RESUMO
A novel ratiometric electrochemical sensor was developed based on a carbon cloth electrodeposited with silver nanoparticles and drop-coated by covalent organic framework (COF-LZU1) for simultaneous determination of bisphenol A (BPA) and bisphenol S (BPS). Carbon cloth exhibited a significantly larger electrochemical active area than common glassy carbon electrodes (27.5 times). Silver nanoparticles not only provided a stable reference signal but also enhanced electroactivity for the oxidation of BPA and BPS. COF-LZU1 with good adsorption performance and large periodic π-arrays promoted the enrichment of BPA and BPS to further increase the current response. Compared with the traditional single-signal electrochemical sensor, the developed ratiometric sensor exhibited better reproducibility and a wider linear range for BPA and BPS from 0.5 to 100 µM with a limit of detection of 0.15 µM. Furthermore, the developed sensor showed excellent stability and superior anti-interference ability. The real sample analysis for BPA and BPS has been successfully carried out in mineral water, electrolyte drink, tea, juice, and beer with recoveries of 88.3-111.7%. The developed ratiometric sensor is expected to be a candidate for the preparation of other electrochemical sensors and the analysis of additional practical samples.
Assuntos
Nanopartículas Metálicas , Estruturas Metalorgânicas , Compostos Benzidrílicos , Carbono , Fenóis , Reprodutibilidade dos Testes , PrataRESUMO
Cervical cancer is common cancer among women with high morbidity. MicroRNAs (miRs) are involved in the progression and development of cervical cancer. This study aimed to explore the effect of miR-99b-5p (miR-99b) on invasion and migration in cervical cancer through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway. The microarray-based analysis was used to screen out differentially expressed miRNAs. Expression of miR-99b, PI3K, AKT, mTOR, and ribosomal protein S6 kinase (p70S6K) was determined in both cervical cancer tissues and paracancerous tissues. Next, alteration of miR-99b expression in cervical cancer was conducted to evaluate levels of PI3K, AKT, mTOR, p70S6K matrix metallopeptidase 2, epithelial cell adhesion molecule, and intercellular adhesion molecule 1, as well as the effect of miR-99b on cell proliferation, invasion, migration, cell cycle distribution, and apoptosis. The results demonstrated that miR-99b expression was decreased and levels of PI3K, AKT, mTOR, and p70S6K were elevated in cervical cancer tissues. More important, overexpressed miR-99b repressed the PI3K/AKT/mTOR signaling pathway, inhibited cell proliferation, invasion, and migration, blocked cell cycle entry, and promoted apoptosis in cervical cancer. These results indicate that miR-99b attenuates the migration and invasion of human cervical cancer cells through downregulation of the PI3K/AKT/mTOR signaling pathway, which provides a therapeutic approach for cervical cancer treatment.
Assuntos
MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Apoptose/genética , Sequência de Bases , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Regulação para Cima/genéticaRESUMO
The antimicrobial peptide (AMP) Pc-pis, a member of Piscidin family from ï¬sh with cationic amphipathic structure, has potent, broad-spectrum antimicrobial activity against bacteria, fungi and parasite, and lower hemolytic activity. Here, we reported that Pc-pis had antitumor activity. Pc-pis killed tumor cells including HeLa cells. Previously, it is reported that AMPs bind to the membrane of bacteria to generate the pores to lyse the target cells, and similarly, the cancer cell incorporate phosphatidyl-serine on the outer leaflet of plasma membrane so that amphipathic AMPs can bind to the membrane to kill it. Our data supported that notion because suitable size osmo-protectant PEG4000 prevented HeLa cells from death induced by Pc-pis. Additionally, Fusion protein GFP-Pc-pis accumulated mainly at the nuclear membranes of HeLa cells and positive net charge in modified Pc-pis intensified but negative net charges eliminated this effect. Thus, positively charged residues were important for its affinity to the membrane. Our work will lay the groundwork of the development of Pc-pis antitumor activity.
Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Antineoplásicos/farmacologia , Proteínas de Peixes/farmacologia , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Sobrevivência Celular/efeitos dos fármacos , Proteínas de Peixes/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/farmacologia , Células HeLa , Humanos , Membrana Nuclear/metabolismo , Perciformes , Proteínas Recombinantes de Fusão/farmacologiaRESUMO
We recorded time-resolved infrared absorption spectra of transient species produced on irradiation at 308 nm of a flowing mixture of CH2I2/O2/N2/SO2 at 298 K. Bands of CH2OO were observed initially upon irradiation; their decrease in intensity was accompanied by the appearance of an intense band at 1391.5 cm-1 that is associated with the degenerate SO-stretching mode of SO3, two major bands of HCHO at 1502 and 1745 cm-1, and five new bands near >1340, 1225, 1100, 940, and 880 cm-1. The band near 1340 cm-1 was interfered by absorption of SO2 and SO3, so its band maximum might be greater than 1340 cm-1. SO3 in its internally excited states was produced initially and became thermalized at a later period. The rotational contour of the band of thermalized SO3 agrees satisfactorily with the reported spectrum of SO3. These five new bands are tentatively assigned to an intermediate 1,3,2-dioxathietane-2,2-dioxide [cyc-(CH2)O(SO2)O] according to comparison with anharmonic vibrational wavenumbers and relative IR intensities predicted for this intermediate. Observation of a small amount of cyc-(CH2)O(SO2)O is consistent with the expected reaction according to the potential energy scheme predicted previously. SO3+HCHO are the major products of the title reaction. The other predicted product channel HCOOH+SO2 was unobserved and its branching ratio was estimated to be <5%.
RESUMO
Criegee intermediates are carbonyl oxides that play critical roles in the ozonolysis of alkenes in the atmosphere. So far, the infrared spectra of only the simplest Criegee intermediates CH2OO and CH3CHOO are reported. We report the transient infrared spectrum of the next member (CH3)2COO, produced from ultraviolet irradiation of a mixture of (CH3)2CI2 + O2 in a flow reactor and detected with a step-scan Fourier-transform spectrometer. The four observed bands near 1424, 1368, 1040, and 887.4 cm-1 provide definitive identification of (CH3)2COO. The observed vibrational wavenumbers and rotational contours agree with those predicted with quantum-chemical calculations; contributions of the hot bands from excited states of the low-lying torsional modes are significant. The rapid decay yields an estimate of the rate coefficient â¼1.6 × 10-10 cm3 molecule-1 s-1 for the self-reaction of (CH3)2COO. The direct IR detection of (CH3)2COO should prove useful for field measurements and laboratory investigations of related Criegee mechanism.
RESUMO
OBJECTIVE: To identify the pathological features of superficial esophageal carcinoma and esophageal intraepithelial neoplasia resected through endoscopic submucosal dissection (ESD). METHODS: The clinical and pathologic profiles of 130 cases were reviewed, including gross type, histology type, infiltration depth, infiltrative growth pattern, presence of tumor budding, lymphatic and vascular invasion, and margin status. RESULTS: The patients had a median age of 62 years old. The predominant gross type was mixed type (78/130, 60.0%), followed by Type 0-II (49/130, 37.7%). The longest diameter of lesionshad a median of 13.8 mm. Morphologically, there were 3 cases (2.3%) of undetermined dysplasia, 25 cases (19.2%) of low grade intraepithelial neoplasia, 56 cases (43.1%) of high grade of intraepithelial neoplasia, and 46 cases (35.4%) of invasive carcinoma. No correlation was found between histological type and gross type. Intramucosal and submucosal invasive carcinoma accounted for 87.0% (40/46) and 13.0% (6/46) of the cases, respectively; sm1 and sm2 accounted for 4.3% (2/46) and 8.7% (4/46) of the cases, respectively. Infiltrative growth pattern was identified as infiltrative growth pattern (INF) a (23/46, 50.0%), INFbeta (17/46, 37.0%) and INFc (6/46, 13.0%). Tumor budding was found in 3 cases and lymphatic and vascular invasion was found in 2 cases. Margin was positive in 30 cases (23.1%). Invasive carcinomahad a higher margin positive rate (24/46, 52.1%) than low grade intraepithelial neoplasia (1/25, 4.0%) and high grade intraepithelial neoplasia (5/56, 89%) (P<0.001). No association between margin positivity and invasive pattern was found (P=0.208). Fifteen cases (11.5%) recurred, with invasive carcinoma being more likely to recur (17.4%, 8/46) than low grade intraepithelial neoplasia (8.0%, 2/25) and high grade intraepithelial neoplasia (8.9%, 5/56) (P<0.05). No association between margin positivity and recurrence rate was found (P= 0.590). CONCLUSION: The superficial esophageal carcinoma and esophageal intraepithelial neoplasia resected by ESD are predominantly mixed type under endoscope, with histological features of high grade intraepithelial neoplasia and invasive carcinoma. Invasive carcinomas are more likely to recur and present with a positive margin.
