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BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a common complication in patients with cirrhosis. The diagnosis of SBP is still mostly based on ascites cultures and absolute ascites polymorphonuclear (PMN) cell count, which restricts the widely application in clinical settings. This study aimed to identify reliable and easy-to-use biomarkers for both diagnosis and prognosis of cirrhotic patients with SBP. METHODS: We conducted a retrospective study including 413 cirrhotic patients from March 2013 to July 2022 in the First Affiliated Hospital of Guangxi Medical University. Patients' clinical characteristics and laboratory indices were collected and analyzed. Two machine learning methods (Xgboost and LASSO algorithms) and a logistic regression analysis were adopted to screen and validate the indices associated with the risk of SBP. A predictive model was constructed and validated using the estimated area under curve (AUC). The indices related to the survival of cirrhotic patients were also analyzed. RESULTS: A total of 413 cirrhotic patients were enrolled in the study, of whom 329 were decompensated and 84 were compensated. 52 patients complicated and patients with SBP had a poorer Child-Pugh score (P < 0.05). Patients with SBP had a greater proportion of malignancies than those without SBP(P < 0.05). The majority of laboratory test indicators differed significantly between patients with and without SBP (P < 0.05). Albumin, neutrophil-to-lymphocyte ratio (NLR), and ferritin-to-neutrophil ratio (FNR) were found to be independently associated with SBP in decompensated cirrhotic patients using LASSO algorithms, and logistic regression analysis. The model established by the three indices showed a high predictive value with an AUC of 0.808. Furthermore, increased neutrophils, ALP, and C-reactive protein-to-albumin ratio (CAR) were associated with the shorter survival time of patients with decompensated cirrhosis, and the combination of these indices showed a greater predictive value for cirrhotic patients. CONCLUSIONS: The present study identified FNR as a novel index in the diagnosis of SBP in decompensated patients with cirrhosis. A model based on neutrophils, ALP and CAR showed high performance in predicting the prognosis of patients with decompensated cirrhosis.
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Infecções Bacterianas , Peritonite , Humanos , Prognóstico , Ascite/complicações , Estudos Retrospectivos , Infecções Bacterianas/complicações , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , China , Peritonite/microbiologia , Cirrose Hepática/diagnóstico , Proteína C-ReativaRESUMO
In recent years, porous titanium (Ti) scaffolds with BaTiO3 coatings have been designed to promote bone regeneration. However, the phase transitions of BaTiO3 have been understudied, and their coatings have yielded low effective piezoelectric coefficients (EPCs < 1 pm/V). In addition, piezoelectric nanomaterials bring many advantages in eliciting cell-specific responses. However, no study has attempted to design a nanostructured BaTiO3 coating with high EPCs. Herein, nanoparticulate tetragonal phase BaTiO3 coatings with cube-like nanoparticles but different effective piezoelectric coefficients were fabricated via anodization combining two hydrothermal processes. The effects of nanostructure-mediated piezoelectricity on the spreading, proliferation, and osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (hJBMSCs) were explored. We found that the nanostructured tetragonal BaTiO3 coatings exhibited good biocompatibility and an EPC-dependent inhibitory effect on hJBMSC proliferation. The nanostructured tetragonal BaTiO3 coatings of relatively smaller EPCs (<10 pm/V) exhibited hJBMSC elongation and reorientation, broad lamellipodia extension, strong intercellular connection and osteogenic differentiation enhancement. Overall, the improved hJBMSC characteristics make the nanostructured tetragonal BaTiO3 coatings promising for application on implant surfaces to promote osseointegration.
