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BACKGROUND: Prolonged exposure to interleukin-17A (IL-17A) can induce autoimmune myocarditis, and MLN4924, an inhibitor of NEDD8 activating enzyme (NAE), has been reported to effectively suppress various inflammatory reactions. However, the effects of MLN4924 in IL-17A-mediated inflammation associated with autoimmune myocarditis remain uncertain. METHODS: An experimental autoimmune myocarditis (EAM) model was established and treated with MLN4924. The inflammation degree of heart tissues was assessed histopathologically. The expression levels of inflammatory cytokines and chemokines were measured using ELISA and RT-qPCR, respectively. Additionally, the interaction of biomacromolecules was detected through co-immunoprecipitation (Co-IP) and RNA immunoprecipitation (RIP). RESULTS: MLN4924 could attenuate IL-17A-induced inflammation. In the in vivo studies, MLN4924 treatment improved inflammatory responses, diminished immune cell infiltration and tissue fibrosis, and reduced the secretion of various inflammatory cytokines in serum, including IL-1ß, IL-6, TNF-α, and MCP-1. In vitro experiments further corroborated these findings, showing that MLN4924 treatment reduced the secretion and transcription of pro-inflammatory factors, particularly MCP-1. Mechanistically, we confirmed that MLN4924 promoted Act1 ubiquitination degradation and disrupted Act1's interaction with IL-17R, thereby impeding the formation of the IL-17R/Act1/TRAF6 complex and subsequent activation of TAK1, c-Jun, and p65. Moreover, MLN4924 interfered with Act1's binding to mRNA, resulting in mRNA instability. CONCLUSIONS: In conclusion, MLN4924 effectively alleviated inflammatory symptoms in EAM by disrupting the interaction between IL and 17R and Act1, thereby reducing Act1-mediated mRNA stability and resulting in decreased expression of pro-inflammatory factors.
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Proteínas Adaptadoras Transductoras de Señales , Enfermedades Autoinmunes , Ciclopentanos , Citocinas , Miocarditis , Pirimidinas , Estabilidad del ARN , Animales , Miocarditis/tratamiento farmacológico , Miocarditis/inmunología , Miocarditis/metabolismo , Pirimidinas/farmacología , Pirimidinas/uso terapéutico , Enfermedades Autoinmunes/tratamiento farmacológico , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Ciclopentanos/farmacología , Ciclopentanos/uso terapéutico , Ratones , Estabilidad del ARN/efectos de los fármacos , Masculino , Citocinas/metabolismo , Interleucina-17/metabolismo , Modelos Animales de Enfermedad , Humanos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , ARN Mensajero/metabolismo , Ratones Endogámicos BALB CRESUMEN
The pathogenesis of glomerular diseases is strongly influenced by abnormal extracellular matrix (ECM) deposition in mesangial cells. Dipeptidyl peptidase IV (DPPIV) enzyme family contains DPP8 and DPP9, which are involved in multiple diseases. However, the pathogenic roles of DPP8 and DPP9 in mesangial cells ECM deposition remain unclear. In this study, we observed that DPP8 and DPP9 were significantly increased in glomerular mesangial cells and podocytes in CKD patients compared with healthy individuals, and DPP9 levels were higher in the urine of IgA nephropathy (IgAN) patients than in control urine. Therefore, we further explored the mechanism of DPP8 and DPP9 in mesangial cells and revealed a significant increase in the expression of DPP8 and DPP9 in human mesangial cells (HMCs) following TGF-ß1 stimulation. Silencing DPP8 and DPP9 by siRNAs alleviated the expression of ECM-related proteins including collagen â ¢, collagen â £, fibronectin, MMP2, in TGF-ß1-treated HMCs. Furthermore, DPP8 siRNA and DPP9 siRNA inhibited TGF-ß1-induced phosphorylation of Smad2 and Smad3, as well as the phosphorylation of Akt in HMCs. The findings suggested the inhibition of DPP8/9 may alleviate HMCs ECM deposition induced by TGF-ß1 via suppressing TGF-ß1/Smad and AKT signaling pathways.