Assuntos
Carcinoma in Situ/patologia , Neoplasias Esofágicas/patologia , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de NeoplasiaRESUMO
BACKGROUND: Metadherin (MTDH) is a key oncogene in most cancer types, including hepatocellular carcinoma (HCC). Notably, MTDH does not affect the stemness pheno-type or immune infiltration of HCC. AIM: To explore the role of MTDH on stemness and immune infiltration in HCC. METHODS: MTDH expression in HCC tissues was detected using TCGA and GEO databases. Immunohistochemistry was used to analyze the tissue samples. MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines. The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays. Next, we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium. Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR. Flow cytometry, immunofluorescence, and tumor sphere formation assays were used to characterize stem-like cells. The effects of MTDH inhibition on tumor growth were evaluated in vivo. The correlation of MTDH with immune cells, immunomodulators, and chemokines was analyzed using ssGSEA and TISIDB databases. RESULTS: HCC tissues expressed higher levels of MTDH than normal liver tissues. High MTDH expression was associated with a poor prognosis. HCC cells overexpressing MTDH exhibited stronger invasion and migration abilities, exhibited a stem cell-like phenotype, and formed spheres; however, MTDH inhibition attenuated these effects. MTDH inhibition suppressed HCC progression and CD133 expression in vivo. MTDH was positively correlated with immature dendritic, T helper 2 cells, central memory CD8+ T, memory B, activated dendritic, natural killer (NK) T, NK, activated CD4+ T, and central memory CD4+ T cells. MTDH was negatively correlated with activated CD8+ T cells, eosinophils, activated B cells, monocytes, macrophages, and mast cells. A positive correlation was observed between the MTDH level and CXCL2 expression, whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression. CONCLUSION: High levels of MTDH expression in patients with HCC are associated with poor prognosis, promoting tumor stemness, immune infiltration, and HCC progression.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Linfócitos T CD8-Positivos , Fatores de Transcrição/genética , Células-Tronco/patologia , Fenótipo , Linhagem Celular Tumoral , Proteínas de Membrana/genética , Proteínas de Ligação a RNA/genéticaRESUMO
Mental well-being relates to multitudinous lifestyle behaviours and morbidities and underpins healthy aging. Thus far, causal evidence on whether and in what pattern mental well-being impacts healthy aging and the underlying mediating pathways is unknown. Applying genetic instruments of the well-being spectrum and its four dimensions including life satisfaction, positive affect, neuroticism and depressive symptoms (n = 80,852 to 2,370,390), we performed two-sample Mendelian randomization analyses to estimate the causal effect of mental well-being on the genetically independent phenotype of aging (aging-GIP), a robust and representative aging phenotype, and its components including resilience, self-rated health, healthspan, parental lifespan and longevity (n = 36,745 to 1,012,240). Analyses were adjusted for income, education and occupation. All the data were from the largest available genome-wide association studies in populations of European descent. Better mental well-being spectrum (each one Z-score higher) was causally associated with a higher aging-GIP (ß [95% confidence interval (CI)] in different models ranging from 1.00 [0.82-1.18] to 1.07 [0.91-1.24] standard deviations (s.d.)) independent of socioeconomic indicators. Similar association patterns were seen for resilience (ß [95% CI] ranging from 0.97 [0.82-1.12] to 1.04 [0.91-1.17] s.d.), self-rated health (0.61 [0.43-0.79] to 0.76 [0.59-0.93] points), healthspan (odds ratio [95% CI] ranging from 1.23 [1.02-1.48] to 1.35 [1.11-1.65]) and parental lifespan (1.77 [0.010-3.54] to 2.95 [1.13-4.76] years). Two-step Mendelian randomization mediation analyses identified 33 out of 106 candidates as mediators between the well-being spectrum and the aging-GIP: mainly lifestyles (for example, TV watching and smoking), behaviours (for example, medication use) and diseases (for example, heart failure, attention-deficit hyperactivity disorder, stroke, coronary atherosclerosis and ischaemic heart disease), each exhibiting a mediation proportion of >5%. These findings underscore the importance of mental well-being in promoting healthy aging and inform preventive targets for bridging aging disparities attributable to suboptimal mental health.
Assuntos
Estudo de Associação Genômica Ampla , Envelhecimento Saudável , Análise da Randomização Mendeliana , Saúde Mental , Humanos , Envelhecimento Saudável/genética , Envelhecimento Saudável/psicologia , Satisfação Pessoal , Feminino , Masculino , Longevidade/genética , Depressão/genética , Depressão/epidemiologia , Idoso , Fenótipo , Nível de Saúde , Resiliência Psicológica , Pessoa de Meia-Idade , Neuroticismo , Envelhecimento/genética , Envelhecimento/psicologiaRESUMO
Carpal tunnel syndrome (CTS) has been reported as one of the most common peripheral neuropathies. Carpal tunnel segmentation from magnetic resonance (MR) images is important for the evaluation of CTS. To date, manual segmentation, which is time-consuming and operator dependent, remains the most common approach for the analysis of the carpal tunnel structure. Therefore, we propose a new knowledge-based method for automatic segmentation of the carpal tunnel from MR images. The proposed method first requires the segmentation of the carpal tunnel from the most proximally cross-sectional image. Three anatomical features of the carpal tunnel are detected by watershed and polygonal curve fitting algorithms to automatically initialize a deformable model as close to the carpal tunnel in the given image as possible. The model subsequently deforms toward the tunnel boundary based on image intensity information, shape bending degree, and the geometry constraints of the carpal tunnel. After the deformation process, the carpal tunnel in the most proximal image is segmented and subsequently applied to a contour propagation step to extract the tunnel contours sequentially from the remaining cross-sectional images. MR volumes from 15 subjects were included in the validation experiments. Compared with the ground truth of two experts, our method showed good agreement on tunnel segmentations by an average margin of error within 1 mm and dice similarity coefficient above 0.9.
