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OBJECTIVE: To explore the role of nuclear factor E2 related factor 2 (Nrf2) / heme oxygenase (HO-1) signal pathway in electroacupuncture (EA) induced improvement of acute myocardial ischemia (AMI) and its relationship with ferroptosis in rats. METHODS: Male SD rats were randomly and equally divided into sham operation, model, EA and EA+ML385 (inhibitor of Nrf2) groups (n=8). The rat model of AMI was established by ligating the descending anterior branch of the left coronary artery. EA (2 Hz/100 Hz) was applied to bilateral "Shenmen"(HT7) and "Tongli"(HT5) for 20 min, once daily for 7 days. The electrocardiogram (ECG) of standard â ¡ (ECG ST) lead and heart rate (HR) in each group was recorded and analyzed before and after modeling and after treatment by using PowerLab physiological recorder system. Histopathological changes of myocardial tissue were observed by H.E. staining, and the ultrastructure of myocardiocytes of cardiac apical tissue was observed under transmission electron microscope. The contents of Fe2+ and glutathione (GSH) in the myocardial tissue were measured by chromato-metry. The protein expression levels of Nrf2, HO-1, glutathione peroxidase 4 (GPX4), ferritin heavy chain polypeptide 1 (FTH1) and long chain acyl CoA synthase 4 (ACSL4) in the myocardial tissue were detected by Western blot. RESULTS: Compared with the sham operation group, the HR, ECG ST, Fe2+ content, expression levels of Nrf2, HO-1, FTH1 and ACSL4 proteins in myocardial tissues were significantly increased (P<0.01), while GSH content and GPX4 protein expression considerably decreased (P<0.01) in the model group. Compared with the model group, both EA and EA+ML385 groups had an obvious decrease in HR, Fe2+ content, and ACSL4 levels (P<0.01), and an increase in the expression levels of GPX4 and FTH1 proteins (P<0.01), EA (rather than EA+ML385) effectively down-regulated ECG ST, and up-regulated GSH, Nrf2 and HO-1 (P<0.01), whereas EA+ML385 apparently down-regulated expression levels of Nrf2 and HO-1 (P<0.01). It shows that ML385 pronouncedly weaken the effects of EA in slowing down ECG ST and HR, down-regulating Fe2+ content and ACSL4 expression (P<0.01), up-regulating GSH content, Nrf2, HO-1, GPX4 and FTH1 expressions (P<0.01). H.E. staining showed disordered arrangement and hyperplasia of myocardiocytes, enlarged myocardial fiber gap, agglomerated and deeply stained myoplasma, and some broken myocardial fibers with irregular mass and local tissue fibrosis in the model group, which was relatively milder in both EA and EA+ML385 groups. Compared with the sham operation group, the model group showed decreased mitochondrial atrophy, increased membrane density, and disappearance or reduction of cristae in myocardial cellsï¼which was improved in the EA group. CONCLUSION: EA of HT7 and HT5 has a protective effect on ischemic myocardium in rats, which may be related to its effects in reducing oxidative stress by regulating Nrf2/HO-1 signaling pathway, and inhibiting "iron death" of myocardial cells.
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Electroacupuntura , Ferroptosis , Isquemia Miocárdica , Ratas , Masculino , Animales , Factor 2 Relacionado con NF-E2/genética , Ratas Sprague-Dawley , Ferroptosis/genética , Ápice del Diente , Isquemia Miocárdica/genética , Isquemia Miocárdica/terapia , Transducción de SeñalRESUMEN
OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of myocardial protein kinase B (Akt) and mammalian target of rapamycin (mTOR) in acute myocardial ischemia (AMI) rats. METHODS: Thirty male SD rats were randomly divided into control, model and EA groups (n=10 in each group). The AMI model was established by occlusion of the descending anterior branch (DAB) of the left coronary artery. EA (2 Hz, 1-2 mA) was applied to bilateral "Shenmen" (HT7) and "Tongli" (HT5) for 20 min, once daily for consecutive 7 days. The electrocardiogram (ECG) of nape-xiphoid lead was recorded for assessing changes of myocardial ischemia. Histopathologic changes of the ischemic myocardial tissue were observed after H.E. staining and ultra-microstructural changes of cardiomyocytes observed by transmission electron microscopy (TEM). The expression levels of Akt, phosphorylated-Akt (p-Akt), mTOR and phosphorylated-mTOR (p-mTOR) in the myocardium were detected by Western blot, followed by calculating the ratios of p-Akt/Akt and p-mTOR/mTOR. RESULTS: Following ligature of DAB, the ECG-ST level was significantly increased in the model group in comparison with the control group (P<0.01). At 30 min after treatment, the ECG-ST level decreased significantly compared with the model group (P<0.01). At the end of the 7-day treatment period, the ECG-ST level increased compared with the model group (P<0.05). The levels of myocardial p-Akt and p-mTOR protein expression, and the ratios of p-Akt/Akt and p-mTOR/mTOR were significantly lower in the model group than those in the control group (P<0.01), and considerably increased in the EA group than in the model group (P<0.01). No significant differences were found among the three groups in the expression levels of Akt and mTOR proteins (P>0.05). Outcomes of H.E. staining and TEM showed damage of mitochondria and occurrence of a large number of autophagosomes in myocardiocytes in the model group, which was milder in the EA group. CONCLUSION: EA at HT5 and HT7 can improve AMI in AMI rats, which may be related to its effect in facilitating Akt/mTOR signaling.
