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Fluorescent hydrogels have recently attracted great attention for medical diagnostics, bioimaging and environmental monitoring. However, additional phosphors or fluorophores are always required to label the hydrogels, and they suffer from marker bleaching, signal drifts, or information misrepresentation. Here we report autofluorescence that universally exists in carbonyl-containing hydrogels without any traditional fluorophore. The fluorescence is successfully employed to self-monitor the gelation process since the fluorescence signal is closely related to the internal structural change of the gels. The crosslinked structure is beneficial to the fluorescence efficiency. Specifically, the fluorescence intensity is amplified with decreasing water content of the gels. The system realizes aggregation-induced emission in a water-deficient environment. The fluorescence is quenched by the addition of some specific metal ions, which can realize the successfully erasure and rewriting of information under visible light and ultraviolet light respectively. We believe that the spontaneous fluorescence of a gel provides the most reliable basis for the detection of a gel structure and opens new prospects in the application of hydrogels.
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Five new ent-pimarane (1-3, 7, and 8) and three new ent-kaurane diterpenoids (4-6) and a new oleanane triterpene acid (9), together with 22 known compounds, were isolated from the root bark of the medicinal herb Acanthopanax gracilistylus. The structures of 1-9 were established based on the interpretation of high-resolution MS and 1D- and 2D-NMR data. The absolute configurations of 7 and 11 were determined by single-crystal X-ray diffraction and electronic circular dichroism analysis. Compounds 7 and 8 represent rare naturally occurring structures based on the devinyl ent-pimarane skeleton. Compounds 3, 10, 14, 16, and 17 exhibited potent inhibitory effects on the release of interleukin-1ß (IL-1ß), interleukin-8 (IL-8), and tumor necrosis factor (TNF-α) in lipopolysaccharide-stimulated peripheral blood mononuclear cells.
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Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Diterpenos do Tipo Caurano/isolamento & purificação , Diterpenos do Tipo Caurano/farmacologia , Eleutherococcus/química , Plantas Medicinais/química , Anti-Inflamatórios/química , Cristalografia por Raios X , Diterpenos do Tipo Caurano/química , Interleucina-1beta/efeitos dos fármacos , Interleucina-8/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Lipopolissacarídeos/sangue , Lipopolissacarídeos/farmacologia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Casca de Planta/química , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
Immune checkpoint blockade therapy with anti-PD-1 monoclonal antibody (mAb) is a treatment for colorectal cancer (CRC). However, some patients remain unresponsive to PD-1 blockade. The gut microbiota has been linked to immunotherapy resistance through unclear mechanisms. We found that patients with metastatic CRC who fail to respond to immunotherapy had a greater abundance of Fusobacterium nucleatum and increased succinic acid. Fecal microbiota transfer from responders with low F. nucleatum, but not F. nucleatum-high non-responders, conferred sensitivity to anti-PD-1 mAb in mice. Mechanistically, F. nucleatum-derived succinic acid suppressed the cGAS-interferon-ß pathway, consequently dampening the antitumor response by limiting CD8+ T cell trafficking to the tumor microenvironment (TME) in vivo. Treatment with the antibiotic metronidazole reduced intestinal F. nucleatum abundance, thereby decreasing serum succinic acid levels and resensitizing tumors to immunotherapy in vivo. These findings indicate that F. nucleatum and succinic acid induce tumor resistance to immunotherapy, offering insights into microbiota-metabolite-immune crosstalk in CRC.
