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Objective To investigate the performance of the combined model based on both clinicopathological features and CT texture features in predicting liver metastasis of high-risk gastrointestinal stromal tumors(GISTs). Methods The high-risk GISTs confirmed by pathology from January 2015 to December 2020 were analyzed retrospectively,including 153 cases from the Cancer Hospital of the University of Chinese Academy of Sciences and 51 cases from the Shaoxing Central Hospital.The cases were randomly assigned into a training set(n=142)and a test set(n=62)at a ratio of 7â¶3.According to the results of operation or puncture,they were classified into a liver metastasis group(76 cases)and a non-metastasis group(128 cases).ITK-SNAP was employed to delineate the volume of interest of the stromal tumors.Least absolute shrinkage and selection operator(LASSO)was employed to screen out the effective features.Multivariate logistic regression was adopted to construct the models based on clinicopathological features,texture features extracted from CT scans,and the both(combined model),respectively.Receiver operating characteristic(ROC)curve and calibration curve were established to evaluate the predictive performance of the models.The area under the curve(AUC)was compared by Delong test. Results Body mass index(BMI),tumor size,Ki-67,tumor occurrence site,abdominal mass,gastrointestinal bleeding,and CA125 level showed statistical differences between groups(all P<0.05).A total of 107 texture features were extracted from CT images,from which 13 and 7 texture features were selected by LASSO from CT plain scans and CT enhanced scans,respectively.The AUC of the prediction with the training set and the test set respectively was 0.870 and 0.855 for the model based on clinicopathological features,0.918 and 0.836 for the model based on texture features extracted from CT plain scans,0.920 and 0.846 for the model based on texture features extracted from CT enhanced scans,and 0.930 and 0.889 for the combined model based on both clinicopathological features and texture features extracted from CT plain scans.Delong test demonstrated no significant difference in AUC between the models based on the texture features extracted from CT plain scans and CT enhanced scans(P=0.762),whereas the AUC of the combined model was significantly different from that of the clinicopathological feature-based model and texture feature-based model(P=0.001 and P=0.023,respectively). Conclusion Texture features extracted from CT plain scans can predict the liver metastasis of high-risk GISTs,and the model established with clinicopathological features combined with CT texture features has best prediction performance.
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Tumores do Estroma Gastrointestinal , Neoplasias Hepáticas , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Curva ROC , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: MicroRNAs were reported to be involved in the progression of intervertebral disc degeneration (IDD). This study focused on the potential prognostic value and the underlying mechanism of miR-182 in IDD. METHODS: The expression level of miR-182 in plasma samples from 60 IDD patients and 60 healthy controls were examined in the present study. Then, the relationship between miR-182 expression and clinical features of IDD patients was analyzed. Moreover, the nucleus pulposus (NP) cells were cultured and transfected with either miR-182 inhibitor, mimics, or NC to explore the effects of miR-182 on cell proliferation and apoptosis. Furthermore, expression levels of proliferation and apoptosis-related proteins Bcl-2, Bax, and Caspase-3 were also evaluated. RESULTS: The expression level of miR-182 was dramatically increased in plasma samples of IDD patients compared with the controls. Moreover, ROC analysis indicated that miR-182 was a feasible diagnostic indicator for the diagnosis of IDD. According to the Japanese Orthopaedic Association (JOA) score, the prognosis of patients with the lower expression levels of miR-182 was better than for those with the higher expression levels of miR-182 in IDD. Furthermore, the miR-182 inhibitor significantly increased the proliferation, decreased the apoptosis of human NP cells, and altered the expression of proliferation and apoptosis-related proteins Bcl-2, Bax, and Caspase-3. On the contrary, miR-182 mimics notably inhibited proliferation but promoted apoptosis of human NP cells and increased Bax and Caspase-3 expressions while reducing the Bcl-2 level. CONCLUSIONS: miR-182 was negatively correlated with the prognosis of the IDD patients and affected the proliferation and apoptosis of NP cells in vitro.