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Células-Tronco Mesenquimais , Nanoestruturas , Humanos , Osteogênese , Titânio/química , Diferenciação Celular , Nanoestruturas/químicaRESUMO
BACKGROUND D-dimer level can reflect the hypercoagulable state of atrial fibrillation (AF) and predict thromboembolic events. However, no effective indicator associated with D-dimer of AF patients has been found to prevent thromboembolic events in AF. This retrospective study from a single center aimed to investigate the correlation between serum albumin and D-dimer levels in 909 patients with non-valvular AF (NVAF) and 653 subjects in sinus rhythm. MATERIAL AND METHODS A total of 909 NVAF patients and 653 sex- and age-matched sinus rhythm participants were used to compare serum albumin and D-dimer levels. Serum albumin was determined by colorimetry, and D-dimer level was determined by latex-enhanced photoimmunoassay. We analyzed the correlation of serum albumin and D-dimer with NVAF by correlation analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve. RESULTS Albumin (P<0.001) and D-dimer (P<0.001) were significantly associated with NVAF. Among NVAF patients, D-dimer level was negatively correlated with albumin levels (P<0.001), and albumin level was an independent risk factor of abnormal D-dimer level (>0.5 ug/mL), which was also an effective predictor of abnormal D-dimer level (the area under the ROC curve was 0.77, P<0.001), and the optimal cutoff value was 36.95 g/L. CONCLUSIONS Serum albumin and D-dimer levels were significantly associated with NVAF. In NVAF patients, D-dimer level was inversely correlated with albumin levels, and albumin level was an independent risk factor and effective predictor of abnormal D-dimer level. Close examination and supplementation of serum albumin can prevent thromboembolic events, but further clinical research and confirmation are needed.
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Fibrilação Atrial , Tromboembolia , Humanos , Fibrilação Atrial/complicações , Estudos Retrospectivos , Albumina Sérica , Biomarcadores , Tromboembolia/etiologiaRESUMO
BACKGROUND The transient receptor potential melastatin 8 (TRPM8) was found to be expressed abnormally in a variety of tumors and is associated with unfavorable prognosis in human cancers. However, its clinical significance in pancreatic cancer (PC) is mostly unknown. MATERIAL AND METHODS qRT-PCR was performed to measure the expression of TRPM8 in 110 pairs of PC tissues and the adjacent non-cancerous tissues. The association of TRPM8 expression with the clinical characters of PC patients was analyzed using the chi-square test. Furthermore, the prognostic value of TRPM8 was determined with Kaplan-Meier survival curve and Cox regression analysis. RESULTS We found that the expression level of TRPM8 was significantly elevated in PC tissues compared to the non-cancerous controls (P<0.001). In addition, a close relationship was observed between elevated TRPM8 expression with large tumor size (P=0.001), advanced TNM (P=0.013), and distant metastasis (P=0.034). Survival analysis suggested that patients with high TRPM8 expression has worse OS (P=0.001) and DFS (P<0.001) than those with low TRPM8 expression. Moreover, TRPM8 was confirmed as a valuable prognostic biomarker for OS (HR=1.913; 95% CI: 1.020-3.589; P=0.043) or DFS (HR=2.374; 95% CI: 1.269-4.443; P=0.007) of PC patients. CONCLUSIONS This study shows that TRPM8 expression is significantly up-regulated in PC and it might be a useful prognostic factor for patients with PC.
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Neoplasias Pancreáticas/metabolismo , Canais de Cátion TRPM/biossíntese , Adulto , Idoso , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Prognóstico , Análise de Sobrevida , Canais de Cátion TRPM/genética , TranscriptomaRESUMO
DREAM (downstream regulatory element antagonist modulator), Calsenilin and KChIP3 (potassium channel interacting protein 3) belong to the neuronal calcium sensor (NCS) superfamily, which transduces the intracellular calcium signaling into a variety of activities. They are encoded by the same gene locus, but have distinct subcellular locations. DREAM was first found to interact with DRE (downstream regulatory element) site in the vicinity of the promoter of prodynorphin gene to suppress gene transcription. Calcium can disassemble this interaction by binding reversibly to DREAM protein on its four EF-hand motifs. Apart from having calcium dependent DRE site binding, DREAM can also interact with other transcription factors, such as cAMP responsive element binding protein (CREB), CREB-binding protein (CBP) and cAMP responsive element modulator (CREM), by this concerted actions, DREAM extends the gene pool under its control. DREAM is predominantly expressed in central nervous system with its highest level in cerebellum, and accumulating evidence demonstrated that DREAM might play important roles in pain sensitivity. Novel findings have shown that DREAM is also involved in learning and memory processes, Alzheimer's disease and stroke. This mini-review provides a brief introduction of its discovery history and protein structure properties, focusing on the mechanism of DREAM nuclear translocation and gene transcription regulation functions.