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Neoplasias Colorretais , Infecções por Fusobacterium , Animais , Camundongos , Fusobacterium nucleatum , Neoplasias Colorretais/tratamento farmacológico , Ácido Succínico , Infecções por Fusobacterium/microbiologia , Imunoterapia , Microambiente TumoralRESUMO
BACKGROUND: Although autophagy is universally involved in tumorigenesis and tumor progression, the roles of autophagy and autophagy-regulating genes in salivary gland adenoid cystic carcinoma (ACC) remain unknown. In this study, we investigated the expression of the autophagy-regulating genes Beclin-1, death-associated protein kinase-1, ultraviolet radiation resistance-associated gene, and phosphatase and tensin homolog in salivary gland ACC samples. METHODS: Immunohistochemistry and real-time polymerase chain reaction were used to analyze the expression of these genes in 89 ACC samples and normal salivary gland tissue samples. The relationship of their expression with clinicopathological features was analyzed. RESULTS: The data showed significantly lower expression of these genes in the tumor samples than in normal salivary gland tissue samples. Furthermore, Beclin-1 expression was significantly correlated with histological pattern of ACC (P<0.05), and high expression of ultraviolet radiation resistance-associated gene was associated with distant metastasis (P<0.05). Most importantly, univariate and multivariate survival analyses suggested that Beclin-1 protein and mRNA expression in cancer cells were independent prognostic indicators for ACC. CONCLUSION: Our results suggest that autophagy-regulating genes may participate in the pathogenesis of salivary gland ACC. Further research will be required to gain a better understanding of autophagy in ACC.
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Proteínas Reguladoras de Apoptose/análise , Autofagia/genética , Carcinoma Adenoide Cístico/patologia , Genes Supressores de Tumor , Proteínas de Membrana/análise , Neoplasias das Glândulas Salivares/patologia , Proteínas Reguladoras de Apoptose/genética , Proteína Beclina-1 , Proteínas Quinases Dependentes de Cálcio-Calmodulina/análise , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/secundário , Núcleo Celular/ultraestrutura , Citoplasma/ultraestrutura , Proteínas Quinases Associadas com Morte Celular , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Metástase Linfática/patologia , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , PTEN Fosfo-Hidrolase/análise , PTEN Fosfo-Hidrolase/genética , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/patologia , Prognóstico , Ductos Salivares/patologia , Neoplasias das Glândulas Salivares/genética , Glândulas Salivares Menores/patologia , Proteínas Supressoras de Tumor/análise , Proteínas Supressoras de Tumor/genéticaRESUMO
OBJECTIVE: To evaluate the impact of surgical modality for gastric cancer on operational trauma. METHODS: A total of 1499 cases of gastric cancer undergoing surgical procedures were divided into the groups of radical resection (RR, n = 1344) and palliative resection group (NRR, n = 155) according to their surgical modalities. And they were further divided into sub-groups according to the profiles of gastrectomy, extent of lymphadenectomy and multi organic resection. The extent of operational trauma (as evaluated by operative duration, transfusion volume, postoperative hospital day and incidence of complications) was compared in different groups and subgroups. RESULTS: In RR and NRR groups, median transfusion volume (Q(1), Q(3)) was 0 (0, 600) vs 400 (0, 800) ml respectively. There was significant difference (P < 0.05). No significant difference existed in operative duration, postoperative hospital day or incidence of complications between two groups (all P > 0.05). In cases of distal gastrectomy, median transfusion volume was 0 (0, 400) vs 400 (200, 800) ml in RR and NRR groups (P < 0.05). No significant difference existed in operative duration, postoperative hospital day or incidence of complications between two groups (all P > 0.05). In cases of total gastrectomy, no significant difference existed in operative duration, postoperative hospital day, median transfusion volume or incidence of complications between two groups (all P > 0.05). In RR group, for the cases treated by D1, D2, D3 and paraaortic lymph node dissection (PAND), there were significant differences in operative duration ((248 ± 71), (271 ± 72), (309 ± 96), (351 ± 103) min), postoperative hospital day ((13 ± 4), (16 ± 12), (18 ± 11), (20 ± 19) days), median transfusion volume (0(0, 500), 0(0, 600), 400(0, 800), 600(200, 1000) ml) (all P < 0.05). But no significant difference existed in incidence of complications (P > 0.05). In RR group, operative duration, postoperative hospital day, median transfusion volume was (315 ± 96) vs (264 ± 66) min, (19 ± 15) vs (15 ± 11) days, 400 (0, 800) vs 0 (0, 400) ml in the patients with and without combined organic resection (all P < 0.05). But no significant difference existed in incidence of complications (P > 0.05). CONCLUSIONS: As compared with palliative resection, radical resection will not increase surgical trauma. For the cases of radical resection, extent of lymphadenectomy and organic resection increase surgical trauma.
