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1.
Front Med (Lausanne) ; 9: 766244, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360742

RESUMO

Importance: Postoperative nausea and vomiting (PONV) gives patients a bad experience and negates their good recovery from surgery. Objective: This trial aims to assess the preventive effectiveness of transcutaneous electrical acupoint stimulation (TEAS) on the incidence of PONV in high-risk surgical patients. Design: The large sample size, multicenter, evaluator-blinded, and randomized controlled study was conducted between September 3, 2019 to February 6, 2021. Setting: The 12 hospitals were from different Chinese provinces. Participants: After obtaining ethics approval and written informed consent, 1,655 patients with Apfel score ≥ 3 points were enrolled for selective laparoscopic non-gastrointestinal surgery under general anesthesia. Interventions: Patients were randomly allocated into the TEAS and Sham group with a 1:1 ratio. The TEAS group was stimulated on bilateral Neiguan and Zusanli acupoints after recovery from anesthesia on the surgical day and the next morning for 30 min, while the Sham group received an identical setting as TEAS but without currents delivered. Electronic patient self-reported scale was used to evaluate and record the occurrence of PONV. Main Outcomes and Measures: Primary clinical end point is the incidence of PONV which was defined as at least one incidence of nausea, retching, or vomiting after operation within postoperative 24 h. Results: Compared with the Sham treatment, the TEAS lowered the PONV incidence by 4.8% (29.4 vs. 34.2%, P = 0.036) and vomiting incidence by 7.4% (10.4 vs. 17.8%, P < 0.001). TEAS also lowered persistent nausea incidence and PONV scores and decreased PONV related complications and Quality of Recovery-40 scores (P < 0.05). TEAS lowered the 24 h PONV risk by 20% (OR, 0.80, 95% CI, 0.65 -0.98; P = 0.032), and lowered hazard ratio by 17% (HR, 0.83, 95% CI, 0.70-0.99; P = 0.035). Both TEAS and palonosetron were the independent PONV risk protective factors for 24 h PONV incidence and cumulative PONV incidence. The combination of TEAS and palonosetron was the most effective strategy to reduce the PONV incidence (P < 0.001). Conclusions and Relevance: TEAS attenuated the PONV incidence and severity in high-risk surgical patients and may be applied clinically as a complement therapy to prevent PONV. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04043247, identifier: NCT04043247.

2.
Zhongguo Zhen Jiu ; 41(1): 59-64, 2021 Jan 12.
Artigo em Chinês | MEDLINE | ID: mdl-33559444

RESUMO

OBJECTIVE: To compare the clinical effect between electroacupuncture (EA) at Neima point and Neiguan (PC 6) and epidural nerve block for preemptive analgesia in patients undergoing thoracic surgery. METHODS: Sixty patients with elective radical esophagectomy were randomly divided into a group A, a group B and a control group, 20 cases in each group. The patients in the group A were treated with injection of 20 mL 0.375% ropivacaine at epidural space 30 min before anesthesia induction, followed by normal anesthesia during operation; the patients in the group B were treated with 30 min EA at bilateral Neima point and Neiguan (PC 6) before anesthesia induction, followed by normal anesthesia during operation; the patients in the control group were treated with general anesthesia alone. Patient-controlled intravenous analgesia was applied for all the patients. The mean arterial pressure (MAP) and heart rate (HR) were recorded at the following time points: before acupuncture/epidural puncture (T0), skin incision (T1), extubation (T2) and 2 h after operation (T3); the dosage of anesthetics and extubation time were recorded; the plasma levels of ß-endorphin (ß-EP), 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2) were measured at the following time points: T0, T3, 12 h after operation (T4), 24 h after operation (T5) and 48 h after operation (T6). Visual analogue scale (VAS) was used to evaluate the analgesic effect. RESULTS: The MAP at T1 and T2 in the group A was lower than that in group B and control group (P<0.05), and HR at T1 and T2 was lower than that in control group (P<0.05). The MAP and HR at T1 and T2 in the group B were lower than those in the control group (P<0.05). The dosage of remifentanil in the group A and group B was lower than that in the control group (P<0.05), and extubation time was earlier than that in the control group (P<0.05). The content of ß-EP at T4, T5 and T6 in the group B was higher than that in the group A and control group (P<0.05); the contents of 5-HT and PGE2 at T3, T4 and T5 in the group A and group B were lower than those in the control group (P<0.05). The VAS scores at T3, T4 and T5 in the group A and group were lower than those in the control group (P<0.05). CONCLUSION: The preemptive analgesia of EA at Neima point and Neiguan (PC 6) and epidural nerve block could both provide effective perioperative analgesia for thoracic surgery. The EA could better maintain intraoperative hemodynamics and has less physiological disturbance.