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Degeneração do Disco Intervertebral , MicroRNAs , Núcleo Pulposo , Apoptose , Proliferação de Células , Humanos , Degeneração do Disco Intervertebral/diagnóstico , Degeneração do Disco Intervertebral/genética , MicroRNAs/genética , PrognósticoRESUMO
Osteosarcoma (OS) is a lethal bone malignancy. Circular RNAs (circRNAs) have emerged as important regulators of OS development. CircRNA cyclin dependent kinase 14 (circ_CDK14) was reported to be a potential oncogene in OS. However, the mechanistic pathway by which circ_CDK14 functions in OS is largely unknown. The relative expression of circ_CDK14, microRNA (miR)-520a-3p, and GRB2 Associated Binding Protein 1 (GAB1) was evaluated by quantitative real-time PCR and western blot assays. Flow cytometry was employed to monitor cell cycle distribution and apoptosis. Methyl thiazolyl tetrazolium (MTT) and colony formation assays were performed to assess cell viability and colony formation ability, respectively. Western blot assay was also used to detect the expression of apoptosis-related proteins. Transwell assay was carried out to monitor cell migration and invasion. Additionally, the target association between miR-520a-3p and circ_CDK14 or GAB1 was confirmed by a dual-luciferase reporter assay. Xenograft assay was applied to investigate the role of circ_CDK14 in vivo. Circ_CDK14 and GAB1 expression was upregulated, while miR-520a-3p was downregulated in OS tissues and cells. Circ_CDK14 depletion hindered OS cell proliferation, metastasis, and tumorigenesis while facilitated apoptosis, which were all ameliorated by miR-520a-3p inhibition. Circ_CDK14 could sponge miR-520a-3p. miR-520a-3p targeted GAB1 to repress OS cell proliferation and metastasis. Circ_CDK14 knockdown blocked OS tumor growth in vivo. Circ_CDK14 might positively affect OS development by modulating the miR-520a-3p/GAB1 axis.
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MicroRNAs , Osteossarcoma , Proteínas Adaptadoras de Transdução de Sinal/genética , Linhagem Celular Tumoral , Quinases Ciclina-Dependentes , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Osteossarcoma/genética , RNA CircularRESUMO
BACKGROUND: Acute kidney injury (AKI) was characterized by loss of renal function, associated with chronic kidney disease, end-stage renal disease, and length of hospital stay. Long non-coding RNAs (lncRNAs) participated in AKI development and progression. Here, we aimed to investigate the roles and mechanisms of lncRNA MALAT1 in AKI. METHODS: AKI serum samples were obtained from 129 AKI patients. ROC analysis was conducted to confirm the diagnostic value of MALAT1 in differentiating AKI from healthy volunteers. After hypoxic treatment on HK-2 cells, the expressions of inflammatory cytokines, MALAT1, miR-204, APOL1, p65, and p-p65, were measured by RT-qPCR and Western blot assays. The targeted relationship between miR-204 and MALAT1 or miR-204 and APOL1 was determined by luciferase reporter assay and RNA pull-down analysis. After transfection, CCK-8, flow cytometry, and TUNEL staining assays were performed to evaluate the effects of MALAT1 and miR-204 on AKI progression. RESULTS: From the results, lncRNA MALAT1 was strongly elevated in serum samples from AKI patients, with the high sensitivity and specificity concerning differentiating AKI patients from healthy controls. In vitro, we established the AKI cell model after hypoxic treatment. After experiencing hypoxia, we found significantly increased MALAT1, IL-1ß, IL-6, and TNF-α expressions along with decreased miR-204 level. Moreover, the targeted relationship between MALAT1 and miR-204 was confirmed. Silencing of MALAT1 could reverse hypoxia-triggered promotion of HK-2 cell apoptosis. Meanwhile, the increase of IL-1ß, IL-6, and TNF-α after hypoxia treatment could be repressed by MALAT1 knockdown as well. After co-transfection with MALAT1 silencing and miR-204 inhibition, we found that miR-204 could counteract the effects of MALAT1 on HK-2 cell progression and inflammation after under hypoxic conditions. Finally, NF-κB signaling was inactivated while APOL1 expression was increased in HK-2 cells after hypoxia treatment, and lncRNA MALAT1 inhibition reactivated NF-κB signaling while suppressed APOL1 expression by sponging miR-204. CONCLUSIONS: Collectively, these results illustrated that knockdown of lncRNA MALAT1 could ameliorate AKI progression and inflammation by targeting miR-204 through APOL1/NF-κB signaling.