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Dipeptidasas , Células Mesangiales , Humanos , Células Cultivadas , Colágeno/metabolismo , Dipeptidasas/metabolismo , Matriz Extracelular/metabolismo , Células Mesangiales/metabolismo , Células Mesangiales/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Interferente Pequeño , Transducción de Señal , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
PURPOSE: The opioid crisis resulting from its use disorder and overdose poses additional challenges for cancer pain management. The American Society of Clinical Oncology Practice Guideline recommends acupuncture therapy for the management of adult cancer-related pain (CRP), but the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) on CRP remains uncertain. METHODS: This 5-week prospective randomized clinical trial was conducted at 2 hospitals in China, and participants with CRP receiving chronic opioid therapy were randomized 1:1 into two groups between December 2014 and June 2018. The true TEAS group underwent 15 sessions of TEAS treatments over 3 consecutive weeks, while the control group received sham stimulation. The primary outcome was the numerical rating scale (NRS) score in the past 24h at week 3. The secondary outcomes included morphine equivalent daily dose, quality of life and adverse events. RESULTS: A total of 159 participants were included in the modified intention-to-treat population. The baseline characteristics were similar in both groups. The mean NRS scores were 0.98 points at week 3 in the true TEAS group and 1.41 points in the sham group, with the mean difference between groups of -0.43 points (P < 0.001; OR = 0.68, P < 0.05). The proportion of patients with NRS reduction more than thirty percentage at week 3 was 50.00% in the true TEAS group and 35.44% in the sham group (RD = 0.15, P > 0.05; RR = 1.41, P > 0.05). No significant difference in pain intensity between the two groups was observed during the follow-up period without TEAS intervention (week 4, OR = 0.83, P > 0.05; week 5, OR = 0.83, P > 0.05). The Karnofsky Performance Status value suggested that patients in the true TEAS group experienced an improved quality of life (Between-group differences: week 3, 3.5%, P < 0.05; week 4, 4.6%, P < 0.001; week 5, 5.6%, P < 0.001). CONCLUSIONS: The 3-week application of TEAS in patients with CRP receiving chronic opioid therapy resulted in a statistically significant reduction in pain scores, but the observed reduction was of uncertain clinical significance. The prolonged analgesic effect of TEAS was not confirmed in this trial. CLINICALTRIAL: GOV: ChiCTR-TRC-13003803.
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Dolor en Cáncer , Neoplasias , Estimulación Eléctrica Transcutánea del Nervio , Adulto , Humanos , Puntos de Acupuntura , Analgésicos Opioides/efectos adversos , Dolor en Cáncer/tratamiento farmacológico , Dolor en Cáncer/etiología , Morfina , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Manejo del Dolor , Estudios Prospectivos , Calidad de Vida , Estimulación Eléctrica Transcutánea del Nervio/métodosRESUMEN
BACKGROUND: Low back pain is a common complaint among adults, and moxibustion and acupuncture are commonly used treatments. In traditional theory, Weizhong (BL40) is a popular acupoint, as supported by the saying "Yao Bei Wei Zhong Qiu." However, the difference in efficacy between acupuncture and moxibustion remains unclear. Therefore, this trial will compare the thermal effects of acupuncture and moxibustion at BL40 and Chize point (LU5) in healthy adults to provide more objective evidence regarding the relationship between the lumbar and BL40. METHOD/DESIGN: The trial will use a two-by-two factorial design, randomly assigning 140 participants to four groups (acupuncture at Weizhong (BL40), acupuncture at Chize (LU5), moxibustion at Weizhong (BL40), and moxibustion at Chize (LU5)) at a ratio of 1:1:1:1. Each group will undergo a 30-minute intervention, with the primary outcome being mean temperature in the lumbar region at the last minute of the intervention period. Secondary outcomes include maximum lumbar temperature in the lumbar region at the last minute of the intervention, average lumbar temperature and average bladder meridian temperature at specific time points during and after the intervention, and scores on the warming sensation questionnaire. Data will be analyzed on an intention-to-treat basis. DISCUSSION: This study will be the first to compare the thermal effect difference in the lumbar area between acupuncture and moxibustion in healthy individuals. The findings of this study will provide new insights for the "Yao Bei Wei Zhong Qiu" theory of traditional Chinese medicine. TRIAL REGISTRATION: ClinicalTrials.gov, Trial number: NCT05665426. Registered on 26 December 2022.
