RESUMO
A practical and efficient copper-catalyzed carbocyclization of 2-functionalized anilines with ethyl bromodifluoroacetate has been developed. Ethyl bromodifluoroacetate is employed as the C1 source via quadruple cleavage in this transformation. This reaction can afford a variety of N-containing heterocyclics with satisfactory yields and excellent functional group compatibility.
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Objective: A case-control study was conducted to explore the efficacy of cohort study and value of CT perfusion imaging in patients with metastatic osteosarcoma after chemotherapy. Methods: Eighty patients with metastatic osteosarcoma treated in our hospital from March 2020 to December 2021 were divided into two groups. According to their different treatment methods, the chemotherapy+antiangiogenesis group had 36 cases and the chemotherapy group had 44 cases. All patients were scanned by 64-slice spiral CT before and after treatment. The differences of tumor volume and perfusion parameters before and after treatment were compared, and the correlation between perfusion parameters and tumor microvessel density (MVD) was analyzed. The receiver working curve (ROC curve) was used to evaluate the efficacy of the two groups after chemotherapy. Results: Blood flow (BF), blood volume (BV), Pallak blood volume (PBV), and time to start (TTS) in the antitumor angiogenesis+chemotherapy group were significantly lower than those before treatment (P < 0.05). Microvessel density was positively correlated with PS, BF, BV, and PBV (P < 0.05). The reduction rate of BV and BF in the remission group after treatment was significantly higher than that in the nonremission group. When the BV and BF decline rates were 47.37% and 21.53% and the areas under the curve were 0.968 and 0.916, respectively, the diagnostic effect was the best. When the decrease rate of BV was 47.48% and the decrease rate of BF was 21.55%, the sensitivity was 94.72% and 89.56% and the specificity was 91.31% and 91.31%. Conclusion: The reduction rate of BV and BF in CT perfusion imaging is of high value in evaluating the efficacy of radiotherapy and chemotherapy in patients with NSCLC and can provide more objective basis for observing the changes and judging the prognosis of osteosarcoma after treatment.
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Neoplasias Pulmonares , Osteossarcoma , Estudos de Casos e Controles , Estudos de Coortes , Humanos , Neoplasias Pulmonares/patologia , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/tratamento farmacológico , Imagem de Perfusão/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
This study explored the mechanism of Shenling Baizhu Powder(SLBZP) in the prevention and treatment of type 2 diabetes from the perspective of flora disorder and chronic inflammation. Fifty rats were randomly divided into normal control group, model control group, low-dose SLBZP group, medium-dose SLBZP group, and high-dose SLBZP group, with 10 rats in each group. The rats of 5 weeks old were administrated by gavage with ultrapure water and different doses of SLBZP decoction. The basic indicators such as body weight and blood glucose were monitored every week, and stool and intestinal contents were collected from the rats of 9 weeks old for 16 S rRNA sequencing and metabolomic analysis. An automatic biochemical analyzer was used to measure the serum biochemical indicators, ELISA to measure serum insulin, and chipsets to measure leptin and inflammatory cytokines. The results showed that SLBZP reduced the body weight as well as blood glucose, glycosylated hemoglobin, and lipid levels. In the rats of 9 weeks, the relative abundance of Anaerostipes, Turicibacter, Bilophila, Ochrobactrum, Acinetobacter, and Prevotella decreased significantly in the model control group, which can be increased in the high-dose SLBZP group; the relative abundance of Psychrobacter, Lactobacillus, Roseburia and Staphylococcus significantly increased in the model control group, which can be down-regulated in the high-dose SLBZP group. The differential metabolites of intestinal flora included 4-hydroxyphenylpyruvic acid, phenylpyruvic acid, octanoic acid, 3-indolepropionic acid, oxoglutaric acid, malonic acid, 3-methyl-2-oxovaleric acid, and methylmalonic acid. Moreover, SLBZP significantly lowered the levels of free insulin, insulin resistance and leptin resistance in rats. The variations in the serum levels of interleukin 1ß(IL-1ß) and monocyte chemoattractant protein-1(MCP-1) showed that SLBZP could alleviate chronic inflammation in rats. In conclusion, SLBZP can regulate intestinal flora and metabolites and relieve chronic inflammation to control obesity and prevent type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inflamação/tratamento farmacológico , Insulina , Pós , RatosRESUMO