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Electroacupuntura , Meridianos , Isquemia Miocárdica , Puntos de Acupuntura , Animales , Masculino , Isquemia Miocárdica/genética , Isquemia Miocárdica/terapia , Miocitos Cardíacos , Proteínas Proto-Oncogénicas c-akt/genética , Ratas , Ratas Sprague-Dawley , Serina-Treonina Quinasas TOR/genéticaRESUMEN
Background: Provisional stenting using drug-eluting stents (DES) has become the preferred treatment for coronary bifurcation lesions (CBLs). We performed a meta-analysis to compare the effects of side branch (SB) protection using a drug-coated balloon (DCB) versus an uncoated balloon (UCB) during the procedure. Methods: Relevant randomized and nonrandomized studies were identified by searching the Medline, Embase, Web of Science, Wanfang, and CNKI databases. We used a random-effect model to pool the data by incorporating the heterogeneity between the included studies. Results: Overall, 803 patients with CBLs treated with provisional stenting using DES were included from seven studies. With a follow-up duration of 6 to 12 months, SB protection with DCB was associated with a lower degree of postoperative diameter stenosis (mean difference (MD): -11.35%, 95% confidence interval (CI): -14.17 to-8.53, p < 0.001; I2 = 0%) and less late lumen loss (MD: -0.19 mm, 95% CI:-0.28 to-0.10, p < 0.001; I2 = 69%) of SB compared to those with UCB. Moreover, SB protection with DCB was associated with reduced risks of target lesion revascularization (risk ratio [RR]: 0.49, 95% CI: 0.27 to 0.88, p = 0.02; I2 = 0%) and major adverse cardiovascular events (RR: 0.42, 95% CI: 0.27 to 0.66, p < 0.01; I2 = 0%). Subgroup analysis according to the study design showed similar results. Conclusions: For patients with CBL treated with provisional stenting using DES, SB protection with DCB was associated with better angiographic and clinical outcomes than those with UCB.
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Angioplastia Coronaria con Balón , Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Humanos , Angioplastia Coronaria con Balón/efectos adversos , Angioplastia Coronaria con Balón/métodos , Angiografía Coronaria , Resultado del Tratamiento , Corazón , Enfermedad de la Arteria Coronaria/terapia , StentsRESUMEN
OBJECTIVE: To observe the effect of long-term inhalation of moxa-smoke on olfactory epithelial cells in rats, in order to explore the safety of moxa-smoke inhalation (MSI). METHODS: A total of 32 SD rats (half male and half female) were randomly divided into 4 groups: normal, low concentration (LCMSI), medium concentration (MCMSI) and high concentration (HCMSI), with 8 rats in each group. Rats of the LCMSI, MCMSI and HCMSI groups were put into closed boxes which were filled with ignited moxa stick-released smoke at concentrations of (0.11±0.05)mg/m3, (0.23±0.05) mg/m3 and (0.53±0.05)mg/m3, respectively. The treatment was given 4 h each time, twice a day for 90 days. Rats of the normal group were fed routinely. The rats' general state and behavior (including fur appearance, activities in cage, response to external stimuli, spirit, stool, diet and water drinking) were recorded, and the olfactory function was assessed by using latency of finding the buried food pellet (BFP) test. The number of apoptotic olfactory epithelial cells was counted after terminal labeling (TUNEL), and the proliferation of basal cells of the nasal mucosa was detected by BrdU incorporation immunohistochemical technique. RESULTS: The latency of BFP was significantly longer in the MCMSI and HCMSI groups than in the normal and LCMSI groups (P<0.01), and had no significant differences between the LCMSI and normal groups, and between the MCMSI and HCMSI groups (P>0.05). The numbers of the apoptotic olfactory epithelial cells and proliferative basal cell in the nasal mucus tissue were markedly more in the LCMSI, MCMSI and HCMSI groups than in the normal group (P<0.01, P<0.05), and obviously more in the MCMSI and HCMSI groups than in the LMCMSI group (P<0.01), and apparently more in the HCMSI group than in the MCMSI group (P<0.01). The general state observation showed that in the first 45 days, only yellowish fur and water intake increase were seen in rats of the 3 moxa smoke inhalation groups, while no obvious changes in rats of the LCMSI group, and decrease in activities, being sensitive to external stimulation and fiddle-footed, and lower spirit in rats of the MCMSI and HCMSI groups in comparison with rats of the normal group after 90 day's MSI. CONCLUSION: Long-term inhalation of medium and high concentrations of moxa smoke may cause a reduction of the olfactory sensitivity and an increase of apoptosis of olfactory epithelial cells and proliferation of basal cells.
