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1.
Mol Cell ; 81(16): 3368-3385.e9, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34375583

RESUMO

The mechanistic understanding of nascent RNAs in transcriptional control remains limited. Here, by a high sensitivity method methylation-inscribed nascent transcripts sequencing (MINT-seq), we characterized the landscapes of N6-methyladenosine (m6A) on nascent RNAs. We uncover heavy but selective m6A deposition on nascent RNAs produced by transcription regulatory elements, including promoter upstream antisense RNAs and enhancer RNAs (eRNAs), which positively correlates with their length, inclusion of m6A motif, and RNA abundances. m6A-eRNAs mark highly active enhancers, where they recruit nuclear m6A reader YTHDC1 to phase separate into liquid-like condensates, in a manner dependent on its C terminus intrinsically disordered region and arginine residues. The m6A-eRNA/YTHDC1 condensate co-mixes with and facilitates the formation of BRD4 coactivator condensate. Consequently, YTHDC1 depletion diminished BRD4 condensate and its recruitment to enhancers, resulting in inhibited enhancer and gene activation. We propose that chemical modifications of eRNAs together with reader proteins play broad roles in enhancer activation and gene transcriptional control.


Assuntos
Adenosina/análogos & derivados , Proteínas de Ciclo Celular/genética , Proteínas do Tecido Nervoso/genética , Fatores de Processamento de RNA/genética , RNA/genética , Fatores de Transcrição/genética , Adenosina/genética , Elementos Facilitadores Genéticos/genética , Regulação da Expressão Gênica/genética , Humanos , Metilação , Elementos Reguladores de Transcrição/genética , Ativação Transcricional/genética
2.
Nature ; 595(7869): 735-740, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34040254

RESUMO

The functional engagement between an enhancer and its target promoter ensures precise gene transcription1. Understanding the basis of promoter choice by enhancers has important implications for health and disease. Here we report that functional loss of a preferred promoter can release its partner enhancer to loop to and activate an alternative promoter (or alternative promoters) in the neighbourhood. We refer to this target-switching process as 'enhancer release and retargeting'. Genetic deletion, motif perturbation or mutation, and dCas9-mediated CTCF tethering reveal that promoter choice by an enhancer can be determined by the binding of CTCF at promoters, in a cohesin-dependent manner-consistent with a model of 'enhancer scanning' inside the contact domain. Promoter-associated CTCF shows a lower affinity than that at chromatin domain boundaries and often lacks a preferred motif orientation or a partnering CTCF at the cognate enhancer, suggesting properties distinct from boundary CTCF. Analyses of cancer mutations, data from the GTEx project and risk loci from genome-wide association studies, together with a focused CRISPR interference screen, reveal that enhancer release and retargeting represents an overlooked mechanism that underlies the activation of disease-susceptibility genes, as exemplified by a risk locus for Parkinson's disease (NUCKS1-RAB7L1) and three loci associated with cancer (CLPTM1L-TERT, ZCCHC7-PAX5 and PVT1-MYC).


Assuntos
Fator de Ligação a CCCTC/genética , Elementos Facilitadores Genéticos , Predisposição Genética para Doença , Regiões Promotoras Genéticas , Sistemas CRISPR-Cas , Proteínas de Ciclo Celular/genética , Células Cultivadas , Cromatina , Proteínas Cromossômicas não Histona/genética , Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Células MCF-7 , Neoplasias/genética , Células-Tronco Neurais , Oncogenes , Doença de Parkinson/genética , Coesinas
3.
Eur Arch Otorhinolaryngol ; 280(6): 2741-2748, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36512107

