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2.
J Nanobiotechnology ; 22(1): 55, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331774

RESUMO

BACKGROUND: Exosomes are nanoscale extracellular vesicles (30-160 nm) with endosome origin secreted by almost all types of cells, which are considered to be messengers of intercellular communication. Cancerous exosomes serve as a rich source of biomarkers for monitoring changes in cancer-related physiological status, because they carry a large number of biological macromolecules derived from parental tumors. The ultrasensitive quantification of trace amounts of cancerous exosomes is highly valuable for non-invasive early cancer diagnosis, yet it remains challenging. Herein, we developed an aptamer-carrying tetrahedral DNA (Apt-TDNA) microelectrode sensor, assisted by a polydopamine (PDA) coating with semiconducting properties, for the ultrasensitive electrochemical detection of cancer-derived exosomes. RESULTS: The stable rigid structure and orientation of Apt-TDNA ensured efficient capture of suspended exosomes. Without PDA coating signal amplification strategy, the sensor has a linear working range of 102-107 particles mL-1, with LOD of ~ 69 exosomes and ~ 42 exosomes for EIS and DPV, respectively. With PDA coating, the electrochemical signal of the microelectrode is further amplified, achieving single particle level sensitivity (~ 14 exosomes by EIS and ~ 6 exosomes by DPV). CONCLUSIONS: The proposed PDA-assisted Apt-TDNA microelectrode sensor, which integrates efficient exosome capture, sensitive electrochemical signal feedback with PDA coating signal amplification, provides a new avenue for the development of simple and sensitive electrochemical sensing techniques in non-invasive cancer diagnosis and monitoring treatment response.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Exossomos , Indóis , Neoplasias , Polímeros , Humanos , Microeletrodos , Exossomos/química , DNA/análise , Neoplasias/diagnóstico , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Limite de Detecção
3.
J Back Musculoskelet Rehabil ; 36(5): 1139-1150, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37458014

RESUMO

BACKGROUND: Myofascial pain syndrome (MPS) is a common disease with easy persistence and recurrence. In clinical practice, although many methods have been adopted to prevent and treat MPS, the control of MPS is still not satisfactory. OBJECTIVE: To compare the safety and effectiveness of buccal acupuncture, inactivation of trigger points (MTrPs), and their combination in the treatment of MPS. METHODS: Two hundred MPS patients in the pain clinic were randomly divided into four groups (n= 50) to receive oral drugs (Group A), oral drugs + buccal needle (Group B), oral drugs + MTrP inactivation (Group C), or oral drugs + buccal needle + MTrP inactivation (Group D). RESULTS: The visual analogue scale (VAS) and cervical range of motion (ROM) of Group D were significantly lower than those of the other three groups, and the pressure pain threshold (PPT) value of labelled MTrPs was significantly higher than those of the other three groups (P< 0.05). The excellent rate and total effective rate of Group D were significantly higher than those of the other three groups. Group C had the highest pain score and the lowest acceptance score. The results showed that buccal acupuncture combined with ultrasound-guided dry needle-evoked inactivation of MTrPs can significantly reduce the VAS score of MPS patients, improve the range of motion of the cervical spine, and improve patient satisfaction. CONCLUSIONS: This study provides a highly accepted and satisfactory treatment for MPS, which is worthy of clinical promotion.


Assuntos
Terapia por Acupuntura , Fibromialgia , Síndromes da Dor Miofascial , Humanos , Pontos-Gatilho , Ombro , Síndromes da Dor Miofascial/terapia , Ultrassonografia de Intervenção
4.
BMC Pediatr ; 23(1): 81, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36797693