Assuntos
Algoritmos , Imageamento por Ressonância Magnética/métodos , Reconhecimento Automatizado de Padrão/métodos , Síndrome do Túnel Carpal/diagnóstico , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodosRESUMO
A portable device is conducive to the on-site detection of heavy metal ions at trace level in food and the prevention of related food safety issues. In this work, an electrochemical device stacked up with flat electrodes was developed for the detection of Pb2+ and Cd2+. The top layer of the device is a carbon paper as working electrode, which is modified with amino functionalized cobalt-based metal-organic framework and gold nanoparticles. The bottom layer was constructed with the carbon counter electrode and Ag/AgCl reference electrode, and a punched sample cell (Φ = 8 mm) was in the middle. The proposed method could simultaneously determinate Pb2+ and Cd2+ via anodic stripping voltammetry with the detection limit of 7.0 × 10-2 ng mL-1 and 1.1 × 10-2 ng mL-1, and was applied in real food samples (drinking water, juice, tea, grain, fruits, vegetables, liver and aquatic products) with the recovery of 91.2-105.4 % and 90.2-111.2 %, respectively.
Assuntos
Nanopartículas Metálicas , Estruturas Metalorgânicas , Cádmio , Carbono , Eletrodos , Ouro , Íons , ChumboRESUMO
OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of Governor Vessel on chloridion (Cl-) homeostasis and the expression of γ-aminobutyric acid (GABA) and Na+-K+-Cl- cotransporter 1 (NKCC1) in the cerebral cortex of cerebral ischemia-reperfusion injury (CIRI) model rats, so as to explore its mechanism underl-ying alleviating limb spasm after stroke. METHODS: Forty-five male SD rats were randomly divided into normal, sham-operation, model, EA and baclofen groups, with 9 rats in each group. The CIRI model was established by occlusion of the middle cerebral artery and reperfusion. EA(100 Hz) was applied to "Dazhui" (GV14), "Jizhong"(GV6) and "Houhui" for 30 min. Rats of the baclofen group received gavage of baclofen solution (0.4 mg/kg, 1 mL/100 g), once daily for 7 consecutive days. Neurological deficit score was assessed according to Zea Longa's method. The muscular tone of quadriceps femoris of the limb was evaluated by modified Ashworth scale and electrophysiological recor-ding methods, separately. TTC staining was used to detect cerebral infarction volume, and the brain water content of rats in each group was determined by wet and dry weight method. The contents of Cl- and GABA in the cerebral cortex were detected by colorimetric method, and the expression levels of NKCC1 mRNA and protein in the cerebral cortex were detected by quantitative real-time PCR and Western blot, separately. RESULTS: No significant differences were found between the normal and sham-operation groups in all the indexes. Compared with the normal and sham-operation groups, the neurological deficit score, modified Ashworth muscle tone score, brain water content, cerebral infarct volu-me percent, Cl- content and expression levels of NKCC1 mRNA and protein were all evidently increased (P<0.01), and muscle tone of electrophyiological electromyogram (EMG) signal and GABA content were strikingly decreased (P<0.01) in the model group. Compared with the model group, both EA and baclofen groups had an obvious increase in EMG signal displayed muscle tone, and GABA content (P<0.05, P<0.01), and a marked decrease in the neurological deficit score, modified Ashworth score, brain water content, cerebral infarct percent, Cl- content and expression levels of NKCC1 mRNA and protein (P<0.05, P<0.01). CONCLUSION: EA stimulation of acupoints of the Governor Vessel can improve the degree of limb spasm and reduce the degree of cerebral edema and infarction in rats with stroke, which may be related to its functions in protecting Cl- homeostasis, up-regulating GABA concentration, and down-regulating the expression of NKCC1 protein and mRNA in the cerebral cortex.
