -0.170). Binary logistic regression analysis revealed that drug loading microspheres (odds ratio [OR] = 0.075, 95% confidence interval [CI] = 0.031-0.180) and serum albumin (OR = 0.182, 95% CI = 0.068-0.487) were the protective factors influencing PES, while drug loading was the risk factor of PES (OR = 1.407, 95% CI = 1.144-1.173). CONCLUSIONS: Drug loading microspheres, serum albumin, and drug loading were the predictors of PES after the first TACE.
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Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Neoplasias Hepáticas/terapia , Complicações Pós-Operatórias/epidemiologia , Dor Abdominal/epidemiologia , Dor Abdominal/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/métodos , Feminino , Artéria Femoral/cirurgia , Febre/epidemiologia , Febre/etiologia , Humanos , Fígado/irrigação sanguínea , Fígado/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Masculino , Microesferas , Pessoa de Meia-Idade , Náusea/epidemiologia , Náusea/etiologia , Tamanho da Partícula , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica Humana/análise , Síndrome , Vômito/epidemiologia , Vômito/etiologia , Adulto JovemRESUMO
Mitochondrial dysfunction with oxidative damage plays the fundamental roles in the pathogenesis of Alzheimer's disease. In traditional Chinese medicine (TCM) practice, animal tissue-derived gelatins are often used as nootropic agents to treat cognitive deterioration and senile dementia. Tortoise plastron gelatin (TPG) and deer antler gelatin (DAG) are the two most commonly used gelatins for this purpose. This study sought to examine the effects of the two gelatins in preventing neuronal mitochondria from oxidative damage. PC12 cells, a cell line derived from rat pheochromocytoma, exposed to the neurotoxin Aß25-35 served as an in vitro model of Alzheimer's disease. The cells were separately pre-treated with TPG and DAG at various concentrations ranging from 6.26 µg/ml-200 µg/ml, followed by co-incubation with 20 µM Aß25-35 for different duration. Cell viability, mitochondrial membrane potential (MMP) and ultrastructure, intracellular ATP, reactive oxygen species (ROS) and calcium (Ca2+) level, the expression of mitochondrial dynamic proteins and biomarkers of apoptosis were measured. Pretreatment with TPG and DAG reversed the Aß-induced reduction of cell viability in a dose-dependent manner. Both TPG and DAG significantly increased MMP and ATP, alleviated the accumulation of damaged mitochondrial fragments, and normalized the aberrant expression of multiple mitochondrial dynamic proteins of the Aß-exposed cells. Both gelatins also suppressed intracellular ROS overproduction and Ca2+ overload, overexpression of cytochrome c and pro-apoptosis biomarkers induced by the Aß exposure. These results suggest that TPG and DAG may have the anti-dementia potential by preventing neuronal mitochondria from oxidative damage.
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Depression is a common psychiatric illness affecting over 300 million people globally. Acupuncture has been reported to be a safe complementary treatment for depression. This study is aimed to investigate the efficacy and mechanism of combining acupuncture with antidepressants in treating depression compared to the sole use of antidepressants. Seventy depression patients were randomly assigned to the treatment group (n = 50) and control group (n = 20). The treatment group received acupuncture combined antidepressants treatment for 3 weeks, while the control group took antidepressants monotherapy for 3 weeks. Among the 70 patients, 40 participants (20 control; 20 treatment) were randomized for studying functional connectivity (FC) of the dorsolateral prefrontal cortex (DLPFC) measured by the functional near-infrared spectroscopy. The primary outcome was HAMD-17 and secondary outcomes were PHQ-9, and the relationships of resting-state FC (rsFC) with the depression severity. PHQ-9 and HAMD-17 scores in the treatment group were significantly lower than those in the control group at Week 3 (p = 0.01) with effect sizes of -0.4 and -0.61 respectively. The rsFC in F1, F3, AF3, AF7, FC3, FC5 (left DLPFC, 10-20 system), AF8, and F6 (right DLPFC) in the treatment group had significant temporal correlation (p < 0.05, FDR corrected) in DLPFC compared to the channels in the control group. No significant correlation was found between the changes of rsFC and depression severity. In conclusion, depressed patients receiving acupuncture combined with antidepressants have improvement of depressive symptoms and the stronger rsFC in the DLPFC compared to those using antidepressants alone.
