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2.
Technol Cancer Res Treat ; 19: 1533033820909112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32329416

RESUMO

Radiotherapy is one of the most important cancer treatments, but its response varies greatly among individual patients. Therefore, the prediction of radiosensitivity, identification of potential signature genes, and inference of their regulatory networks are important for clinical and oncological reasons. Here, we proposed a novel multiple genomic fused partial least squares deep regression method to simultaneously analyze multi-genomic data. Using 60 National Cancer Institute cell lines as examples, we aimed to identify signature genes by optimizing the radiosensitivity prediction model and uncovering regulatory relationships. A total of 113 signature genes were selected from more than 20,000 genes. The root mean square error of the model was only 0.0025, which was much lower than previously published results, suggesting that our method can predict radiosensitivity with the highest accuracy. Additionally, our regulatory network analysis identified 24 highly important 'hub' genes. The data analysis workflow we propose provides a unified and computational framework to harness the full potential of large-scale integrated cancer genomic data for integrative signature discovery. Furthermore, the regression model, signature genes, and their regulatory network should provide a reliable quantitative reference for optimizing personalized treatment options, and may aid our understanding of cancer progress mechanisms.

3.
Colloids Surf B Biointerfaces ; 190: 110938, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32172164

RESUMO

Dental materials are susceptible to dental plaque formation, which increases the risk of biofilm-associated oral diseases. Physical-chemical properties of dental material surfaces can affect salivary pellicle formation and bacteria attachment, but relationships between these properties have been understudied. We aimed to assess the effects of surface properties and adsorbed salivary pellicle on Streptococcus gordonii adhesion to traditional dental materials. Adsorption of salivary pellicle from one donor on gold, stainless steel, alumina and zirconia was monitored with a quartz crystal microbalance with dissipation monitoring (QCM-D). Surfaces were characterized by X-ray photoelectron spectroscopy, atomic force microscopy and water contact angles measurement before and after pellicle adsorption. Visualization and quantification of Live/Dead stained bacteria and scanning electron microscopy were used to study S. gordonii attachment to materials with and without pellicle. The work of adhesion between surfaces and bacteria was also determined. Adsorption kinetics and the final thickness of pellicle formed on the four materials were similar. Pellicle deposition on all materials increased surface hydrophilicity, surface energy and work of adhesion with bacteria. Surfaces with pellicle had significantly more attached bacteria than surfaces without pellicle, but the physical-chemical properties of the dental material did not significantly alter bacteria attachment. Our findings suggested that the critical factor increasing S. gordonii attachment was the salivary pellicle formed on dental materials. This is attributed to increased work of adhesion between bacteria and substrates with pellicle. New dental materials should be designed for controlling bacteria attachment by tuning thickness, composition and structure of the adsorbed salivary pellicle.

4.
Bone ; 135: 115320, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32179168

RESUMO

C-type natriuretic peptide (CNP) activation of guanylyl cyclase (GC)-B, also known as NPR2, stimulates cGMP synthesis and bone elongation. CNP activation requires the phosphorylation of multiple GC-B residues and dephosphorylation inactivates the receptor. GC-B7E/7E knockin mice, expressing a glutamate-substituted, "pseudophosphorylated," form of GC-B, exhibit increased CNP-dependent GC activity. Since mutations that constitutively activate GC-B in the absence of CNP result in low bone mineral density in humans, we determined the skeletal phenotype of 9-week old male GC-B7E/7E mice. Unexpectedly, GC-B7E/7E mice have significantly greater tibial and L5 vertebral trabecular bone volume fraction, tibial trabecular number, and tibial bone mineral density. Cortical cross-sectional area, cortical thickness, periosteal diameter and cortical cross-sectional moment of inertia were also significantly increased in GC-B7E/7E tibiae. Three-point bending measurements demonstrated that the mutant tibias and femurs had greater ultimate load, stiffness, energy to ultimate load, and energy to failure. No differences in microhardness indicated similar bone quality at the tissue level between the mutant and wildtype bones. Procollagen 1 N-terminal propeptide and osteocalcin were elevated in serum, and osteoblast number per bone perimeter and osteoid width per bone perimeter were elevated in tibias from the mutant mice. In contrast to mutations that constitutively activate GC-B, we report that mutations that enhance GC-B activity only in the presence of its natural ligand, increase bone mass, bone strength, and the number of active osteoblasts at the bone surface.