Assuntos
Eletroacupuntura , Bloqueio Nervoso , Cirurgia Torácica , Anestesia Geral , Espaço Epidural , Humanos
3.
Life Sci ; 253: 117675, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32360621

RESUMO

AIMS: Gliomas are responsible for the majority of deaths from primary brain tumours. Sevoflurane showed inhibition effects on the tumor progression in vitro. However, whether sevoflurane could affect the stemness of glioma stem cells (GSCs) and the potential molecular mechanism have not been well elucidated. MAIN METHODS: Effects of sevoflurane on cell viability, proliferation and invasion ability of glioma cells as well as tumor growth in vivo were assessed. Sphere formation assay was performed to evaluate the effect of sevoflurane on the stemness of GSCs. Effects of sevoflurane on mitochondrial function was evaluated by intracellular/mitochondrial reactive oxygen species (ROS) level and mitochondrial membrane potential. Expression levels of proliferation-related proteins, stemness markers and proteins in CaMKII/JNK cascade were measured by Western blot. KEY FINDINGS: Sevoflurane inhibited the viability, proliferation and invasion ability of glioma cells (U87MG and U373MG). Western blot showed that sevoflurane decreased the expression levels of proliferation and invasion-related proteins. Sphere formation ability of GSCs, expression levels of stemness markers and mitochondrial function were significantly suppressed by sevoflurane. Moreover, sevoflurane treatment significantly increased the Ca2+ concentration and stimulated phosphorylation of CaMKII, JNK and IRS1. Ca2+ chelator BAPTA-AM combined with sevoflurane synergistically inhibited colony forming ability and the expression levels of proliferation-related proteins and stemness markers. In addition, the in vivo study further confirmed that sevoflurane inhibited tumor growth via Ca2+-dependent CaMKII/JNK cascade. SIGNIFICANCE: The present study demonstrated that sevoflurane inhibited glioma tumorigenesis and modulated the cancer stem cell-like properties and mitochondrial membrane potential via activation of Ca2+-dependent CaMKII/JNK cascade.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , MAP Quinase Quinase 4/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Sevoflurano/metabolismo , Sevoflurano/farmacologia , Animais , Cálcio/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Quelantes/metabolismo , Ácido Egtázico/análogos & derivados , Ácido Egtázico/metabolismo , Glioma , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
4.
Zhen Ci Yan Jiu ; 45(10): 845-50, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33788453