PURPOSE: Diabetic cardiomyopathy (DCM), a common complication of diabetes mellitus and is characterized by myocardial hypertrophy and myocardial fibrosis. Pyrroloquinoline quinone (PQQ), a natural nutrient, exerts strong protection against various myocardial diseases. Pyroptosis, a type of inflammation-related programmed cell death, is vital to the development of DCM. However, the protective effects of PQQ against DCM and the associated mechanisms are not clear. This study aimed to investigate whether PQQ protected against DCM and to determine the underlying molecular mechanism. METHODS: Diabetes was induced in mice by intraperitoneal injection of streptozotocin, after which the mice were administered PQQ orally (10, 20, or 40 mg/kg body weight/day) for 12 weeks. AC16 human myocardial cells were divided into the following groups and treated accordingly: control (5.5 mmol/L glucose), high glucose (35 mmol/L glucose), and HG + PQQ groups (1 and 10 nmol/L PQQ). Cells were treated for 24 h. RESULTS: PQQ reduced myocardial hypertrophy and the area of myocardial fibrosis, which was accompanied by an increase in antioxidant function and a decrease in inflammatory cytokine levels. Moreover, myocardial hypertrophy-(ANP and BNP), myocardial fibrosis-(collagen I and TGF-ß1), and pyroptosis-related protein levels decreased in the PQQ treatment groups. Furthermore, PQQ abolished mitochondrial dysfunction and the activation of NF-κB/IκB, and decreased NLRP3 inflammation-mediated pyroptosis in AC16 cells under high-glucose conditions. CONCLUSION: PQQ improved DCM in diabetic mice by inhibiting NF-κB/NLRP3 inflammasome-mediated cell pyroptosis. Long-term dietary supplementation with PQQ may be greatly beneficial for the treatment of DCM. Diagram of the underlying mechanism of the effects of PQQ on DCM. PQQ inhibits ROS generation and NF-κB activation, which stimulates activation of the NLRP3 inflammasome and regulates the expression of caspase-1, IL-1ß, and IL-18. The up-regulated inflammatory cytokines trigger myocardial hypertrophy and cardiac fibrosis and promote the pathological process of DCM.
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Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Animais , Cardiomegalia , Diabetes Mellitus Experimental/complicações , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/metabolismo , Fibrose , Glucose , Inflamassomos/metabolismo , Inflamação/complicações , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Cofator PQQ/metabolismo , Cofator PQQ/farmacologia , Cofator PQQ/uso terapêutico , Piroptose , Transdução de SinaisRESUMO
Self-immolative polymers are a special kind of degradable polymers that depolymerize into small molecules through a cascade of reactions upon stimuli-triggered cleavage of the polymer chain ends. This work reports the design and synthesis of a fluoride-triggered self-immolative polyester. A 2,4-disubstitued 4-hydroxy butyrate is first confirmed to quickly cyclize in solution to form a γ-butyrolactone derivative. Then, the Passerini three component reaction (P-3CR) of an AB dimer (A: aldehyde, B: carboxylic acid) with tert-butyl isocyanide or oligo(ethylene glycol) isocyanide affords two poly(2,4-disubstitued 4-hydroxybutyrate) derivatives (P2 and P3). Two silyl ether end-capped polymers (P4 and P5) are abtained from P2 and P3, and their degradation in solution is examined by NMR spectrum and size exclusion chromatography. Polymers P4 and P5 are stable in the absence of tetrabutylammonium fluoride (TBAF), while in the presence of TBAF, the molar masses of P4 and P5 gradually decrease with time together with the increase of the amount of formed 2,4-disubstitued γ-butyrolactone. The depolymerization mechanism is proposed. The first step is the fast removal of the silyl ether by fluoride. Then, the released hydroxyl group initiates the quick head-to-tail depolymerization of the polyester via intramolecular cyclization.
