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1.
J Vasc Interv Radiol ; 33(12): 1507-1512, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35964879

RESUMO

PURPOSE: To assess clinical outcomes and patency after transjugular intrahepatic portosystemic shunt (TIPS) reduction for overshunting adverse events. MATERIALS AND METHODS: This multicenter, retrospective observational study included 33 patients (male-to-female ratio, 20:13; mean age, 59 years; mean Model for End-Stage Liver Disease [MELD] score, 15) who underwent TIPS reduction between 2007 and 2020. Procedure indications included medically refractory hepatic encephalopathy (HE) (85%), post-TIPS hepatic insufficiency (HI) (12%), and heart failure (3%). The measured outcomes included improvement in HE (classified using the West Haven system) and HI, patency of reduced TIPS, and transplant-free survival (TFS). RESULTS: TIPS reductions were successfully performed using parallel stent (94%) or other (6%) techniques at a median of 120 days after TIPS creation (HE, median, 164 days; HI, median, 5 days). The portosystemic pressure gradient increased from a mean of 10 to 17 mm Hg (P < .001). The overall HE rate after TIPS reduction was 54%; HE was persistent, improved, and resolved in 21%, 32%, and 46% cases, respectively. In patients with HI, the MELD score increased from a mean of 22 before TIPS to 34 after TIPS (P = .061), but without improvement (0%) in HI after TIPS reduction (mean MELD score, 30; P = .266). Recurrent ascites occurred in 14% of the patients. The median shunt patency was 961 days (95% confidence interval, 476-1,447). The 30-day, 6-month, 1-year, and 3-year shunt patency rates were 92%, 81%, 74%, and 37%, respectively. The median TFS was not reached. The 30-day, 6-month, 1-year, and 3-year survival rates were 97%, 90%, 81%, and 60%, respectively. CONCLUSIONS: Although TIPS reduction may be an effective and durable approach to treat post-TIPS medically refractory HE, shunt reduction may not achieve meaningful benefit for HI.


Assuntos
Doença Hepática Terminal , Encefalopatia Hepática , Hipertensão Portal , Derivação Portossistêmica Transjugular Intra-Hepática , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Hipertensão Portal/etiologia , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/cirurgia , Doença Hepática Terminal/etiologia , Resultado do Tratamento , Índice de Gravidade de Doença , Encefalopatia Hepática/etiologia , Estudos Retrospectivos
2.
Nanotechnology ; 29(25): 255302, 2018 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-29694334

RESUMO

A facile one-pot synthetic method for preparing the Ag nanoparticle inks with a bimodal size distribution was newly devised and they were successfully employed as a conducting filler to form the metal-mesh type transparent conducting electrodes on the flexible substrate. Bimodal-sized Ag nanoparticles were synthesized through the polyol process, and their size variation was occurred via finely tuned composition ratio between Ag+ ions and polymeric capping agents. The prepared bimodal-sized Ag nanoparticles exhibited the form of well-dispersed Ag nanoparticle inks without adding any dispersants and dispersion process. By filling the patterned micro-channels engraved on the flexible polymer substrate using a bimodal-sized Ag nanoparticle ink, a metal-mesh type transparent electrode (transmittance: 90% at 550 nm, haze: 1.5, area: 8 × 8 cm2) was fabricated. By applying DC voltage to the mesh type electrode, a flexible transparent joule heater was successfully achieved with a performance of 4.5 °C s-1 heat-up rate at a low input power density.

3.
Biochem Biophys Res Commun ; 493(2): 1102-1108, 2017 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-28919421

RESUMO

Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) play an important role in cutaneous wound healing, and recent studies suggested that MSC-derived exosomes activate several signaling pathways, which are conducive in wound healing and cell growth. In this study, we investigated the roles of exosomes that are derived from USC-CM (USC-CM Exos) in cutaneous collagen synthesis and permeation. We found that USC-CM has various growth factors associated with skin rejuvenation. Our in vitro results showed that USC-CM Exos integrate in Human Dermal Fibroblasts (HDFs) and consequently promote cell migration and collagen synthesis of HDFs. Moreover, we evaluated skin permeation of USC-CM Exos by using human skin tissues. Results showed that Exo-Green labeled USC-CM Exos approached the outermost layer of the epidermis after 3 h and gradually approached the epidermis after 18 h. Moreover, increased expressions of Collagen I and Elastin were found after 3 days of treatment on human skin. The results showed that USC-CM Exos is absorbed into human skin, it promotes Collagen I and Elastin synthesis in the skin, which are essential to skin rejuvenation and shows the potential of USC-CM integration with the cosmetics or therapeutics.