RESUMO

OBJECTIVES: The comparative efficacy of microscopic tympanoplasty (MT) and endoscopic tympanoplasty (ET) has been widely studied to some extent through meta-analyses. However, most studies on learning curve comparisons between the two surgeries were performed by experienced ET surgeons. We compared the surgical outcomes of MT and ET and evaluated the difference of learning curve between ET and MT performed by a single unskilled, in both MT and ET, surgeon. DESIGN: A total of 91 patients underwent ET and MT at a tertiary hospital. We reviewed the patients' medical records and analyzed all findings, including otoscopic pictures, pure tone audiometry (PTA) before and after surgery, and operation records. All operations were performed by a single otologist who had an experience of a year of otology fellowship at a tertiary university hospital. We compared the demographic and clinical characteristics, including age, sex, admission duration, and audiological outcomes before and after surgery. We also assessed the difference in the decrease in operation time. RESULTS: Among 91 patients, 44 were in the ET group and 47 were in the MT group. The mean age was 51.15 years, and 37 (40.7%) were men. Eighty-two (90.1%) patients were administered local anesthesia. Graft failure was observed in 19 (20.9%) patients, and the mean postoperative follow-up duration was 66.42 days. There were no statistically significant differences in age, sex, affected side, graft failure rate, and operation time between the ET and MT groups. There was a significant improvement in air conduction hearing and air-bone gap after surgery in both groups. Bone conduction hearing did not change before and after the surgery in either group. However, the improvement in air condition and reduction in the air-bone gap did not differ between the two groups. Multivariate linear regression analysis showed that there were no significant variables that affected operation time among age, sex, operation method (ET or MT), anesthesia, graft material, and technique. The spline regression analysis showed the decrease in operative time in ET was significantly faster than MT in the period from 8th to 19th cases. CONCLUSIONS: The surgical outcomes of ET are comparable to those of MT in terms of operation time, graft uptake, and postoperative hearing results, even in surgeons who are not experienced with both MT and ET. The operation time of ET was longer than that of MT in the early phase, and the decrease in the operating time was significantly faster in ET than in MT. Both MT and ET reached a plateau in the operation time, and this plateau appeared to be similar in both surgeries.


Assuntos
Curva de Aprendizado , Timpanoplastia , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Timpanoplastia/métodos , Estudos Retrospectivos , Miringoplastia/métodos , Endoscopia/métodos , Resultado do Tratamento
4.
Eur Arch Otorhinolaryngol ; 280(9): 4121-4129, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37039894

RESUMO

PURPOSE: Accumulating evidence suggests that Staphylococcus aureus plays a significant role as a disease modifier in upper and lower airway diseases. We aimed to assess the association between staphylococcal enterotoxins (SEs) with allergic diseases and the degree of allergen sensitisation in children, which remains unclear. METHODS: We retrospectively reviewed the medical records of 455 patients aged 3-18 years between March 2018 and March 2022. Clinical history and demographic data were obtained. The baseline study included paranasal sinus X-ray scan, multiple allergen simultaneous test, and ImmunoCAP® for measuring serum total and specific immunoglobulin E (IgE) levels to allergens and staphylococcal enterotoxin A and B (SEA and SEB). RESULTS: The mean age was 9.77 ± 4.3 years. 133 patients (29.2%) were sensitised to one inhalant allergen, and 188 patients (41.3%) showed polysensitisation. Patients sensitised to SEs showed higher total and specific IgE levels and total eosinophil counts compared to non-SE-sensitised patients. Sensitisation to SEs is closely associated with polysensitisation to inhalant allergens and allergic multimorbidity. When the SE-IgE value was 0.35 or higher, the odds ratio for allergen polysensitisation was significantly higher than when the SE-IgE value was lower than 0.35. CONCLUSIONS: Association between polysensitisation and sensitisation to SEs in children shows the higher the specific IgE levels for SEs, the higher the likelihood of polysensitisation. Considering the relationship between polysensitisation, high IgE levels, and the severity of allergic morbidity, sensitisation to SEs is thought to be related to allergy severity.