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Fluoretos , Polímeros , Hidroxibutiratos , PoliésteresRESUMO
This research was to evaluate the economics of Shexiang Tongxin Dropping Pills combined with conventional therapy for patients with coronary heart disease(CHD) in Chinese medical environment. From the perspective of medical insurance, a Markov model was established in this study based on the results of Meta-analysis comparing the effectiveness and safety of Shexiang Tongxin Dripping Pills combined with conventional treatment and conventional treatment alone. The experimental group was treated with She-xiang Tongxin Dropping Pills combined with conventional Western medicine treatment, while the control group was treated with conventional Western medicine treatment alone. The cost-utility analysis and sensitivity analysis were performed for the two regimens using Treeage pro. After 30 cycles of model simulation, according to the results of Markov model, the total cost and health output were CNY 237 795.73 and 16.36 QALYs(the quality adjusted life years, QALYs), respectively for Shexiang Tongxin Dropping Pills combined with conventional Western medicine treatment, CNY 247 396.55 and 16.36 QALYs respectively for the conventional Western medicine treatment alone. Compared with the conventional treatment alone, the Shexiang Tongxin Dropping Pills combined with conventional treatment had lower long-term cost and higher health output, with advantages of cost-utility and pharmacoeconomic advantages. The sensitivity analysis results showed that the conclusion was relatively stable. Based on the above results, it is considered that compared with the conventional Western medicine alone, Shexiang Tongxin Dropping Pill combined with conventional Western medicine is a treatment regimen with pharmacoeconomic advantages for the treatment of CHD.
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Doença das Coronárias , Medicamentos de Ervas Chinesas , Doença das Coronárias/tratamento farmacológico , Farmacoeconomia , Feminino , HumanosRESUMO
Microbial fermentation can endow food with unique flavors, increase its nutritional value and enhance functional characteristics. Our previous research has shown that liquid fermentation of soymilk by Bacillus subtilis BSNK-5 imparted new functional properties of to the fermented product via production of nattokinase. In this study, in order to further investigate the changes in the flavor, nutritional quality and functional characteristics of soymilk during fermentation using proton nuclear magnetic resonance (1H NMR) metabolomics to monitor the metabolite profile of BSNK-5-fermented soymilk. A total of 44 differential metabolites were identified between BSNK-5-fermented soymilk and uninoculated/unfermented soymilk, among which the levels of flavor-related substances (acetate, isovalerate and 2-methylbutyrate), nutrient-related substances (12 free amino acids), and functional substances (taurine, GABA and genistein) significantly increased after fermentation. These metabolites were closely associated with eight potential metabolic pathways. This work highlighted the significance of BSNK-5 strain in improving the nutritional quality and functional characteristics of fermented soymilk; however, the use of the strain also caused flavor deterioration. This study lays a theoretical foundation for the improvement and development of fermented soy products via liquid fermentation with B. subtilis.
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Bacillus subtilis , Leite de Soja , Espectroscopia de Ressonância Magnética , Metabolômica , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
Objective Many physiological and pathological conditions, including cyanotic congenital heart diseases (CCHD), are accompanied by chronic hypoxia, which might interfere with the transcription process. However, the transcriptome profile in peripheral blood under hypoxia is still unidentified. The present work aimed to explore the transcriptional profile alteration of peripheral blood in chronic hypoxia. Methods The present study used a chronic hypoxia rat model to simulate the hypoxic state of CCHD patients. Two groups of Sprague-Dawley rats (n=6 per group) were either exposed to hypoxia (10% O2) or normoxia (21% O2) for 3 weeks. Body weight was measured weekly. Peripheral blood was collected and total RNA was extracted for RNA-Seq at the end of the hypoxia treatment. After quality assessment, the library was sequenced by the Illumina Hiseq platform. The differentially expressed genes were screened (false discovery rate<0.05 and fold change>2). The functional annotation analysis and cluster analysis of differentially expressed genes were performed based on the adjusted P-value (padj<0.05). Results Compared with the control group, the body weight of the rats in the hypoxia group was significantly lowered (P<0.01). RNA-Seq results showed that the transcriptome patterns of the two groups had significant differences. In total, 872 genes were identified as differentially expressed. Among all, 803 genes were down-regulated, while only 69 genes were up-regulated in the hypoxia group. The functional enrichment analysis of the 872 genes showed that multiple biological processes involved, such as porphyrin-containing compound metabolic process, hemoglobin complex and oxygen transporter activity. Conclusions Our study demonstrated the transcriptional profile alteration in peripheral blood of chronic hypoxia rat model. This study provided basic data and directions to further understand the physiological and pathological changes in patients with CCHD.