Assuntos
Exossomos/metabolismo , Sangue Fetal/citologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Células-Tronco Mesenquimais/metabolismo , Rejuvenescimento , Fenômenos Fisiológicos da Pele , Adulto , Células Cultivadas , Colágeno/metabolismo , Cosméticos , Elastina/metabolismo , Exossomos/química , Feminino , Sangue Fetal/química , Sangue Fetal/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/isolamento & purificação , Peptídeos e Proteínas de Sinalização Intercelular/farmacocinética , Células-Tronco Mesenquimais/química , Células-Tronco Mesenquimais/citologia , Absorção Cutânea , Fenômenos Fisiológicos da Pele/efeitos dos fármacos
4.
J Mol Recognit ; 30(4)2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27891685

RESUMO

Pancreatic cancer remains one of the most common and lethal cancers. Most patients (80%) present with inoperable advanced pancreatic cancer at initial diagnosis, and their early diagnosis is a significant unmet challenge. Recent studies indicate that cancer, including pancreatic cancer, is initiated and propagated by cancer stem cells (CSCs). CSCs are responsible not only for the pathogenesis of cancer but also for the heterogeneity, malignant degree, anticancer therapy resistance, and recurrence of tumors. Therefore, the identification of CSCs may be a crucial stepping stone for overcoming this disastrous pancreatic cancer. Here, we investigated pancreatic CSC-associated aptamers as a novel tool for diagnosis and therapeutic agents. Aptamers that bind to stemness-enriched cancer cells in pancreatic cancer were developed by modified Cell-SELEX method. Positive selection was performed by the sphere cells generated by pancreatic cancer cell line, HPAC, and then the aptamer pool was negatively selected by pancreatic normal cell line, HPDE. Aptamers 1 and 146 showing high specificity upon the KD values with 22.18 and 22.62 nM were selected. These 2 aptamers were validated by binding to HPAC sphere cells and to HPDE cells, and both aptamers showed specificity to HPAC sphere cells only. Aptamer-positive cells showed high expression levels of CSC-associated genes compared with the aptamer-negative cells by FACS analysis. The colocalization of CD44, CD24, ESA, and CD133 was also observed in the aptamer-positive cells by confocal microscopy. In the present study, these 2 pancreatic CSC-associated aptamers may be potential candidates for novel diagnostic markers, CSC-targeting drug delivery, or circulating tumor cell detection.


Assuntos
Aptâmeros de Nucleotídeos/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neoplasias Pancreáticas/metabolismo , Antígeno AC133/metabolismo , Aptâmeros de Nucleotídeos/química , Biomarcadores Tumorais/metabolismo , Antígeno CD24/metabolismo , Linhagem Celular Tumoral , Humanos , Receptores de Hialuronatos/metabolismo , Técnica de Seleção de Aptâmeros
5.
AJR Am J Roentgenol ; 209(5): W322-W332, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28929809

RESUMO

OBJECTIVE: The objective of this study was to investigate the impact of decreasing breast compression during digital mammography and breast tomosynthesis (DBT) on perceived pain and image quality. MATERIALS AND METHODS: In this two-part study, two groups of women with prior mammograms were recruited. In part 1, subjects were positioned for craniocaudal (CC) and mediolateral oblique (MLO) views, and four levels of compression force were applied to evaluate changes in breast thickness, perceived pain, and relative tissue coverage. No imaging was performed. In part 2, two MLO DBT images of one breast of each patient were acquired at standard and reduced compression. Blurring artifacts and tissue coverage were judged by three breast imaging radiologists, and compression force, breast thickness, relative tissue coverage, and perceived pain were recorded. RESULTS: Only the first reduction in force was feasible because further reduction resulted in inadequate breast immobilization. Mean force reductions of 48% and 47% for the CC and MLO views, respectively, resulted in a significantly reduced perceived pain level, whereas the thickness of the compressed breast increased by 0.02 cm (CC view) and 0.09 (MLO view, part 1 of the study) and 0.38 cm (MLO view, part 2 of the study), respectively, with no change in tissue coverage or increase in motion blurring. CONCLUSION: Mammography and DBT acquisitions may be possible using half of the compression force used currently, with a significant and substantial reduction in perceived pain with no clinically significant change in breast thickness and tissue coverage.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mamografia/métodos , Dor/prevenção & controle , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Mamografia/efeitos adversos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Dor/etiologia , Pressão , Estresse Mecânico
6.
Nucleic Acids Res ; 43(15): 7462-79, 2015 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-26202967