RESUMO

OBJECTIVE: To observe the clinical efficacy and safety of electroacupuncture (EA) at Neimadian-point for cancer pain. METHODS: A total of 140 cancer patients with pain were randomly divided into EA and control groups, with 70 cases in each group. The patients of the EA group received EA at Neimadian-point plus analgesia pump (all prepared with normal saline). The patients of the control group were treated by Sufentanil patient-controlled intravenous analgesia plus sham EA (without stimulation). The treatment was conducted once daily for two days at 8 o'clock every morning. Respectively, in 1 h before treatment (T0), 1 h (T1), 8 h (T2), 24 h (T3) after treatment of the first day, 1 h (T4), 8 h (T5), 24 h (T6) after treatment of the second day, the visual analogue scale (VAS) score of pain, and the plasma levels of norepinephrine, 5-HT, leucine enkephalin, ß-endorphin and dynorphin A1-13 were tested. The security level (1-4 grade) was assessed during the treatment. RESULTS: Compared with their own pre-treatment, in T1 to T6, the VAS scores, and the contents of plasma norepinephrine and 5-HT obviously decreased in both groups (P<0.05), and the contents of leucine enkephalin, ß-endorphin and dynorphin A1-13 all increased (P<0.05) in the EA group. The analgesia effects were significantly higher in the EA group than in the control group in T1, T2, T4 and T5 (P<0.05,P<0.01). The therapeutic effect of EA at Neimadian-point was significantly superior to that of the Sufentanil in down-regulating plasma norepinephrine and 5-HT levels, and in up-regulating leucine enkephalin, ß-endorphin and dynorphin A1-13 levels (P<0.05,P<0.01). CONCLUSION: EA at Neimadian-point can effectively relieve the pain of cancer patients and improve their quality of daily life.


Assuntos
Dor do Câncer , Eletroacupuntura , Neoplasias , Dor do Câncer/terapia , Humanos , Neoplasias/complicações , Neoplasias/terapia , Dor/etiologia , Manejo da Dor , beta-Endorfina
5.
Int J Mol Med ; 44(5): 1963-1970, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545398

RESUMO

Rheumatoid arthritis (RA) is a debilitating joint disease characterized by chronic inflammation, pathologic alteration of fibroblast­like synoviocytes (FLS), destruction of cartilage and bone, and the formation of an invasive pannus. RA­FLS exhibit increased proliferation and resistance to apoptosis. The retinoid X receptor (RXR) has a role in regulating cell cycle, differentiation and apoptosis, and agonism of RXR has been investigated as a treatment strategy in several types of cancer. However, there is little research on the effects of RXR agonism in other diseases. Bexarotene is a novel selective RXR ligand used in the treatment of T­cell lymphoma. In the present study, bexarotene was used to investigate the involvement of RXR in tumor necrosis factor­α (TNF­α)­induced RA conditions in human FLS. To the best of our knowledge, this is the first time that RXR has been demonstrated to be expressed in FLS and to be downregulated in response to TNF­α stimulation. The present study also demonstrated that bexarotene exerted an anti­inflammatory effect by downregulating expression of interleukin (IL)­6, IL­8, monocyte chemoattractant protein­1, and high mobility group box­1. Notably, bexarotene also rescued the TNF­α­induced downregulation of the anti­inflammatory cytokines IL­4 and transforming growth factor­ß1. Bexarotene treatment exhibited a potential protective effect against cartilage degradation by downregulating the expression of matrix metalloproteinase (MMP)­1, MMP­3 and MMP­13. In addition, the present results demonstrated that the effects of bexarotene were mediated through the p38 mitogen­activated protein kinase/nuclear factor­κB pathway, via inhibition of p38 protein and the inhibitor α of κB phosphorylation. Taken together, the present findings demonstrated the potential of RXR agonism using bexarotene as a treatment against the development and progression of RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Bexaroteno/farmacologia , Fibroblastos/efeitos dos fármacos , Inflamação/tratamento farmacológico , Receptores X de Retinoides/metabolismo , Sinoviócitos/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Artrite Reumatoide/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Quimiocina CCL2/metabolismo , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Inflamação/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sinoviócitos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
6.
Cell Stress Chaperones ; 23(5): 967-974, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29728856