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Terapia por Acupuntura , Moxibustión , Humanos , Adulto , Moxibustión/métodos , Puntos de Acupuntura , Región Lumbosacra , Temperatura , Terapia por Acupuntura/métodos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Objective: To study the clinical efficacy of nutritional intervention combined with muscle exercise on sarcopenia patients with femoral fracture. Methods: From January 2019 to January 2021, a total of 100 sarcopenia patients with femoral fracture were included in this study and were divided into a control group (routine postoperative care) and a research group (nutritional intervention and muscle exercise), 50 cases in each group. Primary clinical outcomes included sarcopenia-related indicators and functional independence assessed by activities of daily living scale (ADL). Secondary clinical outcomes included time of fracture healing and hospital stay, pain score as assessed by visual analogue scale (VAS), and nursing satisfaction. Results: Before the intervention, there was no significant difference in the indicators of sarcopenia and the indicators of functional independence assessed by ADL between the two groups (P > 0.05). After 3 months of intervention, the BMI, grip strength, calf circumference, pace, and body muscle rate of the patients in the research group were significantly higher than those in the control group (P < 0.05), while body fat rates were significantly lower than those in the control group (P < 0.05), and the capability of eating, walking, bathing, and doing housework in research group were all significantly higher than those in control group (P < 0.05). In addition, the time of fracture healing and hospital stay in research group were all significantly lower than those in control group (P < 0.05), and the VAS scores of the control group at each time point after intervention were significantly higher than those of the research group (P < 0.05). The nursing satisfaction of the patients in the research group was significantly higher than that in the control group (94.00% vs. 76.00%, P < 0.05). Conclusion: Nutritional intervention combined with muscle exercise can help improve sarcopenia symptoms and promote fracture recovery in patients with sarcopenic femoral fractures.
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Fracturas del Fémur , Sarcopenia , Humanos , Actividades Cotidianas , Proyectos Piloto , Resultado del Tratamiento , MúsculosRESUMEN
Myocarditis is defined as an inflammatory disease of the myocardium, and the autoimmune response specific to myocardium plays an important role in chronic myocarditis. Inhibiting myocardial-specific autoimmune response and inflammation is crucial to treat myocarditis. Myricetin is a plant-derived flavonoid in nature which has potent anti-inflammatory and cardiovascular protective properties. However, the pharmacological effect of myricetin in autoimmune myocarditis is undefined. It is necessary to investigate the role and potential mechanisms of myricetin in autoimmune myocarditis. Therefore, purified cardiac myosin was subcutaneously injected to mice to establish the experimental autoimmune myocarditis (EAM) model. Myricetin was solubilized in normal saline and administered everyday by gavage from the day of immunization. After 21 days of treatment, it was found that myricetin significantly alleviated myocardial injury in EAM mice. The serum anti-cardiac myosin antibody, immunoglobulin (Ig) G, IgM levels and the proportion of T helper 17 (Th17) cells were decreased and the proportion of regulatory T (Treg) cells was increased with the treatment of myricetin in EAM mice. The myosin-specific T cell proliferation was inhibited by myricetin. Meanwhile, myricetin suppressed the expressions of monocyte chemoattractant protein-1 (MCP-1), phospho (p)-p65, p-c-Jun and Act1/TRAF6/TAK1 in H9C2 cells and myocardial tissues of EAM mice. These results revealed that myricetin inhibited the autoimmune response specific to myocardium and the expression of MCP-1 in cardiomyocytes, which suggested that myricetin ameliorated autoimmune myocarditis by modulating immune response and the expression of MCP-1. Therefore, myricetin may be a promising therapeutic strategy for autoimmune myocarditis.