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Regulação da Expressão Gênica , Proteínas Interatuantes com Canais de Kv/fisiologia , Proteínas Repressoras/fisiologia , Animais , Sinalização do Cálcio/fisiologia , Humanos , Proteínas Interatuantes com Canais de Kv/genética , Limiar da Dor , Proteínas Repressoras/genéticaRESUMO
Objective To observe the effect of Fuxin Mixture(FXM) on the ß,-AR(adrenergic receptor) -cAMP(cyclic adenosine monophosphate, cAMP) -PKA ( protein kinase A, PKA) pathway of rats with heart failure. Methods Male Wistar rats were randomly divided into blank control group, captopril group, FXM low dose group, FXM high dose group and model group.Models of CHF were established. After drug intervention for 6 weeks, the left ventricular mass index (LVMI) was analysed, the expression of ß1 - AR mRNA in myocardial tissue was measured,the level of cAMP in rat plasma,the OD value PKA content of spleen tissue homogenate were detected. Results Compared with the blank control group, the LVMI and the cAMP in plasma of model group were increased (P <0. 05), the expression of ß1,-AR mRNA, the OD value of spleen tissue homogenate and PKA were decreased (P <0. 01). Compared with the model group, the LVMI were decreased,and the expression of ß1-AR mRNA were increased in FXM high dose group and captopril group (P <0. 01 , P <0. 05) ; the level of cAMP in plasma of each drug group were decreased (P <0. 01) , the OD value of spleen tissue homogenate and PKA were increased (P <0. 01). Compared with the captopril group, the expression of ß1-AR mRNA, the OD value of spleen tissue homogenate and PKA were decreased, and the LVMI and the cAMP were increased in the FXM low dose group (P <0. 01 , P <0. 05). Compared with the FXM low dose group, the LVMI and the cAMP of FXM high dose group were decreased (P <0. 05), the expression of ß1-AR mRNA, the OD value of spleen tissue homogenate and PKA were increased (P <0. 01). Conclusion FXM could play the role of anti-heart fail- ure through regulating P1-AR-cAMP-PKA pathway.
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Proteínas Quinases Dependentes de AMP Cíclico , Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Animais , AMP Cíclico , Proteínas Quinases Dependentes de AMP Cíclico/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Masculino , Miocárdio , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
The superfamily of importin-ß-related proteins is the largest class of nuclear transport receptors and can be generally divided into importins and exportins according to their transport directions. Eleven importins and seven exportins have been identified, and the expression patterns of both classes are important for their functions in nucleocytoplasmic transport activities. This study demonstrates that all of the importins (importin-ß; transportin-1, -2, and -3; and importin-4, -5, -7, -8, -9, -11, and -13) and all the exportins (exportin-1, -2, -4, -5, -6, -7, and -t) are differentially expressed in the cerebral cortex, cerebellum, hippocampus, and brainstem and in primary cultures of cerebral cortical astrocytes and neurons. For astrocytes, we observed that different importins and exportins displayed different expression changes during 0-6 hr of ischemia treatment, especially an increase of both the mRNA and the protein of exportin-7. Immunostaining showed that exportin-7 accumulated inside the nucleus and around the nuclear envelope. In addition, we noticed an increased cytoplasmic distribution of one of the cargo proteins of exportin-7, LKB1, an important element in maintaining energy homeostasis. This increased cytoplasmic distribution was accompanied by an increased expression of exportin-7 under ischemia in astrocytes. We demonstrate that exportin-7 responds to ischemia in astrocytes and that this response involves translocation of LKB1, a protein that plays important roles during metabolic stress, from the nucleus to the cytoplasm.