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Modelos Animais de Doenças , Perfilação da Expressão Gênica/métodos , Cardiopatias Congênitas/genética , Hipóxia/genética , Animais , Doença Crônica , Análise por Conglomerados , Ontologia Genética , Redes Reguladoras de Genes , Cardiopatias Congênitas/sangue , Humanos , Hipóxia/sangue , Mapas de Interação de Proteínas/genética , Ratos Sprague-DawleyRESUMO
In heart transplantation, time restriction is an unavoidable thorny problem during cardiac transport. Cold storage is an important organ preservation method in donor heart transport. Cold-inducible RNA binding protein (CIRBP) has been proven to play a protective role under cold stress. In this study, we investigated the role of CIRBP in hypothermic cardioprotection during heart preservation in UW solution and explored a new approach to extend the heart preservation time. Cirbp-knockout (Cirbp-/- ), Cirbp-transgenic (Cirbp-Tg), and wild-type rats were, respectively, randomized into two groups based on various heart preservation times (6 or 12-hour group) (n = 8 per group). After preservation in UW solution, all hearts were mounted on a Langendorff apparatus and underwent measurement of cardiac parameters, histological analysis, and molecular study. Within the 6-hour preservation group, no significant difference was found in cardiac functions and histological changes between different rat species. However, after 12 hours of preservation, Cirbp-/- rat hearts showed more apoptosis and worse cardiac function, but less apoptosis and better cardiac function were observed in Cirbp-Tg rat hearts. Furthermore, we found CIRBP-mediated cardiac ubiquinone (CoQ10 ) biosynthesis plays an important role in extending heart preservation, and ubiquinone biosynthesis protein COQ9 was an essential down-stream regulator during this process. Finally, we found that zr17-2, a CIRBP agonist, could enhance the expression of CIRBP, which further enhances the synthesis of CoQ10 and promotes scavenging of reactive oxygen species and ATP production to extend heart preservation. This study demonstrated that CIRBP-enhanced CoQ10 biosynthesis during hypothermic heart preservation and zr17-2-supplemented UW solution could be a promising approach to ameliorate heart damage and extend heart preservation during cardiac transport.
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Isquemia Fria/efeitos adversos , Proteínas e Peptídeos de Choque Frio/agonistas , Coração/efeitos dos fármacos , Soluções para Preservação de Órgãos/farmacologia , Preservação de Órgãos/métodos , Proteínas de Ligação a RNA/agonistas , Trifosfato de Adenosina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas e Peptídeos de Choque Frio/genética , Proteínas e Peptídeos de Choque Frio/metabolismo , Técnicas de Inativação de Genes , Transplante de Coração/métodos , Preparação de Coração Isolado , Masculino , Miocárdio/metabolismo , Perfusão/métodos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Ratos , Ratos Transgênicos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Ubiquinona/análogos & derivados , Ubiquinona/biossínteseAssuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , COVID-19 , Infecções por Coronavirus/virologia , Progressão da Doença , Humanos , Masculino , Pandemias , Pneumonia Viral/virologia , SARS-CoV-2 , Tórax/diagnóstico por imagemRESUMO
BACKGROUND: Depression and anxiety have been correlated with elevated risks for quality-of-life (QOL), adverse outcomes, and medical expenditure in patients with acute coronary syndrome (ACS). However, the relevant data are lacking for Chinese ACS populations, especially regarding different effects of major depression, anxiety, and comorbidity. The objective of this study was to evaluate the dynamic changes of depression and/or anxiety over 12 months and examine the effects of depression, anxiety, and comorbidity on QOL, adverse outcomes, and medical expenditure in Chinese patients with ACS. METHODS: For this prospective longitudinal study, a total of 647 patients with ACS were recruited from North China between January 2013 and June 2015. Among them, 531 patients (82.1%) completed 12-month follow-ups. Logistic regression model was utilized for analyzing the association of baseline major depression, anxiety, and comorbidity with 12-month all-cause mortality, cardiovascular events, QOL, and health expenditure. RESULTS: During a follow-up period of 12 months, 7.3% experienced non-fatal myocardial infarction (MI) and 35.8% cardiac re-hospitalization. Baseline comorbidity, rather than major depression/anxiety, strongly predicted poor 12-month QOL as measured by short-form health survey-12 (odds ratio [OR]: 1.77, 95% confidence interval [CI]: 1.22-2.52, Pâ=â0.003). Regarding 12-month non-fatal MI and cardiac re-hospitalization, baseline anxiety (OR: 2.83, 95% CI: 1.33-5.89, Pâ<â0.01; OR: 4.47, 95% CI: 1.50-13.00, Pâ<â0.01), major depression (OR: 2.58, 95% CI: 1.02-6.15, Pâ<â0.05; OR: 5.22, 95% CI: 1.42-17.57, Pâ<â0.03), and comorbidity (OR: 6.33, 95% CI: 2.96-13.79, Pâ<â0.0001, OR: 14.08, 95% CI: 4.99-41.66, Pâ<â0.0001) were all independent predictors, and comorbidity had the highest predictive value. Number of re-hospitalization stay, admission frequency within 12 months and medical expenditure within 2 months were the highest in patients with ACS with comorbidity. CONCLUSIONS: Major depression and anxiety may predict 12-month non-fatal MI and cardiac re-hospitalization. However, comorbidity has the highest predictive value with greater medical expenditure and worse QOL in Chinese patients with ACS. And depression with comorbid anxiety may be a new target of mood status in patients with ACS.