Assuntos
Eletroacupuntura , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Animais , Masculino , Ratos , Baclofeno , Córtex Cerebral , Infarto Cerebral/genética , Infarto Cerebral/terapia , Ácido gama-Aminobutírico , Reperfusão , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/terapia , Ratos Sprague-DawleyRESUMO
Alzheimer's disease (AD) is closely related to hippocampal synapse loss, which can be alleviated by running exercise. However, further studies are needed to determine whether running exercise reduces synapse loss in the hippocampus in an AD model by regulating microglia. Ten-month-old male wild-type mice and APP/PS1 mice were randomly divided into control and running groups. All mice in the running groups were subjected to voluntary running exercise for four months. After the behavioral tests, immunohistochemistry, stereological methods, immunofluorescence staining, 3D reconstruction, western blotting and RNA-Seq were performed. Running exercise improved the spatial learning and memory abilities of APP/PS1 mice and increased the total number of dendritic spines, the levels of the PSD-95 and Synapsin Ia/b proteins, the colocalization of PSD-95 and neuronal dendrites (MAP-2) and the number of PSD-95-contacting astrocytes (GFAP) in the hippocampi of APP/PS1 mice. Moreover, running exercise reduced the relative expression of CD68 and Iba-1, the number of Iba-1+ microglia and the colocalization of PSD-95 and Iba-1+ microglia in the hippocampi of APP/PS1 mice. The RNA-Seq results showed that some differentially expressed genes (DEGs) related to the complement system (Cd59b, Serping1, Cfh, A2m, and Trem2) were upregulated in the hippocampi of APP/PS1 mice, while running exercise downregulated the C3 gene. At the protein level, running exercise also reduced the expression of advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGE), C1q and C3 in the hippocampus and AGEs and RAGE in hippocampal microglia in APP/PS1 mice. Furthermore, the Col6a3, Scn5a, Cxcl5, Tdg and Clec4n genes were upregulated in the hippocampi of APP/PS1 mice but downregulated after running, and these genes were associated with the C3 and RAGE genes according to protein-protein interaction (PPI) analysis. These findings indicate that long-term voluntary exercise might protect hippocampal synapses and affect the function and activation of microglia, the AGE/RAGE signaling pathway in microglia and the C1q/C3 complement system in the hippocampus in APP/PS1 mice, and these effects may be related to the Col6a3, Scn5a, Cxcl5, Tdg and Clec4n genes. The current results provide an important basis for identifying targets for the prevention and treatment of AD.
Assuntos
Doença de Alzheimer , Precursor de Proteína beta-Amiloide , Atividade Motora , Animais , Masculino , Camundongos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Complemento C1q/genética , Complemento C1q/metabolismo , Espinhas Dendríticas/metabolismo , Modelos Animais de Doenças , Produtos Finais de Glicação Avançada/metabolismo , Produtos Finais de Glicação Avançada/farmacologia , Hipocampo/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos Transgênicos , Microglia/metabolismo , Presenilina-1/genética , Presenilina-1/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Receptores Imunológicos/metabolismoRESUMO
The medial prefrontal cortex (mPFC), one of the most vulnerable brain regions in Alzheimer's disease (AD), plays a critical role in cognition. Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein-1 (LINGO-1) negatively affects nerve growth in the central nervous system; however, its role in the pathological damage to the mPFC remains to be studied in AD. In this study, an anti-LINGO-1 antibody was administered to 10-month-old APP/PS1 mice, and behavioral tests, stereological methods, immunohistochemistry and immunofluorescence were used to answer this question. Our results revealed that LINGO-1 was highly expressed in the neurons of the mPFC of AD mice, and the anti-LINGO-1 antibody improved prefrontal cortex-related function and reduced the protein level of LINGO-1, atrophy of the volume, Aß deposition and massive losses of synapses and neurons in the mPFC of AD mice. Antagonizing LINGO-1 could effectively alleviate the pathological damage in the mPFC of AD mice, which might be an important structural basis for improving prefrontal cortex-related function. Abnormal expression of LINGO-1 in the mPFC may be one of the key targets of AD, and the effect initiated by the anti-LINGO-1 antibody may provide an important basis in the search for drugs for the prevention and treatment of AD.