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Astrócitos/metabolismo , Astrócitos/ultraestrutura , Isquemia Encefálica/patologia , Regulação da Expressão Gênica/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteína ran de Ligação ao GTP/metabolismo , Proteínas Quinases Ativadas por AMP , Animais , Hipóxia Celular/fisiologia , Núcleo Celular/metabolismo , Células Cultivadas , Embrião de Mamíferos , Regulação da Expressão Gênica/genética , Carioferinas/genética , Carioferinas/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neurônios/citologia , Neurônios/metabolismo , Fotodegradação , Proteínas Serina-Treonina Quinases/genética , Transporte Proteico/genética , Transporte Proteico/fisiologia , RNA Mensageiro/metabolismo , beta Carioferinas/genética , beta Carioferinas/metabolismo , Proteína ran de Ligação ao GTP/genéticaRESUMO
Cadmium (Cd), a highly ubiquitous toxic heavy metal, can contaminate the environment, including agricultural soil, water and air, via industrial runoff and other sources of pollution. Cd accumulated in the body via direct exposure or through the food chain results in neurodegeneration and many other diseases. Previous studies on its toxicity in the central nervous system (CNS) focused mainly on neurons. To obtain a more comprehensive understanding of Cd toxicity for the CNS, we investigated how astrocytes respond to acute and chronic Cd exposure and its toxic molecular mechanisms. When primary cultures of cerebral cortical astrocytes incubated with 1-300 µM CdCl2, morphological changes, LDH release and cell death were observed in a time and dose-dependent manner. Further studies demonstrated that acute and chronic Cd treatment phosphorylated JNK, p38 and Akt to different degrees, while ERK1/2 was only phosphorylated under low doses of Cd (10 µM) exposure. Inhibition of JNK and PI3K/Akt, but not of p38, could partially protect astrocyte from cytotoxicity in chronic and acute Cd exposure. Moreover, Cd also induced a strong calcium signal, while BAPTA, a specific intracellular calcium (Ca(2+)) chelator, prevented Cd-induced intracellular increase of calcium levels in astrocytes; inhibited the Cd-induced activation of ERK1/2, JNK, p38 and Akt; and also significantly reduced astrocyte cell death. All of these results suggested that the Cd-Ca(2+)-MAPK and PI3K/Akt signaling pathways were involved in Cd-induced toxicity in astrocytes. This toxicity involvement indicates that these pathways may be exploited as a target for the prevention of Cd-induced neurodegenerative diseases.
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Astrócitos/efeitos dos fármacos , Cádmio/toxicidade , Sinalização do Cálcio , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Animais , Astrócitos/enzimologia , Relação Dose-Resposta a Droga , Camundongos , Camundongos Endogâmicos ICRRESUMO
Increasing evidence shows that dysregulation of microRNAs is correlated with tumor development. This study was performed to determine the expression of miR-141 and investigate its clinical significance in pancreatic ductal adenocarcinoma (PDAC). Taqman quantitative RT-PCR was used to detect miR-141 expressions in 94 PDAC tissues and 16 nontumorous pancreatic tissues. Correlations between miR-141 expression and clinicopathologic features and prognosis of patients were statistically analyzed. The effects of miR-141 expression on growth and apoptosis of PDAC cell line (PANC-1) were determined by MTT, colony formation, and flow cytometry assays. Potential target genes were identified by luciferase reporter and Western blot assays. The expression level of miR-141 in PDAC tissues was significantly lower than that in corresponding nontumorous tissues. Downregulation of miR-141 correlated with poorer pT and pN status, advanced clinical stage, and lymphatic invasion. Also, low miR-141 expression in PDAC tissues was significantly correlated with shorter overall survival, and multivariate analysis showed that miR-141 was an independent prognostic factor for PDAC patients. Further, functional researches suggested that miR-141 inhibits growth and colony formation, and enhances caspase-3-dependent apoptosis in PANC-1 cells by targeting Yes-associated protein-1 (YAP1). Therefore, miR-141 is an independent prognostic factor for PDAC patients, and functions as a tumor suppressor gene by targeting YAP1.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma/genética , Carcinoma Ductal Pancreático/genética , MicroRNAs/genética , Neoplasias Pancreáticas/genética , Fosfoproteínas/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Apoptose/genética , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Caspase 3 , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , MicroRNAs/biossíntese , Pessoa de Meia-Idade , Pâncreas/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Interferência de RNA , RNA Interferente Pequeno , Fatores de Transcrição , Proteínas de Sinalização YAPRESUMO