Assuntos
Hipersensibilidade , Humanos , Criança , Pré-Escolar , Adolescente , Estudos Retrospectivos , Alérgenos , Enterotoxinas , Imunoglobulina E
5.
Nucleic Acids Res ; 48(5): 2621-2642, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-31863590

RESUMO

Transposable elements (TEs) comprise a large proportion of long non-coding RNAs (lncRNAs). Here, we employed CRISPR to delete a short interspersed nuclear element (SINE) in Malat1, a cancer-associated lncRNA, to investigate its significance in cellular physiology. We show that Malat1 with a SINE deletion forms diffuse nuclear speckles and is frequently translocated to the cytoplasm. SINE-deleted cells exhibit an activated unfolded protein response and PKR and markedly increased DNA damage and apoptosis caused by dysregulation of TDP-43 localization and formation of cytotoxic inclusions. TDP-43 binds stronger to Malat1 without the SINE and is likely 'hijacked' by cytoplasmic Malat1 to the cytoplasm, resulting in the depletion of nuclear TDP-43 and redistribution of TDP-43 binding to repetitive element transcripts and mRNAs encoding mitotic and nuclear-cytoplasmic regulators. The SINE promotes Malat1 nuclear retention by facilitating Malat1 binding to HNRNPK, a protein that drives RNA nuclear retention, potentially through direct interactions of the SINE with KHDRBS1 and TRA2A, which bind to HNRNPK. Losing these RNA-protein interactions due to the SINE deletion likely creates more available TDP-43 binding sites on Malat1 and subsequent TDP-43 aggregation. These results highlight the significance of lncRNA TEs in TDP-43 proteostasis with potential implications in both cancer and neurodegenerative diseases.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteostase/genética , RNA Longo não Codificante/genética , Elementos Nucleotídeos Curtos e Dispersos/genética , Apoptose , Linhagem Celular , Citoplasma/metabolismo , Dano ao DNA , Estresse do Retículo Endoplasmático , Ativação Enzimática , Dosagem de Genes , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Humanos , Mitose , Modelos Biológicos , Transporte Proteico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Deleção de Sequência/genética , eIF-2 Quinase
6.
Small ; 16(3): e1906109, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31859444

RESUMO

Organic semiconductors (OSCs) are highly susceptible to the formation of metastable polymorphs that are often transformed by external stimuli. However, thermally reversible transformations in OSCs with stability have not been achieved due to weak van der Waals forces, and poor phase homogeneity and crystallinity. Here, a polymorph of a single crystalline 2,7-dioctyl[1] benzothieno[3,2-b][1]benzothio-phene rod on a low molecular weight poly(methyl methacrylate) (≈120k) that limits crystal coarsening during solvent vapor annealing is fabricated. Molecules in the polymorph lie down slightly toward the substrate compared to the equilibrium state, inducing an order of greater resistivity. During thermal cycling, the polymorph exhibits a reversible change in resistivity by 5.5 orders with hysteresis; this transition is stable toward bias and thermal cycling. Remarkably, varying cycling temperatures leads to diverse resistivities near room temperature, important for nonvolatile multivalue memories. These trends persist in the carrier mobility and on/off ratio of the polymorph field-effect transistor. A combination of in situ grazing incident wide angle X-ray scattering analyses, visualization for electronic and structural analysis simulations, and density functional theory calculations reveals that molecular tilt governs the charge transport characteristics; the polymorph transforms as molecules tilt, and thereby, only a homogeneous single-crystalline phase appears at each temperature.