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Gastrectomia/efeitos adversos , Gastrectomia/métodos , Neoplasias Gástricas/cirurgia , Ferimentos e Lesões/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Adulto JovemRESUMO
BACKGROUND: Metastasis was the major cause of the high mortality in ovarian cancer. Although some mechanisms of metastasis in ovarian cancer were proposed, few have been targeted in the clinical practice. In the study, we aimed to identify novel genes contributing to metastasis and poor clinical outcome in ovarian cancer from bioinformatics databases. METHODS: Studies collecting matched primary tumors and metastases from ovarian cancer patients were searched in the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened by software R language. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the DEGs were implemented by Metascape. Venn diagram was plotted to present overlapping DEGs. The associations between the overlapping DEGs and prognosis were tested by Cox proportional hazard regression model using a cohort of ovarian cancer patients from the TCGA database. Genes affecting patients' outcomes significantly were served as hub genes. The mechanisms of the hub genes in promoting ovarian cancer metastasis were then predicted by R software. RESULTS: Two gene expression profiles (GSE30587 and GSE73168) met the inclusion criteria and were finally analyzed. A total of 259 genes were significantly differentially expressed in GSE30587, whereas 712 genes were in GSE73168. In GSE30587, DEGs were mainly involved in extracellular matrix (ECM) organization; For GSE73168, most of DEGs showed ion trans-membrane transport activity. There were 9 overlapping genes between the two datasets (RUNX2, FABP4, CLDN20, SVEP1, FAM169A, PGM5, ZFHX4, DCN and TAS2R50). ZFHX4 was proved to be an independent adverse prognostic factor for ovarian cancer patients (HR = 1.44, 95%CI: 1.13-1.83, p = 0.003). Mechanistically, ZFHX4 was positively significantly correlated with epithelial-mesenchymal transition (EMT) markers (r = 0.54, p = 2.59 × 10-29) and ECM-related genes (r = 0.52, p = 2.86 × 10-27). CONCLUSIONS: ZFHX4 might promote metastasis in ovarian cancer by regulating EMT and reprogramming ECM. For clinical applications, ZFHX4 was expected to be a prognostic biomarker for ovarian cancer metastasis.
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Biologia Computacional , Neoplasias Ovarianas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Proteínas de Homeodomínio/genética , Humanos , Neoplasias Ovarianas/patologia , Fatores de Transcrição/genéticaRESUMO
The presence of foreign or misplaced nucleic acids is a dangerous signal that triggers innate immune responses by activating cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) and binding to its downstream signaling effector stimulator of interferon genes (STING). Then the cGAS-STING pathway activation links nucleic acid-sensing to immune responses and pathogenic entities clearance. However, the overactivation of this signaling pathway leads to fatal immune disorders and contributes to the progression of many human inflammatory diseases. Therefore, optimal activation of this pathway is crucial for the elimination of invading pathogens and the maintenance of immune homeostasis. In this review, we will summarize its fundamental roles in initiating host defense against invading pathogens and discuss its pathogenic roles in multiple neuro-inflammatory diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and other neurodegenerative diseases.