RESUMO

ΔNp63 is required for both the proliferation and differentiation of keratinocytes, but its role in the differentiation of these cells is poorly understood. The corresponding gene, TP63, harbors the MIR944 sequence within its intron. However, the mechanism of biogenesis and the function of miR-944 are unknown. We found that miR-944 is highly expressed in keratinocytes, in a manner that is concordant with that of ΔNp63 mRNA, but the regulation of miR-944 expression under various conditions did not correspond with that of ΔNp63. Bioinformatics analysis and functional studies demonstrated that MIR944 has its own promoter. We demonstrate here that MIR944 is a target of ΔNp63. Promoter analysis revealed that the activity of the MIR944 promoter was markedly enhanced by the binding of ΔNp63, which was maintained by the supportive action of AP-2 during keratinocyte differentiation. Our results indicated that miR-944 biogenesis is dependent on ΔNp63 protein, even though it is generated from ΔNp63 mRNA-independent transcripts. We also demonstrated that miR-944 induces keratin 1 and keratin 10 expression by inhibiting ERK signaling and upregulating p53 expression. Our findings suggested that miR-944, as an intronic miRNA and a direct target of ΔNp63, contributes to the function of ΔNp63 in the induction of epidermal differentiation.


Assuntos
Diferenciação Celular/genética , Células Epidérmicas , MicroRNAs/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Células Cultivadas , Regulação da Expressão Gênica , Humanos , Íntrons , Queratinócitos/metabolismo , MicroRNAs/biossíntese , MicroRNAs/genética , Regiões Promotoras Genéticas
7.
Mol Biol Rep ; 42(3): 617-24, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25366176

RESUMO

Preadipocyte factor 1 (Pref-1), also known as a delta-like 1 protein, is a transmembrane and secreted protein containing the epidermal growth factor-like repeat. Pref-1 inhibits adipocyte differentiation by activating the ERK1/2 pathway. MicroRNAs, a new class of small noncoding RNAs of 20-24 nucleotides, act as negative regulators of gene expression and result in mRNA degradation or translational repression. MicroRNA-143 (miR-143) is known to induce adipocyte differentiation; however, miR-143 targets in the regulation of adipocyte differentiation remain unknown. In this study, we investigated whether pref-1 is a miR-143 target to regulate adipogenesis. After the induction of adipocyte differentiation the level of miR-143 was increased, whereas the expression of pref-1 mRNA was decreased. The pref-1 protein level was also down-regulated in preadipocytes ectopically expressing miR-143, and recovered by miR-143 inhibitor. The binding region for miR-143 was predicted to be located between positions 247 and 252 in the 3'-UTR of pref-1. The luciferase activity of the vector containing the wild-type 3'-UTR of pref-1 was decreased by 65 % in cells transfected with miR-143 mimic compared to that of the corresponding control. In contrast, the activity of the pref-1 mutant cells was not affected by the treatment with miR-143 mimic. The ectopic expression of miR-143 mimic suppressed the phosphorylation of ERK1/2 induced by pref-1 in 3T3-L1 cells. However, the suppressed phosphorylation was restored by miR-143 inhibitor. Taken together, these data suggest that miR-143 promotes adipogenesis by directly modulating the pref-1 expression in adipocytes.