RESUMO

Sevoflurane, an inhaled ether general anesthetic agent, exerts a variety of neurotoxic effects, including oxidative stress, mitochondrial dysfunction, and neuronal apoptosis. However, the underlying molecular mechanisms remain to be elucidated. DJ-1 is a protein that exerts neuroprotective effects against different kinds of stress through multiple pathways. This study aimed to investigate the neuroprotective effects of DJ-1 against sevoflurane-induced neurotoxicity. Here, we found that sevoflurane treatment significantly increased DJ-1 expression in human neuroblastoma M17 cells in a dose-dependent manner at both the mRNA and protein levels. Interestingly, we found that overexpression of wild-type (WT) DJ-1 prevented sevoflurane-induced generation of reactive oxygen species (ROS) and nitric oxide (NO), deletion of reduced GSH, reduction of adenosine triphosphate (ATP), and mitochondrial membrane potential. Interestingly, we found that WT DJ-1 could inhibit sevoflurane-induced apoptosis by modulating the mitochondrial pathway. However, its "loss of function" mutation DJ-1(L166P) exacerbated sevoflurane-induced neurotoxicity in M17 cells. Our findings suggest that WT DJ-1 protects neuronal cells against sevoflurane-induced neurotoxicity.


Assuntos
Anestésicos Inalatórios/toxicidade , Neurônios/efeitos dos fármacos , Proteína Desglicase DJ-1/metabolismo , Sevoflurano/toxicidade , Apoptose , Linhagem Celular Tumoral , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mutação , Neurônios/metabolismo , Neurônios/fisiologia , Estresse Oxidativo , Proteína Desglicase DJ-1/genética
7.
Biomed Pharmacother ; 103: 284-289, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29656184

RESUMO

As a new generation of amide-type local anesthetics (LAs), ropivacaine has been widely used for pain management in clinical settings. Increasing evidence has shown that administration of ropivacaine causes cytotoxic effects and apoptosis. However, the underlying molecular mechanisms still need to be elucidated. In the current study, our results indicated that ropivacaine treatment caused a significant induction of heme oxygenase-1 (HO-1) at both the mRNA and protein levels in human SHSY5Y cells. Levels of HO-1 mRNA and protein peaked at 1 h and 18 h, respectively, in response to ropivacaine treatment. Additionally, ropivacaine treatment enhanced HO-1 activity in a dose-dependent manner. Interestingly, we found that ropivacaine treatment induced phosphorylation of p38. Blockage of p38 phosphorylation with its specific inhibitor SB203580 or by transfection with p38 siRNA restrained ropivacaine-stimulated HO-1 expression. Additionally, we found that ropivacaine treatment promoted nuclear translocation of Nrf2 and amplified ARE promoter activity. Silencing of Nrf2 abolished ropivacaine-induced HO-1 expression. Notably, we found that inhibition of HO-1 activity promoted ropivacaine-induced production of reactive oxygen species (ROS), deletion of reduced glutathione (GSH), and release of lactate dehydrogenase (LDH), suggesting that induction of HO-1 by ropivacaine acted as a compensatory survival response against ropivacaine.


Assuntos
Amidas/farmacologia , Heme Oxigenase-1/metabolismo , Linhagem Celular Tumoral , Genes Reporter , Heme Oxigenase-1/antagonistas & inibidores , Humanos , Luciferases/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Protoporfirinas/farmacologia , Ropivacaina , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
8.
Zhongguo Zhen Jiu ; 37(7): 705-709, 2017 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-29231542