RESUMO

BACKGROUND: Post-infectious bronchiolitis obliterans (PIBO) is the most common sequelae in children with adenovirus pneumonia (ADVP). However, there are few studies on the risk factors for PIBO occurrence. This study aims to investigate the risk factors for PIBO in pediatric patients with severe ADVP, especially after invasive mechanical ventilation (IMV), as well as to build a nomogram prediction model. METHODS: The clinical data, laboratory and imaging features, and treatment of 863 children with ADVP under 3 years old who were admitted to our hospital from January to December 2019 were retrospectively analyzed. Among them, 66 children with severe ADVP received IMV treatment. The situation and the influencing factors of PIBO in children with severe ADVP were explored, and a nomogram prediction model was constructed. RESULTS: Among the 863 cases of ADVP, 46 cases (5.33%) developed PIBO. Duration of fever, IMV, complications, and neutrophil percentage were independent risk factors for PIBO in children with ADVP. Among the 66 patients with ADVP who underwent IMV, 33 patients (50.0%) developed PIBO. Gender, duration of fever, adenovirus (ADV) load, and mixed fungal coinfections were independent risk factors for PIBO. In the nomogram prediction model analysis, the area under the curve (AUC) was 0.857; in addition, Hosmer‒Lemeshow (H-L) detection reflected good alignment (χ2 = 68.75, P < 0.01). CONCLUSIONS: A nomogram prediction model, which can be utilized to predict PIBO occurrence in pediatric patients with ADVP after IMV at an early time period, was successfully built.


Assuntos
Infecções por Adenoviridae , Bronquiolite Obliterante , Pneumonia Viral , Criança , Humanos , Pré-Escolar , Estudos Retrospectivos , Nomogramas , Respiração Artificial/efeitos adversos , Bronquiolite Obliterante/diagnóstico , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/epidemiologia , Infecções por Adenoviridae/complicações , Infecções por Adenoviridae/diagnóstico , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Adenoviridae
5.
Can Respir J ; 2022: 9595184, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35979256

RESUMO

Background: The study aimed to explore risk factors for bronchial mucus plugs (BMP) formation in children with adenovirus (AdV) pneumonia. Methods: A retrospective study was conducted on children with AdV pneumonia who underwent bronchoscopy from January 2019 to December 2019. Children were divided into the BMP group and the control group, depending on whether BMP was formed or not. The clinical information and treatment proposals of the two groups of children were counted and analyzed via multiple logistic regression analysis, ROC curve analysis, and correlation analysis. Results: Among 453 patients with AdV pneumonia, 185 (40.84%) were in the BMP group. Among all the cases, there were 188 patients with a single AdV infection, including 64 (34.04%) in the BMP group and 124 (65.96%) in the control group. The incidence of dyspnea, poor spirits, mixed infections, and other symptoms in the BMP group was higher than in the control group. Children in the BMP group had a longer heat range. C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer (DD), and AdV load levels were higher in the MBP group. AdV load, Mycoplasma coinfection, DD, heat range, and LDH were independent risk factors for BMP, among which AdV load was the most significant (AUC = 0.819). AdV load was positively correlated with other risk factors, respectively. AdV load and heat range were independent risk factors for BMP patients with a single AdV infection. Conclusion: AdV load might have important clinical value in predicting BMP development in AdV pneumonia.


Assuntos
Coinfecção , Pneumonia Viral , Adenoviridae , Brônquios , Criança , Humanos , L-Lactato Desidrogenase , Muco , Pneumonia Viral/terapia , Estudos Retrospectivos
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(11): 1198-1203, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33172555