Assuntos
Regulação da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/genética , MicroRNAs/genética , Interferência de RNA , Regiões 3' não Traduzidas , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/metabolismo , Adipogenia/genética , Animais , Sequência de Bases , Sítios de Ligação , Proteínas de Ligação ao Cálcio , Diferenciação Celular/genética , Expressão Gênica , Camundongos , MicroRNAs/química , RNA Mensageiro/química , RNA Mensageiro/genética , Transfecção
8.
Mol Biol Rep ; 41(8): 5267-72, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24859974

RESUMO

Phosphatidylinositol 3-kinase (PI3K) plays an important role in the metabolic actions of insulin and is required for adipogenesis. Regulatory subunit 1 of PI3K (PIK3R1) is a critical component of the PI3K signaling pathway. Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipogenesis. Although the PPARγ agonist rosiglitazone induces the expression of PIK3R1, the transcriptional regulation of PIK3R1 in adipocytes remains unknown. In this study, we investigated whether PIK3R1 is a direct target of PPARγ. The level of PIK3R1 expression in 3T3-L1 cells was increased after the induction of adipocyte differentiation and was also induced by overexpression of PPARγ. Furthermore, the upregulation of PPARγ-mediated PIK3R1 expression enhanced the insulin-stimulated AKT activation in 3T3-L1 cells. Two putative peroxisome proliferator response elements (PPREs) in the PIK3R1 promoter were identified as PPARγ binding sites. By chromatin immunoprecipitation, we observed that PPARγ interacts with the two PPRE regions of the PIK3R1 promoter in mature adipocytes. In addition, luciferase reporter assays showed that the -1183/-1161 and -573/-551 regions of the PIK3R1 promoter contain essential elements for PPARγ binding. Taken together, these results suggest that PPARγ is essential for the transcriptional activity of PIK3R1 during adipogenesis.


Assuntos
Adipócitos/metabolismo , Proteínas de Transporte/genética , PPAR gama/genética , Ativação Transcricional/genética , Células 3T3-L1 , Adipogenia , Animais , Sítios de Ligação , Células COS , Proteínas de Transporte/metabolismo , Diferenciação Celular , Chlorocebus aethiops , Imunoprecipitação da Cromatina , Regulação da Expressão Gênica , Insulina/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana , Camundongos , PPAR gama/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Regiões Promotoras Genéticas , Regulação para Cima
10.
ACS Nano ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38320154

RESUMO

Simultaneous in situ detection of transcript and protein markers at the single-cell level is essential for gaining a better understanding of tumor heterogeneity and for predicting and monitoring treatment responses. However, the limited accessibility to advanced 3D imaging techniques has hindered their rapid implementation. Here, we present a 3D single-cell imaging technique, termed 3D digital rolling circle amplification (4DRCA), capable of the multiplexed and amplified simultaneous digital quantification of single-cell RNAs and proteins using standard fluorescence microscopy and off-the-shelf reagents. We generated spectrally distinguishable DNA amplicons from molecular markers through an integrative protocol combining single-cell RNA and protein assays and directly enumerated the amplicons by leveraging an open-source algorithm for 3D deconvolution with a custom-built automatic gating algorithm. With 4DRCA, we were able to simultaneously quantify surface protein markers and cytokine transcripts in T-lymphocytes. We also show that 4DRCA can distinguish BCR-ABL1 fusion transcript positive B-cell acute lymphoblastic leukemia cells with or without CD19 protein expression. The accessibility and extensibility of 4DRCA render it broadly applicable to other cell-based diagnostic workflows, enabling sensitive and accurate single-cell RNA and protein profiling.

11.
Biochem Biophys Res Commun ; 439(3): 401-6, 2013 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-23994134

RESUMO

Adrenocorticotropic hormone (ACTH) in rodents decreases lipid accumulation and body weight. Melanocortin receptor 2 (MC2R) and MC2R accessory protein (MRAP) are specific receptors for ACTH in adipocytes. Peroxisome proliferator-activated receptor γ (PPARγ) plays a role in the transcriptional regulation of metabolic pathways such as adipogenesis and ß-oxidation of fatty acids. In this study we investigated the transcriptional regulation of MRAP expression during differentiation of 3T3-L1 cells. Stimulation with ACTH affected lipolysis in murine mature adipocytes via MRAP. Putative peroxisome proliferator response element (PPRE) was identified in the MRAP promoter region. In chromatin immunoprecipitation and reporter assays, we observed binding of PPARγ to the MRAP promoter. The mutagenesis experiments showed that the -1209/-1198 region of the MRAP promoter could function as a PPRE site. These results suggest that PPARγ is required for transcriptional activation of the MRAP gene during adipogenesis, which contributes to understanding of the molecular mechanism of lipolysis in adipocytes.