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Moxibustión , Humo , Animales , Apoptosis , Células Epiteliales , Femenino , Masculino , Ratas , Ratas Sprague-Dawley , Regeneración , Humo/efectos adversosRESUMEN
PTEN/AKT signaling plays pivotal role in myocardial ischemia reperfusion injury (MIRI), and miRNAs are involved in the regulation of AKT signaling. This study was designed to investigate the interaction between miR-129 and PTEN in MIRI. A MIRI rat model and a hypoxia reoxygenation (H/R) H9C2 cell model were constructed to simulate myocardial infarction clinically. TTC staining, creatine kinase (CK) activity, TUNEL/Hoechst double staining, Hoechst staining and flow cytometer were used for evaluating myocardial infarction or cell apoptosis. miR-129 mimic transfection experiment and luciferase reporter gene assay were conducted for investigating the function of miR-129 and the interaction between miR-129 and PTEN, respectively. Real-time PCR and western blotting were performed to analyze the gene expression. Compared to the control, MIRI rats presented obvious myocardial infarction, higher CK activity, increased expression of caspase-3 and PTEN, decreased expression of miR-129, and insufficient AKT phosphorylation. Consistently, H/R significantly increased the apoptosis of H9C2 cells, concomitant with the downregulation of miR-129, upregulation of PTEN and caspase-3, and insufficient phosphorylation of AKT, while miR-129 mimic obviously inhibited the expression of PTEN and caspase-3, increased the AKT phosphorylation, and decreased the cell apoptosis. Additionally, miR-129 mimic obviously decreased the relative luciferase activity in H9C2 cells. To our best knowledge, this study firstly found that the low expression of miR-129 accelerates the myocardial cell apoptosis by directly targeting 3'UTR of PTEN. miR-129 is an important biomarker for MIRI, as well as a potential therapy target.
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MicroARNs/genética , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos/patología , Fosfohidrolasa PTEN/metabolismo , Animales , Apoptosis/fisiología , Células Cultivadas , Modelos Animales de Enfermedad , Masculino , MicroARNs/metabolismo , Infarto del Miocardio/genética , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/metabolismo , Fosfohidrolasa PTEN/genética , Ratas , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
OBJECTIVE: To observe the effect of long-term moxa smoke exposure of different concentrations on olfactory function in rats, and provide experimental basis of safety study of moxa smoke produced by moxibustion. METHODS: Forty SD rats were randomly divided into a normal control group, a low-concentration moxa smoke group, a moderate-concentration moxa smoke group and a high-concentration moxa smoke group, 10 rats in each one. The rats in the moxa smoke groups were put into three plexiglass moxibustion boxes with different moxa smoke concentrations, 4 hours per times, twice a day for 90 days. The general state of rats was evaluated before and during the experiment. After the intervention, the olfactory function was evaluated by two-bottle experiment (TBE); the morphology of nasal mucosa was observed by HE staining; the apoptosis of olfactory epithelial cells in nasal mucosa was detected by TUNEL method; the serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by ELISA method. RESULTS: In the late stage of moxa smoke exposure (45-90 days into intervention), the behavioral activity of rats in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was weaker than that in the normal control group, and their response to stimulation was strong, and their mental state was worse. After intervention, the drinking rate of vinegar-water mixture in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was higher than that in the normal control group and the low-concentration moxa smoke group (P<0.01). The hierarchical structure of nasal mucosa in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was unclear, disordered, necrotic and inflammatory cell infiltration was serious; the number of apoptotic cells in olfactory epithelium of nasal mucosa in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was more than that in the normal control group and the low-concentration moxa smoke group (P<0.01), that in the high-concentration moxa smoke group was more than the moderate-concentration group (P<0.01). The serum levels of IL-1, IL-6 and TNF-α in the low-concentration moxa smoke group, the moderate-concentration moxa smoke group and the high-concentration moxa smoke group were higher than the normal control group (P<0.01), and those in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group were higher than the low-concentration moxa smoke group (P<0.01), and those in the high-concentration moxa smoke group were higher than moderate-concentration moxa smoke group (P<0.01). CONCLUSION: The long-term exposure to low, moderate and high concentrations of moxa smoke could cause pathological changes in nasal mucosa and increase the serum levels of IL-1, IL-6 and TNF-α; the moderate and high concentrations of moxa smoke exposure could cause a series of damage to olfactory function and reduce olfactory sensitivity in rats.