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Terapia por Acupuntura , Espectroscopia de Luz Próxima ao Infravermelho , Antidepressivos/uso terapêutico , Terapia Combinada , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Jie-Yu Pill (JYP) is a proprietary herbal medicine initially developed to treat menstrual mood disorders. This study sought to determine whether JYP could alleviate menopausal psychiatric symptoms in ovariectomized (OVX) mice, an animal model of estrogen deprivation, exposed to chronic unpredictable mild stress (CUMS) and the underlying mechanisms in comparison with estrogen therapy. The OVX+CUMS mice were treated with 0.3 mg/kg estradiol (E2), 2.5 g/kg or 5 g/kg JYP for 36 days, and tested in multiple behavioral paradigms. Serum, uterus, and brain tissues were collected for the measurement of hypothalamus-pituitary-ovarian axis (HPO) and hypothalamus-pituitary-adrenal (HPA) axis hormones, γ-aminobutyric acid (GABA), glutamate, neurotrophins, and estrogen receptors. JYP and E2 had comparable efficacy in reducing anxiety- and depression-like behavior and cognitive impairment of the OVX+CUMS mice. E2 strikingly increased ratio of uterus to body weight of the OVX+CUMS mice, but JYP did not. Both agents suppressed HPO-axis upstream hormones, inhibited HPA-axis hyperactivity by reinstating hypothalamic GABA, restored hippocampal and prefrontal glutamate contents and its receptor expression in the OVX+CUMS mice. While JYP and E2 protected against decreases in hippocampal and prefrontal neurotrophins and estrogen receptors of the OVX+CUMS mice, unlike E2, JYP had no significant effects on these biomarkers in the uterus. These results suggest that JYP has comparable efficacy in ameliorating mood disorder-like behavior and cognitive impairment induced by a combination of estrogen deprivation and chronic stress in association with certain differential uterus-brain mechanisms compared to estrogen therapy. JYP may be a potential therapy for menopause-associated psychiatric disorders.
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Electroacupuncture (EA) and electroconvulsive therapy (ECT) are often used in the management of schizophrenia. This study sought to determine whether additional EA and ECT could augment antipsychotic response and reduce related side effects. In this retrospective controlled study, 287 hospitalized schizophrenic patients who received antipsychotics (controls, n = 50) alone or combined with EA (n = 101), ECT (n = 55) or both (EA + ECT, n = 81) were identified. EA and ECT were conducted for 5 and 3 sessions per week, respectively, with a maximum of 12 sessions for ECT during hospitalization. The Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS) were used to assess the severity of psychotic symptoms. Clinical response on SAPS and SANS, weight gain, and adverse events were compared. Survival analysis revealed that the ECT and EA + ECT groups had markedly greater clinical response rate than controls on SAPS [72.7 and 90.1% vs. 64.0%; relative risk (RR), 1.974 and 2.628, respectively, P ≤ 0.004] and on SANS (67.3 and 70.4% vs. 42.0%; RR, 1.951 and 2.009, respectively, P ≤ 0.015). A significantly greater response rate on SANS than controls was also observed in the EA group (64.4% vs. 42.0%; RR = 1.938, P = 0.008). EA-containing regimens remarkably reduced weight gain and incidences of headache, insomnia, dry mouth, and electrocardiographic abnormalities. These results suggest that EA and ECT can serve as additional treatment for enhancing antipsychotic response and reduce the side effects in hospitalized patients with schizophrenia. Clinical Trial Registration: http://www.chictr.org.cn/showprojen.aspx?proj=38901, identifier ChiCTR1900023563.