RESUMO

OBJECTIVE: To investigate the respiratory pathogens and clinical features in children with acute exacerbation of bronchial asthma. METHODS: Nasopharyngeal swabs were collected from 225 children with acute exacerbation of bronchial asthma, aged <14 years, who attended the outpatient service or were hospitalized from August 2017 to August 2019. Quantitative real-time PCR was used to detect 12 pathogens, i.e., respiratory syncytial virus (RSV), human rhinovirus (HRV), influenza virus A (IFVA), influenza virus B (IFVB), parainfluenza virus types 1-3 (PIV1-3), human metapneumovirus (HMPV), adenovirus (ADV), Bordetella pertussis (BP), Chlamydia pneumoniae (CP), and Mycoplasma pneumoniae (MP). RESULTS: The overall detection rate of virus was 46.2% (104/225), and 7 kinds of viruses were detected, i.e., HRV (19.6%, 44/225), ADV (16.0%, 36/225), IFVB (5.8%, 13/225), RSV (4.9%, 11/225), IFVA (3.6%, 8/225), PIV3 (1.8%, 4/225), and HMPV (0.4%, 1/225). Of all pathogens, BP had the highest detection rate of 28.4% (64/225), and the detection rates of MP and CP were 16.4% (37/225) and 0.4% (1/225), respectively. The mild exacerbation group had a higher detection rate of BP than the severe exacerbation group (P<0.05), while the severe exacerbation group had significantly higher detection rates of RSV and MP than the mild exacerbation group (P<0.05). There were significant differences in the proportion of children with paroxysmal cough, spasmodic cough, fever, lung rales and abnormal lung imaging findings among the simple BP infection, simple virus infection and simple MP infection groups (P<0.05). CONCLUSIONS: BP, HRV, and MP are common respiratory pathogens detected in children with acute exacerbation of bronchial asthma, and respiratory virus infection is an important pathogen of acute exacerbation of asthma in children. Acute exacerbation of asthma caused by different pathogens has different clinical features and severities.


Assuntos
Asma , Pneumonia por Mycoplasma , Vírus Sincicial Respiratório Humano , Adolescente , Asma/diagnóstico , Criança , Humanos , Mycoplasma pneumoniae
7.
Pain Res Manag ; 2020: 4298509, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509046

RESUMO

Objective: To evaluate ultrasound-guided inactivation of myofascial trigger points (MTrPs) combined with abdominal muscle fascia stripping by liquid knife in the treatment of postherpetic neuralgia (PHN) complicated with abdominal myofascial pain syndrome (AMPS). Methods: From January 2015 to July 2018, non-head-and-neck PHN patients in the Pain Department, The First Affiliated Hospital of Soochow University, were treated with routine oral drugs and weekly paraspinal nerve block for two weeks. Patients with 2 < VAS (visual analogue scale) score < 6 were subjects of the study. They were assigned into control group 1 (C1, n = 33) including those with PHN and without myofascial pain syndrome (MPS) and control group 2 (C2, n = 33) including those with PHN complicated with MPS and observation group 1 (PL, n = 33) including those with PHN complicated with limb myofascial pain syndrome (LMPS) and observation group 2 (PA, n = 33) including those with PHN complicated with AMPS. All groups received zero-grade treatment: routine oral drugs and weekly paraspinal nerve block. PL and PA groups were also treated step by step once a week: primary ultrasound-guided inactivation of MTrPs with dry needling, secondary ultrasound-guided inactivation of MTrPs with dry and wet needling, and tertiary ultrasound-guided dry and wet needling combined with muscle fascia stripping by liquid knife. At one week after primary treatment, patients with a VAS score > 2 proceeded to secondary treatment. If the VAS score was <2, the treatment was maintained, and so on, until the end of the four treatment cycles. Pain assessment was performed by specialized nurses at one week after each treatment, including VAS score, McGill pain questionnaire (MPQ) score, pressure pain sensory threshold (PPST), and pressure pain tolerance threshold (PPTT). VAS score was used as the main index and VAS <2 indicated effective treatment. At 3 months after treatment, outpatient and/or telephone follow-up was performed. The recurrence rate was observed and VAS > 2 was regarded as recurrence. Results: At one week after primary treatment, the effective rate was 66.7% in PL group, significantly higher than that in PA group (15.2%, P < 0.05). At one week after secondary treatment, the effective rate was 100% and 37.5% in PL and PA groups, respectively, with significant difference between the groups (P < 0.05). The effective rate increased to 90.6% in PA group at one week after tertiary treatment. At one week after the end of treatment cycles, the scores of VAS and MPQ were significantly lower in C1, PL, and PA groups than in C2 group (P < 0.05), while PPST and PPTT were significantly higher than in C2 group (P < 0.05). There was no significant difference between C1 group and PL group (P > 0.05). At follow-up at 3 months after treatment, the recurrence rate was low in each group, with no significant difference between the groups (P > 0.05). Conclusion: About 57% of PHN patients with mild to moderate pain are complicated with MPS, and ultrasound-guided inactivation of MTrPs with dry and wet needling can effectively treat PHN patients complicated with LMPS. However, patients with PHN complicated with AMPS need to be treated with ultrasound-guided MTrPs inactivation combined with muscle fascia stripping by liquid knife as soon as possible.