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Injúria Renal Aguda/genética , Apolipoproteína L1/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/sangue , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Adulto , Apolipoproteína L1/metabolismo , Estudos de Casos e Controles , Hipóxia Celular/genética , Linhagem Celular , Feminino , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Testes de Função Renal , Masculino , MicroRNAs/antagonistas & inibidores , Pessoa de Meia-Idade , NF-kappa B/genética , NF-kappa B/metabolismoRESUMO
Nanocarriers with strong tumor cell targeting ability have been expected to overcome limitations of cancer chemotherapy. Herein, cell membrane mimetic micelles were prepared from a random copolymer (PMNCF) containing cell membrane phosphorylcholine zwitterion, cholesterol, and tumor cell targeting folic acid (FA) at the side chain ends. Surface orientation of the FA ligand was optimized during PMNCF micelle preparation by controlling solvent solubility for FA. The out-oriented ligands on the micelles were immobilized by the strongly associated hydration layer around the closely packed phosphorylcholine zwitterions. The doxorubicin (DOX) loaded PMNCF micelles were demonstrated to reduce normal cell toxicity to less than 20%. More significantly, HeLa and MCF-7 tumor cell killing efficacy of the optimized formulation was enhanced to 160% compared with that of free DOX. The excellent performances of the drug loaded PMNCF micelles on both tumor cell killing and normal cell toxicity reducing efficacies reveal great potential for developing advanced drug delivery system.
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Antineoplásicos/farmacologia , Materiais Biomiméticos/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Micelas , Polímeros/química , Linhagem Celular Tumoral , Membrana Celular/química , Colesterol/análogos & derivados , Liberação Controlada de Fármacos , Ácido Fólico/análogos & derivados , Humanos , Ligantes , Fosforilcolina/análogos & derivadosRESUMO
Objective To observe the effect of Shengqing Capsule (SC) on serum contents of TC, LDL-C, and HDL-C, hepatic scavenger receptor B I (SRB I ) , and CD36 in rats with cholesterol cal- culus. Methods Totally 80 mice were divided into 4 groups according to random number table, i.e., the normal group, the model group, the Western medicine (WM) group, and the Chinese medicine (CM) group, 20 in each group. Mice in the normal group were fed with common forage, while mice in the other 3 groups were fed with lithogenic diet. Mice in the CM group and the WM group were fed with SC (at the daily dose of 0.35 g/kg) and Ursodeoxycholic Acid Tablet (UDCA, at the daily dose of 39. 55 mg/kg) re- spectively for 7 weeks. The general condition and gallstone formation rate were observed. Serum contents of TC, LDL-C, and HDL-C, and protein expressions of SBR I and CD36 were detected by oxidase meth- od and Western blot respectively. Results No gallbladder stone formed in the normal group, and gall- stone formed in 15 mice of the model group with gallstone formation rate of 75%. Compared with the nor- mal group, serum contents of TC and LDL-C and protein expressions of SRB I and CD36 increased, HDL-C content decreased in the model group (P <0. 01). The gallstone formation rate was 35% (7 mice) in the WM group and 30% (6 mice) in the CM group, lower than that of the model group (75%; P <0. 05). Contents of TC and LDL-C, and protein expressions of SRB I and CD36 decreased, HDL-C content in- creased in the WM group and the CM group (P <0.01). Compared with the WM group, TC content and protein expressions of SRB I and CD36 decreased in the CM group (P <0.01). Conclusion SC could prevent and treat gallbladder stone possibly through lowering expression levels of SRB I and CD36.