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BACKGROUND: Tanshinone IIA sodium sulfonate (TSS) is known to possess anti-inflammatory effects and has exhibited protective effects in various inflammatory conditions; however, its role in lipopolysaccharide- (LPS-) induced intestinal injury is still unknown. OBJECTIVE: The present study is designed to explore the role and possible mechanism of TSS in LPS-induced intestinal injury. METHODS: Male C57BL/6J mice, challenged with intraperitoneal LPS injection, were treated with or without TSS 0.5 h prior to LPS exposure. At 1, 6, and 12 h after LPS injection, mice were sacrificed, and the small intestine was excised. The intestinal tissue injury was analyzed by HE staining. Inflammatory factors (TNF-α, IL-1ß, and IL-6) in the intestinal tissue were examined by ELISA and RT-PCR. In addition, expressions of autophagy markers (microtubule-associated light chain 3 (LC3) and Beclin-1) were detected by western blot and RT-PCR. A number of autophagosomes were also observed under electron microscopy. RESULTS: TSS treatment significantly attenuated small intestinal epithelium injury induced by LPS. LPS-induced release of inflammatory mediators, including TNF-α, IL-1ß, and IL-6, were markedly inhibited by TSS. Furthermore, TSS treatment could effectively upregulate LPS-induced decrease of autophagy levels, as evidenced by the increased expression of LC3 and Beclin-1, and more autophagosomes. CONCLUSION: The protective effect of TSS on LPS-induced small intestinal injury may be attributed to the inhibition of inflammatory factors and promotion of autophagy levels. The present study may provide novel insight into the molecular mechanisms of TSS on the treatment of intestinal injury.
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OBJECTIVE: To investigate the effect of acupuncture intervention on the depression behavior and expression of extracellular signal-regulated protein kinases (ERK 1/2), p-ERK 1/2 and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex of chronic unpredictable mild stress (CUMS) induced depression rats, so as to explore its antidepressant mechanism. METHODS: Sixty-four male SD rats were randomly divided into control, model, acupuncture, Fluoxetine, model ï¼ Dimethyl sulfoxide (DMSO), model ï¼ PD 98059(an ERK pathway inhibitor), acupuncture ï¼ PD 98059 and Fluoxetine ï¼ PD 98059 groups (nï¼8 rats in each). The CUMS depression model was established by using chronic mild and unpredictable stress methods for 21 days. Manual acupuncture stimulation was applied to "Baihui" (GV 20) and "Yintang" (GV 29) for 10 min before modeling, once daily for 21 days. Fluoxetine hydrochloride suspension (1.8 mgâ¢kgï¼1â¢dï¼1) was given to rats of the Fluoxetine group and Fluo-xetine ï¼ PD 98059 group by gavage 30 min before CUMS. PD 98059 (dissolved in DMSO, 10 µL) was administered to rats of model ï¼ PD 98059 group, acupuncture ï¼ PD 98059 and Fluoxetine ï¼ PD 98059 group, and DMSO (10 µL) to rats of model ï¼ DMSO group by intracerebroventricular injection 1 h before CUMS. Sucrose consumption test was carried out to evaluate the depressive behavior. Western blot was performed to detect the expression of ERK 1/2, p-ERK 1/2 and BDNF of prefrontal cortex. RESULTS: Compared with the control group, the sucrose consumption and the expression levels of p-ERK 1/2 and BDNF protein in the prefrontal cortex were significantly reduced in the model and modelï¼DMSO group (P<0. 01). After the intervention, modeling induced decrease of the sucrose consumption, and p-ERK 1/2 and BDNF expression was significantly up-regulated in both acupuncture and Fluoxetine groups (P<0.01, P<0.05), but not in the modelï¼PD 98059, Fluoxetine ï¼PD 98059 and acupunctureï¼PD 98059 groups (P>0.05). No significant differences were found among the modelï¼PD 98059, Fluoxetine ï¼PD 98059 and acupunctureï¼PD 98059 groups in the sucrose consumption, and ERK 1/2, p-ERK 1/2 and BDNF expression levels (P>0.05), and in the expression levels of ERK 1/2 protein among the 8 groups (P>0.05). CONCLUSION: Acupuncture intervention has an anti-depressive role in CUMS induced depression rats, which may be related to its effects in up-regulating the expression of p-ERK 1/2 and BDNF in the prefrontal cortex tissue.