Assuntos
Adipócitos/citologia , Proteínas de Membrana/genética , PPAR gama/metabolismo , Ativação Transcricional , Células 3T3-L1 , Adipócitos/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Animais , Sequência de Bases , Sítios de Ligação , Diferenciação Celular , Técnicas de Silenciamento de Genes , Lipólise , Camundongos , Regiões Promotoras Genéticas
12.
J Nanosci Nanotechnol ; 13(5): 3464-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23858880

RESUMO

This paper reported a research on space charge distribution in low-density polyethylene (LDPE) nanocomposites with different types of graphene and graphene oxide (GO) at low filler content (0.05 wt%) under high DC electric field. Effect of addition of graphene oxide or graphene, its dispersion in LDPE polymer matrix on the ability to suppress space charge generation will be investigated and compared with MgO/LDPE nanocomposite at the same filler concentration. At an applied electric field of 80 kV/mm, a positive packet-like charge was observed in both neat LDPE, MgO/LDPE, and graphene/LDPE nanocomposites, whereas only little homogenous space charge was observed in GO/LDPE nanocomposites, especially with GO synthesized from graphite nano fiber (GNF) which is only -100 nm in diameter. Our research also suggests that dispersion of graphene oxide particles on the polymer matrix plays a significant role to the performance of nanocomposites on suppressing packet-like space charge. From these results, it is expected that nano-sized GO synthesized from GNF can be a promising filler material to LDPE composite for HVDC applications.


Assuntos
Grafite/química , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Polietileno/química , Impedância Elétrica , Teste de Materiais , Óxidos/química , Tamanho da Partícula , Eletricidade Estática , Propriedades de Superfície
13.
Ann Dermatol ; 35(3): 165-172, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37290950

RESUMO

BACKGROUND: The exact definition of sensitive skin is not established yet. Since its high prevalence and significant influence on quality of life, it has become an important topic of research. Among various ingredients, conditioned media from umbilical cord blood-derived mesenchymal stem cells (UCB-MSC-CM) can be a promising source for the treatment of sensitive skin. OBJECTIVE: We evaluated the efficacy and safety of UCB-MSC-CM on patients with sensitive skin. METHODS: We designed a randomized, single blinded, prospective, split-face comparison study and enrolled thirty patients. All patients underwent nonablative fractional laser over the entire face before UCB-MSC-CM or normal saline was applied. Each facial area was randomly assigned to undergo treatment with either UCB-MSC-CM or normal saline. We performed three sessions at two-week intervals, and final results were assessed on six weeks after the last session. As an outcome measure, we evaluated a five-point global assessment scale, transepidermal water loss (TEWL), erythema index (EI) and Sensitive Scale-10. Twenty seven subjects were included in final analysis. RESULTS: The treated side exhibited greater improvement compared to the untreated side based on a five-point global assessment scale. TEWL, EI of the treated side were significantly lower than those of the untreated side throughout study period. Sensitive Scale-10 was significantly improved after treatment. CONCLUSION: The application of UCB-MSC-CM resulted in improved skin barrier function and reduced inflammatory responsiveness, which could provide beneficial effect on sensitive skin.

14.
Tech Vasc Interv Radiol ; 25(2): 100819, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35551807

RESUMO

Symptomatic solid benign thyroid nodules may present either as nonfunctioning nodules causing compressive symptoms or as hyperfunctioning nodules causing symptoms of hyperthyroidism. While surgical resection or radioiodine ablation of these nodules can be performed, percutaneous radiofrequency ablation (RFA) of benign solid thyroid nodules has been shown to be a safe and effective alternative in select patients. Preprocedural evaluation should include a history focusing on signs and symptoms of thyroid dysfunction, a physical exam, thyroid ultrasound, thyroid function tests, and discussion of key intraprocedural details with the patient such as the anesthesia plan and risks. Thyroid RFA can be safely performed as an outpatient procedure with less than 2% major and minor complication rates. This report will focus on the basic technique of performing RFA for symptomatic thyroid nodules.