Assuntos
Agulhamento Seco/métodos , Síndromes da Dor Miofascial/etiologia , Síndromes da Dor Miofascial/terapia , Neuralgia Pós-Herpética/terapia , Ultrassonografia de Intervenção/métodos , Adulto , Anestésicos Locais/uso terapêutico , Fáscia/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bloqueio Nervoso/métodos , Neuralgia Pós-Herpética/complicações , Estudos Prospectivos , Ropivacaina/uso terapêutico , Resultado do Tratamento , Pontos-Gatilho
8.
J Craniofac Surg ; 30(1): e85-e92, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30507881

RESUMO

There are various respiratory tract complications in patients undergoing general anesthesia, with postoperative sore throat (POST) being the most commonly seen. Although measures have been taken to prevent and treat POST in clinical practice, the control of POST is still not satisfactory. In this study, 880 ASA patients with grade I to II general anesthesia were randomly assigned into control group and experimental group. After patients entered into the operating room, the plasters were applied to the designated points (Tianzhu, Lianquan, Dazhui, etc), and the clinical efficacy of acupoint application in prevention and treatment of respiratory tract complications after general anesthesia was observed. The results showed that patients starting using acupoint application before operation could significantly reduce the incidence of postoperative respiratory tract complications, and the effects lasted for up to 24 hours. In this study, acupoint application was used, providing a simple, safe, efficient, and durable approach to prevent and treat respiratory tract complications after operation under general anesthesia.


Assuntos
Anestesia Geral/efeitos adversos , Terapias Complementares/métodos , Faringite/prevenção & controle , Náusea e Vômito Pós-Operatórios/prevenção & controle , Pontos de Acupuntura , Adulto , Tosse/etiologia , Tosse/prevenção & controle , Feminino , Humanos , Intubação Intratraqueal/efeitos adversos , Masculino , Pessoa de Meia-Idade , Faringite/etiologia , Náusea e Vômito Pós-Operatórios/etiologia
9.
Neurosci Res ; 125: 37-45, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28668500

RESUMO

Our previous research suggested that the P2X4 receptor (P2X4R) expression in microglia was involved in the activation of toll-like receptor-4 (TLR4) in the dorsal horn in the rat model of cancer induced bone pain (CIBP). In this study, we focused on whether TLR4- mitogen-activated protein kinases, p38 (p38 MAPK) contributes to P2X4R activation and brain-derived neurotrophic factor (BDNF) over-secretion in CIBP. In in vitro experiment, the results showed that BDNF expression evoked by ATP stimulation was dependent on TLR4-p38. In in vivo experiment, the results demonstrated that an intrathecal injection of TLR4 siRNA alleviated nociception induced by lipopolysaccharide (LPS) plus ATP or CIBP with decreased expression of P2X4R, TLR4, BDNF, interleukin-6 (IL-6) and phosphorylated-p38 MAPK (p-p38 MAPK). Moreover, injection with p38MAPK inhibitor SB203580 resulted in an identical pattern compared with treatment with TLR4 siRNA. Our results demonstrate that the activation of TLR4-p38MAPK-P2X4R signaling in microglial possibility plays an important role in the process of nociceptive transmission in CIBP, suggesting new mechanism and potential therapeutic targets for CIBP.