5.
Scand J Gastroenterol ; 55(3): 362-370, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150478

RESUMO

Objective: Endoscopic resection of colorectal polyps is widely established as the optimal method to manage precancerous lesions. But the optimal technique for removal of the polyps is uncertain. The aim of this study was to compare the efficacy and safety of three methods for the management of 6-20mm colorectal polyps.Methods: A prospective, randomised controlled trial was conducted at the 900TH Hospital of Joint Logistics Support Force in Fujian, China. Endoscopically diagnosed colorectal polyps, 6-20 mm in size, were randomly assigned to the cold snare polypectomy (CSP), cold snare endoscopic mucosal resection (CS-EMR) or endoscopic mucosal resection (EMR) group. After polypectomy, additional 3-5 forceps biopsies by leading narrow-band imaging (NBI) were performed at the base and margins of polypectomy sites to assess the presence of residual polyp tissue and all samples were sent for histopathological analysis to assess completeness of resection. Polypectomy timing, tissue retrieval and complications were recorded at the time of the procedure.Results: A total of 781 polyps in 404 patients were assessed and randomly assigned to each group. Of these, 763 polyps were finally analyzed based on the pathology results. The complete resection rates with CSP, CS-EMR and EMR were 81.6%, 94.1% and 95.5%, respectively (p < .001). The intraprocedural bleeding rate, immediately after polypectomy, was significantly higher in the CSP group than in the CS-EMR and EMR group (9.4% vs. 4.4% vs. 1.9%; p < .001). However,delayed bleeding was higher in the EMR group than in the CSP and CS-EMR group (2.6% vs. 1.2% vs. 0.8%, respectively; p = .215). In the multivariate analysis showed that the operation method, lesion size, morphology and the number of resection were independent risk factors for complete resection rate (CRR) (p < .05), but the location and pathological classification of polyps had no significant influence on CRR.Conclusions: CS-EMR is safe and effective in the treatment of 6-20 mm colorectal polyps. Especially for 6-15 mm non-pedunculated polyps, CS-EMR has a high histological complete resection rate comparable to EMR, and retains the low risk of delayed complications after polypectomy with cold snare. CS-EMR is expected to become a more valuable new cold-cutting technique after cold snare polypectomy.

6.
Medicine (Baltimore) ; 99(1): e18363, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895770

RESUMO

INTRODUCTION: Duplication of the gallbladder (GB) is a rare congenital abnormality occurring in 1 in 4000 to 5000 births. Three types have been reported: type I (split primordial GB), type II (2 separate GBs with their own cystic ducts), and type III (triple GBs drained by 1 to 3 separate cystic ducts). Patients with a duplicated GB are usually asymptomatic and are sometimes not diagnosed on preoperative imaging, which might increase the difficulty and risk of cholecystectomy. The key to successful treatment is total removal of the duplicated GB to avoid the recurrence of disease. Intraoperative cholangiography is recommended for identifying and resecting duplicated GBs. The final diagnosis depends on the histopathology. PATIENT CONCERNS: A 62-year-old woman had recurrent upper abdominal pain and nausea for 1 year, with no fever, jaundice, or other symptoms. An ultrasound of the abdomen indicated polyps in the GB. Computed tomography (CT) revealed moderate dense structures attached to the wall of the GB and an unusual 47 × 21 mm elliptical structure with an extra tubule located above the main GB. DIAGNOSIS: A diagnosis of duplicated GB was made based on the histopathology. INTERVENTIONS: The patient underwent a laparoscopic cholecystectomy with total removal of the duplicated GB. OUTCOMES: The patient's postoperative course was uneventful and she was discharged from the hospital on the second postoperative day. She had no upper abdominal pain at the 6-month follow-up. CONCLUSION: Duplicated gallbladder is a rare congenital biliary anatomy, which is usually asymptomatic and sometimes cannot be diagnosed on preoperative imaging. With gallbladder disease, the duplicated GBs should be removed totally; a laparoscopic approach should be attempted first and cholangiography is recommended to aid in identifying and resecting the duplicated GBs. The final diagnosis depends on the histopathology. There is still insufficient evidence on the need to remove duplicated GBs found incidentally.