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Colesterol , Medicamentos de Ervas Chinesas , Cálculos Biliares , Receptores Depuradores , Animais , Cálculos , Colesterol/sangue , Medicamentos de Ervas Chinesas/farmacologia , Cálculos Biliares/tratamento farmacológico , Cálculos Biliares/prevenção & controle , Camundongos , Ratos , Receptores Depuradores/efeitos dos fármacosRESUMO
OBJECTIVE: To compare the perioperative outcomes of patients with primary hepatic carcinoma treated with laparoscopic hepatectomy (LH) with those treated with open hepatectomy (OH). METHODS: From January 2010 to August 2014, 100 patients with primary hepatic carcinoma were randomly divided into the LH group and OH group respectively, 50 patients in each group. And the incision length, blood loss, operative time, postoperative liver function, anus exhaust time, complications, length of postoperative hospital stay, and cost measures were compared. RESULTS: LH could achieve shorter incision length, less blood loss, more rapid recovery in liver function and gastrointestinal function, and shorter postoperative hospital stay length compared with OH for primary hepatic carcinoma patients (all P<0.05). However, LH could not significantly shorten operative time, and reduce postoperative complications and hospitalization cost (all P>0.05). CONCLUSION: Compared with OH, LH could improve perioperative outcomes of primary hepatic carcinoma patients.
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Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controleRESUMO
OBJECTIVE: To investigate the effect of photodynamic therapy (PDT) mediated by hematoporphyrin derivative (HPD) on apoptosis and invasion of cholangiocarcinoma QBC939 cell lines. METHODS: In vitro cultured cholangiocarcinoma QBC939 cell line was exposed to 2, 4, 6, 8, 10, 12, and 14 µg/ml HPD with 5, 10, and 15 J/cm2 light intensity, respectively. The optical density at 450 nm of the QBC939 cells was measured by CCK8 assay and its growth inhibition ratio was calculated. Flow cytometry and transwell migration assay were applied to detect cell apoptosis and invasion respectively. RT-PCR and immunocytochemistry analyses were used to detect expressions of vascular endothelial growth factor-C (VEGF-C), cyclooxygenase-2 (COX-2), and proliferating cell nuclear antigen (PCNA). Enzyme-linked immunosorbent assay (ELISA) was carried out to examine the secretion of VEGF-C and COX-2 in QBC939 cells. RESULTS: Exposure to HPD-PDT can significantly suppress the growth of QBC939 cells (all P<0.05). HPD-PDT can promote apoptosis of QBC939 cells at the early stage. When the concentration of HPD was 2 µg/ml and light irradiation was 5 J/cm2, HPD-PDT had no obvious inhibitory effect on QBC939 cell growth, but can obviously inhibit cell invasion, and significant difference was observed between the HPD-PDT and control groups (P<0.01). The HPD-PDT can reduce the mRNA and protein expressions of VEGF-C, COX-2, and PCNA, and decrease the secretion of VEGF-C and COX-2 in QBC939 cells. CONCLUSION: PDT could promote apoptosis and inhibit growth and invasion of cholangiocarcinoma cells QBC939 in vitro.
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Apoptose/efeitos dos fármacos , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/tratamento farmacológico , Fotoquimioterapia , Neoplasias dos Ductos Biliares/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Colangiocarcinoma/patologia , Humanos , Invasividade Neoplásica , Antígeno Nuclear de Célula em Proliferação/análiseRESUMO
A scheme with usage of metallic nonlinearity, especially in generating the surface plasmon polariton (SPP) time-reversal wave (TRW), is investigated. It is composed of a metal film and an attached photonic crystal, in which both a far-field-excitable tunneling mode and an SPP guided mode could exist. Two modes are degenerated, deeply penetrated into metal, well overlapped, and localized. Therefore, the tunneling mode acts as the pumping field, while the SPP mode acts as the signal field. Because of the large metallic nonlinear susceptibility, the TRW efficiency could increase thousand times. This scheme can be widely used as a high-efficiency platform for other nonlinear devices.