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Interferon Tipo I , Proteínas de Membrana , Doenças Neuroinflamatórias , Nucleotidiltransferases , DNA/imunologia , Humanos , Imunidade Inata , Interferon Tipo I/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Doenças Neuroinflamatórias/imunologia , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismoRESUMO
Background: Age was important prognostic factors for operable hepatocellular carcinoma patients. The aim of the present study was to assess the difference in gut microbiota in patients with operable hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) at different ages ; to investigate the features of the microbiota and its function associated with different ages; to provide a preliminary look at effects of the gut microbiota dimension on prognostic. Methods: From September 2020 to May 2021, patients with HBV-HCC were able to undergo liver resection and were recruited consecutively and divided into the younger age group (age <45 years) (Y.AG) (n=20), middle age group (age from 45 to 65 years) (M.AG) (n=13) 45-65 years, and older age group (age >65 years) (O.AG) (n=20). The relationships between gut microbiota and different ages were explored using 16S rRNA gene sequencing data. PICRUST2 was used to examine the metagenomic data in PHLF patients. Fisher's exact and Mann-Whitney U-test were used for the data analysis. Results: Pairwise comparison between the three groups showed that the α-diversity of Y.AG was significantly higher than that of O.AG (ACE Index, P=0.017; chao1 Index, P=0.031; observed_species Index, P=0.011; and goods_coverage Index, P=0.041). The ß-diversity in the 3 groups differed significantly (stress =0.100), while the composition (ß-diversity) differed significantly between the Y.AG and the M.AG (stress =0.090), the M.AG and the O.AG (stress =0.095), and the Y.AG and the O.AG (stress =0.099). At the genus level, 7 bacterial genera were significantly enriched in the O.AG compared with the Y.AG, of which Streptococcus, Blautia, Erysipelotrichaceae_UCG-003, and Fusicatenibacter represented the major variances in O.AG microbiomes. Eleven genera were significantly increased in the O.AG, of which Prevotella, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Ruminiclostridium, and Phascolarctobacterium represented the major variances in the O.AG. The Y.AG and the O.AG were predicted by PICRUSt2 analysis, which found 72 pathways related to differential gut microbiome at the genus level. Redundancy analysis showed that 7 environmental factors were significantly correlated with intestinal microorganisms, especially in the Y.AG compared with the O.AG. Conclusions: Analysis of gut microbiota characteristics in patients of different ages could ultimately contribute to the development of novel avenues for the treatment of HCC at different ages.
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The paper is to report the development of an optic-fiber sensing technology method to analyze metronidazole tablets rapidly. In this fiber-optic sensing system, the light from source delivering to probe can be dipped into simple-handling sample solution, absorbed by the solution and reflected to the fiber-optic and detected in the detection system at last. Then the drug content can be shown in the screen from the ultraviolet absorption spectra and the consistency between that obtained by this method and that in China Pharmacopoeia can be compared. With regard to data processing, a new method is explored to identify the authenticity of drugs using the similarity between the sample map and the standard pattern by full ultraviolet spectrum. The results indicate that ultraviolet spectra of tablets can be obtained from this technology and the determination results showed no significant difference as compared with the method in China Pharmacopoeia (P > 0.05), and the similarity can be a parameter to identify the authenticity of drugs.
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Contaminação de Medicamentos , Tecnologia de Fibra Óptica/métodos , Metronidazol/análise , Espectrofotometria Ultravioleta/métodos , Química Farmacêutica , Metronidazol/administração & dosagem , Fibras Ópticas , Solubilidade , ComprimidosRESUMO
The styrene-maleic acid copolymer (SMC) was obtained by selective and complete cleavage of ester groups from waste thermosetting unsaturated polyester resins (WTUPR). The degradation was performed in glycol at 180 °C for 5 h with potassium carbonate as a catalyst and the resultant potassium salt of SMC (SMC-K) can be very easily separated by precipitation using ethanol with a yield of 63.8%. The SMC-K was integrated with polyvinyl alcohol to form amphiphilic aerogels via freeze-thaw and freeze-drying processes. The aerogel exhibits a low density of 0.024 g·mL-1 due to hierarchical pore structures with a size range from nanometer to micrometer scale. Besides, the good compressibility and resilience of the aerogel are demonstrated. The amphiphilic aerogel displayed high absorption of both water and oily liquids (over 30 g.g-1 and 20 g.g-1 for water and dichloromethane respectively), together with a good recycle adsorption efficiency (>90% after 10 cycles). This work provides a new strategy on upcycling of WTUPR.
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Óleos , Reciclagem , Adsorção , Géis , PoliésteresRESUMO
We analyzed the effects of meteorological factors and soil properties on vertical variation of SOC, based on soil organic carbon (SOC) density in different soil layers (0-10, 10-20, 20-30, 30-50, and 50-100 cm) from 131 mature natural forests in different climate zones in China. The results showed that SOC density decreased with increasing soil depth (0-30 cm) in temperate coniferous, temperate deciduous broadleaved, subtropical deciduous broadleaved and subtropical evergreen broadleaved forests. There were significant regional variations of SOC density in 0-100 cm soil layer. SOC density of 0-100 cm soil layer in temperate coniferous forests was higher than temperate deciduous broadleaved forests, and was higher in subtropical evergreen broadleaved forests than subtropical deciduous broadleaved forests. SOC density was significantly positively correlated with soil clay content, mean annual precipitation, and aboveground net primary production, and significantly negatively correlated with soil pH and mean annual temperature. Mean annual precipitation and mean annual temperature influenced input and output of SOC, while soil pH and clay content affected SOC accumulation. Therefore, protecting mature natural coniferous and evergreen broadleaved forests would benefit forest carbon sequestration in China.