Assuntos
Colecistectomia Laparoscópica/métodos , Vesícula Biliar/anormalidades , Vesícula Biliar/cirurgia , Dor Abdominal/etiologia , Colangiografia , Feminino , Vesícula Biliar/diagnóstico por imagem , Doenças da Vesícula Biliar/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
7.
Mol Pharm ; 17(2): 683-694, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-31913047

RESUMO

Plant-based saponins are amphipathic glycosides composed of a hydrophobic aglycone backbone covalently bound to one or more hydrophilic sugar moieties. Recently, the endosomal escape activity of triterpenoid saponins has been investigated as a potentially powerful tool for improved cytosolic penetration of protein drugs internalized by endocytic uptake, thereby greatly enhancing their pharmacological effects. However, only a few saponins have been studied, and the paucity in understanding the structure-activity relationship of saponins imposes significant limitations on their applications. To address this knowledge gap, 12 triterpenoid saponins with diverse structural side chains were screened for their utility as endosomolytic agents. These compounds were used in combination with a toxin (MAP30-HBP) comprising a type I ribosome-inactivating protein fused to a cell-penetrating peptide. Suitability of saponins as endosomolytic agents was assessed on the basis of cytotoxicity, endosomal escape promotion, and synergistic effects on toxins. Five saponins showed strong endosomal escape activity, enhancing MAP30-HBP cytotoxicity by more than 106 to 109 folds. These saponins also enhanced the apoptotic effect of MAP30-HBP in a pH-dependent manner. Additionally, growth inhibition of MAP30-HBP-treated SMMC-7721 cells was greater than that of similarly treated HeLa cells, suggesting that saponin-mediated endosomolytic effect is likely to be cell-specific. Furthermore, the structural features and hydrophobicity of the sugar side chains were analyzed to draw correlations with endosomal escape activity and derive predictive rules, thus providing new insights into structure-activity relationships of saponins. This study revealed new saponins that can potentially be exploited as efficient cytosolic delivery reagents for improved therapeutic drug effects.

8.
ACS Appl Mater Interfaces ; 11(45): 42486-42495, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31638768

RESUMO

Bioinspired by the aligned structure and building blocks of bone, this work mineralized the aligned bacterial cellulose (BC) through in situ mineralization using CaCl2 and K2HPO4 solutions. The cellulose nanofibers were aligned by a scalable stretching process. The aligned and mineralized bacterial cellulose (AMBC) homogeneously incorporated hydroxyapatite (HAP) with a high mineral content and exhibited excellent mechanical strength. The ordered 3D structure allowed the AMBC composite to achieve a high elastic modulus and hardness and the development of a nanostructure inspired by natural bone. The AMBC composite exhibited an elastic modulus of 10.91 ± 3.26 GPa and hardness of 0.37 ± 0.18 GPa. Compared with the nonaligned mineralized bacterial cellulose (NMBC) composite with mineralized crystals of HAP randomly distributed into the BC scaffolds, the AMBC composite possessed a 210% higher elastic modulus and 95% higher hardness. The obtained AMBC composite had excellent mechanical properties by mimicking the natural structure of bone, which indicated that the organic BC aerogel with aligned nanofibers was a promising template for biomimetic mineralization.

9.
ACS Appl Mater Interfaces ; 11(31): 27598-27604, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31302999

RESUMO

We used cellulose and a nonclassical mineralization process to fabricate a bioinspired nanohybrid material that exhibited structural features and properties similar to those of human hard tissues. We made a hydrogel with highly compacted and aligned cellulose nanofibers. We thoroughly mineralized the cellulose hydrogel with hydroxyapatite nanocrystals, using poly(acrylic acid) as a soluble template for precursor minerals, which infiltrated the nanocompartments of the aligned cellulose nanofiber network. The ultrastructure and mechanical properties of the mineralized gels were strikingly similar to those of bone and dentin, which supports further use of cellulose-based fibrillary materials as affordable, biocompatible scaffolds for repair and regeneration of hard tissues. The versatility of the bioinspired mineralization processes used here can broaden the applications of these cellulosic nanohybrids.