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Interleucina-6 , Factor de Necrosis Tumoral alfa , Animales , Interleucina-1 , Ratas , Ratas Sprague-Dawley , Humo/efectos adversosRESUMEN
OBJECTIVE: To observe the impact of moxa-stick with different diameters and at different distances on skin temperature in local "Zusanli"(ST36) region, so as to select suitable specifications for moxibustion. METHODS: A total of 120 male SD rats were randomly divided into diameters of 0.5, 0.9, 1.2 and 1.8 cm, and distances of 1, 2, 3, 4 and 5 cm groups, with 6 rats in each group. Moxa-stick with different diameters mentioned above was applied to the right ST36 (right hind limb) for 10 min every time at different distances (between the ignited moxa-stick tip and the skin) mentioned above, and the left ST36 was used as the control point. The skin temperature was detected by using an infrared thermometer. RESULTS: After application of moxibustion to ST36 region, the skin temperature was increased gradually along with the increased diameter of moxa-sticks and decreased along with the increased distance from the ignited moxa-stick tip to the skin. There were no significant changes in the skin temperature of the left control acupoint ST36. The skin temperature was below 40 â, between 43 to 55 â, over 43â and between 43 to 61 â, when the moxa-stick was 0.5 cm, 0.9 cm, 1.2 cm and 1.8 cm in diameter, and was kept 1, 2, 3 and 3 to 5 cm away from the skin surface, respectively. When the moxa-stick with a diameter of 1.8 cm was kept at a distance of 1 to 2 cm, the skin temperature reached 71 to 93 â to cause obvious local burn lesion. CONCLUSION: During moxibustion, the ignited moxa-sticks with diameters of 0.5, 0.9, 1.2 and 1.8 cm are suitable to be kept less than 1, 1 to 2, 2 to 3, and 3 to 5 cm away from the skin surface of ST36, respectively.
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Moxibustión , Puntos de Acupuntura , Animales , Masculino , Ratas , Ratas Sprague-Dawley , Piel , Temperatura CutáneaRESUMEN
In this study, a fully bio-based coating was constructed by layer-by-layer deposition of chitosan (CS) and ammonium phytate (AP), to obtain fire-safety and antibacterial cotton fabrics. With about 8% weight gains of CS/AP coatings, the treated cotton fabrics self-extinguished in the vertical burning test. The data obtained from cone calorimetry showed CS/AP/cotton had much lower smoke and heat production, which indicated the fire safety of the fabrics was significantly improved for the presence of CS/AP coatings. The flame-retardant mechanism of this system was finally proposed according to the analysis of gaseous products and char residues. What is more, CS/AP coatings had higher antibacterial activity in Gram-negative bacteria and did improve the tensile strength of cotton fabrics compared with AP coating. With its ease of operation and use of non-toxic chemicals, this fully bio-based coating can further offer a feasible flame-retardant and antibacterial solution of the inflammable natural fabrics.
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Compuestos de Amonio , Antibacterianos , Quitosano , Fibra de Algodón , Retardadores de Llama , Ácido Fítico , Textiles , Calorimetría , CalorRESUMEN
Small cell lung cancer (SCLC) is recognized as one of the most aggressive and fatal malignant tumors. No significant improvement has been made to prolong the survival of SCLC patients. This study aimed to examine the mutation status of K-Ras (KRAS) and phosphatase and tensin homolog (PTEN) in SCLC patients in order to identify potential therapeutic targets for SCLC. Nineteen primary SCLC tumor specimens were enrolled in the study. Direct sequencing was performed to detect the mutations of KRAS exon 3 and PTEN exon 7 in the specimens. Kaplan- Meier and Cox regression analysis was performed to determine the overall survival (OS) of these SCLC patients. KRAS exon 3 mutation was found in 4 (21%) SCLC patients, and PTEN exon 7 mutation in only 1 (5%) SCLC patient. Kaplan Meier analysis showed that clinical stage and brain metastasis were significantly associated with OS (both P<0.05), but neither KRAS exon 3 mutation nor PTEN exon 7 mutation was significantly associated with OS (P>0.05). Cox proportional hazards regression model indicated that extensive stage of disease was the only independent negative prognostic factor for OS in SCLC patients. In conclusion, KRAS exon 3 and PTEN exon 7 mutations had no significant impact on OS of SCLC patients. Further study is still necessary to validate the molecular profiles of SCLC.