Assuntos
Ablação por Cateter , Ablação por Radiofrequência , Nódulo da Glândula Tireoide , Ablação por Cateter/efeitos adversos , Humanos , Radioisótopos do Iodo , Ablação por Radiofrequência/efeitos adversos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/cirurgia , Resultado do Tratamento
15.
Biosens Bioelectron ; 218: 114760, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36201999

RESUMO

The sensitive detection of the multiple immuno-subtypes of cancer-specific extracellular vesicles (EVs) has emerged as a promising method for multiclass cancer diagnosis; however, its limitations in sensitivity, accessibility, and multiple detection of EV subtypes have hindered its further implementation. Here, we present a platform for sensitive EV detection enabled by sessile droplet array (eSD) that exploits enhanced immuno-capture of EVs via evaporation-driven radial flows in a sessile droplet. Compared to a micro-well without internal flows, this platform demonstrates significantly enhanced EV capture and detection by detecting low levels of EVs with a detection limit of 384.7 EVs per microliter, which is undetectable in the micro-well. In addition, using a small sample consumption of ∼0.2 µL plasma per droplet, the platform detects EV immuno-subtypes against seven different antibodies in patient plasma samples of different cancer types (liver, colon, lung, breast and prostate cancers). Further, using the profiling data, the platform exhibits a sensitivity of 100% (95% confidence interval (CI): 83-100%) and a specificity of 100% (95% CI: 40-100%) for the diagnosis of cancer, and classified cancer types with an overall accuracy of 96% (95% CI: 86-100%) using a two-staged algorithm based on quadratic discriminant analysis technique for machine learning.


Assuntos
Técnicas Biossensoriais , Vesículas Extracelulares , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico
16.
Cell Death Dis ; 13(4): 374, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440077

RESUMO

Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by poor response to standard therapies and therefore unfavorable clinical outcomes. Better understanding of TNBC and new therapeutic strategies are urgently needed. ROR nuclear receptors are multifunctional transcription factors with important roles in circadian pathways and other processes including immunity and tumorigenesis. Nobiletin (NOB) is a natural compound known to display anticancer effects, and our previous studies showed that NOB activates RORs to enhance circadian rhythms and promote physiological fitness in mice. Here, we identified several TNBC cell lines being sensitive to NOB, by itself or in combination. Cell and xenograft experiments showed that NOB significantly inhibited TNBC cell proliferation and motility in vitro and in vivo. ROR loss- and gain-of-function studies showed concordant effects of the NOB-ROR axis on MDA-MB-231 cell growth. Mechanistically, we found that NOB activates ROR binding to the ROR response elements (RRE) of the IκBα promoter, and NOB strongly inhibited p65 nuclear translocation. Consistent with transcriptomic analysis indicating cancer and NF-κB signaling as major pathways altered by NOB, p65-inducible expression abolished NOB effects, illustrating a requisite role of NF-κB suppression mediating the anti-TNBC effect of NOB. Finally, in vivo mouse xenograft studies showed that NOB enhanced the antitumor efficacy in mammary fat pad implanted TNBC, as a single agent or in combination with the chemotherapy agent Docetaxel. Together, our study highlights an anti-TNBC mechanism of ROR-NOB via suppression of NF-κB signaling, suggesting novel preventive and chemotherapeutic strategies against this devastating disease.


Assuntos
Flavonas , Neoplasias de Mama Triplo Negativas , Animais , Linhagem Celular Tumoral , Proliferação de Células , Flavonas/farmacologia , Flavonas/uso terapêutico , Humanos , Quinase I-kappa B/metabolismo , Camundongos , NF-kappa B/metabolismo , Transdução de Sinais , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
17.
J Am Coll Radiol ; 19(11S): S433-S444, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36436968

RESUMO

Mesenteric ischemia is a serious medical condition characterized by insufficient vascular supply to the small bowel. In the acute setting, endovascular interventions, including embolectomy, transcatheter thrombolysis, and angioplasty with or without stent placement, are recommended as initial therapeutic options. For nonocclusive mesenteric ischemia, transarterial infusion of vasodilators, such as papaverine or prostaglandin E1, is the recommended initial treatment. In the chronic setting, endovascular means of revascularization, including angioplasty and stent placement, are generally recommend, with surgical options, such as bypass or endarterectomy, considered alternative options. Although the diagnosis of median arcuate ligament syndrome remains controversial, diagnostic angiography can be helpful in rendering a diagnosis, with the preferred treatment option being a surgical release. Systemic anticoagulation is recommended as initial therapy for venous mesenteric ischemia with acceptable rates of recanalization. If anticoagulation fails, transcatheter thrombolytic infusion can be considered with possible adjunctive placement of a transjugular intrahepatic portosystemic shunt to augment antegrade flow. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.