Assuntos
Doença de Alzheimer , Neurônios , Camundongos , Animais , Camundongos Transgênicos , Neurônios/metabolismo , Doença de Alzheimer/metabolismo , Sinapses/metabolismo , Córtex Pré-Frontal/metabolismo , Modelos Animais de Doenças , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismoRESUMO
Human longevity correlates with socio-economic status, and there is evidence that educational attainment increases human lifespan. However, to inform meaningful health policies, we need fine-grained causal evidence on which dimensions of socio-economic status affect longevity and the mediating roles of modifiable factors such as lifestyle and disease. Here we performed two-sample Mendelian randomization analyses applying genetic instruments of education, income and occupation (n = 248,847 to 1,131,881) to estimate their causal effects and consequences on parental lifespan and self-longevity (n = 28,967 to 1,012,240) from the largest available genome-wide association studies in populations of European ancestry. Each 4.20 years of additional educational attainment were causally associated with a 3.23-year-longer parental lifespan independently of income and occupation and were causally associated with 30-59% higher odds of self-longevity, suggesting that education was the primary determinant. By contrast, each one-standard-deviation-higher income and one-point-higher occupation was causally associated with 3.06-year-longer and 1.29-year-longer parental lifespans, respectively, but not independently of the other socio-economic indicators. We found no evidence for causal effects of income or occupation on self-longevity. Mediation analyses conducted in predominantly European-descent individuals through two-step Mendelian randomization suggested that among 59 candidates, cigarettes per day, body mass index, waist-to-hip ratio, hypertension, coronary heart disease, myocardial infarction, stroke, Alzheimer's disease, type 2 diabetes, heart failure and lung cancer individually played substantial mediating roles (proportion mediated, >10%) in the effect of education on specific longevity outcomes. These findings inform interventions for remediating longevity disparities attributable to socio-economic inequality.
Assuntos
Diabetes Mellitus Tipo 2 , Longevidade , Humanos , Longevidade/genética , Análise da Randomização Mendeliana/métodos , Estudo de Associação Genômica Ampla , População Europeia , Classe SocialRESUMO
The sensitivity and selectivity of electrochemical analysis are challenging due to the materials used for electrode modification as well as electrical conductivity, catalytic activity and recognition ability of the working electrode. In this work, a portable 3D-printed electrochemical electrode clamp was designed and applied in combination with the developed covalent organic framework (COF DQTP)-modified pencil graphite electrode (DQTP/PGE). The ß-ketoenamine-linked COF DQTP synthesized by 1,3,5-triformylphloroglucinol (TP) and 2,6-diaminoanthraquinone (DQ) through solvothermal method is a porous crystalline with excellent conductivity and large periodic π-arrays, coupled with commercial available pencil graphite electrode to fabricate a disposable sensor for simultaneous determination of environmental endocrine disruptors bisphenol A and bisphenol S. The DQTP/PGE sensor exhibited high electrical conductivity and catalytic activity, and a good linearity was obtained in a range of 0.5-30 µM for two bisphenols with a detection limit of 0.15 µM (S/N = 3). Moreover, the sensor showed a reproducible and stable response over one month with negligible interference, and an accepted recovery with real food packaging samples.
Assuntos
Grafite , Estruturas Metalorgânicas , Compostos Benzidrílicos , Eletrodos , Fenóis , SulfonasRESUMO
OBJECTIVE: To observe the effect of electroacupuncture (EA) of Governor Vessel (GV) on the expressions of glutamate decarboxylase 67 (GAD67) and γ-aminobutyric acid transaminase (GABA-T) in the cerebral cortex of rats with post-stroke limb spasticity, so as to explore its mechanism underlying improvement of limb spasticity. METHODS: Twenty four male SD rats were randomly and equally divided into control, sham operation, model, and EA groups. The cerebral ischemia model was established by occlusion of the middle cerebral artery (MCAO). EA (100 Hz, 1-3 mA) was applied to "Dazhui"(GV14), "Jizhong"(GV6) and "Houhui"( anteromedial of transverse process of the sixth lumbar vertebra) for 30 min, once daily for 7 consecutive days. The neurologic deficit score (0-5 points) was evaluated according to Zea Longa's method, and the muscular tension severity (0-5 points) was assessed according to the modified Ashworth muscle tone rating scale, and the tension signals of the quadriceps ferroris of the affected limb were recorded using tonotransducer and BL-420F electrophysiological recorder. The expression levels of GAD67 and GABA-T proteins and mRNAs in the cerebral cortex were detected by immunohistochemistry, fluorescence quantitative real-time PCR and Western blot, separately. RESULTS: After modeling, the neurological deficit score, muscle tone score, and the expression levels of GABA-T mRNA and protein in cerebral cortex were significantly increased (P<0.01, P<0.05), tension signal value and the expression levels of GAD67 mRNA and protein in cerebral cortex were significantly decreased (P<0.01) in the model group relevant to the control and sham operation groups. Following the intervention, the neurological deficit score, muscle tone score, and expression levels of GABA-T mRNA and protein in cerebral cortex were significantly decreased (P<0.01), tension signal value and the expression levels of GAD67 mRNA and protein in cerebral cortex were significantly increased (P<0.01, P<0.05) in the EA group in contrast to the model group. CONCLUSION: EA stimulation of Governor Vessel can ameliorate the limb spasticity symptom in MCAO rats, which may be associated with its functions in increasing the expressions of GAD67 protein and mRNA and inhibiting the expressions of GABA-T protein and mRNA, thereby playing the inhibitory role of GABA.