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Neoplasias Encefálicas/genética , Neoplasias Pulmonares/genética , Mutación , Fosfohidrolasa PTEN/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Carcinoma Pulmonar de Células Pequeñas/genética , Anciano , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/secundario , Análisis Mutacional de ADN , Exones , Femenino , Expresión Génica , Humanos , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Carcinoma Pulmonar de Células Pequeñas/diagnóstico , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/secundarioRESUMEN
BACKGROUND: Young ischemic stroke patients are common while classification and analysis based upon imaging characteristics are rarely reported. We intend to compare the clinical and MRI characteristics of cerebral stroke induced by intracranial atherosclerosis between young patients with branch occlusive disease (BOD) and those with non-branch occlusive disease (non-BOD) or small artery disease (SAD). METHODS: A total of 151 subjects with acute infarction within the middle cerebral artery (MCA) territory were included and patients with ipsilateral internal carotid artery stenosis or cardioembolism were excluded. Based on the distribution characteristics of infarction and the presence of ipsilateral MCA stenosis, the patients were divided into three groups: BOD-striatocapsular area infarction with ipsilateral MCA stenosis; non-BOD -infarction size exceeds the striatocapsular area and accompanied by ipsilateral MCA stenosis; SAD. The clinical and MCA stenosis characteristics of the three groups were compared. RESULTS: The number of BOD patients with hypertension was significantly higher than that of SAD (92.9% vs 53.7%, p = 0.000) and non-BOD (92.9% vs 57.1%, p = 0.001); subjects with smoking history significantly exceeded that of SAD (50% vs 26.9%, p = 0.03) and subjects with family history of cardiovascular disease was significantly less than that of non-BOD (14.3% vs 41.1%). Baseline NIHSS scores and mRS scores at discharge in patients with BOD were significantly lower than those with non-BOD (p = 0.000, p = 0.001). Majority of patients in non-BOD group displayed severe MCA stenosis (39 cases, 69.6%) while that in BOD group displayed mild stenosis (26 cases, 92.9%), and the difference was statistically significant (p = 0.000). Compared with non-BOD group, the stenosis in BOD group located at a relatively distal end in the M1 segment of MCA (S/M1, 58% vs 40%, p = 0.000) and was more localized (stenosis level/ (SL/M1), 1.86 (1.35-2.6) vs 2.9 (2.0-5.0), p = 0.002). CONCLUSION: BOD in young patients with ischemic stroke induced by intracranial atherosclerosis is not rare (33.3%) and its clinical manifestations and prognosis are similar to those of SAD. This may be related to the mild localized stenosis at the distal end in the M1 segment of MCA. Control of hypertension might play a positive role in secondary prevention.
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Estenosis Carotídea , Infarto de la Arteria Cerebral Media , Arteriosclerosis Intracraneal , Ataque Isquémico Transitorio , Accidente Cerebrovascular , Adulto , Estenosis Carotídea/complicaciones , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/fisiopatología , Femenino , Humanos , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Infarto de la Arteria Cerebral Media/etiología , Infarto de la Arteria Cerebral Media/fisiopatología , Arteriosclerosis Intracraneal/complicaciones , Arteriosclerosis Intracraneal/diagnóstico por imagen , Arteriosclerosis Intracraneal/fisiopatología , Ataque Isquémico Transitorio/diagnóstico por imagen , Ataque Isquémico Transitorio/etiología , Ataque Isquémico Transitorio/fisiopatología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/fisiopatologíaRESUMEN
BACKGROUND: Multiple organ dysfunction syndromes (MODS) is reported as a leading cause of mortality in intensive care units. Recently, continuous blood purification (CBP) has been mostly applied for MODS treatment. Thus, the purpose of this study was to investigate the effects of CBP on plasma phospholipid level in patients with MODS. METHODS: A total of 126 patients with MODS and 120 healthy people were collected. The serum cytokine levels, blood biochemical parameters, and blood gas indexes were detected, and the correlation among phospholipid compounds with serum cytokine levels, blood biochemical parameters, and blood gas indexes was analyzed. RESULTS: Before CBP, levels of body temperature, RR, HR, CVP, IL-6, IL-10, TNF-α, BUN, SCr, PaCO2 , SM747, and LPC540 were obviously higher, and pH, HCO3- , PaO2 , SaO2 , PE750, PI885, PC792, PC826, PC830, PC854, PC802, and PG747 were lower in the MODS group than those in the control group. During CBP, the MODS group had gradually declined RR, CVP, levels of IL-6, IL-10 and TNF-α, BUN, SCr, PaCO2 , SM747, and LPC540 and increased HCO3- , PaO2 and SaO2 , PE750, PI885, PC792, PC826, PC830, PC854, PC802, and PG747. Besides, levels of PE750, PI885, PC792, PC826, PC830, PC854, PC802, and PG747 had an obvious negative correlation with levels of TNF-α, IL-10, IL-6, BUN, SCr, and PaCO2 , and a significant positive correlation with levels of HCO3- , PaO2 , and SaO2 . CONCLUSION: CBP could effectively ameliorate clinical signs of patients with MODS and correct the plasma phospholipid levels.