Assuntos
Resinas Acrílicas/química , Materiais Biomiméticos/química , Celulose/química , Durapatita/química , Hidrogéis/química , Nanofibras/química , Nanofibras/ultraestrutura
10.
J Hematol Oncol ; 12(1): 46, 2019 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-31023384

RESUMO

BACKGROUND: PD-1/PD-L1 blockade can confer durable benefits in the treatment of metastatic cancers, but the response rate remains modest and potential adverse effects occur sometimes. Concentrating immunotherapeutic agents at the site of disease was believed to break local immune tolerance and reduce systemic toxicity. E1A-engineered mesenchymal stromal cell (MSC.E1A) was an attractive transfer system that preferentially homing and treating cancer metastasis, through which the tumor cells were modified by locally replicated adenoviruses to release CD3-HAC, a bifunctional fusion protein that anti-CD3 scfv linked with high-affinity consensus (HAC) PD-1. Subsequently, CD3-HAC, wbich was bound on PD-L1-positive breast cancer cells, recruited T cells to exhibit a potent antitumor immunity incombination with immune checkpoint blockade. METHODS: We constructed the CD3-HAC gene driven by human telomerase reverse transcriptase (hTERT) promoter into an adenoviral vector and the E1A gene into the lentiviral vector. The homing property of MSCs in vivo was analyzed with firefly luciferase-labeled MSCs (MSC.Luc) by bioluminescent imaging (BLI). The cytotoxicity of T cells induced by CD3-HAC towards PD-L1-positive cells was detected in vitro and in vivo in combination with 5-FU. RESULTS: Our data suggest that CD3-HAC could specifically bind to PD-L1-positive tumor cells and induce lymphocyte-mediated lysis effectively both in vitro and in vivo. The intervention with HAC diminished the effects of PD-1/PD-L1 axis on T cells exposed to MDA-MB-231 cells and increased lymphocytes activation. MSCs infected by AdCD3-HAC followed by LentiR.E1A could specially migrate to metastasis of breast cancer and produce adenoviruses in the tumor sites. Furthermore, treatment with MSC.CD3-HAC.E1A in combination with 5-FU significantly inhibited the tumor growth in mice. CONCLUSIONS: This adenovirus-loaded MSC.E1A system provides a promising strategy for the identification and elimination of metastasis with locally released immuno-modulator.

11.
Nanoscale ; 11(1): 266-275, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30534763

RESUMO

Recent studies have shown that antimicrobial peptides (AMPs) can self-assemble into supramolecular structures, but this has been overlooked as causative of their antimicrobial activity. Also, the higher antimicrobial potency of d-enantiomers compared to l-enantiomers of AMPs cannot always be attributed to their different resistance to protease degradation. Here, we tested all l- and d-amino acid versions of GL13K, an AMP derived from a human protein, to study structural links between the AMP secondary structure, supramolecular self-assembly dynamics, and antimicrobial activity. pH dependence and the evolution of secondary structures were related to a self-assembly process with differences among these AMPs. The two GL13K enantiomers formed analogous self-assembled twisted nanoribbon structures, but d-GL13K initiated self-assembly faster and had notably higher antimicrobial potency than l-GL13K. A non-antimicrobial scrambled amino acid version of l-GL13K assembled at a much higher pH to form distinctively different self-assembled structures than l-GL13K. Our results support a functional relationship between the AMP self-assembly and their antimicrobial activity.