RESUMO

OBJECTIVE: To discuss the clinical therapeutic effects of electroacupuncture at Neimadian (Extra) and Neiguan (PC 6) on the analgesic effect of thoracic perioperative stage and its effect mechanism. METHODS: Sixty cases of esophageal cancer with elective radical resection under general anesthesia were divided into an observation group and a control group according to the operation sequence, 30 cases in each one. In the control group, the general anesthesia was simply applied and sufentanil was administered for patient controlled intravenous analgesia (PCIA) after operation. In the observation group, on the basis of the scheme as the control group, the electroacupuncture was used at Neimadian (Extra) and Neiguan (PC 6) 30 min before anesthesia induction and after operation, with continuous wave, tolerable intensity, lasting for 30 min. Separately, before acupuncture (T1) and 2h (T2), 12h (T3), 24h (T4) and 48h (T5) after operation, the plasma ß-endorphin (ß-EP), 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2) were determined. During operation, under the same state (from 50 to 60) of bispectrum of EEG (BIS), the intraoperative anesthetic dose was recorded. Using visual analogue scale (VAS), the pain degree was evaluated at T2, T3, T4 and T5 separately and the grade assessment of the therapeutic effects and safety were recorded at each time point. RESULTS: ①The total dosage of sufentanil in the observation group was less than that in the control group[(1.83±0.56) mg vs (2.54±0.62) mg, P<0.05]. ②VAS scores at T2, T3 and T4 in the patients of the observation group were all lower than those in the control group (all P<0.05). ③The levels of plasma ß-EP at T3, T4 and T5 in the observation group were increased significantly as compared with those in the control group (all P<0.05) and the levels of plasma 5-HT and PGE2 at T2, T3 and T4 were reduced significantly as compared with those in the control group (all P<0.05). ④ The excellent analgesia rates 2h、12h and 24h after operation in the observation group were better than those in the control group (all P<0.05). ⑤The rate of the A grade safety in the observation group was higher than that in the control group (P<0.05). CONCLUSIONS: Electroacupuncture at Neimadian (Extra) and Neiguan (PC 6) provides the safe and effective postoperative anesthesia of thoracic surgery and reduces the dosage of analgesics during the operation, which is possibly related to the increase of endogenous ß-EP and the inhibition on the release of 5-HT and PGE2.


Assuntos
Analgesia por Acupuntura , Eletroacupuntura/métodos , Neoplasias Esofágicas/cirurgia , Pontos de Acupuntura , Anestesia Geral , Anestésicos Intravenosos/administração & dosagem , Pesquisa Biomédica , Estudos de Casos e Controles , Dinoprostona/sangue , Humanos , Manejo da Dor , Medição da Dor , Serotonina/sangue , Sufentanil/administração & dosagem , beta-Endorfina/sangue
9.
Neurochem Res ; 42(5): 1524-1532, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28247333

RESUMO

Microglia have undergone extensive characterization and have been shown to present distinct phenotypes, such as the M1 or M2 phenotypes, depending on their stimuli. As a highly specific neurotoxin, 6-hydroxydopamine (6-OHDA) can be used to further our understanding of the immune response in Parkinson's disease (PD). Dexmedetomidine (DEX), a centrally selective α2-adrenoceptor agonist, performs very well as an anti-anxiety medication, sedative and analgesic. In the present study, we investigated the effects of DEX on 6-OHDA-induced microglial polarization. Our results indicate that treatment with 6-OHDA promotes microglial polarization toward the M1 state in BV2 microglia cells by increasing the release of interleukin (IL)-6, IL-1ß, or tumor necrosis factor-α, which can be prevented by pretreatment with DEX. In addition, we found that 6-OHDA blocked IL-4-mediated microglial M2 polarization by suppressing expression of the microglial M2 markers arginase-1 (Arg-1), resistin-like α (Retnla/Fizz1), and chitinase 3-like 3 (Chi3l3/Ym1), which could be ameliorated by pretreatment with DEX. Notably, the inhibitory effects of 6-OHDA on IL-4-mediated induction of the anti-inflammatory marker genes IL-10, IL-13, and transforming growth factor-ß2 could be significantly alleviated by pretreatment with DEX in a dose-dependent manner (P < 0.01). Mechanistically, alternations in the activation of signal transducer and activator of transcription 6 were involved in this process. These findings suggest that administration of DEX has the potential to interrupt the process of microgliosis in PD.


Assuntos
Dexmedetomidina/farmacologia , Microglia/efeitos dos fármacos , Microglia/metabolismo , Oxidopamina/toxicidade , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Animais , Linhagem Celular , Polaridade Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Camundongos , Microglia/patologia , Oxidopamina/farmacologia
10.
Int Immunopharmacol ; 34: 114-128, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26945830