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OBJECTIVE: To investigate the role of angiopoietin-2 (Ang-2) in tumor necrosis factor-α (TNF-α) induced apoptosis of alveolar epithelium cells (AECs). METHODS: TNF-α was used to induce human alveolar epithelial HPAEpiC cells, and Ang-2 siRNA vector was transfected to the HPAEpiC cells. RT-PCR and Western blot were used. TUNEL staining was applied to observe apoptosis, and annexin V-FITC-PI staining was used to calculate apoptosis rate. RESULTS: mRNA and protein expressions of Ang-2, activated Bax, and cleaved caspase-3 in HPAEpiC cells were up-regulated, but the expression level of Bcl-2 decreased (P < 0.05). After transfection of Ang-2 siRNA, mRNA and protein expressions of Ang-2, activated Bax, and cleaved caspase-3 in HPAEpiC cells were down-regulated, but the expression level of Bcl-2 increased (P < 0.05). The number of apoptotic cells increased after TNF-α treatment; however, the number decreased after Ang-2 siRNA transfection. Annexin V-FITC-PI staining verified that the total number of apoptotic cells was elevated with TNF-α treatment, but declined after transfection of Ang-2 siRNA. CONCLUSIONS: The expression level of Ang-2 increased during TNF-α-induced apoptosis. Inhibiting Ang-2 expression may suppress the early stages of cell apoptosis and the degree of TNF-α-induced apoptosis.
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Mitochondrial genome plays a central role in aging, cancer, apoptosis and metabolism. We sequenced a complete mitochondrial genome sequence of a rat chronic obstructive pulmonary disease rat strain for the first time. The total length of the mitochondrial genome was 16,310 bp and coding 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes. This genome describing information will supply the potential use of mtDNA mutations as markers in cancer.
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Genoma Mitocondrial , Enfermedad Pulmonar Obstructiva Crónica/genética , Animales , Codón Iniciador , Codón de Terminación , ADN Mitocondrial/química , ADN Mitocondrial/aislamiento & purificación , ADN Mitocondrial/metabolismo , Modelos Animales de Enfermedad , Complejo IV de Transporte de Electrones/química , Complejo IV de Transporte de Electrones/genética , Complejo IV de Transporte de Electrones/metabolismo , NADH Deshidrogenasa/química , NADH Deshidrogenasa/genética , NADH Deshidrogenasa/metabolismo , Sistemas de Lectura Abierta/genética , Enfermedad Pulmonar Obstructiva Crónica/patología , ARN Ribosómico/química , ARN Ribosómico/genética , ARN de Transferencia/química , ARN de Transferencia/genética , Ratas , Análisis de Secuencia de ADNRESUMEN
The study describes the development of polylactide-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS)-based nanosystem as a carrier of crizotinib (CZT) to achieve superior anticancer efficacy in lung cancer therapy. We have demonstrated that block copolymer and hydrophobic drug is capable of self-assembling into a very stable nanocarrier, with suitable properties that allow their application for cancer drug delivery. Drug release study showed a sustained release pattern as a result of entrapment in the hydrophobic core of micelles. CZT/PT NP showed a noticeable cytotoxic effect in NCIH3122 lung cancer cells in a dose-dependent manner. Furthermore, morphological imaging and Live/Dead assay revealed a superior anticancer efficacy for nanoformulations. The polymeric nanoparticle showed a predominant presence in the cytoplasmic region of cell, indicating a typical endocytosis-mediated cellular uptake. The annexin V/PI staining-based apoptosis assay showed a remarkable ~40 % apoptosis (early and late apoptosis cells) comparing to only ~25 % apoptosis by free CZT. Taken together, Vitamin E TPGS-modified PLA nanoparticles would be a potential drug delivery system to increase the chemotherapeutic efficacy of CZT in lung cancer chemotherapy.
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Neoplasias Pulmonares/tratamiento farmacológico , Nanopartículas/administración & dosificación , Polímeros/administración & dosificación , Pirazoles/administración & dosificación , Piridinas/administración & dosificación , Antineoplásicos/administración & dosificación , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Crizotinib , Portadores de Fármacos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Humanos , Polietilenglicoles/administración & dosificación , Succinatos/administración & dosificaciónRESUMEN
Megakaryocytes (MKs) are one of the few cell types that become polyploid; however, the mechanisms by which these cells are designated to become polyploid are not fully understood. In this investigation, we successfully established two relatively synchronous polyploid cell models by inducing Dami and CMK cells with SP600125. We found that SP600125 induced the polyploidization of Dami and CMK cells, concomitant with the phosphorylation of ribosomal protein S6 kinase 1 (S6K1) at Thr421/Ser424 and dephosphorylation at Thr389. The polyploidization was partially blocked by H-89, a cAMP-dependent protein kinase (PKA) inhibitor, through direct binding to S6K1, leading to dephosphorylation at Thr421/Ser424 and phosphorylation at Thr389, independent of PKA. Overexpression of a rapamycin-resistant mutant of S6K1 further enhanced the inhibitory effect of LY294002 on the SP600125-induced polyploidization of Dami and CMK cells. SP600125 also induced the polyploidization of Meg-01 cells, which are derived from a patient with chronic myelogenous leukemia, without causing a significant change in S6K1 phosphorylation. Additionally, SP600125 induced the polyploidization of HEL cells, which are derived from a patient with erythroleukemia, and phosphorylation at Thr389 of S6K1 was detected. However, the polyploidization of both Meg-01 cells and HEL cells as a result of SP600125 treatment was lower than that of SP600125-induced Dami and CMK cells, and it was not blocked by H-89 despite the increased phosphorylation of S6K1 at Thr389 in both cell lines in response to H-89. Given that the Dami and CMK cell lines were derived from patients with acute megakaryocytic leukemia (AMKL) and expressed high levels of platelet-specific antigens, our data suggested that SP600125-induced polyploidization is cell-type specific, that these cell lines were more differentiated, and that phosphorylation at Thr421/Ser424 and dephosphorylation at Thr389 of S6K1 may play an important role in the SP600125-induced polyploidization of these cell lines synergistically with other signaling pathways.