Assuntos
Isquemia Mesentérica , Radiologia , Humanos , Isquemia Mesentérica/diagnóstico por imagem , Isquemia Mesentérica/terapia , Sociedades Médicas , Medicina Baseada em Evidências , Anticoagulantes/uso terapêutico
18.
Chemosphere ; 268: 129319, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33359995

RESUMO

In this study, carbon-based aerogels derived from waste paper (CWP) were explored as an efficent adsorbent to remove organic pollutants including phenol (Ph) and 2-chlorophenol (2CP) from wastewater. CWP exhibited a highly porous structure and large specific surface area of 892 m2 g-1, which facilitated the adsorption of Ph and 2CP in wastewater. The adsorption behavior of Ph and 2CP on CWP could be well described by the pseudo-second-order kinetics and Langmuir isotherm models. Based on the Langmuir isotherm, the maximum adsorption capacities of CWP for Ph and 2CP were 238 and 278 mg g-1, respectively, and these values were much higher than those of other adsorbents. The removal of the organic pollutants mainly occurred through electrostatic attraction, pore-filling, hydrogen bonding, and π-π interactions. The CWP can be directly applied for the removal of Ph and 2CP at low concentration (<200 mg L-1) in the wastewater, while they can be used with additional pre-treatment for wastewater containing high concentration of organic pollutants. The adsorptive recovery of organic compounds and potential reuse of treated wastewater were also discussed. This work provides an efficient approach to produce effective adsorbent for the removal and recovery of chemicals from wastewater.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Adsorção , Carbono , Concentração de Íons de Hidrogênio , Cinética , Águas Residuárias , Poluentes Químicos da Água/análise
19.
Cell Rep ; 35(8): 109184, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34038729

RESUMO

Autophagy dysregulation is implicated in metabolic diseases, including type 2 diabetes. However, the mechanism by which the autophagy machinery regulates metabolism is largely unknown. Autophagy is generally considered a degradation process via lysosomes. Here, we unveil a metabolically important non-cell-autonomous, non-degradative mechanism regulated by the essential autophagy protein Becn1 in adipose tissue. Upon high-fat diet challenge, autophagy-hyperactive Becn1F121A mice show systemically improved insulin sensitivity and enhanced activation of AMP-activated protein kinase (AMPK), a central regulator of energy homeostasis, via a non-cell-autonomous mechanism mediated by adiponectin, an adipose-derived metabolic hormone. Adipose-specific Becn1F121A expression is sufficient to activate AMPK in non-adipose tissues and improve systemic insulin sensitivity by increasing adiponectin secretion. Further, Becn1 enhances adiponectin secretion by interacting with components of the exocyst complex via the coiled-coil domain. Together, our study demonstrates that Becn1 improves insulin sensitivity by facilitating adiponectin secretion through binding the exocyst in adipose tissue.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adiponectina/metabolismo , Proteína Beclina-1/metabolismo , Insulina/metabolismo , Lisossomos/metabolismo , Animais , Autofagia , Humanos , Camundongos , Transfecção
20.
Radiol Case Rep ; 16(6): 1447-1450, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33912261

RESUMO

Internal iliac artery aneurysms (IIAAs), isolated or associated with abdominal aortic aneurysms, are at rupture risk with growth. Treatment is recommended when symptomatic or greater than 3 cm. Surgical or endovascular therapy should exclude the arterial origin and outflow branches. If all outflow branches are not completely embolized, an endoleak can develop, pressurizing the sac leading to growth and rupture. Accessing the arteries involved can be technically challenging and understanding potential targets is critical. We describe two percutaneous approaches for treatment: percutaneously accessing the sac from an anterior trans-iliopsoas approach and percutaneously accessing the gluteal artery from a posterior approach.

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