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Enfermedades Autoinmunes , Miocarditis , Animales , Ratones , Enfermedades Autoinmunes/tratamiento farmacológico , Quimiocina CCL2/metabolismo , Modelos Animales de Enfermedad , Flavonoides/farmacología , Flavonoides/uso terapéutico , Flavonoides/metabolismo , Inmunidad , Miocarditis/tratamiento farmacológico , Miocarditis/metabolismo , Miocardio/metabolismo , Miosinas/metabolismoRESUMEN
Osteoarthritis (OA) is a joint disorder that is associated with chondrocyte damage under inflammatory environment. Calycosin is an astragalus extract with potential anti-inflammatory and anti-tumor activities. The purpose of this research is to explore the activity and mechanism of calycosin in interleukin-1beta (IL-1ß)-induced chondrocyte injury. In the present study, the targets of calycosin and OA were analyzed according to HERB, DisGeNet, String, GO terms, and KEGG pathway enrichment assays. Human primary chondrocytes were treated with calycosin, and stimulated with IL-1ß. Cell viability was detected by CCK-8 assay. Cell apoptosis was investigated by flow cytometry, and caspase-3 activity analyses. Inflammation was analyzed according to inflammatory cytokines levels by enzyme-linked immunosorbent assay (ELISA). The proteins associated with extracellular matrix (ECM) degradation and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/forkhead box O1 (FoxO1) signaling pathways were measured using Western blotting. The results showed that total of 25 overlapping targets of calycosin against OA were predicted. These targets might drive the FoxO pathway. Calycosin alone induced little cytotoxicity to chondrocytes, and it alleviated IL-1ß-induced viability inhibition, cell apoptosis, inflammatory cytokine secretion, and ECM degradation in chondrocytes. Calycosin repressed IL-1ß-induced activation of the PI3K/AKT/FoxO1 signaling. Activation of the PI3K/AKT/FoxO1 signaling mitigated the suppressive effect of calycosin on chondrocyte apoptosis, inflammation, and ECM degradation induced by IL-1ß. As a conclusion, calycosin prevents IL-1ß-induced chondrocyte apoptosis, inflammation, and ECM degradation through inactivating the PI3K/AKT/FoxO1 pathway.
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Condrocitos , Osteoartritis , Apoptosis , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/farmacología , Humanos , Inflamación/patología , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacología , Isoflavonas , Osteoartritis/patología , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasa/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Myocarditis is a kind of myocardial inflammatory infiltration disease. Many interventions are not effective in the treatment of myocarditis because the mechanism of myocarditis has not been elucidated. Previous studies have found that interleukin-17 (IL-17) could stimulate the expression of monocyte chemokine protein 1 (MCP-1) and mediate myocardial inflammatory infiltration. This study aimed to explore the role of Act1/TRAF6/TAK1 cascade in IL-17-induced MCP-1 expression based on a well-designed experimental autoimmune myocarditis (EAM) model. It was found that IL-17 could stimulate the expression of MCP-1 by activating Act1/TRAF6/TAK1 cascade in EAM. The expression of Act1, TRAF6 and TAK1 followed downregulation by the application of IL-17 antibody. Additionally, myocardial inflammatory cell infiltration was observably alleviated by interfering TAK1 with TAK1 siRNA, and both MCP-1 mRNA and protein expression followed downregulation. This study suggested that IL-17 could activate the Act1/TRAF6/TAK1 pathway to upregulate MCP-1 expression in the EAM, and will offer a new perspective for the study on the mechanism of myocarditis.
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Enfermedades Autoinmunes , Miocarditis , Enfermedades Autoinmunes/genética , Quimiocinas/metabolismo , Conexina 43/metabolismo , Humanos , Interleucina-17/metabolismo , Quinasas Quinasa Quinasa PAM/metabolismo , Monocitos/metabolismo , Miocarditis/genética , Fragmentos de Péptidos/metabolismo , Factor 6 Asociado a Receptor de TNF/metabolismoRESUMEN
Abnormal expression of microRNAs (miRNAs) is closely associated with a diverse of important biological processes, such as metastasis, myocardial ischemia and progression. Development of a facile and enzyme-free method for sensitive miRNA detection remains a huge challenge. Herein, we proposed a cross-catalytic circuit for trace miRNA detection by facilely integrating hairpin catalytic reaction (HCR) and DNAzyme biocatalyst through an ingenious feedback loop. The DNAzyme functional part was originally grafted in the designed hairpin structure probes, which would be released from hairpin structure probe and induce subsequent signal amplification after the recognition of target miRNA and the formation of double-strand DNA products. Through the dual signal amplification, the method exhibited a favorable detection sensitivity with a low of detection of 56 fM. These two indispensable catalytic reactions play vital roles in executing high-performance signal amplification, as demonstrated experimentally and theoretically.