Asunto(s)
Antracenos/farmacología , Megacariocitos/efectos de los fármacos , Megacariocitos/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Antracenos/química , Línea Celular , Proliferación Celular/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Isoquinolinas/farmacología , Modelos Moleculares , Conformación Molecular , Mutación , Fosforilación/efectos de los fármacos , Poliploidía , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Inhibidores de Proteínas Quinasas/química , Proteínas Quinasas S6 Ribosómicas 70-kDa/química , Proteínas Quinasas S6 Ribosómicas 70-kDa/genética , Sulfonamidas/farmacologíaRESUMEN
OBJECTIVE: To study the histogenesis of giant cell tumor (GCT) and factors related to tumor recurrence, invasiveness and malignant transformation. METHODS: The clinical features, radiologic classification, surgical approach, pathologic findings, immunophenotypes and follow-up data of 123 cases of GCT were analyzed. RESULTS: There was a significant correlation between tumor recurrence and radiographic classification (P = 0.032), over-expression of CD147 (P = 0.034) and p53 (P = 0.005), and surgical approach (P = 0.0048) in GCT. The biologic behavior showed no correlation with intramedullary infiltration, cortical bone involvement, parosteal soft tissue extension, tumor thrombi, fusiform changes of mononuclear tumor cells, mitotic count, Ki-67 index, coagulative tumor necrosis, secondary aneurysmal bone cyst formation, and adjoining bony reaction. The positive rate of p63 in stromal cells of GCT (79.7%, 94/118) was significantly higher than that in chondroblastoma (44.7%, 21/47), osteosarcoma (22.2%, 10/45) and other giant cell-rich tumors. CONCLUSIONS: GCT is a bone tumor of low malignant potential. It is sometimes characterized by locally invasive growth, active proliferation, coagulative necrosis, secondary aneurysmal bone cyst and surrounding bony reaction. It is difficult to predict the biologic behavior of GCT. Over-expression of p53 in the tumor cells and CD147 in all components of GCT correlate with tumor invasiveness, recurrence and malignant transformation. Selection of suitable surgical approach with reference to radiologic classification is considered as an important factor in reducing the recurrence rate.
Asunto(s)
Neoplasias Óseas/patología , Tumor Óseo de Células Gigantes/patología , Proteínas de la Membrana/metabolismo , Adolescente , Adulto , Anciano , Basigina/metabolismo , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/metabolismo , Neoplasias Óseas/cirugía , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Tumor Óseo de Células Gigantes/diagnóstico por imagen , Tumor Óseo de Células Gigantes/tratamiento farmacológico , Tumor Óseo de Células Gigantes/metabolismo , Tumor Óseo de Células Gigantes/cirugía , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Osteosarcoma/patología , Fosfoglucomutasa/metabolismo , Radiografía , Proteína p53 Supresora de Tumor/metabolismo , Adulto JovenRESUMEN
Giant cell angioblastoma (GCAB) is an extremely rare soft tissue tumor of early childhood and only five cases have been described to date. As such the clinical, pathological, and prognostic features are poorly defined. We prensent here a new case of GCAB in bone of a child aged 4-years old. The lesion was composed of dense and loose cell regions. The dense regions were characterized by nodular, linear, and plexiform aggregates of oval- to spindle-shaped tumor cells around small vascular channels and interspersed with large mononuclear cells and multinucleate giant cells. The loose cell areas were characterized by distributed fibroblasts and abundant myxoid matrix, which diminished with patient age. Infiltrative growth was observed in some areas. Oval-to-spindle cells showed positivity for Vimentin, CD31 and CD34 staining, and partial positivity for smooth muscle actin. Mononuclear cells and multinucleate giant cells showed Vimentin and CD68 positivity. Seventeen months after thorough curettage of the lesion, a local recurrence was found. Based upon the clinical, histological and immunohistochemical findings, infiltrate condition, and prognosis, we classified GCAB into two subtypes. Type I does not infiltrate surrounding tissues and has good prognosis. Type II infiltrates the surrounding tissues, relapses earlier, and has worse prognosis. This report augments the limited GCAB literature to promote our understanding and guide therapy of this rare disease. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6699811297488137.