Assuntos
Neoplasias Ósseas/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Microglia/metabolismo , Receptores Purinérgicos P2X4/metabolismo , Receptor 4 Toll-Like/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Neoplasias Ósseas/tratamento farmacológico , Feminino , Humanos , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Dor/metabolismo , Ratos Sprague-Dawley , Receptores Purinérgicos P2X4/efeitos dos fármacos , Corno Dorsal da Medula Espinal/efeitos dos fármacos , Corno Dorsal da Medula Espinal/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos
10.
Clin Ther ; 38(1): 192-201.e2, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26699739

RESUMO

PURPOSE: Patients undergoing awake lumbar disc surgery need adequate sedation and analgesia. This study investigated whether use of a dexmedetomidine-fentanyl (DF) regimen could be superior to midazolam-fentanyl (MF) for these patients. METHODS: Sixty patients scheduled for elective lumbar laminotomy and discectomy were randomly assigned to receive either DF or MF for conscious sedation. Patient-controlled intravenous analgesia with fentanyl was used for postoperative pain management. Hemodynamic and respiratory changes, sedation scores, pain scores, fentanyl consumption, patient satisfaction, postoperative hospital stay, and adverse events were assessed. FINDINGS: The patient and surgical characteristics, sedation levels, and pain scores were similar in the 2 groups. Compared with the MF group, heart rate was lower in the DF group at six time points from skin incision to 15 minutes in the postanesthesia care unit (PACU), they are skin incision, 15 min after the beginning of surgery, 30 min after the beginning of surgery, skin closure, entering PACU, and 15 min in PACU (P = 0.016, 0.002, 0.000, 0.000, 0.000, and 0.001, respectively), whereas pulse oxygen saturation was higher at 3 time points from 15 minutes after the beginning of surgery to skin closure (P = 0.022, 0.026, and 0.025, respectively). The intraoperative, postoperative, and total consumption of fentanyl were lower in the DF group (total: mean difference = -69.3 µg; 95% CI, = -114.3 to -24.4; P = 0.003). No significant differences were found for adverse events, postoperative hospital stay, or satisfaction between the 2 groups. IMPLICATIONS: Although awake lumbar disc surgery can be performed successfully under sedation with either MF or DF combination, the latter may be a better alternative because of less consumption of opioid analgesics. ChiCTR.org identifier: ChiCTR-TRC-13003645.


Assuntos
Analgésicos Opioides/administração & dosagem , Sedação Consciente/métodos , Dexmedetomidina/administração & dosagem , Fentanila/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Midazolam/administração & dosagem , Adulto , Discotomia/efeitos adversos , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Laminectomia/efeitos adversos , Tempo de Internação , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Manejo da Dor , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Satisfação do Paciente , Período Pós-Operatório
11.
Yao Xue Xue Bao ; 50(4): 464-8, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-26223129

RESUMO

According to the super-position principle of the reinforcement of biological activities, a series of novel E-substituted 2, 3-diaryl propenoic acyloxy phosphonate derivatives were designed and synthesized. And the structures of the target compounds were confirmed by IR, 1H NMR, 13C NMR and elemental analysis. Furthermore, the cytotoxicities of all compounds on A-549, SGC-7901 and EC-109 in vitro were evaluated by MTT assay, and some of them showed good antitumor activity. Among the active compounds, especially, the IC50 value of compound 3e was (12.7 ± 1.9) µmol x L(-1) against A-549 cells, similar to cisplatin [IC50 = (8.0 ± 1.5) µmol x L(-1)], compounds 3g and 3k had better inhibition effect on EC-109 cells growth, with the IC50 values of (9.5 ± 1.8) µmol x L(-1) and (11.5 ± 0.9) µmol x L(-1) respectively, and compounds 3i and 3k exhibited good cytotoxic property on A-549, SGC-7901 and EC-109, which were worth further investigation.