Assuntos
Aminoácidos/química , Peptídeos Catiônicos Antimicrobianos/química , Oligopeptídeos/química , Peptídeos/química , Estrutura Secundária de Proteína , Dicroísmo Circular , Humanos , Concentração de Íons de Hidrogênio , Substâncias Macromoleculares , Conformação Molecular , Estereoisomerismo
12.
ACS Biomater Sci Eng ; 4(8): 2758-2766, 2018 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-30581990

RESUMO

Inspired by nature, poly(acrylic acid) (PAA) and other polyelectrolytes have been used as noncollagenous proteins (NCPs) surrogates for biomimetic intrafibrillar mineralization of collagen fibrils and thus, to model the ultrastructure of bone, to study the mechanism of bone mineralization and, more scarcely to fabricate scaffolds for hard tissue engineering. The objective of this study was to systematically investigate the effect of the molecular weight (MW) and the concentration of PAA on the rate and pattern of biomineralization of collagen matrices. Densified type I collagen films were mineralized in supersaturated PAA-stabilized amorphous calcium-phosphate (PAA-ACP) solutions containing increasing MW (2 kDa, 50 kDA, 450 kDa) and concentrations (10, 25, 50 mg/L) of PAA up to 7 days. The stability and physical properties of collagen-free PAA-ACP solutions were also investigated. In our system, lowering PAA MW and increasing PAA concentration resulted in solutions with increasing stability. Over stable PAA-ACP solutions that fully inhibited mineralization of the collagen matrices were achieved using PAA 2k-50. Conversely, unstable solutions were obtained using high PAA MW at low concentrations. Nucleation and growth of significant amount of extrafibrillar minerals on the collagen fibrils was obtained using these solutions. In a wide range of combined MW and concentration of PAA we obtained intrafibrillar mineralization of collagen with hydroxyapatite crystals aligned parallel to the collagen fibril as in natural tissues. Intrafibrillar mineralization was correlated with PAA-ACP stability and growth of the PAA-ACP particles in solution. Our results support using PAA to surrogate NCPs function as selective inhibitors or promoters of biological mineralization and provide parameters to manufacture new biomimetic scaffolds and constructs for bone and dentin tissue engineering.

13.
BMC Surg ; 18(1): 109, 2018 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-30482184

RESUMO

BACKGROUND: Spigelian hernia (SH) is rare and constitutes less than 2% of all hernias. It is reported that more than 90% of SHs lie in the "Spigelian belt", but SH in the upper abdominal wall is extremely uncommon. Here, we report a case of SH in the right upper quadrant of abdomen. CASE PRESENTATION: A 38-year-old female was admitted to hospital with complaints of abdominal pain and right upper quadrant mass for 10 days. Contrast-enhanced computed tomography (CECT) of abdomen revealed the dilated small intestine between the swelling ventral muscles in the right upper abdominal wall which suggested a ventral hernia. The surgeons considered it was a spontaneous hernia because there was no history of surgery or trauma in the upper abdomen. About two hours later, the patient underwent emergency surgery. According to laparotomy, a diagnosis of SH with ileum herniation in the right upper abdominal wall was confirmed. The necrotic ileum segment was resected. Meanwhile the abdominal wall defect was repaired by suturing the internal oblique and transverse muscles to the rectus sheath. The patient had a favorable outcome for 1 year without recurrence. CONCLUSION: A mass and pain in the upper abdominal wall may suggest an atypical SH. SH occurring in the upper abdominal wall is a rare condition with possibility of dire outcome if not managed early.


Assuntos
Parede Abdominal/cirurgia , Hérnia Ventral/cirurgia , Parede Abdominal/diagnóstico por imagem , Adulto , Feminino , Hérnia Ventral/diagnóstico por imagem , Humanos , Tomografia Computadorizada por Raios X
14.
Materials (Basel) ; 11(8)2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30127240

RESUMO

DBSA was used as a solubilizer together with conventional rejuvenator (CR) to produce a solubilized rejuvenator (SR), two kinds of aged bitumen involving TFOT aged bitumen and PAV aged bitumen were obtained by thin film oven test (TFOT) and pressurized aging vessel (PAV), respectively. Effects of CR and SR on the physical properties, chemical components, colloidal structure and micro-morphology of TFOT aged bitumen and PAV aged bitumen were investigated. Testing results of physical properties and chemical components indicated that CR and SR can replenish aged bitumen with necessary aromatics, TFOT aged bitumen that chemical component variation deteriorates its physical properties. With regard to PAV aged bitumen, of which the performance attenuation lies in chemical components variation and colloidal structure transformation, even if the content of CR reached up to 10 wt %, the regenerated bitumen cannot meet the regeneration requirement yet due to its definite influence on colloidal structure transformation, comparatively, sulfonic group in SR can react with the superficial atoms of asphaltenes to reform a solvation layer to facilitate the colloidal structure transformation of PAV aged bitumen, performance and beelike structure of regenerated PAV aged with bitumen with 10 wt % SR were approximated to that of virgin bitumen.