RESUMO

High mobility group box protein 1 (HMGB1) and receptor for the advanced glycation end product (RAGE) play important roles in the development of sepsis-induced acute lung injury (ALI). Ketamine is considered to confer protective effects on ALI during sepsis. In this study, we investigated the effects of ketamine on HMGB1-RAGE activation in a rat model of sepsis-induced ALI. ALI was induced in wild type (WT) and RAGE deficient (RAGE(-/-)) rats by cecal ligation and puncture (CLP) or HMGB1 to mimic sepsis-induced ALI. Rats were randomly divided to six groups: sham-operation+normal saline (NS, 10 mL/kg), sham-operation+ketamine (10 mg/kg), CLP/HMGB1+NS (10 mL/kg), CLP/HMGB1+ketamine (5 mg/kg), CLP/HMGB1+ketamine (7.5 mg/kg), and CLP/HMGB1+ketamine (10 mg/kg) groups. NS and ketamine were administered at 3 and 12 h after CLP/HMGB1 via intraperitoneal injection. Pathological changes of lung, inflammatory cell counts, expression of HMGB1 and RAGE, and concentrations of various inflammatory mediators in bronchoalveolar lavage fluids (BALF) and lung tissue were then assessed. Nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathways in the lung were also evaluated. CLP/HMGB1 increased the wet to dry weight ratio and myeloperoxidase activity in lung, the number of total cells, neutrophils, and macrophages in the BALF, and inflammatory mediators in the BALF and lung tissues. Moreover, expression of HMGB1 and RAGE in lung tissues was increased after CLP. Ketamine inhibited all the above effects. It also inhibited the activation of IκB-α, NF-κB p65, and MAPK. Ketamine protects rats against HMGB1-RAGE activation in a rat model of sepsis-induced ALI. These effects may partially result from reductions in NF-κB and MAPK.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Proteína HMGB1/administração & dosagem , Proteína HMGB1/imunologia , Ketamina/uso terapêutico , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Sepse/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Animais , Animais Geneticamente Modificados , Anticorpos Bloqueadores/administração & dosagem , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Técnicas de Inativação de Genes , Humanos , Mediadores da Inflamação , Masculino , NF-kappa B/metabolismo , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/imunologia , Sepse/complicações , Transdução de Sinais
11.
J Mol Neurosci ; 56(1): 122-30, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25522790

RESUMO

Lidocaine has been indicated to promote apoptosis and to promote endoplasmic reticulum (ER) stress. However, the mechanism underlining ER stress-mediated apoptosis is unclear. In the present study, we investigated the promotion to ER stress in the lidocaine-induced apoptosis in human neuroblastoma SH-SY5Y cells. Firstly, we confirmed that lidocaine treatment induced apoptosis in SH-SY5Y cells, time-dependently and dose-dependently, via MTT cell viability assay and annexin V/FITC apoptosis detection with a FACScan flow cytometer. And the anti-apoptosis Bcl-2 and Bcl-xL were downregulated, whereas the apoptosis-executive caspase 3 was promoted through Western blot assay and caspase 3 activity assay. Moreover, the ER stress-associated binding immunoglobulin protein (BiP), PKR-like ER kinase (PERK), activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein homologous protein (CHOP) were also upregulated at both mRNA and protein levels by lidocaine treatment. On the other hand, downregulation of the ER stress-associated BiP by RNAi method not only blocked the lidocaine-promoted ER stress but also attenuated the lidocaine-induced SH-SY5Y cell apoptosis. In conclusion, the present study confirmed the involvement of ER stress in the lidocaine-induced apoptosis in human neuroblastoma SH-SY5Y cells. Our study provides a better understanding on the mechanism of lidocaine's neurovirulence.


Assuntos
Anestésicos Locais/farmacologia , Apoptose , Estresse do Retículo Endoplasmático , Lidocaína/farmacologia , Neurônios/efeitos dos fármacos , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Anestésicos Locais/toxicidade , Linhagem Celular Tumoral , Humanos , Lidocaína/toxicidade , Neurônios/metabolismo , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismo
12.
Int J Mol Sci ; 15(12): 23519-36, 2014 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-25526566