BACKGROUND/AIMS: Colorectal cancer (CRC) is one of the most common malignancies, and liver metastasis is one of the major causes of death of CRC. This study aimed to compare the genetic difference between metachronous lesions (MC) and synchronous lesions (SC) and explore the molecular pathology of CRC metastasis. METHODOLOGY: Microarray expression profile data (GSE10961) including 8 MC and 10 SC was downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) between the two groups were identified based on T test. Furthermore, GO enrichment analysis was performed for the down-regulated DEGs using DAVID. Finally, Classify validation of known CRC genes based on previous studies between MC and SC samples was conducted. RESULTS: Total of 36 DEGs including 35 down-regulated DEGs and 1 up-regulated DEGs were identified. The expressional differences of the 5 informative oncogenes: EGFr, PIK3R1, PTGS2 (COX-2), PTGS1 (COX1), and ALOX5AP between SC and MC were really tiny. CONCLUSIONS: Some DEGs, such as NFAT5, OLR1, ERAP2, HOXC6 and TWIST1 might play crucial roles in the regulation of CRC metastasis (both SC and MC) and by disrupting some pathways. However, our results indeed demand further research and experiment.
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Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Primárias Múltiplas/patologia , Segunda Neoplasia Primária/patologia , Transcriptoma , Humanos , Análise de Sequência com Séries de OligonucleotídeosRESUMO
To improve the efficiency of frozen soil excavation, the new shaft tunneling machine was developed. The new shaft tunneling machine exerts pressure on the frozen soil through the cutter under the joint action of its own gravity, the drum rotational force and the inertia force, and the frozen soil is damaged. By unique way of breaking frozen soil to improve the efficiency of frozen soil excavation, the drum rotation speed is one of the factors affecting the performance of frozen soil excavation. This article applies SolidWorks software to establish the model of cutter breaking frozen soil, takes advantage of Hyper Mesh finite element software coupled with LS-DYNA solver to acquire the regular pattern of change in the force change, frozen soil stress-strain and specific energy of cutter crushing frozen soil, etc., which analyzes the destruction of frozen soil when the drum of the new shaft tunneling machine is rotating at the speed of 25-40 rpm. Combine with field test to investigate the mechanism of cutter breaking frozen soil under the optimal drum rotation speed. The investigation results demonstrate that: when frozen soil's self-bearing capacity is lower than the force of cutter, it breaks up and detaches from the soil body, and frozen soil undergoes tensile, compressive and shear damages. For this research, it is instructive for practical engineering.
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Purpose: The association between serum uric acid (SUA) and atrial fibrillation (AF) has been widely focused on and studied in recent years. However, the exact association between SUA and AF is unclear, and the effect of gender on the association between SUA levels and AF has been controversial. This study aimed to investigate the association between SUA levels and non-valvular AF (NVAF) and the potential effect of gender on it. Patients and Methods: A total of 866 NVAF patients (463 males, age 69.44 ± 8.07 years) and 646 sex-matched control patients in sinus rhythm, with no history of arrhythmia were included in this study. t-test, ANOVA, and chi-square test were used for baseline data analysis. The receiver operating characteristic curve, logistic regression and Pearson correlation analysis were used for correlation analysis. Results: Compared to controls, NVAF patients exhibited higher SUA (P<0.001). After adjusting for confounders of NVAF, SUA remained significantly associated with NVAF, regardless of gender (OR= 1.31, 95% CI 1.18-1.43, P<0.001). SUA demonstrated higher predictability and sensitivity in predicting the occurrence of female NVAF compared to male (area under the curve was 0.68 (95% CI 0.64-0.72, P<0.001), sensitivity 87.3%), with the optimal cut-off point identified as 5.72 mg/dL. Furthermore, SUA levels correlated with APOA1, Scr and NT-proBNP in NVAF patients. SUA levels varied significantly among NVAF subtypes. Conclusion: High SUA levels were independently associated with NVAF, regardless of gender. SUA exhibited higher predictability and sensitivity in predicting the occurrence of NVAF in females compared to males. High SUA levels may affect other NVAF-related factors and participate in the pathophysiological process of NVAF.