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ADN CatalíticoRESUMEN
BACKGROUND: Dyspnea is a multidimensional experience similar to pain and is one of the most common clinical presentations in patients with respiratory diseases. Accurately evaluating the experience of dyspnea allows nurses and physicians to deliver better medical services to patients. The multidimensional dyspnea profile emphasizes the psychosocial factors of dyspnea and assesses immediate discomfort, sensory qualities, and the emotional responses of patients with dyspnea. At present, the validity, reliability, and test-retest reliability of the multidimensional dyspnea profile in patients with respiratory diseases in China are unclear. OBJECTIVES: The aim of this study was to investigate the validity, reliability, and test-retest reliability of the Chinese version of the multidimensional dyspnea profile and to assess the convergent validity between the Chinese version of the multidimensional dyspnea profile and the modified Medical Research Council Dyspnea Scale. METHODS: The factorial construct, intraclass correlations, internal consistency, and convergent validity of the Chinese version of the multidimensional dyspnea profile was evaluated using data from 231 inpatients with dyspnea from the respiratory department of a hospital. In the principal component analysis stage, 131 inpatients were evaluated. In the test-retest reliability analysis stage, 50 out of the 131 patients responded to the questionnaire again. In the confirmatory factor analysis, 100 inpatients from an independent sample were assessed. RESULTS: The principal component analysis showed that the Chinese version of the multidimensional dyspnea profile had a two-factor structure: the immediate perceptual-related problem factor (6 items) and the emotional response-related problem factor (5 items). The convergent validity between the Chinese version of the multidimensional dyspnea profile and the modified Medical Research Council Dyspnea Scale was significant and acceptable based on the average variance extracted (r = .56, p < .001). The confirmatory factor analysis revealed a good model fit and provided support for the construct validity of the Chinese version of the multidimensional dyspnea profile. Overall, the internal consistency and intraclass correlation coefficient of the Chinese version of the multidimensional dyspnea profile were good. CONCLUSION: The 11-item Chinese version of the multidimensional dyspnea profile has acceptable validity and reliability in patients with respiratory diseases in China. In the future, more studies should be performed to further explore its clinical application.
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An auxiliary isolation device of cupping therapy for cross-infection prevention is designed to reduce the disinfection steps and be against cross transmission. This device is composed of a disposable isolation unit made of fire proof plastic material and a disposable cup-mouth fixator made of elastic material. The disposable isolation unit includes two parts, the cup neck isolation unit and the inner isolation unit of fire cup. These two parts connect with the disposable cup-mouth fixator. All of those three sections of the device are center-connected ring-like structure. This device can well prevent the direct contact of fire cup with the patient's skin surface, characterized as safety protection, simple operation and saving time and manpower.
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Ventosaterapia , HumanosRESUMEN
BACKGROUND: Headache attacks severely impaired life quality and increase the economic burden of migraineurs. Electroacupuncture (EA) has been used worldwidely to treat several pain-related diseases including migraines. However, whether EA with low or high frequency exerts a distinct analgesic effect remains unknown and needs further study. METHODS/DESIGN: This study is a randomised, single-blinded, placebo-controlled trial with three parallel arms. A total of 144 migraine outpatients will be randomly allocated to the 2 Hz EA group, 100 Hz EA group and placebo control group. The duration of the trial is 20 weeks, including a 4-week-long baseline assessment period (weeks - 4-0), a 4-week-long treatment period (weeks 1-4) and a 12-week-long follow-up period (weeks 5-16). Twelve treatment sessions will be performed over a 4-week period (weeks 1-4). The primary outcome will be measured by the frequency of migraine attacks in the past 4 weeks at the end of week 4 post-randomisation. The secondary outcome will be measured by the frequency of migraine attacks in the past 4 weeks at the end of weeks 8, 12 and16 post-randomisation; number of days with migraine; dosage of ibuprofen; the scores of visual analogue scale (VAS); Self-Rating Anxiety Scale (SAS); Self-Rating Depression Scale (SDS); and Migraine Specific Quality of Life questionnaire (MSQ) in the past 4 weeks at the end of weeks 4, 8, 12 and 16 post-randomisation. Safety assessment, compliance and blinding evaluation will be carried out at the end of week 16 post-randomisation. DISCUSSION: The recruitment will be started on 1 June 2021 and expected to finish on 31 May 2023. We aimed to clarify the dominant frequency of EA on headache attacks in a migraineur. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-1800017259 . Registered on 20 July 2018.