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Carbono , Solo , Carbono/análise , Sequestro de Carbono , China , FlorestasRESUMO
Obesity is an important public-health problem worldwide. This study aimed to determine effects of porphyromonas gingivalis lipopolysaccharide (Pg-LPS) on adipocytes injuries and explore associated mechanisms. Adipocytes were isolated from SD rats. pLVX-XBP1 (XBP1 over-expression) and pLVX-XBP1-RNAi (silencing XBP1) were structured and transfected into adipocytes. All adipocytes were divided into pLVX-NC, pLVX-XBP1, pLVX-NC+Pg-LPS and pLVX-XBP1+ Pg-LPS group. Oil-Red O staining was employed to identify isolated adipocytes. Quantitative real-time PCR (qRT-PCR) was used to examine gene transcription of IL-6, TNF-α, leptin, adiponectin. Western blotting was used to detect Bax and caspase-3 expression. Adipocytes were successfully isolated and identified with Oil-Red O staining. Both XBP1 mimic and XBP1 RNAi were effectively transfected into adipocytes with higher expressing efficacy. XBP1 over-expression significantly aggravated Pg-LPS induced inflammatory response compared to adipocytes without Pg-LPS treatment (p<0.05). Pg-LPS significantly enhanced leptin and inhibited adiponectin expression by up-regulating XBP1 expression (p<0.05). XBP1 silence significantly alleviated Pg-LPS induced inflammatory response and reduced leptin, enhanced adiponectin expression in Pg-LPS treated adipocytes compared to adipocytes without Pg-LPS treatment (p<0.05). Pg-LPS induced apoptosis of adipocytes by enhancing XBP1 expression and modulating Bcl-2/Bax pathway associated molecules. In conclusion, Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) induces adipocytes injuries through modulating XBP1 expression and initialling mitochondria-mediated apoptosis.
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Adipócitos/metabolismo , Lipopolissacarídeos/metabolismo , Proteína 1 de Ligação a X-Box/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , China , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Células HEK293 , Humanos , Mitocôndrias/metabolismo , Porphyromonas gingivalis/metabolismo , Porphyromonas gingivalis/patogenicidade , Ratos , Ratos Sprague-Dawley , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/fisiologiaRESUMO
OBJECTIVE: To explore the relationship between hepatic cytochrome P450 2C19 (CYP2C19) gene polymorphisms and the effectiveness and safety of thalidomide in the treatment of patients with immune-related bowel disease (IRBD). METHODS: CYP2C19 variants in 79 patients treated with thalidomide were analyzed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The clinical response and adverse events of the thalidomide treatment were recorded. The potential influences of the CYP2C19 genotype polymorphisms on the clinical efficacy and adverse events of thalidomide were then investigated. RESULTS: Altogether 79 patients with IRBD (70 with Crohn's disease, three with ulcerative colitis and six with Behcet's disease) receiving thalidomide therapy were recruited from January 2013 to February 2015 in a tertiary IBD center in China. Overall, 21.5% (17/79) of these patients had CYP2C19 poor metabolizers genotype (PM). The overall response rate and the incidence of adverse events of CYP2C19 extensive metabolizers genotype were not significantly different from that of the PM when IRBD patients were treated with thalidomide (P = 0.517 and 0.816, respectively). CONCLUSION: CYP2C19 polymorphisms do not seem to be associated with efficacy of thalidomide and the incidence of adverse events in treating IRBD.