15.
Medicine (Baltimore) ; 97(26): e11207, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29952974

RESUMO

RATIONALE: Uveal melanoma is the most common primary intraocular malignancy, which could metastasize at an early stage of the disease and associated with poor prognoses. Liver, small bowel, stomach, and colon are the most common locations for metastatic visceral melanoma, however, solitary abdominal metastasis from uveal melanoma is extremely rare. PATIENT CONCERNS: The current study reports the case of a 33-year-old man with history of treated choroidal melanoma of the left eye that developed metastasis to the abdomen, preoperative endoscopic ultrasonography and computed tomography strongly suggested as a gastrointestinal stromal tumor (GIST). DIAGNOSES: The patient was diagnosed with abdominal metastatic melanoma according to his medical history and histopathological results. INTERVENTIONS: The young adult underwent robot-assisted laparoscopic surgery. OUTCOMES: The patient finally got the definite diagnosis with his medical history and histopathological results and he has been living disease free for nearly 3 years after the surgery. LESSONS: Although rare, the possibility of abdominal metastatic melanoma presenting with the clinical picture of gastrointestinal stromal tumor must be always considered by the surgeon especially the patients with a history of primary malignant melanoma.


Assuntos
Neoplasias Abdominais/secundário , Tumores do Estroma Gastrointestinal/diagnóstico , Laparoscopia/métodos , Melanoma/diagnóstico , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Uveais/diagnóstico , Abdome/patologia , Neoplasias Abdominais/cirurgia , Adulto , Diagnóstico Diferencial , Endossonografia , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Masculino , Melanoma/patologia , Melanoma/cirurgia , Tomografia Computadorizada por Raios X , Neoplasias Uveais/patologia , Neoplasias Uveais/cirurgia
16.
Materials (Basel) ; 11(5)2018 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-29783675

RESUMO

Epoxidized soybean oil (ESO) was employed as a novel penetrant cooperating with a conventional rejuvenator (CR) for the recycling of reclaimed asphalt pavement (RAP). The influence of ESO on the diffusibility and the regenerating effects of CR on RAP were investigated. The diffusibility testing result shows that the diffusibility of CR is enhanced by the addition of ESO because the epoxy group in ESO can facilitate asphaltene dispersion due to its high polarity, which simultaneously reduces the viscosity and improves the fluidity of aged bitumen so as to allow diffusion of the rejuvenator into the aged bitumen. Road performance testing of a recycled hot mix asphalt mixture (RHMA) indicates that the fatigue and cracking resistance properties as well as the water stability of RHMA containing CR can be improved by the addition of ESO due to the diffusibility enhancement of CR, which boosts the regenerating effect of CR on aged bitumen in RAP. The fatigue and cracking resistance properties as well as the water stability of the recycled hot mix asphalt mixture containing CR with 7 wt % ESO approximate those of the hot mix asphalt mixture composed of the same virgin aggregates and bitumen. Taking into account the rutting resistance decline versus the addition of ESO, the content of ESO should not exceed 7 wt % of the conventional rejuvenator.