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Depressão , Terapia por Acupuntura , Animais , Comportamento Animal , Fator Neurotrófico Derivado do Encéfalo , Modelos Animais de Doenças , Hipocampo , Masculino , Proteína Quinase 1 Ativada por Mitógeno , Proteína Quinase 3 Ativada por Mitógeno , Córtex Pré-Frontal , Ratos , Ratos Sprague-Dawley , Estresse PsicológicoRESUMO
OBJECTIVE: To observe the protective effects of angiopoietin-1 on acute lung injury (ALI) induced by oleic acid at early stage in mice and to investigate the expression changes of vascular endothelial growth factor (VEGF). METHODS: Ninety-six female BALB/c mice were randomly divided into 4 groups (n = 24). The control group was given normal saline (0.9 ml/kg) intravenously. The ALI group was treated with oleic acid (0.9 ml/kg) intravenously to induce ALI. In the control + angiopoietin-1 group, the mice were injected intraperitoneally with angiopoietin-1 (312.5 microg/kg) 4 h after normal saline administration. In the ALI + angiopoietin-1 group, the mice were injected intraperitoneally with angiopoietin-1 (312.5 microg/kg) 4 h after oleic acid treatment. Then 8 h later 12 mice were randomly taken from each group for bronchoalveolar lavage fluid (BALF) analysis including the protein level, cell count and differentials, and the level of IL-6 and VEGF. The wet/dry weight (W/D) of the right lung, the level of IL-6 and VEGF in serum, pathological changes of the left lung and VEGF expressions in lung tissues were examined for the rest of mice in each group. The level of IL-6 and VEGF in both serum and BALF were measured by enzyme-linked-immunosorbent assay (ELISA). Pathological changes of the lung tissue were examined and scored with light microscrope. The expression of VEGF was immunohistochemically detected in lung tissues as integrated optic density (A) measured with Image Pro Plus 5.1 software. RESULTS: The W/D, the protein level, the tota1 cel1 number and differential of polymorphonuclear leukocytes in BALF, the IL-6 level in both serum and BALF, the VEGF level in serum were significantly decreased in the ALI + angiopoietin-1 group [4.09 +/- 0.14, (176 +/- 13) microg/ml, (34.4 +/- 4.1) x 10(4)/L, (19.85 +/- 3.93) x 10(3)/L, (1318 +/- 62) pg/ml, (652 +/- 17) pg/ml, (48 +/- 5) pg/ml] as compared to the ALI group [5.32 +/- 0.51, (227 +/- 12) microg/ml, (42.2 +/- 5.2) x 10(4)/L, (26.22 +/- 2.22) x 10(3)/L, (1510 +/- 117) pg/ml, (744 +/- 13) pg/ml, (74 +/- 5) pg/ml, t = 8.16, 9.92, 4.02, 4.88, 5.03, 19.18, 14.81 respectively, all P < 0.01]. Pathological scores in the ALI + angiopoietin-1 group (1.84 +/- 0.12) improved as compared to those in the ALI group (3.44 +/- 0.21, t = 24.16, P < 0.01), and the VEGF level in BALF of the ALI + angiopoietin-1 group (179 +/- 15) pg/ml was higher than that of the ALI group (140 +/- 20) pg/ml (t = 5.31, P < 0.01). The expressions of VEGF in the lung tissues indicated by A (549 +/- 72) in the ALI + angiopoietin-1 group were higher than those in the ALI group (342 +/- 85, t = 5.22, P < 0.01), but lower than those in the control group (768 +/- 111) (t = 5.35, P < 0.01). The above measurements of the control + angiopoietin-1 group showed no difference compared to the control group (t = 0.12, 0.53, 1.27, 2.28, 1.18, 0.34, 0.13, 0.25, 0.58, 0.69 respectively, all P > 0.05). Statistical analysis was done using SPSS 10.0 software. Data are expressed as mean +/- s, with statistical significance declaved for probility valaes < 0.05. LSD-t test was used for group comparison. One-factor ANOVA was used for mdlti-group comparison. CONCLUSIONS: Angiopoietin-1 is effective in relieving the severity of acute lung injury induced by oleic acid in mice at early stage and up-regulating VEGF expression in BALF and lung tissues but down-regulating VEGF expression in serum. The results suggest that angiopoietin-1 may exert beneficial effects on ALI.