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Citocromo P-450 CYP2C19/efeitos dos fármacos , Imunossupressores/farmacocinética , Enteropatias/tratamento farmacológico , Variantes Farmacogenômicos/efeitos dos fármacos , Polimorfismo de Fragmento de Restrição/efeitos dos fármacos , Talidomida/farmacocinética , Adulto , Síndrome de Behçet/tratamento farmacológico , Síndrome de Behçet/genética , Síndrome de Behçet/imunologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Colite Ulcerativa/imunologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/genética , Doença de Crohn/imunologia , Feminino , Genótipo , Humanos , Enteropatias/genética , Enteropatias/imunologia , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Microwave-assisted selective degradation successfully converts thermosetting unsaturated polyester resins into a low-swelling (below 10â¯g g-1) gel material (GM) with a high yield (58-65%) in water at 100°C for only 1â¯h. The obtained GM possesses rough and porous structure while the content of carboxylate group obtained by cleavage of partial ester groups is more than 10%, varying with the concentration of the catalyst. It is suitable for use as packing of adsorption column to rapidly purify sewage. Super high filtering rates of 18582-27002â¯Lâ¯h-1â¯m-3 without external pressure and high removal efficiency of more than 99.8% were achieved, promoting practical application for rapid removal of organic pollutants.
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The present study aimed to investigate the role of lysosomalassociated transmembrane protein 5 (LAPTM5) in osteoclast differentiation induced by osteoblasts. The results demonstrated that the expression levels of LAPTM5 were downregulated following runtrelated transcription factor 2 (RUNX2) silencing and upregulated following RUNX2 overexpression in ST2 cells. Chromatin immunoprecipitation analysis identified the binding of RUNX2 to the LAPTM5 promoter at the 1176 to 1171 position. Dualluciferase reporter assays confirmed that RUNX2 directly activated the LAPTM5 gene. The concentration of receptor activator of nuclear factorκB ligand (RANKL) protein in the cytoplasm and in the media was significantly increased following LAPTM5 knockdown. LAPTM5 silencing in ST2 cells enhanced osteoclastic differentiation of cocultured RAW264.7 cells. The present study indicated that expression of LAPTM5 was regulated by the interaction of RUNX2 with its promoter region and that LAPTM5 was involved in the trafficking of RANKL. These findings suggested a possible coupling mechanism between osteogenesis and osteoclastogenesis in which RUNX2 may be involved in osteoclast differentiation through the regulation of the lysosomeassociated genes that modulate RANKL expression.
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Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Proteínas Imediatamente Precoces/genética , Proteínas de Membrana/genética , Osteoblastos/metabolismo , Ligante RANK/metabolismo , Ativação Transcricional , Animais , Biomarcadores , Linhagem Celular , Células Cultivadas , Técnicas de Cocultura , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Expressão Gênica , Regulação da Expressão Gênica , Proteínas Imediatamente Precoces/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Regiões Promotoras Genéticas , Ligação Proteica , Transporte Proteico , Ligante RANK/genéticaRESUMO
This study aimed to explore the prognostic impact of KRAS and BRAF mutations in patients who underwent simultaneous resection for synchronous colorectal liver metastases (SCRLMs) that were initially resectable. Clinicopathological and outcome data of 139 consecutive patients with SCRLMs who underwent resection between July 2003 and July 2013 was collected from our prospectively established SCRLM database. The KRAS and BRAF genotypes were evaluated in the primary cancer tissues by pyrosequencing. The prognostic value of KRAS and BRAF status was assessed by Kaplan-Meier and Cox regression analyses. KRAS and BRAF mutated in 28.8% and 7.2% of the patients with SCRLMs, respectively, but the genotypes did not significantly associate with any clinicopathologic characteristics. By Kaplan-Meier survival analysis, we found KRAS mutation was not significantly associated with short overall survival (OS) (P = 0.213), but was significantly correlated with short disease-free survival (DFS) (P = 0.041); BRAF mutation was significantly associated with both short OS and DFS (P = 0.001, P<0.001, respectively). Multivariate survival analysis showed KRAS mutation was an independent negative prognostic factor for DFS (P = 0.005) and BRAF mutation was an independent negative prognostic factor for OS and DFS (P = 0.001, P<0.001, respectively). KRAS and BRAF mutation similarly contributed to an adverse prognostic effect in patients who underwent simultaneous resection for SCRLMs that were initially resectable. These findings should suggest the use of KRAS and BRAF status in current practice as an important determinant for precision surgery for initially resectable SCRLMs.