Asunto(s)
Neoplasias Femorales/patología , Tumor Óseo de Células Gigantes/patología , Biomarcadores de Tumor/análisis , Preescolar , Legrado , Diagnóstico Diferencial , Neoplasias Femorales/química , Neoplasias Femorales/cirugía , Tumor Óseo de Células Gigantes/química , Tumor Óseo de Células Gigantes/cirugía , Humanos , Inmunohistoquímica , Masculino , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Valor Predictivo de las Pruebas , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
OBJECTIVE: Analyze the immunophenotype of the different cells in the various subtypes of giant cell tumor of tendon sheath (GCTS) and investigate the value of clusterin in pathological diagnosis and histogenesis of giant cell tumor of tendon sheath. METHODS: A total of 104 cases of GCTS from the surgical pathology files of Shanghai Jiaotong university affiliated the sixth people's hospital were identified. Immunohistochemistry (IHC) for clusterin, desmin, CD163, CD68, p63, p53, Ki-67 and CD35 was performed on all cases, using EnVision technique. RESULTS: All cases of GCTS were researched, including 44 cases of localized type (L-GCTS), 32 cases of diffused type (D-GCTS), 26 cases of pigmented villonodular synovitis (PVNS) and 2 cases of malignant type. There was a slight female predominance in all these subtypes, and the male to female ratio was about 38:66. L-GCTS usually occured within the small joints (90.9%, 40/44), while D-GCTS, PVNS and M-GCTS commonly occured within the large weight-bearing joints [68.8% (22/32), 100% (26/26) and 2/2 respectively]. Of 74 cases with follow-up, the recurrence rates of L-GCTS, D-GCTS, PVNS and M-GCTS respectively were 30.3% (10/33), 30.4% (7/23), 18.8% (3/16) and 2/2. The different subtypes of GCTS had the same cell components, including the large synovial-like mononuclear cells, the small histiocytoid cells, foamy histiocytes cells, inflammatory cells, fibroblasts and the osteoclast-like multinucleated giant cells. There were obvious differences among immunophenotype of the various cell components in GCTS: the large synovial-like mononuclear cells were strong positive for clusterin, partly positive for desmin and Ki-67, and negative for CD163. The small histiocytoid cells were strong positive for CD163 but negative for clusterin and desmin. The osteoclast-like multinucleated giant cells were strong positive for CD68 but negative for clusterin, CD163 and desmin. Normal synoviocytes were strong positive for clusterin, partly positive for desmin. The number of the large synovial-like mononuclear cells that were positive for clusterin in D-GCTS were more than that in L-GCTS (P < 0.01) and PVNS (P < 0.05). CONCLUSIONS: GCTS was synovial tumors, not belonged to the category of fibrohistiocytic lesions. The true tumor cells may be the large synovial-like mononuclear cells, and the number of the cells in the D-GCTS was obviously more than that in L-GCTS and PVNS. This may be the reason that the biological behavior of D-GCTS was more aggressive, destructive and recurrent. Clusterin was an useful marker in pathological differential diagnosis of GCTS.
Asunto(s)
Clusterina/metabolismo , Tumores de Células Gigantes/patología , Neoplasias de los Tejidos Blandos/patología , Tendones , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Biomarcadores de Tumor/metabolismo , Desmina/metabolismo , Femenino , Estudios de Seguimiento , Tumores de Células Gigantes/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Receptores de Superficie Celular/metabolismo , Factores Sexuales , Neoplasias de los Tejidos Blandos/metabolismoRESUMEN
OBJECTIVE: To study the radiologic and pathologic features of primary intermediate hemangioendothelioma of the bone. METHODS: Five cases of primary intermediate hemangioendothelioma of bone encountered in the past three years were enrolled into the study. The clinical, radiologic, pathologic and immunohistochemical features of the tumors were reviewed. RESULTS: The patients included 3 children with Kaposiform hemangioendothelioma and 2 elderly with retiform hemangioendothelioma. Four of the cases affected long bones and the remaining case affected the clavicle. One case showed multifocal involvement of the humerus. Radiologically, the tumors showed borderline to low-grade bony destruction, with various degrees of cortical defect. Intralesional or perilesional bone formation was demonstrated in 4 cases and radial spicules were seen in 1 case. The histopathologic features of primary intermediate hemangioendothelioma of bone were similar to those of soft tissue, except for the presence of reactive bone formation. Immunohistochemically, the tumor cells were positive for CD31 (5/5), CD34 (5/5), vimentin (5/5) and smooth muscle actin (3/5) but negative for cytokeratin and epithelial membrane antigen. CONCLUSIONS: Primary intermediate hemangioendothelioma of bone is a distinct entity and similar histologic classification applies as in its soft tissue counterparts. Comparison of the biologic behavior requires long-term follow-up studies.