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Ansiedade/fisiopatologia , Depressão/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Síndrome Coronariana Aguda/economia , Síndrome Coronariana Aguda/fisiopatologia , Idoso , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/economia , Estudos Prospectivos , Qualidade de VidaAssuntos
Anomalias dos Vasos Coronários/diagnóstico , Anomalias dos Vasos Coronários/etiologia , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Doenças Vasculares/congênito , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Vasculares/diagnóstico , Doenças Vasculares/etiologiaRESUMO
In this work, we developed an innovative closed bipolar electrode (BPE)-electrochemiluminescence (ECL) sensing strategy with generality for target detection. Based on charge balance and 100% current efficiency between the closed BPE poles and the driving electrodes, one of the driving electrodes in one cell of the closed BPE system was employed as ECL sensing surface to reflect the target on the BPE pole in the opposite cell. Compared with traditional BPE-ECL sensing method, which in general adopted the anodic ECL reagents such as Ru(bpy)32+ and its coreactant on one pole (anode) to reflect the target (occurring reduction reaction) on the other pole (cathode), the difference was that the targets occurring oxidation reaction could be detected by the anodic ECL reagents based on this strategy. To verify the feasibility of this strategy, the detection principle was stated first, and Fe(CN)64- as model target at anodic BPE pole were detected by anodic ECL reagents (Ru(bpy)32+ and TprA) on the driving electrode first. The ECL signals showed good performance for target detection. By changing the size and the material of the BPE pole where the targets were located, the detection of l-ascorbic acid (AA), uric acid (UA), and dopamine (DA) as other model targets with higher detection limit were accomplished. Visual and high-throughput detection of AA, UA, and DA were also successfully realized by an array of the closed BPE system. This closed BPE (array) system is an effective supplement of traditional BPE-ECL sensing and could greatly expand the scope of the detection target.
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Ácido Ascórbico/análise , Dopamina/análise , Técnicas Eletroquímicas/métodos , Ferrocianetos/análise , Medições Luminescentes/métodos , Ácido Úrico/análise , Ácido Ascórbico/química , Complexos de Coordenação/química , Dopamina/química , Técnicas Eletroquímicas/instrumentação , Eletrodos , Ferrocianetos/química , Limite de Detecção , Luminescência , Oxirredução , Propilaminas/química , Ácido Úrico/químicaRESUMO
RATIONALE: Spontaneous coronary artery dissection is a highly unusual cause of acute coronary disease. It is a result of a hematoma formation within the outer third of the tunica media,with subsequent expansion leading to compression of the true lumen and resultant myocardial ischemia. PATIENT CONCERNS: We present a case of a middle-aged woman presenting with chest pain with acute anterior myocardial infarction, who did not reveal any of the cardiovascular risk factors. Finally,when pressed further about her past history, the patient revealed she had been taking oral contraceptives for the past 2 years. DIAGNOSES: The diagnosis is usually confirmed by coronary angiography, but it has some limitations. If necessary, intravascular ultrasound (IVUS) may help in further examinations to reduce the incidence of erroneous diagnosis or missed diagnosis. INTERVENTIONS: There is no guiding suggestion for the treatment of SCAD. The main treatment methods are 3 aspects: conservative internal medical treatment, stent implantation, coronary artery bypass grafting. The treatment strategy depends mainly on the patienst' clinical symptoms, the hemodynamic state, and the position and quantity of the dissection. In this case,we used stent implantation treatment originally and then we resorted to medical treatment. OUTCOMES: After careful review and analysis, coronary arteriography results was able to prove the existence of the spiral shaped dissection. We then resorted to medical treatment and her symptoms were gradually relieved. LESSONS: SCAD should be suspected in young to middle-aged women with chest pain symptoms, particularly during the perinatal period or for subjects who use oral contraceptives. Doctors should be able to obtain a detailed past history and analyze coronary angiography results carefully.