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4-cyanobenzoic acid serves as a crucial intermediate for the synthesis of various high-value organic compounds. The enzymatic hydrolysis of terephthalonitrile to produce 4-cyanobenzoic acid using nitrilase offers the advantages of a simple reaction pathway, environmental friendliness, and easy product separation. In order to efficiently develop nitrilases that meet industrial production requirements, the virtual screening method used in the study is established and mature. From a total of 371 amino acids in the nitrilase AfNIT, which exhibits activity in terephthalonitrile hydrolysis, three candidate sites (F168, S192, and T201) were identified, and a "small and accurate" mutant library was constructed. The triple mutant F168V/T201N/S192F was screened from this small mutant library with a specific activity of 227.3 U mg-1 , which was 3.8 times higher than that of the wild-type AfNIT. Using the whole-cell biocatalyst containing the mutant F168V/T201N/S192F, terephthalonitrile was successfully hydrolyzed at a concentration of 150 g L-1 to produce 4-cyanobenzoic acid with a final yield of 170.3 g L-1 and a conversion rate of 98.7%. The obtained nitrilase mutant F168V/T201N/S192F in this study can be effectively applied in the biomanufacturing of 4-cyanobenzoic acid using terephthalonitrile as a substrate. Furthermore, the results also demonstrate the significant improvement in predictive accuracy achieved through the latest AI-assisted computer simulation methods. This approach represents a promising and feasible new technological pathway for assisting enzyme engineering research, laying a theoretical foundation for other related studies.
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Aminoidrolases , Benzoatos , Simulação por Computador , Aminoidrolases/genética , Aminoidrolases/químicaRESUMO
Water movement plays vital roles in both physiological and pathological conditions in the brain. Astrocytes are responsible for regulating this water movement and are the major contributors to brain edema in pathological conditions. Aquaporins (AQPs) in astrocytes play critical roles in the regulation of water movement in the brain. AQP1, 3, 4, 5, 8, and 9 have been reported in the brain. Compared with AQP1, 4, and 9, AQP3, 5, and 8 are less studied. Among the lesser known AQPs, AQP5, which has multiple functions identified outside the central nervous system, is also indicated to be involved in hypoxia injury in astrocytes. In our study, AQP5 expression could be detected both in primary cultures of astrocytes and neurons, and AQP5 expression in astrocytes was confirmed in 1- to 4-week old primary cultures of astrocytes. AQP5 was localized on the cytoplasmic membrane and in the cytoplasm of astrocytes. AQP5 expression was downregulated during ischemia treatment and upregulated after scratch-wound injury, which was also confirmed in a middle cerebral artery occlusion model and a stab-wound injury model in vivo. The AQP5 increased after scratch injury was polarized to the migrating processes and cytoplasmic membrane of astrocytes in the leading edge of the scratch-wound, and AQP5 over-expression facilitated astrocyte process elongation after scratch injury. Taken together, these results indicate that AQP5 might be an important water channel in astrocytes that is differentially expressed during various brain injuries.