Assuntos
Isquemia Encefálica , Eletroacupuntura , Glutamato Descarboxilase/metabolismo , Acidente Vascular Cerebral , Animais , Córtex Cerebral , Masculino , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Transaminases , Ácido gama-AminobutíricoRESUMO
OBJECTIVE: To compare the clinical efficacy between wrist-ankle acupuncture and conventional acupuncture on shoulder-hand syndrome (SHS) phaseâ after stroke. METHODS: A total of 64 patients with SHS phaseâ after stroke were randomized into a wrist-ankle acupuncture group and a conventional acupuncture group, 32 cases in each group. On the basis treatment of internal medicine and conventional rehabilitation, wrist-ankle acupuncture was applied at upper 4 area, upper 5 area and upper 6 area on the affected side in the wrist-ankle acupuncture group, while acupuncture was applied at Jianyu (LI 15), Quchi (LI 11), Shousanli (LI 10), etc. on the affected side in the conventional acupuncture group. The treatment was given 30 min each time, once a day, 5 days a week for 3 weeks in both groups. Before and after treatment, the visual analogue scale (VAS) score, degree of hand swelling, shoulder-hand syndrome scale (SHSS) score, Fugl-Meyer assessment for upper extremity (FMA-UE) score and modified Barthel index (MBI) score were observed, and the clinical therapeutic effect was evaluated in both groups. RESULTS: After treatment, the VAS scores, degree of hand swelling and SHSS scores were decreased (P<0.05), and the FMA-UE scores and MBI scores were increased (P<0.05) compared before treatment in both groups; in the wrist-ankle acupuncture group, the VAS score, degree of hand swelling and SHSS score were lower (P<0.05), and the FMA-UE score and MBI score were higher (P<0.05) than those in the conventional acupuncture group. The total effective rate was 96.9% (31/32) in the wrist-ankle acupuncture group, which was superior to 90.6% (29/32) in the conventional acupuncture group (P<0.05). CONCLUSION: Wrist-ankle acupuncture can effectively relieve pain and hand swelling, improve motor function of upper extremity and self-care ability of daily life in patients with shoulder-hand syndrome phaseâ after stroke, the therapeutic effect is superior to conventional acupuncture.
Assuntos
Terapia por Acupuntura , Distrofia Simpática Reflexa , Acidente Vascular Cerebral , Pontos de Acupuntura , Tornozelo , Humanos , Distrofia Simpática Reflexa/terapia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Extremidade Superior , PunhoRESUMO
In this work, electro-enhanced solid-phase microextraction (EE-SPME) and covalent organic framework (COF) were adopted to improve the extraction efficiency. A conductive COF synthesized of 2,6-diaminoanthraquinone (DQ) and 1,3,5-triformylphloroglucinol (TP) was in situ bonded to the stainless steel wire via facile solution-phase approach and used as the EE-SPME fiber coating to preconcentrate a typical endocrine disruptor bisphenol A (BPA). Compared with conventional SPME, the DQTP bonded fiber coupled with EE-SPME device exhibited higher extraction efficiency and achieved extraction equilibrium within 10 min. The proposed approach based on EE-SPME and gas chromatography coupled with flame ionization detector gave a linear range of 0.05-10 µg mL-1 and detection limit of 3 µg L-1 (S/N = 3) with good precision (<6.7%) and reproducibility (<7.1%) spiked with 0.1, 0.5, 1.0 µg mL-1 BPA. Quantitative determination of BPA in extracts of food packagings (mineral water bottles, milk boxes and milk tea cups) was achieved with recoveries from 88.6 to 118.0%.