17.
Cell Physiol Biochem ; 47(3): 1007-1024, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29843149

RESUMO

BACKGROUND/AIMS: Pancreatic cancer is an aggressive malignancy as a result of highly metastatic potential. The current study was carried out to alter the expression of LINC01121 in pancreatic cancer, with the aim of elucidating its effects on the biological processes of cell proliferation, migration, invasion, and apoptosis. We hypothesized that both the GLP1R gene and cAMP/PKA signaling pathway participate in the aforementioned process. METHODS: Microarray data (GSE14245, GSE27890 and GSE16515) and annotating probe files linked to pancreatic cancer were downloaded through the GEO database. The Multi Experiment Matrix (MEM) site was used to predict the target gene of lncRNA. Both pancreatic cancer tissues (n = 56) and paracancerous tissues (n = 45) were collected from patients diagnosed with pancreatic cancer. Immunohistochemistry was applied to identify the positive expression rate of GLP1R protein. Isolated pancreatic cancer cells and PANC-1 cells were independently classified into the blank, negative control (NC), LINC01121 vector, siRNA-LINC01121, siRNA-GLP1R and siRNA-LINC01121 + siRNA-GLP1R groups. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were applied to detect the expressions of LINC01121, GLP1R, cAMP, PKA, CREB, Bcl-2, Bad and PCNA. Cell proliferation, migration, invasion, cycle progression, and apoptosis were examined by MTT assay, scratch test, Transwell assay and flow cytometry analyses of Annexin V-FITC/PI staining. RESULTS: Observations were made indicating that LINC01121 was highly expressed, while low expressions of GLP1R in pancreatic cancer were detected based on microarray data, which was largely in consistent with the data collected of LINC01121 and GLP1R within the tissues. The target prediction program and luciferase activity analysis was testament to the notion suggesting that GLP1R was indeed a target of LINC01121. In contrast to the blank and NC groups, the LINC01121 vector group exhibited increased expressions of LINC01121; decreased mRNA and protein levels of GLP1R, Bad, cAMP, and PKA; increased protein levels of CREB, Bcl-2, PCNA, p-PKA and p-CREB; increased cell proliferation, migration and invasion; and decreased cell apoptosis. There was no significant difference detected among the blank, NC, and siRNA-LINC01121 + siRNA-GLP1R groups, except that decreased LINC01121 expression was determined in the siRNA-LINC01121 + siRNA-GLP1R group. Parallel data were observed in the pancreatic cancer cells and PANC-1 cells. CONCLUSION: The current study presents evidence indicating that LINC01121 might inhibit apoptosis while acting to promote proliferation, migration, and invasion of pancreatic cancer cells, supplementing the stance held that LINC01121 functions as a tumor promoter by means of its involvement in the process of translational repression of the GLP1R and inhibition of the cAMP/PKA signaling pathway.


Assuntos
Apoptose , Movimento Celular , Proliferação de Células , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/metabolismo , RNA Longo não Codificante/metabolismo , RNA Neoplásico/metabolismo , Sistemas do Segundo Mensageiro , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/patologia
18.
ACS Appl Mater Interfaces ; 10(18): 15477-15486, 2018 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-29637776

RESUMO

Surface-associated microbial communities, known as biofilms, pose significant challenges in clinical and industrial settings. Micro-/nanoscale substratum surface features have been shown to disrupt firm adhesion of planktonic microbes to surfaces, thereby interfering with the earliest stage of biofilm formation. However, the role of geometry and size of surface features in microbial retention is not completely understood. In this study, we developed a biophysical model that describes the changes in the total free energy (adhesion energy and stretching energy) of an adherent Candida albicans cell on nanofiber-coated surfaces as a function of the geometry (i.e., diameter) and configuration (i.e., interfiber spacing) of the surface features (i.e., nanofibers). We then introduced a new nondimensional parameter, Π, to represent the ratio of cell rigidity to cell-substratum interfacial energy. We show that the total free energy is a strong function of topographical feature size at higher Π and lower spacing values. To confirm our biophysical model predictions, we performed 24 h dynamic retention assays and quantified cell attachment number density on surfaces coated with highly ordered polystyrene nanofibers. We show that the total free energy of a single adherent cell on a patterned surface is a key determinant of microbial retention on that surface. The cell attachment density trend closely correlates with the predictions based on the adherent single-cell total energy. The nanofiber coating design (1.2 µm diameter, 2 µm spacing) that maximized the total energy of the adherent cell resulted in the lowest microbial retention. We further demonstrate the utility of our biophysical model by showing close correlation between the computed single-cell total free energy and biofilm nucleation on fiber-coated urinary and central venous catheters of different materials. This biophysical model could offer a powerful new paradigm in ab initio design of patterned surfaces for controlled biofilm growth for medical applications and beyond.