Assuntos
Antineoplásicos/farmacologia , Organofosfonatos/farmacologia , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células , Desenho de Fármacos , Humanos , Organofosfonatos/síntese química
12.
Clin Ther ; 37(5): 1114-1121.e1, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25769614

RESUMO

PURPOSE: Pain management for patients who have undergone a craniotomy remains challenging. This study aimed to determine whether intraoperative dexmedetomidine could reduce postoperative pain, analgesic consumption, and possible adverse events in patients after craniotomy. METHODS: Eighty patients scheduled for elective supratentorial craniotomy under sevoflurane-fentanyl anesthesia were randomly allocated into two equal groups, to receive a continuous dexmedetomidine infusion of 0.5 µg/kg/h or placebo, beginning after induction and continuing until the start of skin closure. Intravenous tramadol (0.5 mg/kg) was administered to achieve an 11-point verbal rating scale (a discrete 0-10 scale) score of 4 or less in the postanesthesia care unit and, thereafter, on the ward. Pain scores, tramadol consumption, sedation scores, postoperative nausea and vomiting (PONV) scores, and other adverse events were recorded in the first 24 hours postoperatively. FINDINGS: Seventy-six patients were included in the analyses. Demographic data, surgical characteristics, and sedation levels were similar between the groups. Dexmedetomidine reduced pain scores (30 minutes, P = 0.041; 2 hours, P = 0.021) and tramadol consumption (0-2 hours, P = 0.043; 0-6 hours, P = 0.006; 0-12 hours, P = 0.023; 0-24 hours, P = 0.040) postoperatively. Dexmedetomidine also reduced PONV scores at 20, 60, 90, 120, and 240 minutes (P = 0.038, 0.022, 0.018, 0.037, 0.016, respectively). The dexmedetomidine group exhibited fewer PONV events that required treatment (P = 0.005). IMPLICATIONS: Intraoperative dexmedetomidine infusion was effective for reducing pain and analgesic consumption after craniotomy. In addition, dexmedetomidine may help to reduce PONV in patients after craniotomy treated with tramadol postoperatively. Chinese Clinical Trial Register identifier: ChiCTR-TRC-13003598.


Assuntos
Analgésicos não Narcóticos/uso terapêutico , Craniotomia/efeitos adversos , Dexmedetomidina/uso terapêutico , Dor Pós-Operatória/prevenção & controle , Adulto , Idoso , Analgésicos não Narcóticos/efeitos adversos , Analgésicos Opioides/administração & dosagem , Anestesia Geral/métodos , Sedação Consciente/métodos , Dexmedetomidina/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Cuidados Intraoperatórios/métodos , Masculino , Pessoa de Meia-Idade , Manejo da Dor , Medição da Dor/métodos , Dor Pós-Operatória/etiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Estudos Prospectivos , Tramadol/administração & dosagem , Adulto Jovem
13.
J Neurosci Res ; 92(12): 1690-702, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24984884