RESUMO

It has been reported that lidocaine is toxic to various types of cells. And a recent study has confirmed that lidocaine exerts a demethylation effect and regulates the proliferation of human breast cancer cell lines. To recognize a potential anti-tumor effect of lidocaine, we evaluated the DNA demethylation by lidocaine in human breast cancer lines, MCF-7 and MDA-MB-231 cells, and determined the influence of demethylation on the toxicity to these cells of cisplatin, which is a commonly utilized anti-tumor agent for breast cancer. Results demonstrated that lidocaine promoted a significant global genomic demethylation, and particularly in the promoters of tumor suppressive genes (TSGs), RARß2 and RASSF1A. Further, the lidocaine treatment increased cisplatin-induced apoptosis and enhanced cisplatin-induced cytotoxicity. The combined treatment with both lidocaine and cisplatin promoted a significantly higher level of MCF-7 cell apoptosis than singular lidocaine or cisplatin treatment. Moreover, the abrogation of RARß2 or RASSF1A expression inhibited such apoptosis. In conclusion, the present study confirms the demethylation effect of lidocaine in breast cancer cells, and found that the demethylation of RARß2 and RASSF1A sensitized the cytotoxicity of cisplatin in breast cancer cells.


Assuntos
Neoplasias da Mama/genética , Cisplatino/farmacologia , Metilação de DNA/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Lidocaína/farmacologia , Receptores do Ácido Retinoico/genética , Proteínas Supressoras de Tumor/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Ilhas de CpG , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7
13.
J Surg Res ; 186(1): 240-5, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24007817

RESUMO

BACKGROUND: Dexmedetomidine (DEX) has been shown to decrease ischemia-reperfusion (I/R) injury in kidney and brain tissues. In this study, the effects of DEX were evaluated in skeletal muscle during I/R injury. MATERIALS AND METHODS: Animals were divided into four groups: sham-operated (sham group), saline + I/R, DEX + I/R, and α-tocopherol + I/R groups. Hind limb ischemia was induced by clamping the common femoral artery and vein. After 4 h of ischemia, the clamp was removed and the animals underwent 2 h of reperfusion. Animals in the drug treatment group received DEX or α-tocopherol by intraperitoneal injection 1 h before reperfusion. We measured plasma concentrations of interleukin 1ß and tumor necrosis factor α levels using an enzyme-linked immunosorbent assay. The right gastrocnemius muscle was harvested and immediately stored at -80°C for the assessment of superoxide dismutase (SOD) and catalase (CAT) activities as well as glutathione (GSH), malondialdehyde (MDA), and protein oxidation (PO) levels. DEX (25 µg/kg) and normal saline (10 mL/kg) were administered by intraperitoneal injection 1 h before reperfusion. RESULTS: Plasma tumor necrosis factor α or interleukin 1ß levels increased significantly in the I/R group (P < 0.01 compared with sham group) and decreased significantly in the DEX group (P < 0.01 compared with I/R group). Muscle tissues of the I/R group had significantly decreased SOD, GSH, and CAT activities and increased levels of MDA and PO content compared with the sham group. The activity of antioxidant enzymes in the DEX + I/R group was greatly elevated compared with that in the I/R group (SOD, 1.068 ± 0.120 versus 0.576 ± 0.072 U/mg protein; GSH, 2.436 ± 0.144 versus 1.128 ± 0.132 µmol/g; and CAT, 69.240 ± 6.456 versus 31.884 ± 6.312 U/mg protein; P < 0.01), whereas the levels of MDA and PO content were clearly reduced (23.268 ± 3.708 versus 53.604 ± 5.972 nmol/g protein and 1.908 ± 0.192 versus 5.208 ± 0.612 nmol/mg protein, respectively; P < 0.01). Moreover, DEX exhibited more potent antioxidant activity than vitamin E in the skeletal muscle I/R. CONCLUSIONS: We found that DEX exhibits protective effects against skeletal muscle I/R injury. These results underscore the necessity of human studies with DEX to determine if it is beneficial for preventing skeletal muscle I/R injury.