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Electroacupuntura , Trastornos Migrañosos , Cefalea , Humanos , Trastornos Migrañosos/diagnóstico , Trastornos Migrañosos/terapia , Pacientes Ambulatorios , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
OBJECTIVE: To review systematically the effectiveness of acupuncture in treatment of chemotherapy-induced bone marrow suppression. METHODS: From the date of database establishment to April 1, 2020, the articles on randomized controlled trials of chemotherapy-induced bone marrow suppression were retrieved by computer from the following databases, i.e. PubMed, Cochrane central register of controlled trials (CENTRAL), EMbase, cumulative index to nursing & allied health literature (CINAHL), JBI database of systematic reviews and implementation reports, CNKI, Wanfang, VIP and SinoMed. Using RevMan5.3, Meta-analysis was conducted. With GRADEpro GDT, the evidence quality was evaluated. RESULTS: A total of 12 articles were included, 10 articles of which were analyzed by quantitative Meta-analysis. Compared with the control group, the improvements in the decrease of post-chemotherapy leukocyte (P<0.01, MD=0.88, 95%CI=[0.71, 1.05]) and platelet (P<0.01, MD=25.91, 95%CI=[16.86, 34.97]) were better in the observation group. The difference in reducing hemoglobin was not significant between the two groups (P>0.05, MD=2.19, 95%CI=[-1.22, 5.61]). Regarding the improvement in the decrease of post-chemotherapy neutrophile granulocyte (P=0.03, MD=0.40, 95%CI=[0.04, 0.77]) and erythrocyte (P=0.03ï¼MD=0.15ï¼95%CI=[0.01, 0.28]), Karnofsky score (P<0.01, MD=4.19, 95%CI=[3.40, 4.98]) and quality of life (QOL) score (P<0.01, MD=5.01ï¼95%CI=[1.61, 8.42]), the effects in the observation group were better than those in the control group. CONCLUSION: Acupuncture alleviates the decrease of leukocyte, platelet, neutrophile granulocyte and erythrocyte counts and improves the survival quality of patients with chemotherapy-induced bone marrow suppression.
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Terapia por Acupuntura , Antineoplásicos , Humanos , Antineoplásicos/efectos adversos , Médula Ósea , Calidad de VidaRESUMEN
To explore the protective mechanism of L-arginine against T-2 toxin-induced apoptosis in mouse Leydig cells, we investigated whether L-arginine can prevent T-2 toxin-induced apoptosis in mouse Leydig cells and explored the underlying mechanisms. Leydig cells were isolated and cultured with control, T-2 toxin (10 nM), L-arginine (0.25, 0.5, and 1.0 mM), and T-2 toxin (10 nM T-2 toxin) + L-arginine (0.25, 0.5, or 1.0 mM) for 24 h. Cells and supernatants were harvested to examine proliferation of the cells, the apoptosis rate, activity of caspase-3 and mitochondria, and the gene expression levels of Bcl-2, Bax, PARP, and caspase-3. Results showed that proliferation and mitochondrial activity of Leydig cells were inhibited by administration of T-2 toxin. Bcl-2 gene expression levels was decreased, while the gene expression levels of Bax and PARP were increased, which could trigger mitochondria-mediated apoptosis, activate downstream caspase-3, and then increased caspase-3 at both activity and gene expression levels. The expression of the Bcl-2 gene was upregulated and the expression of Bax, caspase-3, and PARP gene were downregulated when L-arginine was added to the cultured cells. The results of this study showed that L-arginine could block T-2 toxin-induced apoptosis in mouse Leydig cells by regulating specific intracellular death-related pathways.