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We theoretically investigate efficient third-harmonic generation (THG) in the heterostructure with a one-dimensional photonic crystal (PC) and a thick metal film. There are both the fundamental Tamm plasmon mode and the high-order mode in the heterostructure. Commonly these two Tamm plasmon modes just satisfy single-resonance condition, but the double-resonance condition can be fulfilled by using a binary PC in the heterostructure. Taking advantage of the tunneling effect of Tamm plasmon modes, THG in the single-resonance heterostructure is enhanced over 3 orders of magnitude more than that in the single metal film, and that in the double-resonance one is further enhanced nearly 2 orders of magnitude.
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OBJECTIVE: To discuss the feasibility and safety of different approaches for CT-guided percutaneous needle biopsy and subsequent iodine-125 seed interstitial implantation for pancreatic cancer. METHODS: A retrospective study was carried out on the complete data of 35 patients with pancreatic cancer who have received CT-guided percutaneous needle biopsy with or without subsequent iodine-125 seed interstitial implantation. There were 9 lesions located in the head of pancreas, 20 located in the body, and 6 in the tail. The maximum diameter of the lesions varied from 12 mm to 60 mm (mean 37.1 mm). The patients were treated with a needle in diameter of 16-21G. Operations were undertaken via anterior, posterior and lateral approaches. RESULTS: Thirty-five patients underwent 43 times of CT-guided percutaneous needle biopsies. Thirty-one cases were pathologically diagnosed as cancer, 2 cases inflammatory lesions, and 2 were suspected tumors (one of which was finally diagnosed as cancer, while another was pancreatic pseudocyst). The ratio of correct diagnosis was 94.3%. Fourteen patients were treated subsequently with CT-guided iodine-125 seed interstitial implantation therapy, with a total of 65 times of needle puncture. The operations were performed via direct approach to the tumor in 18 cases, transhepatic approach in 2 cases, transgastric approach in 4 cases, transintestinal approach in 10 cases, and through mesenteric vessels in one case. Incidence of complications in the biopsy group was 2.32% (1/43), and in the implantation group was 6.15% (4/65), with a statistically non-significant difference (P = 0.600) between the two groups. Incidence of complications in the group using 16-18G needle was 4.65% (4/86), while in the group using 20-21G needle was 4.55% (1/22), also with a non-significant difference (P = 0.064). The accuracy rate of needle biopsy in this study was 94.28% (33/35). CONCLUSION: CT-guided percutaneous needle biopsy and subsequent iodine-125 seed interstitial implantation are both feasible and safe for pancreatic cancer.
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Biópsia por Agulha/métodos , Braquiterapia/métodos , Radioisótopos do Iodo/uso terapêutico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/radioterapia , Radiografia Intervencionista/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To study the effect of Songling Xuemaikang Capsule (SXC) on blood pressure of spontaneously hypertensive rats (SHR) and regulatory mechanisms for peroxisome proliferator activated receptor-gamma (PPARgamma). METHODS: Totally 24 10-week-old SHR rats were randomly divided into the blank control group, the Chinese medicine (CM) group, and the Western medicine (WM) group, 8 in each group. Rats in the CM group were administered with SXC at the daily dose of 20 mg/kg by gastrogavage. Those in the WM group were administered with ramipril at the daily dose of 1 mg/kg by gastrogavage. Those in the blank control group were administered with equal volume of normal saline. The blood pressure was measured once per week. The cardiac ultrasound was performed 4 weeks later. Rats were killed and then blood was sampled from abdominal aorta. mRNA expressions of liver PPARgamma and angiotensin II type 1 receptor (AT1R) were detected by fluorescence real-time quantitative PCR. Protein expressions of PPARgamma and AT1R were detected using immunohistochemical assay (SP). The contents of PPARgamma and AT1R were quantitatively analyzed by Western blot. RESULTS: After 4 weeks of treatment, the blood pressure decreased in the CM group, showing statistical difference when compared with the blank control group (P < 0.01). CM was inferior to WM in lowering blood pressure. But as a whole, CM was more stable and could maintain blood pressure at a relatively stable level. The cardiac ejection fraction increased in the CM group, showing statistical difference when compared with the blank control group (P < 0.05, P < 0.01). The mRNA and protein expressions of liver PPARgamma were up-regulated in the CM group, showing statistical difference when compared with the blank control group (P < 0.05, P < 0.01). CM could obviously inhibit the AT1R mRNA expression, and down-regulate the protein expression of AT1R, showing statistical difference when compared with the blank control group and the WM group respectively (P < 0.01). CONCLUSION: SXC decreased blood pressure and improved the cardiac ejection fraction, which might be partially achieved by up-regulating the PPARgamma mRNA expression and protein synthesis, and inhibiting the AT1R mRNA expression and AT1R protein synthesis.