RESUMO

Previous studies have suggested that the microglial P2X7 purinoceptor is involved in the release of tumor necrosis factor-α (TNFα) following activation of toll-like receptor-4 (TLR4), which is associated with nociceptive behavior. In addition, this progress is evoked by the activation of the P2X4 purinoceptor (P2X4R). Although P2X4R is also localized within spinal microglia in the dorsal horn, little is known about its role in cancer-induced bone pain (CIBP), which is in some ways unique. With the present rat model of CIBP, we demonstrate a critical role of the microglial P2X4R in the enhanced nociceptive transmission, which is associated with TLR4 activation and secretion of brain-derived neurotrophic factor (BDNF) and TNFα in the dorsal horn. We assessed mechanical threshold and spontaneous pain of CIBP rats. Moreover, P2X4R small interfering RNA (siRNA) was administered intrathecally, and real-time PCR, Western blots, immunofluorescence histochemistry, and ELISA were used to detect the expression of P2X4R, TLR4, OX-42, phosphorylated-p38 MAPK (p-p38), BDNF, and TNFα. Compared with controls, intrathecal injection of P2X4R siRNA could prevent nociceptive behavior induced by ATP plus lipopolysaccharide and CIBP and reduce the expression of P2X4R, TLR4, p-p38, BDNF, and TNFα. In addition, the increase of BDNF protein in rat microglial cells depended on P2X4 receptor signaling, which is partially associated with TLR4 activation. The ability of microglial P2X4R to activate TLR4 in spinal cord leading to behavioral hypersensitivity and oversecretion of BDNF could provide an opportunity for the prevention and treatment of CIBP.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Dor/patologia , Células do Corno Posterior/metabolismo , Receptores Purinérgicos P2X4/metabolismo , Receptor 4 Toll-Like/metabolismo , Trifosfato de Adenosina/farmacologia , Adjuvantes Imunológicos/farmacologia , Animais , Neoplasias Ósseas/complicações , Carcinoma/complicações , Células Cultivadas , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Microglia/metabolismo , Dor/etiologia , Medição da Dor , Ratos , Ratos Sprague-Dawley , Receptores Purinérgicos P2X4/genética , Fatores de Tempo , Receptor 4 Toll-Like/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
14.
Brain Res ; 1346: 213-23, 2010 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-20478276

RESUMO

Molecular mechanisms underlying bone cancer pain are poorly understood. Recently, p38 mitogen-activated protein kinase (MAPK) activation was shown to play a major role not only in the production of proinflammatory cytokines but also in the progression of inflammatory and neuropathic pain. We have demonstrated that tactile allodynia and spontaneous pain of female rats with tibia tumors were correlated with the increase of both phosphorylated-p38MAPK (p-p38MAPK) and proinflammatory cytokines (IL-1beta and TNF-alpha) in the spinal cord 6 days after Walker 256 cells' inoculation. This change was specific to bone cancer pain because rats without tibia tumors failed to show such an increase. On the other hand, a 3-day administration [4 microg/rat/day, intrathecally (i.t.)] of 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580), an inhibitor of p38MAPK, could suppress tactile allodynia and spontaneous pain of the bone cancer pain rats and decrease the phosphorylation of p38 as well as the expression of IL-1beta and TNF-alpha. To characterize the cellular events upstream of p38MAPK, we have examined the role of the toll-like receptor 4 (TLR4), which had been suggested to be involved in pain hypersensitivity. We found that prolonged knockdown of TLR4 during the 3-day administration of TLR4 small interfering RNA (siRNA; 2 microg/rat/day, i.t.) could attenuate hyperalgesia developed by Walker 256 cells' inoculation and decrease the phosphorylation of p38 as well as the increase of IL-1beta and TNF-alpha expression. These results demonstrate that TLR4-dependent phosphorylation of p38MAPK in spinal cord of rats might contribute to the development and maintenance of bone cancer pain, and p38MAPK and TLR4 would possibly be the potential targets for pain therapy.


Assuntos
Neoplasias Ósseas/complicações , Dor Intratável/etiologia , Dor Intratável/metabolismo , Tíbia , Receptor 4 Toll-Like/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Western Blotting , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Carcinoma 256 de Walker/patologia , Ativação Enzimática , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/uso terapêutico , Feminino , Imidazóis/administração & dosagem , Imidazóis/uso terapêutico , Imuno-Histoquímica , Injeções Espinhais , Interleucina-1beta/metabolismo , Transplante de Neoplasias , Estimulação Física , Piridinas/administração & dosagem , Piridinas/uso terapêutico , RNA Interferente Pequeno/farmacologia , Radiografia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medula Espinal/metabolismo , Tíbia/diagnóstico por imagem , Tíbia/patologia , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
15.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 21(2): 127-32, 2005 May.
Artigo em Chinês | MEDLINE | ID: mdl-21171321