Assuntos
Nanofibras , Biofilmes , Candida albicans , Cateteres , Propriedades de Superfície
19.
J Investig Med ; 66(3): 676-683, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29141872

RESUMO

MicroRNAs have been reported to play an important role in tumor development and progression by targeting oncogenes and tumor suppressors. miR-23a has been described as significantly upregulated in multiple cancers and involved in tumorigenesis. The aim of this study was to evaluate the potential roles of miR-23a in pancreatic ductal adenocarcinoma (PDAC). We found that miR-23a level was significantly increased in tissues of PDAC compared with that in the control by real-time PCR. FOXP2 expression was downregulated and inversely correlated with miR-23a. miR-23a directly targeted the 3'-untranslated region of FOXP2 mRNA and repressed its expression. Mechanistically, enhancement of miR-23a by transfection with mimics in Aspc-1 cells significantly promoted cell proliferation and invasion, while miR-23a inhibitors transfection in SW1990 cells induced an inhibitory effect. Moreover, restoration of FOXP2 impaired the pro-proliferation and proinvasion effects of miR-23a, indicating FOXP2 is a direct mediator of miR-23a functions. In conclusion, our findings suggest a novel miR-23a/FOXP2 link contributing to PDAC development and invasion. It may be a potential diagnostic and therapeutic target for PDAC.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , MicroRNAs/metabolismo , Oncogenes , Neoplasias Pancreáticas/genética , Adulto , Idoso , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/patologia
20.
J Ultrasound Med ; 37(4): 823-831, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29027678

RESUMO

OBJECTIVES: To examine the repeatability of quantitative time-intensity curve analysis of neovascularization within carotid plaques with contrast-enhanced ultrasonography (US) and to investigate carotid plaque neovascularization in patients with coronary heart disease using contrast-enhanced US and the correlation between risk factors and acute coronary syndrome (ACS). METHODS: Sixty patients with ACS and 60 with stable coronary artery disease (CAD) underwent conventional carotid and contrast-enhanced US, and plaque enhancement was observed and analyzed quantitatively. Carotid contrast-enhanced US was performed within 1 month of ACS occurrence. Interobserver and intraobserver variability of the measurements was assessed. The peak signal intensity was the maximum number of contrast microbubbles that local tissues could accumulate, reflecting the local microvascular density and representing the capillary volume. RESULTS: The ACS group had higher low-density lipoprotein cholesterol (mean ± SD, 3.21 ± 0.75 versus 2.53 ± 0.71 mmol/L; P < .01) and high-sensitivity C-reactive protein (CRP; 3.76 ± 0.19 versus 2. 93 ± 0.15 mg/L; P < .01) levels than the stable CAD group. The proportion of soft plaques in the ACS group (81%) was higher than in the stable CAD group (53%). The proportion of plaque enhancement, peak signal intensity, and plaque-to-carotid lumen enhancement intensity ratio were higher in the ACS group than the stable CAD group. The peak signal intensity was correlated with the high-sensitivity CRP value. Logistic regression analyses indicated that age (65-74 years), high-sensitivity CRP, and enhancement intensity were correlated with the occurrence of ACS. The sensitivity and specificity of the peak signal intensity in carotid plaques were 80.0% and 88.3%, respectively (cutoff value, 9.97 dB; area under the receiver operating characteristic curve, 0.865). The time-intensity curve measurements had good repeatability. CONCLUSIONS: Carotid plaque enhancement is a potential independent risk factor for ACS occurrence. These results illustrate the correlation of carotid plaque vulnerability with the coronary artery symptomatic state according to the common pathogenetic mechanism of atherosclerosis.


Assuntos
Meios de Contraste , Doença da Artéria Coronariana/diagnóstico por imagem , Aumento da Imagem/métodos , Neovascularização Patológica/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Ultrassonografia/métodos , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/patologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Placa Aterosclerótica/patologia , Sensibilidade e Especificidade
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