Assuntos
Dexmedetomidina/uso terapêutico , Músculo Esquelético/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Animais , Catalase/metabolismo , Glutationa/metabolismo , Interleucina-1beta/sangue , Malondialdeído/análise , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Fator de Necrose Tumoral alfa/sangue
14.
Zhongguo Zhen Jiu ; 33(9): 829-32, 2013 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-24298779

RESUMO

OBJECTIVE: To observe the effectiveness and safety of electroacupuncture (EA) at Neimadian (Extra) and Neiguan (PC 6) for analgesia after thoracic surgery. METHODS: One hundred and twenty cases of thoracic surgery were randomly divided into an electroacupuncture (EA) group (60 cases) and a medication group (60 cases). EA was applied at Neimadian (Extra) and Neiguan (PC 6) for postoperation analgesia in the EA group, while patient-controlled intravenous analgesia (PCIA) was applied in the medication group. The score of visual analogue scale (VAS), analgesia effect, safety and beta-endorphin level after the treatment in both groups were compared. RESULTS: Compared with those before the treatment, the VAS scores in every time point after surgery were decreased (all P < 0.05), which were lower in the EA group (P < 0.01). The excellent and good rates were 96.7% (58/60) and 75.0% (45/60) seperately, the analgesia effect in the EA group (2 h after operation) was superior to that in the medication group (P < 0.01). The safety degree in EA group was higher to that in the medication group (P < 0.01). Compared with that before the treatment, the beta-endorphin level in two groups after treatment was both increased, which was higher in the EA group (P < 0.01). CONCLUSION: Electroacupuncture at Neimadian (Extra) and Neiguan (PC 6) has better analgesia effect (2 h after operation) and safety than PICA on analgesia after thoracic surgery.


Assuntos
Analgesia por Acupuntura , Pontos de Acupuntura , Eletroacupuntura , Dor Pós-Operatória/terapia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/sangue , Cirurgia Torácica , beta-Endorfina/sangue
15.
Hepatogastroenterology ; 59(119): 2285-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22456434

RESUMO

BACKGROUND/AIMS: We conducted a case-control study in China to clarify the association between XRCC1-Arg-399Gin polymorphism and HCC risk. METHODOLOGY: A total of 150 cases and 158 controls were selected from May 2008 to May 2010. XRCC1-Arg399Gin and XRCC3-Thr241Met polymorphisms were based upon duplex polymerase-chain-reaction with the confronting-two-pair primer (PCR-CTPP) method. All analysis was performed by using the STATA statistical package. RESULTS: A significant increased risk of HCC was associated with XRCC1 399Arg/Gin, and a heavy risk of HCC was also found in individuals with XRCC3 241Met/Met genotypes. A significant association was found between positive HBsAg and Arg/Gin. XRCC3 Thr/Met genotypes had a significant positive association with HBsAg (+) and a heavy risk of HCC was found in HBsAg (+) individuals with XRCC3 Met/Met genotype. Individuals carrying XRCC1 Gin/Gin genotypes showed significantly lower median survival than XRCC1 Arg/ Arg genotypes and significant hazard ratio (HR=l.38, 95% CI=l.04-1.84) was found. Meanwhile, we found a moderate HR for XRCC3 Thr/Met (HR=l.96, 95% CI=l.23-3.15) and a heavy HR for XRCC3 Met/Met (HR=2.98, 95% CI=1.77-7.54). CONCLUSIONS: In conclusion, we observed that XRCC1-Arg399Gln and XRCC3-Thr241Met polymorphism is associated with susceptibility to HCC and XRCC1 Gin allele and XRCC3 Met allele genotype showed significant poor prognosis of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Reparo do DNA , Proteínas de Ligação a DNA/genética , Neoplasias Hepáticas/genética , Polimorfismo Genético , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Biomarcadores/sangue , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China , Feminino , Predisposição Genética para Doença , Hepatite B/complicações , Hepatite B/diagnóstico , Antígenos de Superfície da Hepatite B/sangue , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase/métodos , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Proteína 1 Complementadora Cruzada de Reparo de Raio-X
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