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Medicamentos de Ervas Chinesas/farmacologia , Hipertensão/metabolismo , PPAR gama/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Animais , Medicamentos de Ervas Chinesas/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , RNA Mensageiro/genética , Ratos , Ratos Endogâmicos SHRRESUMO
Low back pain (LBP) is a prevalent health problem worldwide that affects over 80% of adults during their lifetime. Intervertebral disc degeneration (IDD) is a well-recognized leading cause of LBP. IDD is classified into five grades according to the Pfirrmann classification system. The purpose of this study was to identify potential biomarkers in different IDD grades through an integrated analysis of proteome sequencing (PRO-seq), bulk RNA sequencing (bRNA-seq) and single-cell RNA sequencing (scRNA-seq) data. Eight cases of grade I-IV IDD were obtained. Grades I and II were considered non-degenerative discs (relatively normal), whereas grades III and IV were considered degenerative discs. PRO-seq analysis was performed to identify differentially expressed proteins (DEPs) in various IDD grades. Variation analysis was performed on bRNA-seq data to differentiate expressed genes (DEGs) in normal and degenerated discs. In addition, scRNA-seq was performed to validate DEGs in degenerated and non-degenerated nucleus pulposus (NP). Machine learning (ML) algorithms were used to screen hub genes. The receiver operating characteristic (ROC) curve was used to validate the efficiency of the screened hub genes to predict IDD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to analyze function enrichment and signaling pathways. Protein-protein interaction (PPI) network was used to prioritize disease-related proteins. SERPINA1, ORM2, FGG and COL1A1 were identified through PRO-seq as the hub proteins involved in regulating IDD. ML algorithms selected ten hub genes, including IBSP, COL6A2, MMP2, SERPINA1, ACAN, FBLN7, LAMB2, TTLL7, COL9A3, and THBS4 in bRNA-seq. Since serine protease inhibitor clade A member 1 (SERPINA1) was the only common gene, its accuracy in degenerated and non-degenerated NP cells was validated using scRNA-seq. Then, the rat degeneration model of caudal vertebra was established. The expression of SERPINA1 and ORM2 was detected using immunohistochemical staining of human and rat intervertebral discs. The results showed that SERPINA1 was poorly expressed in the degenerative group. We further explored the potential function of SERPINA1 by Gene Set Enrichment Analysis (GSEA) and cell-cell communication. Therefore, SERPINA1 can be used as a biomarker to regulate or predict the progress of disc degeneration.