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Lesão Pulmonar Aguda/prevenção & controle , Angiopoietina-1/farmacologia , Pulmão/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Imuno-Histoquímica , Interleucina-6/biossíntese , Interleucina-6/sangue , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Ácido Oleico , Distribuição Aleatória , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
The clinical effect of electroacupuncture on depression is widely recognized. However, the signal transduction pathways and target proteins involved remain unclear. In the present study, rat models of chronic restraint stress were used to explore the mechanism by which electroacupuncture alleviates depression. Rats were randomly divided into control, model, and electroacupuncture groups. Chronic restraint stress was induced in the model and electroacupuncture groups by restraining rats for 28 days. In the electroacupuncture group, electroacupuncture pretreatment at Baihui (GV20) and Yintang (GV29) acupoints was performed daily (1 mA, 2 Hz, discontinuous wave, 20 minutes) prior to restraint for 28 days. Open field tests and body weight measurements were carried out to evaluate the depressive symptoms at specific time points. On day 28, the crossing number, rearing number, and body weights of the model group were significantly lower than those in the control group. Behavior test results indicated that rat models of depressive-like symptoms were successfully established by chronic restraint stress combined with solitary raising. On day 28, an isobaric tag for a relative and absolute quantitation-based quantitative proteomic approach was performed to identify differentially expressed proteins in hippocampal samples obtained from the model and electroacupuncture groups. The potential function of these differential proteins was predicted through the use of the Cluster of Orthologous Groups of proteins (COG) database. Twenty-seven differential proteins (uncharacteristic proteins expected) were selected from the model and electroacupuncture groups. In addition to unknown protein functions, COG are mainly concentrated in general prediction function, mechanism of signal transduction, amino acid transport and metabolism groups. This suggests that electroacupuncture improved depressive-like symptoms by regulating differential proteins, and most of these related proteins exist in nerve cells.
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BACKGROUND & OBJECTIVE: Cytokine-induced killer (CIK) cells have high cytotoxic activity against tumor cells. Dendritic cells (DCs) are the strongest antigen-presenting cells (APC) and could increase the cytotoxic activity of immunologic effector cells against tumor cells. This study was to investigate the changes of phenotype, proliferative activity, and in vitro and in vivo cytotoxicity of CIK cells after in vitro co-culturing with DCs. METHODS: DCs and CIK cells were prepared routinely from human peripheral blood mononuclear cells (PBMC), then CIK cells were cocultured with autologous DCs for 5 days at a stimulator-to-responder ratio of 1:10 to prepare immunologic effector DC-CIK cells. Phenotypes of DC-CIK cells were analyzed by flow cytometry; The in vitro cytotoxicity of DC-CIK cells was detected by 3H-TdR incorporation method; the in vivo antitumor activity was evaluated in BALB/c nude mice bearing A549 lung cancer. RESULTS: At the 14th day of culture, compared with CIK cells, DC-CIK cells got a significant increase of proliferation rate [(17.0+/-1.8) times vs. (10.9+/-2.0) times, P<0.05] and CD3+CD56+ expression rate [(36.0+/-4.2)% vs. (25.7+/-2.9)%, P<0.05], and resulted in an enhancement of cytotoxicity to A549 cells (P<0.05) in vivo. At the 51st day after inoculation of tumor cells, the inhibition rate was significantly higher in DC-CIK group than in CIK group (62.9% vs. 41.5%, P<0.05). DC-CIK cells and CIK cells showed significant inhibitory effects on the growth of transplanted tumor cells as compared with control group (P<0.01). CONCLUSION: DC-CIK cells have higher proliferative activity and cytotoxicity in vitro and in vivo against lung cancer in comparison with CIK cells alone.