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Anomalias dos Vasos Coronários/complicações , Anomalias dos Vasos Coronários/diagnóstico , Infarto do Miocárdio/etiologia , Doenças Vasculares/congênito , Anticoncepcionais Orais/efeitos adversos , Anomalias dos Vasos Coronários/etiologia , Anomalias dos Vasos Coronários/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Vasculares/complicações , Doenças Vasculares/diagnóstico , Doenças Vasculares/etiologia , Doenças Vasculares/terapiaRESUMO
To determine the prevalence of pulmonary complications in primary Sjögren syndrome (pSS), and to identify the risk factors and the prognosis associated with pulmonary involvement in pSS patients.A total of 1341 hospitalized patients (853 with pSS and 488 with secondary Sjögren syndrome [sSS]) were retrospectively reviewed. Of these, 165 hospitalized patients with pSS-associated interstitial lung disease (ILD) were analyzed and recruited as a study group. Eighty-four pSS patients without organ damage were included as a control group.One hundred and sixty-five patients (19.34%) from the pSS group and 126 patients (25.82%) from the sSS group presented with lung involvement. Of the 165 pSS patients with lung complications, 151 (91.5%) were women. The mean age was 61.25â±â9.79 years, and the median disease duration was 84 (24-156) months. Non-specific interstitial pneumonia (NSIP; 39.1%) was the predominant pattern on high-resolution computed tomography (HRCT). The total HRCT score was 9.71â±â4.77. Impairment in diffusion capacity was the most common (74.3%) and severe complication (predicted value of TLCO was 57.5â±â21.2%). The 5-year survival rate for all patients with pSS-ILD was 88.5%. Age, disease duration, rheumatoid factor (RF), and C-reactive protein (CRP) were significantly higher than in controls, whereas anti-SSA was less common. Age, RF, and CRP were independent predictors of ILD after adjustment for confounders.Lung involvement is a common and severe complication of Sjögren syndrome. Age and disease activity are correlated with pulmonary involvement in pSS patients.
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Doenças Pulmonares Intersticiais/epidemiologia , Síndrome de Sjogren/complicações , Idoso , Povo Asiático , Estudos de Casos e Controles , Feminino , Humanos , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Síndrome de Sjogren/mortalidade , Taxa de Sobrevida , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: The aim of this study was to elucidate the mechanism underlying the neuroprotective effects of the phosphatase and tensin homolog (PTEN) inhibitor, bisperoxovanadium-pic [bpV(pic)]. METHODS: We determined the effects of bpV(pic) on amyloid-ß-peptide-(25-35)-induced neurotoxicity, particularly intracellular reactive oxygen species (ROS) production and mitochondria-mediated apoptotic signaling, in a human neuroblastoma (SH-SY5Y) cell model. RESULTS: We found that exposure of SH-SY5Y cells to amyloid ß peptides (Aß25-35) resulted in a significant reduction in cell viability accompanied by increased lactate dehydrogenase (LDH) release, elevated levels of intracellular ROS, and decreased superoxide dismutase (SOD) activities, all of which were reversed by co-treatment with bpV(pic). Moreover, bpV(pic) induced significant protection against Aß25-35-induced apoptosis, and effectively suppressed mitochondria-dependent apoptotic signaling triggered by Aß25-35. DISCUSSION: Aß peptides are thought to cause neurodegeneration in Alzheimer's disease (AD), via the induction of free radical oxidative stress. Our results indicate that bpV(pic) provides protection against Aß25-35-induced oxidative stress and neurotoxicity, suggesting that bpV(pic) could be a potential therapeutic candidate in the treatment of neurodegenerative diseases such as AD.