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Studies reported the positive and negative osteogenic effects of MEG3 in mesenchymal stem cells (MSCs). This study aims at clarifying the osteogenic potential of MEG3 and the underlying mechanism. Bone morphogenetic protein 9- (BMP9-) transfected MSCs were recruited as an osteogenic model in vitro, and ectopic bone formation were used in vivo to explore the effect of MEG3 on osteogenesis. We found that overexpression of MEG3 facilitated BMP9-induced osteogenic markers, ALP activities, and matrix mineralization. However, knockdown of MEG3 attenuated BMP9-induced osteogenic markers. MEG3 increased the phosphorylation of GSK-3ß and the protein level of ß-catenin. Pyruvate dehydrogenase kinase 4 (PDK4) can also combine with GSK-3ß and increase the latter phosphorylation. Moreover, MEG3 increased the mRNA level of PDK4. The ceRNA analysis showed that MEG3 may regulate the expression of PDK4 via microRNA 532-5p (miR-532-5p). The MEG3-enhanced GSK-3ß/ß-catenin axis can be attenuated by miR-532-5p, and miR-532-5p inhibitor partly rescued endogenous PDK4 and MEG3-mediated expression of PDK4. MEG3 may potentiate PDK4 and GSK-3ß/ß-catenin by inhibiting miR-532-5p.
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MicroRNAs , RNA Longo não Codificante , Glicogênio Sintase Quinase 3 beta/genética , Diferenciação Celular/fisiologia , RNA Longo não Codificante/genética , beta Catenina/genética , beta Catenina/metabolismo , Osteogênese , MicroRNAs/genética , MicroRNAs/metabolismo , Células CultivadasRESUMO
BACKGROUND: All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1. METHODS: ATRA content was detected with ELISA and HPLC-MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro-computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism. RESULTS: We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/ß-catenin, and reduced by inhibiting this pathway. ß-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1. CONCLUSIONS: Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering.
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Fator 2 de Diferenciação de Crescimento , Células-Tronco Mesenquimais , Via de Sinalização Wnt , beta Catenina/metabolismo , Fator 2 de Diferenciação de Crescimento/metabolismo , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Espectrometria de Massas em Tandem , Tretinoína/farmacologiaRESUMO
We study the normal-mode splitting when an oscillator is placed in a two-dimensional photonic crystal microcavity embedded with an impedance-matched or an impedance-mismatched zero-index medium (ZIM). Because of the (nearly) uniform localized fields in the ZIM, the normal-mode splitting remains (almost) invariant no matter where the oscillator is. When a split ring resonator is coupled to a transmission-line- based effective ZIM at various locations, nearly position-independent mode splitting is observed.
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Manufaturas , Modelos Teóricos , Oscilometria/métodos , Refratometria/métodos , Simulação por Computador , Luz , Espalhamento de RadiaçãoRESUMO
Chitosan extracted from natural products has gained tremendous attention in the field of adsorption and separation due to its inherent biocompatibility and potential applications. In this research, we synthesized a new type of spherical chitosan adsorbent (SCA) by controlling the mass transfer rate of the entanglement of the polymer chains in the recombination process. This SCA is a highly crystalline polymer material with outstanding mechanical strength, high adsorption capacity, a porous surface and suitable particle size distribution. The value of the sphericity of attrition of this SCA was 89.8%, which is the same as that of the commercial macroporous resin with a polystyrene matrix. The X-ray diffraction (XRD) patterns and differential scanning calorimetry (DSC) curves showed a significant change from powder to spherical structure and confirmed that the SCA is highly ordered and crystalline. Optical microscopy (OM) and scanning electron microscopy (SEM) demonstrated that the SCA was composed of a tightly stacked fiber structure, indicating the homogeneity of the polymerization. The porous structure of the surface provided a channel for mass transfer, which was indicated by a test of the ion exchange capacity and the adsorption performance of the SCA with Cu(ii) as the adsorbed subject. The adsorption capacity was higher than those of all reported non-composite chitosan materials. Therefore, we have successfully synthesized a completely green, nontoxic and environmentally friendly adsorbing resin equipped with excellent mechanical properties and adsorption capacity for future applications in many new fields.