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Aquaporina 5/metabolismo , Astrócitos/metabolismo , Lesões Encefálicas/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Regulação da Expressão Gênica/fisiologia , Animais , Animais Recém-Nascidos , Hipóxia Celular/fisiologia , Células Cultivadas , Córtex Cerebral/citologia , Modelos Animais de Doenças , Embrião de Mamíferos , Infarto da Artéria Cerebral Média/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Frações Subcelulares/metabolismo , Frações Subcelulares/patologia , Fatores de Tempo , Transfecção , Ferimentos e Lesões/patologiaRESUMO
Astrocyte activation is a hallmark of central nervous system injuries resulting in glial scar formation (astrogliosis). The activation of astrocytes involves metabolic and morphological changes with complex underlying mechanisms, which should be defined to provide targets for astrogliosis intervention. Astrogliosis is usually accompanied by an upregulation of glial fibrillary acidic protein (GFAP). Using an in vitro scratch injury model, we scratched primary cultures of cerebral cortical astrocytes and observed an influx of calcium in the form of waves spreading away from the wound through gap junctions. Using the calcium blocker BAPTA-AM and the JNK inhibitor SP600125, we demonstrated that the calcium wave triggered the activation of JNK, which then phosphorylated the transcription factor c-Jun to facilitate the binding of AP-1 to the GFAP gene promoter to switch on GFAP upregulation. Blocking calcium mobilization with BAPTA-AM in an in vivo stab wound model reduced GFAP expression and glial scar formation, showing that the calcium signal, and the subsequent regulation of downstream signaling molecules, plays an essential role in brain injury response. Our findings demonstrated that traumatic scratch injury to astrocytes triggered a calcium influx from the extracellular compartment and activated the JNK/c-Jun/AP-1 pathway to switch on GFAP expression, identifying a previously unreported signaling cascade that is important in astrogliosis and the physiological response following brain injury.
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Astrócitos/metabolismo , Cálcio/metabolismo , Genes jun/fisiologia , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Fator de Transcrição AP-1/metabolismo , Animais , Astrócitos/citologia , Sinalização do Cálcio/genética , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/metabolismo , Gliose/genética , Camundongos , Camundongos Endogâmicos ICR , Fator de Transcrição AP-1/genética , Ativação TranscricionalRESUMO
OBJECTIVE: To explore the effect of Chinese herbs for Shen invigorating and blood activating (CHSIBA) on the number of endothelial progenitor cells (EPCs) in the bone marrow and the peripheral blood and the signaling pathway of bone marrow matrix metalloproteinase 9 (MMP-9) of the myocardial infarction (MI) model rats. METHODS: The MI rat model was established by ligation. Thirty successfully modeled rats were randomly divided into the high dose CHSIBA group, the low dose CHSIBA group, and the model group, 10 in each group. Besides, another 10 normal rats were recruited as the blank group. Rats in the high dose CHSIBA group and the low dose CHSIBA group were administered with CHSIBA at 3 g/kg and 1.5 g/kg body weight by gastrogavage (by adding them in 4 mL physiological saline), once daily. Rats in the model group and the blank group were administered with 4 mL physiological saline once daily. The EPCs were collected from the bone marrow and the peripheral blood 4 weeks later. Seven days later the CD34/CD133 phenotype was identified in collected sticking wall cells using flow cytometry. The MMP-9 and water soluble Kit ligand (sKitL) were detected using Western blot. The expressions of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1alpha (SDF-1alpha) were detected using ELISA. RESULTS: The CD34/CD133 positive rate and the EPC quantity in the bone marrow and the peripheral blood were higher in the high dose CHSIBA group and the low dose CHSIBA group than in the model group (P < 0.05, P < 0.01). Besides, the expressions of VEGF, SDF-1alpha, MMP-9, and sKitL in the bone marrow and the peripheral blood were also higher in the high dose CHSIBA group and the low dose CHSIBA group than in the model group (P < 0.05, P < 0.01). CONCLUSION: CHSIBA could activate MMP-9 signaling pathway, increase its upstream and downstream signal expression levels, and mobilize EPCs in the bone marrow to enter the blood circulation.
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Células da Medula Óssea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Infarto do Miocárdio/metabolismo , Transdução de Sinais , Animais , Células da Medula Óssea/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismoRESUMO
Some photosensitive resins have poor mechanical properties after 3D printing. To overcome these limitations, a polyurethane acrylate oligomer (PUA) microsphere was prepared using the Pickering emulsion template method and ultraviolet (UV) curing technology in this paper. The prepared PUA microspheres were added to PUA-1,6-hexanediol diacrylate (HDDA) photosensitive resin system for digital light processing (DLP) 3D printing technology. The preparation process of PUA microspheres was discussed based on micromorphology, and it was found that the oil-water ratio of the Pickering emulsion and the emulsification speed had a certain effect on the microsphere size. As the oil-water ratio and the emulsification speed increased, the microsphere particle size decreased to a certain extent. Adding a suitable proportion of PUA microspheres to the photosensitive resin can improve the mechanical properties and thermal stability. When the modified photosensitive resin microsphere content was 0.5%, the tensile strength, elongation at break, bending strength, and initial thermal decomposition temperature were increased by 79.14%, 47.26%, 26.69%, and 10.65%, respectively, compared with the unmodified photosensitive resin. This study provides a new way to improve the mechanical properties of photosensitive resin 3D printing. The resin materials studied in this work have potential application value in the fields of ceramic 3D printing and dental temporary replacement materials.