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Apoptosis/efectos de los fármacos , Arginina/farmacología , Células Intersticiales del Testículo/efectos de los fármacos , Sustancias Protectoras/farmacología , Toxina T-2/farmacología , Animales , Caspasa 3/biosíntesis , Proliferación Celular , Células Cultivadas , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Mitocondrias/efectos de los fármacos , Proteínas de Neoplasias , Poli(ADP-Ribosa) Polimerasa-1/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteína X Asociada a bcl-2/biosíntesisRESUMEN
The testosterone levels decreased by T-2 toxin in mouse Leydig cells were reported previously. It is not known, however, whether l-arginine improves the situation and what's the mechanism. Leydig cells were isolated and cultured with control, 10â¯nM T-2 toxin, 0.25, 0.5 or 1.0â¯mM l-arginine, and 10â¯nM T-2 toxin supplemented with 0.25, 0.5 or 1.0â¯mM l-arginine for 24â¯h. Cells and supernatants were collected to detect the mRNA expression and activities of P450scc (cholesterol side-chain cleavage enzyme), 3ß-HSD-1 (3ß-hydroxysteroid dehydrogenase/isomerase-1) and StAR (steroidogenic acute regulatory protein). Results revealed that l-arginine increased the testosterone levels declined by T-2 toxin and up-regulated the activities and mRNA expression of P450scc, 3ß-HSD-1 and StAR down-regulated by T-2 toxin in Leydig cells. Therefore, we concluded that l-arginine ameliorated the testosterone levels decreased by T-2 Toxin via regulating the mRNA expression and activities of P450scc, 3ß-HSD-1 and StAR in mouse Leydig cells.
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Arginina/farmacología , Células Intersticiales del Testículo/metabolismo , Sustancias Protectoras/farmacología , Toxina T-2/toxicidad , Testosterona/biosíntesis , Animales , Células Cultivadas , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/metabolismo , Masculino , Ratones , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Transcutaneous electrical acupoint stimulation (TEAS), which is also known as acupuncture-like transcutaneous electrical nerve stimulation (TENS), has been widely used in acute or chronic pain. However, previous research has not demonstrated that TEAS is effective for cancer-related pain. Opioid drugs are strongly recommended for treating cancer-related pain, but opioid-induced immunosuppression is still the most intractable drug-induced medical problem. Evaluating the efficacy and potential advantage of TEAS combined with opioid drugs in moderate and severe cancer-related pain in China is important because such studies are lacking. METHODS/DESIGN: This trial is a multicenter, prospective randomized controlled clinical trial. In total, 160 patients who were enrolled from two hospitals in the Zhejiang Province (China) will be randomly allocated into two groups: a TEAS group and sham TEAS group without acupoint electrical stimulation. Both groups will receive a 21-day interval of chemotherapy and conventional cancer pain therapy. Fifteen treatment sessions will be performed over a three-week period. The primary outcomes will be measured by changes in the Numerical Rating Scale (NRS) scores and equivalent dosage of morphine at baseline, three weeks of treatment and one two-week follow-up. The secondary outcome measures include cellular immunity function, life quality assessment, opioids side effects assessment, and safety and compliance evaluation. DISCUSSION: This trial is expected to clarify whether TEAS is effective for cancer-related pain. These results demonstrate the advantage of TEAS combined with opioid drugs on improving immune function and decreasing opioid induced side effects. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-13003803 . Registered on 27 August 2013.