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Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , PTEN Fosfo-Hidrolase/antagonistas & inibidores , Compostos de Vanádio/farmacologia , Peptídeos beta-Amiloides/toxicidade , Linhagem Celular Tumoral , Humanos , Neuroproteção , Fragmentos de Peptídeos/toxicidade , Espécies Reativas de OxigênioRESUMO
OBJECTIVE: To determine the effect and mechanism of combination treatment of the total glycosides from Cimicifuga dahurica (TGCD) and cisplatin (CDDP) in vitro in human colon cancer cells (HCT-8) and in vivo in mouse hepatoma cells (H22)-bearing mice. METHODS: H22 tumor-bearing imprinting control region (ICR) mice were treated with TGCD, CDDP, and TGCD + CDDP for 10 days. Tumor volume and tumor weight were evaluated. TGCD and CDDP in different concentrations were added separately and in combination to cultures of different cancer cell lines, including the HCT-8. Effects of TGCD and CDDP on cell proliferation were detected by 3-(4,5-dimethyl-2-thiazole)-2-5-biphenly-tetrazole bromide (MTT) method and effects on cell apoptosis were tested by flfl ow cytometry and western blotting at 24 h after treatment. RESULTS: Combination index values (CI<0.8) suggested the synergistic effects of the TGCD + CDDP. This combination resulted in the highest increase in the percentage of apoptotic HCT-8 cells, caused cell cycle arrest in G2/M phase and increased expression of cleaved caspase-3, -8, and -9, Bax, phospho-c-Jun N-terminal kinase (p-JNK), and phospho-p38 mitogen-activated protein kinase (p-p38 MAPK), as well as decreased expression of Bcl-2, JNK, p38 MAPK, Poly (ADP-ribose) polymerase 1 (PARP1), caspase-3, and caspase-8 compared with single-agent treated and control groups. TGCD + CDDP treatment reduced tumor weight by 86.1%±7.2% compared with 64.5%±6.8% by CDDP or 46.9%±6.9% by the TGCD alone in vivo. CONCLUSIONS: TGCD enhanced the anticancer activity of CDDP in an additive-to-synergistic manner by activating multiple signaling pathways (including apoptosis). These fifi ndings suggest the potential benefifi t of combined treatment of the TGCD and CDDP against cancer of the colon and liver.
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A new phenylethanoid glycoside, 3'''-O-methylcampneoside I (1), was isolated from the 90% ethanolic extract of the roots of Incarvillea compacta, together with three known compounds, campneoside I (2), ilicifolioside A (3), and campneoside II (4). Their structures were determined spectroscopically and compared with previously reported spectral data. Compound 1 existed as epimers and displayed better 1,1-diphenyl-2-picrylhydrazyl (DPPH)-free radical scavenging activity using di-tert-butyl-4-methylphenol (BHT) as the positive control. In addition, pretreatment of human HepG2 cells with compound 1 significantly increased the viability on CCl4-induced cell death.
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Bignoniaceae/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Antioxidantes/farmacologia , Compostos de Bifenilo/farmacologia , Hidroxitolueno Butilado , Tetracloreto de Carbono/farmacologia , Cresóis , Glicosídeos/química , Humanos , Estrutura Molecular , Fenóis , Picratos/farmacologia , Raízes de Plantas/químicaRESUMO
The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.
Assuntos
Aurora Quinase A/antagonistas & inibidores , Neoplasias do Colo/patologia , Inibidores de Proteínas Quinases/farmacologia , Animais , Apoptose , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células , Humanos , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A series of novel sorafenib analogues were designed and synthesized. The cytotoxic activities of these compounds were tested in four tumor cell lines. Some of the compounds showed potent antiproliferative activity against the tested cell lines with IC50 = 4-20 micromol x L(-1). Some compounds demonstrated competitive antiproliferative activities to sorafenib against tested cancer cell lines. Among them, compound 7c demonstrated significant inhibitory activities on ACHN, HCT116 and MDA-MB-231 cell lines with IC50 values of 9.01, 4.97, 6.61 micromol x L(-1), respectively.