RESUMO
The orientation, distribution, and contact point density of BF (basalt fiber) in the concrete matrix play significant roles in the mechanical properties of BF concrete, but represent a weak point in current research. It is meaningful to study the morphological characteristics of BF in concrete. In this study, the transparent model test and joint blocking method were innovatively adopted to investigate the correlation of dosage with the BF morphological parameters and concrete mechanical properties. A focus on a BF dosage of 0-7.5 kg/m3 and the contribution index of fibers Cf was defined. Furthermore, NMR and CT techniques were used to observe the changes in the microstructure of BF concrete. The experimental results show that the BF contribution index Cf reaches the largest value when the BF content is around 3 kg/m3, approximately 2.7; in this case, the mechanical properties of BF concrete were also optimal, and the Cf was only 2.34 when the BF content was 7.5 kg/m3. NMR and CT test results show that there is a strong correlation between the BF morphological parameters and the distribution of pore structure in the concrete matrix. The overlapping contact of BF clusters led to the penetration of pores, which led the macro-pore proportion to increase dramatically. The increase in the macro-pore proportion is the main reason for the deterioration in concrete performance. In addition, these macro-pores may have adverse effects on the chloride ion permeability of BF concrete.
RESUMO
A novel catalyst, consisting of hollow silica-coated porous carbon with embedded iron oxide particles (FeO x @C/SiO2), was synthesized by the extended Stöber method. Iron ions were incorporated in a resorcinol-formaldehyde resin in the presence of citric acid to form a template, which was then coated with a silica layer. The iron oxide-embedded porous carbon and hollow silica were simultaneously formed during calcination under N2 atmosphere. Through this process, silica endowed the iron oxide with low crystallinity and small size, resulting in a higher catalytic activity in the heterogeneous Fenton system for the decolorization of a methylene blue (MB) solution within 25 min. Moreover, the sample maintained 78.71% of its catalytic activity after three cycles.
RESUMO
Porcine decellularized small intestine submucosa (SIS) is a collagen membrane, which offers great potential as an organic substrate template in mineralization processes due to its good biodegradability and biocompatibility. However, a long period of mineralization and low efficiency are apparent, and the mechanism of collagen fiber mineralization has often been neglected in the previous literature. Thus, in this paper, we present a novel model of biomimetic collagen mineralization which uses dopamine (DA) molecules with the activating and retouching function of SIS collagen membranes and regulating collagen mineralization to construct the structure of mineralized collagen hard tissues. The crystal biomimetic mineralization growth of calcium phosphate on membranes is studied in different solid-liquid interfaces with a double ion self-assembled diffusion system under the simulated physiological microenvironment. In the system, pDA@SIS membranes are used to control the concentration of Ca2+ and PO4 3- ionic diffusion to generate supersaturation reaction conditions in 1-14 days. The system can successfully obtain polycrystals with low crystallinity on the pDA-collagen complex template surface of collagen fibers and along the collagen fibers. It initiates a generalized bionic mineralization pathway which can reduce the nucleation interfacial energy to promote rapid hydroxyapatite (HAP) nucleation and crystallization and accelerate the rate of collagen fiber mineralization. The pDA@SIS mineralized collagen membrane shows good biocompatibility with 100% cellular activity in the CCK-8 test, which significantly improved the adhesion proliferation of MC3T3-E1 cells. The pDA-SIS collagen complex, as a new type of mineralization template, may propose a new collagen mineralization strategy to produce a mineralized pDA@SIS scaffold bone-like material for tissue engineering or can potentially be applied in bone repair and regeneration.