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Puntos de Acupuntura , Analgésicos Opioides/uso terapéutico , Dolor en Cáncer/terapia , Estimulación Eléctrica Transcutánea del Nervio/métodos , Adolescente , Adulto , Anciano , Analgésicos Opioides/efectos adversos , Dolor en Cáncer/diagnóstico , Dolor en Cáncer/fisiopatología , Dolor en Cáncer/psicología , China , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Dimensión del Dolor , Estudios Prospectivos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Tiempo , Estimulación Eléctrica Transcutánea del Nervio/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
Background: Since most internal medicine nurses work with chronic obstructive pulmonary disease (COPD) patients daily, their ability to meet the needs of COPD patients is an important issue. Our study aimed to assess COPD-related knowledge in internal medicine nurses. Methods: A descriptive cross-sectional study including 175 participants was conducted to investigate COPD-related knowledge levels among internal medicine nurses in a large top-ranked tertiary hospital in China. The Bristol COPD Knowledge Questionnaire (BCKQ) was used to test COPD-related knowledge levels in the participants. Results: Overall BCKQ score for all nurses in this study was 35.76 ± 5.49. In comparison with non-respiratory nurses, the overall score among respiratory nurses was significantly higher (39.01 ± 3.95 vs 33.32 ± 5.23, p < 0.001). The mean scores for four topics (epidemiology, breathlessness, oral steroids, and inhaled steroids) were less than 3 among both respiratory and non-respiratory nurses. Subgroup analysis of specialist respiratory wards showed that nurses in the chronic airway disease ward had the highest overall knowledge score (40.47 ± 4.03). Linear regression analysis demonstrated that the overall BCKQ score was significantly related to the population of nurses (ß coefficient = 3.016, 95% confidence interval [CI]: 0.953-5.079, p < 0.01), education (ß coefficient = 4.710, 95% CI: 1.979-7.440, p < 0.01) and previous rotation in respiratory wards (ß coefficient = 3.871, 95% CI: 1.776-5.967, p < 0.001). Conclusion: Internal medicine nurses at this tertiary hospital showed deficits in COPD-related knowledge. Appropriate and systematic education about COPD knowledge and strengthening rotation among different wards are necessary for improving COPD-related knowledge levels among internal medicine nurses.
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Enfermeras Especialistas , Evaluación en Enfermería , Enfermedad Pulmonar Obstructiva Crónica/enfermería , China , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Medicina Interna/educación , Masculino , Enfermeras Especialistas/educación , Enfermeras Especialistas/normas , Evaluación en Enfermería/métodos , Evaluación en Enfermería/normas , Investigación en Educación de Enfermería/estadística & datos numéricos , Mejoramiento de la Calidad , Centros de Atención Terciaria/estadística & datos numéricosRESUMEN
OBJECTIVE: To estimate the benefits of non-invasive ventilation (NIV) used immediately after planned postextubation in patients with chronic respiratory disorders. METHODS: Cochrane Library, PubMed, the Chinese BioMedical Literature Database of clinical trials (CBD) and Embase were searched for pertinent studies by 2 trained investigators. Pooled odds ratios and 95% confidence intervals (CIs) were calculated by employing both fixed-effects and random-effects models. RESULTS: Eight studies enrolling 736 patients were included in the meta-analysis. Compared with general oxygen therapy, NIV used immediately after planned extubation in patients with chronic respiratory disease reduced the reintubation rate (p=0.02), ventilator-associated pneumonia (VAP) incidence rate (p=0.000), and ICU mortality (p=0.002) and increased the level of PO2 (p=0.03). CONCLUSION: Non-invasive ventilation used immediately after planned extubation seems to be advantageous for decreasing the reintubation rate, VAP incidence, and ICU death rate in patients with chronic respiratory disease.
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Mortalidad Hospitalaria , Ventilación no Invasiva , Enfermedades Respiratorias/terapia , Extubación Traqueal , Enfermedad Crónica , Humanos , Unidades de Cuidados Intensivos , Intubación Intratraqueal , Neumonía Asociada al Ventilador/prevención & controlRESUMEN
BACKGROUND: MircoRNAs(miRNAs) are short, endogenously non-coding RNAs. The abnormal expression of miRNAs may be valuable for the diagnosis and treatment of tumors. METHODS: To screening the special miRNAs in gastric carcinoma, expression level of miRNAs in gastric carcinoma and normal gaster samples were detected by miRNA gene chip. Then, the expressions of miR-9 and miR-433 in gastric carcinoma tissue and SGC7901 cell line were validated by qRT-PCR. GRB2 and RAB34, targets of miR-433 and miR-9 respectively, were detected by Western blot. RESULTS: We found 19 miRNAs and 7 miRNAs were down-regulated and up-regulated respectively. Compared with normal gaster samples, our data showed that miR-9 and miR-433 were down-regulated in gastric carcinoma. Meanwhile, we also found that miR-433 and miR-9 regulated the expression levels of GRB2 and RAB34 respectively. CONCLUSION: Our data show miR-9 and miR-433 was down-regulated in gastric carcinoma. The targets of miR-433 and miR-9 were tumor-associated proteins GRB2 and RAB34 respectively. This result provided the related information of miRNAs in gastric carcinoma.