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Bone defects resulting from trauma, bone tumors, infections and skeletal abnormalities are a common osteoporotic condition with respect to clinical treatment. Of the known bone morphogenetic proteins (BMPs), BMP9 has the strongest osteogenic differentiation potential, which could be beneficial in the construction of tissue-engineered bone. Silent mating type information regulator 2 homolog-1 (SIRT1) is a highly conserved nicotinamide adenine dinucleotide-dependent deacetylase that deacetylates and modulates histone or non-histone substrates. However, the role of SIRT1 in BMP9-induced osteogenic differentiation of stem cells has not been studied. Furthermore, it is unclear whether SIRT1 interacts with the BMP/Smad and BMP/MAPK pathways in stem cells. We found that SIRT1 expression decreased gradually in a time-dependent manner during BMP9-induced osteogenic differentiation of MSCs. Interactions between SIRT1 and Smad7 promoted degradation of Smad7 and increased Smad1/5/8 phosphorylation. SRT2104, an activator of SIRT, enhanced the expression of osteogenic- and angiogenic-related proteins in BMP9-induced MSCs. In addition, we found that activation of the BMP/MAPK pathway led to osteogenic and angiogenic differentiation of MSCs. Our study demonstrated that SIRT1 expression decreased during BMP9-induced differentiation. The SIRT1 activator SRT2104 promoted BMP9-induced osteogenic and angiogenic differentiation of MSCs through the BMP/Smad and BMP/MAPK signaling pathways.
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Células-Tronco Mesenquimais , Osteogênese , Proteínas Morfogenéticas Ósseas/metabolismo , Diferenciação Celular , Fator 2 de Diferenciação de Crescimento/metabolismo , Fator 2 de Diferenciação de Crescimento/farmacologia , Compostos Heterocíclicos com 2 Anéis , Células-Tronco Mesenquimais/metabolismo , NAD/metabolismo , Sirtuína 1/metabolismoRESUMO
We theoretically investigate nonlinear resonance-enhanced excitation of surface plasmon polaritons in a metal coated by a one-dimensional photonic crystal. Tunneling modes above the air-light line can be directly excited in this structure. Then, with suitable parameters, photon energy and momentum conservation between the tunneling mode and the surface plasmon polaritons can be realized by means of nonlinear four-wave mixing. Compared with the nonlinear excitation of surface plasmon polaritons in a bulk metal [Phys. Rev. Lett. 103, 266802 (2009)], the conversion efficiency in our structure is noticeably enhanced.
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OBJECTIVE: To study the anatomical and biomechanical features of sacral pedicle and lateral mass so as to provide reference for clinical screw fixation technology of sacral pedicle and lateral mass. METHODS: A total of 60 adult patients'spiral CT images of the sacrum and coccyx were selected randomly. The entry points of sacral pedicle and lateral mass screws were determined, and the screw trajectory was measured using the three dimensional reconstruction method. Meanwhile, the gross anatomy was scrutinized in 15 adult cadaver specimens to determine the sacral pedicle and lateral mass screw entry points. The length, width and angle of sacral pedicle and lateral mass screw trajectory were measured. Eight of 15 cadaver specimens were selected to test the maximal extraction force of sacral pedicle and lateral mass screws. The clinical data of 15 cases treated by pedicle and lateral mass screw technology were collected and analyzed. RESULTS: The diameter and length of S(1)-S(5) sacral pedicle and lateral mass screw trajectory were regular, with about 20 degree inclination angle. The S(1) pedicle screw entry point was located at the intersection point of the basal lateral part of articular process and median line of transverse process, and no significant difference was found for the maximal extraction force between pedicle and lateral mass screws (P larger than 0.05). The entry points of S(2)-S(5) pedicle screws were located at the intersection point of the line connecting adjacent posterior sacral foramina and median line of the transverse process. The lateral mass screw entry point of S(2)-S(5) was on the median side of intersection point between median line of the transverse process and lateral sacral crest. The maximal extraction force of pedicle screws was significantly greater than that of lateral mass screws (P less than 0.05). CONCLUSION: Both the sacral pedicle and the lateral mass screw fixation techniques can offer effective fixation and reconstruction for fracture of the sacrum and coccyx, but pedicle screw fixation may be more convenient, safe and reliable than lateral mass screw fixation.