RESUMO

AIM: To investigate the relation between Glu-R and the protective effect of hypothermia on oxygen and glucose deprivation (OGD) injury in hippocampal slices of rat. METHODS: (1) We had established OGD injury model in rat hippocampal slices. The changes of orthodromic population spike(OPS) during OGD and after administration of hypothermia (32 degrees C, 25 degrees C) were observed. (2) We had established Glu excitatory toxicity injury model in rat hippocampal slices. The changes of OPS after exposure to Glu and the effect of hypothermia (32 degrees C, 25 degrees C) against the Glu excitatory toxicity injury were observed. The non-NMDA receptor-mediated excitatory postsynaptic potentials (EPSP) in the CA1 area were recorded via adding the GABA-R specific agonists bicuculline (BMI) and NMDAR agonists D-(-)-2-Amino-5-phosphonopentanoic Acid (AP5) in normal artificial cerebrospinal fluid (nACSF), the NMDA receptor-mediated EPSP were recorded via adding the BMI and non-NMDA-R agonists 6,7-Dinitroquinoxaline-2, 3(1H,4H)-dione(CNQX) in nACSF. The variety of the changes of OPS during OGD14min in nACSF groups and added BMI compounded AP5 or BMI compounded CNQX ACSF groups were observed after administration of 25 degrees C hypothermia 28 min. (3) The changes of ultrastructure of CA1 area after OGD 1 h and the effect of hypothermia (25 degrees C) on it were observed. RESULTS: (1) OPS reduced and abolished quickly during OGD14min, and the recovery amplitude of OPS was very low after reoxygenation/glucose 1 h. While the time of OPS abolishing significantly elongated and the recovery of OPS was higher in hypothermia (32 degrees, 25 degrees C) groups. The effect in groups 25 degrees C was more significant than those in groups 32 degrees C. (2) In control groups, Glu (2 mmol/L, 14 min) decreased the amplitude of OPS, after the end of Glu exposure the recovery amplitude of OPS was very low. After administration of hypothermia (32 degrees C, 25 degrees C), the recovery amplitude and rate of OPS were significantly higher than those in the control groups, while the antagonism on Glu excitatory toxicity injury in H 25 degrees C was more significant than those in H 32 degrees C. The changes of OPS during OGD 14 min were no distinct difference in nACSF groups and added BMI (50 micromol/L) compounded AP5(20 micromol/L) or BMI (50 micromol/L) compounded CNQX (100 micromol/L) ACSF groups. The protection of hypothermia (25 degrees C) could not be cancelled by added AP5 compounded BMI or BMI compounded CNQX in nACSF. (3) After OGD (14 min) 1 h, the nuclear membrane of pyramidal cells in CA1 area was irregular, nucleus were homogenized, the organelle in the cytoplasm was degenerate, even more to necrosis or loss, mitochondrion swelled, ridge was vacuoles. In H 25 degrees C the nuclear membrane was regular, mitochondrion swelled only lightly. Small chromatin gathered to edge. CONCLUSION: Hypothermia shows the protective effects of against OGD injury in hippocampal slices. The mechanism is related to the antagonism of Glu excitor toxicity and maintenance the ATP level in cells, and the antagonism perhaps is mediated by NMDA-R and non-NMDA-R.


Assuntos
Glucose/metabolismo , Ácido Glutâmico/toxicidade , Hipocampo/metabolismo , Hipotermia , N-Metilaspartato/metabolismo , Oxigênio/metabolismo , Animais , Hipóxia Celular , Potenciais da Membrana , Neurônios/metabolismo , Técnicas de Cultura de Órgãos , Ratos , Ratos Sprague-Dawley
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