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The present study aimed to investigate the role of magnitude in adaptive response of osteoblasts exposed to compressive stress. Murine primary osteoblasts and MC3T3-E1 cells were exposed to compressive stress (0, 1, 2, 3, 4, and 5 g/cm2) in 3D culture. Cell viability was evaluated, and expression levels of Runx2, Alp, Ocn, Rankl, and Opg were examined. ALP activity in osteoblasts and TRAP activity in RAW264.7 cells co-cultured with MC3T3-E1 cells were assayed. Results showed that compressive stress within 5.0 g/cm2 did not influence cell viability. Both osteoblastic and osteoblast-regulated osteoclastic differentiation were enhanced at 2 g/cm2. An increase in stress above 2 g/cm2 did not enhance osteoblastic differentiation further but significantly inhibited osteoblast-regualted osteoclastic differentiation. This study suggested that compressive stress regulates osteoblastic and osteoclastic differentiation through osteoblasts in a magnitude-dependent manner.
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Osteoblastos/fisiologia , Estresse Mecânico , Células 3T3 , Adaptação Fisiológica , Animais , Técnicas de Cultura de Células , Diferenciação Celular , Sobrevivência Celular , Camundongos , Osteoblastos/citologia , Esferoides CelularesRESUMO
BACKGROUND: Thalidomide is effective in inducing and maintaining clinical remission in children and adolescents with refractory Crohn's disease (CD). However, little is known about the efficacy and safety of thalidomide for adult patients with CD. METHODS: We conducted a prospective open-label cohort study between January 2013 and April 2015. A total of 47 adult patients with active CD who were dependent/resistant or intolerant to corticosteroids and/or immunomodulators or biologics received 50-100 mg of thalidomide daily. Primary outcome was clinical remission evaluated at week 8. Endoscopic assessment was performed at week 24 and defined as endoscopic response (decrease in Crohn's Disease Endoscopic Index of Severity [CDEIS] score > 5 points from baseline CDEIS of 6 or more), complete endoscopic remission (CDEIS score < 3), and mucosal healing (MH) (no ulceration). RESULTS: A total of 47 adults with active CD were enrolled. The clinical remission rate was 14.9% and 23.4% at week 4 and week 8, but increased to 46.8% at week 12 and 53.2% at week 24 out of all the 47 patients included (intention-to-treat analysis). Altogether 32 patients consented and underwent ileocolonoscopy at week 24. The rate of endoscopic response and complete endoscopic remission were 68.4% and 43.8%. MH (no ulceration) was achieved in 28.1% of patients. Adverse events occurred in 27/47 (57.4%) patients but necessitated therapy discontinuation in only 5/47 (10.6%) of patients. CONCLUSIONS: Low-dose thalidomide was effective and tolerated for inducing and maintaining clinical remission in adult patients with active CD, but the optimal time frame for thalidomide to induce clinical remission may be longer than previously appreciated and is probably optimal at 12 weeks. MH could reasonably be achievable with thalidomide.
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OBJECTIVE: To study the influence of particle size and morphology on zinc cation adsorption by hydroxyapatite (HA) and dentifrice containing HA. METHODS: Four HAs with different particle sizes and morphologies, HA-containing dentifrice and blank dentifrice were prepared into suspensions of serial concentrations. Zinc ion solutions with an initial concentration of 10 mg/L was mixed with the suspensions and kept for 24 h for adsorption reaction. The zinc ion concentration in the supernatant was measured by inductively coupled plasma emission spectrometer and the sorption rate of zinc ion was calculated. RESULTS: HA and HA-containing dentifrice with various particle sizes and morphologies were all capable of absorbing zinc ions from simulated waste water, and the adsorption rate of HA-containing dentifrice was 3%-10% higher than that of HA. HA with a particle size of 12 µm and a spherical morphology showed the strongest adsorption ability, followed by short bar-shaped HA with a particle size of 30 µm. Both Langmuir and Freundlich equation could simulate the sorption processes of HA dentifrice, while only Langmuir equation could simulate the sorption processes of HA. CONCLUSION: Incorporation of HA in dentifrice can enhance zinc ion adsorption capacity of the material. The particle size and morphology of HA both affect the adsorption of zinc ions, and 12-µm HA particle with a spherical morphology has the best adsorption ability.