Assuntos
Estruturas Metalorgânicas , Poluentes Químicos da Água , Adsorção , Compostos Benzidrílicos , Limite de Detecção , Fenóis , Reprodutibilidade dos Testes , Microextração em Fase Sólida , Aço Inoxidável , Poluentes Químicos da Água/análiseRESUMO
OBJECTIVE: To compare the effect of electroacupuncture (EA) of acupoint group for "reinforcing the kidney and regulating Governor Vessel" and acopoint group for "reinforcing the kidney and lung and regulating Governor Vessel" on lear-ning-memory ability and expression of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) proteins in the hippocampus and prefrontal cortex (PFC) in Alzheimer's disease ï¼ADï¼ rats, so as to explore the efficacy of the two acupoint groups and mechanisms underlying improvement of AD. METHODS: Forty male SD rats were randomly divided into control, sham operation, model, "Baihui" + "Shenshu" (GV20+BL23, for "reinforcing the kidney and regulating Governor Vessel") EA and GV20+BL23+ "Feishu" (BL13, GV20+BL23+BL13, for "reinforcing the kidney and lung and regulating Governor Vessel") EA groups (n=8 rats in each group). The AD model was established by bilateral injection of amyloid ß peptide ï¼Aß25-35ï¼10 µL) into bilateral hippocampus, and rats of the sham operation group received injection of normal saline. After successful establishment of the modelï¼EA (2 Hz, 2 mA) was applied to these acupoints for 15 min, once daily for 10 days. Then, the learning-memory ability was assessed by using Morris water maze tests, and the expression levels of TNF-α and IL-1ß proteins in the PFC and hippocampus tissues were detected by using Western blot. RESULTS: Following modeling, the average escape latency of place navigation test were significantly increased (P<0.05) and the platform crossing times of spatial probe test was significantly decreased in the model group than in the control and sham operation groups (P<0.05). The expression levels of IL-1ß and TNF-α proteins in the PFC and hippocampus were apparently up-regulated in the model group than in the control and the sham operation groups (P<0.000 1, P<0.001, P<0.01). After the intervention, the increase of the average escape latency and expression of IL-1ß and TNF-α in the PFC and hippocampus, and the decrease of space exploration test were revised in both GV20+BL23 EA and GV20+BL23+BL13 EA groups (P<0.05,P<0.01). No significant differences were found between the GV20+BL23 and GV20+BL23+BL13 EA groups in the above mentioned indexes (P>0.05). CONCLUSION: EA of both GV20+BL23 and GV20+BL23+BL13 acupoint can improve learning-memory ability of AD rats, which is associated with their effects in down-regulating the expression of IL-1ß and TNF-α in the PFC and hippocampus to reduce inflammatory reaction. There were no significant differences between the two acupoint groups in the therapeutic effects.
Assuntos
Pontos de Acupuntura , Doença de Alzheimer , Eletroacupuntura , Peptídeos beta-Amiloides , Animais , Hipocampo , Interleucina-1beta , Masculino , Córtex Pré-Frontal , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of insulin phosphatidylinositol-3 kinase/glycogen synthetase kinase-3α (PI3K/GSK3α) signal pathway related proteins in the hippocampus in mice with Alzheimer's disease (AD), and to explore the regulatory mechanism of EA on improving the pathological characteristics of AD. METHODS: Twelve male APP/PS1 double transgenic mice were randomly divided a model group and a treatment group, 6 mice in each group; another 6 wild-type male mice were taken as the control group. The mice in the treatment group were treated with EA (continuous wave, 2 Hz of frequency) at "Baihui" (GV 20) and bilateral "Shenshu" (BL 23), once a day; 7-day treatment was taken as a course of treatment, and 2 courses of treatment were given. The immunohistochemistry method and Western blot method were used to detect the distribution and expression level of hippocampal PI3K/GSK3α signal pathway related proteins P85α, P110α, GSK3α and pS21GSK3α, and the number of hippocampal senile plaques (SP) was observed. RESULTS: The proteins of P85α, P110α, GSK3α and pS21GSK3α were mainly distributed in the cytoplasm of hippocampal neurons, and the GSK3α was also distributed in the axons of neurons in the model group and the treatment group. The immunohistochemistry results showed that the distribution level of GSK3α in the hippocampus in the model group was significantly higher than that in the control group (P<0.001), and the distribution level of pS21GSK3α, P85α and P110α was significantly decreased (P<0.01, P<0.001); compared with the model group, the distribution level of GSK3α in the hippocampus in the treatment group was significantly decreased (P<0.001), and the distribution level of pS21GSK3α, P85α and P110α in hippocampus was significantly increased (P<0.05, P<0.001). The Western blot results showed compared with the control group, the expression of pS21GSK3α, P85α and P110α as well as the ratio of pS21GSK3α/GSK3α in the hippocampus in the model group were significantly decreased (P<0.001), and the expression of GSK3α was increased (P<0.05); compared with the model group, the expression of pS21GSK3α, P85α, P110α and the ratio of pS21GSK3α/GSK3α in the hippocampus in the treatment group were significantly increased (P<0.01, P<0.001), and the expression of GSK3α was decreased (P<0.05). Compared with the control group, the number of hippocampal SP in the model group was significantly increased (P<0.001); compared with the model group, the number of hippocampal SP in the treatment group was significantly decreased (P<0.01). CONCLUSION: EA could effectively regulate the expression of PI3K/GSK3α signal pathway related proteins in the hippocampus in mice with AD, so as to reduce the formation and deposition of SP.