7.
RNA Biol ; 17(11): 1550-1559, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-31916476

RESUMO

Enhancers are distal genomic elements critical for gene regulation and cell identify control during development and diseases. Many human cancers were found to associate with enhancer malfunction, due to genetic and epigenetic alterations, which in some cases directly drive tumour growth. Conventionally, enhancers are known to provide DNA binding motifs to recruit transcription factors (TFs) and to control target genes. However, recent progress found that most, if not all, active enhancers pervasively transcribe noncoding RNAs that are referred to as enhancer RNAs (eRNAs). Increasing evidence points to functional roles of at least a subset of eRNAs in gene regulation in both normal and cancer cells, adding new insights into the action mechanisms of enhancers. eRNA expression was observed to be widespread but also specific to tumour types and individual patients, serving as opportunities to exploit them as potential diagnosis markers or therapeutic targets. In this review, we discuss the brief history of eRNA research, their functional mechanisms and importance in cancer gene regulation, as well as their therapeutic and diagnostic values in cancer. We propose that further studies of eRNAs in cancer will offer a promising 'eRNA targeted therapy' for human cancer intervention.


Assuntos
Elementos Facilitadores Genéticos , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , RNA não Traduzido/genética , Animais , Biomarcadores Tumorais , Cromatina/genética , Cromatina/metabolismo , Suscetibilidade a Doenças , Epistasia Genética , Redes Reguladoras de Genes , Humanos , Técnicas de Diagnóstico Molecular , Neoplasias/diagnóstico , Neoplasias/metabolismo , Neoplasias/terapia , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais , Transcrição Gênica
8.
Gynecol Oncol ; 151(1): 32-38, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30122310

RESUMO

OBJECTIVES: The aim of this study was to analyze risk factors for septic complications during adjuvant chemotherapy and their impact on survival in patients with advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). METHODS: We retrospectively reviewed the medical records of 69 patients with advanced epithelial ovarian cancer from 2004 to 2017. All patients underwent three cycles of NACT followed by IDS and adjuvant chemotherapy. We identified grade 3 or 4 hematologic complications and severe adverse events accompanied by neutropenia, including sepsis or septic shock, that occurred during treatment. Clinicopathologic data including demographic factors, preoperative medical conditions, surgical procedures, and survival times were evaluated. RESULTS: Of 69 patients, 27 (39.1%), 6 (8.8%), and 2 (2.9%) patients experienced grade 3 or 4 neutropenia, anemia, and thrombocytopenia, respectively, during NACT. Thirteen patients (18.8%) had a neutropenic fever with sepsis and 2 patients (2.9%) died of septic shock during adjuvant chemotherapy. Concurrent medical disease, splenectomy during IDS, and anemia or thrombocytopenia during NACT were significant risk factors for septic adverse events. In multivariate analysis, anemia (hemoglobin < 8 g/dL, p = 0.004) during NACT was the only significant factor associated with septic adverse events during adjuvant chemotherapy. Although there was no significant difference in progression-free survival, overall survival was significantly shorter in patients with septic adverse events (median, 82.3 vs. 17.3 months, p = 0.007). CONCLUSIONS: Grade 3 anemia during NACT may be an early indicator for septic adverse events during adjuvant chemotherapy. Considering the adverse impact on survival, scheme and dose of adjuvant chemotherapy should be tailored, and careful follow-up evaluation should be ensured in this patient group.


Assuntos
Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/terapia , Complicações Pós-Operatórias/epidemiologia , Sepse/epidemiologia , Adulto , Idoso , Anemia/induzido quimicamente , Anemia/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Procedimentos Cirúrgicos de Citorredução/métodos , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Ovário/patologia , Ovário/cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Sepse/etiologia , Fatores de Tempo , Resultado do Tratamento
9.
J Nanosci Nanotechnol ; 14(8): 6181-4, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25936083

RESUMO

In the previous work, we have reported that organic photovoltaic (OPV) cells using DMDCNQI as an n-type second dopant material showed a high power conversion efficiency (PCE). In the present work, we have synthesized a novel DHDCNQI with long alkyl chains to improve the compatibility between the DHDCNQI dopant molecule and host P3HT polymer. We have fabricated OPV cells consisting of ITO/PEDOT:PSS/P3HT:PCBM:DHDCNQI/Al. We have investigated the characteristics of theses OPV cells using DCNQI derivative dopants from the measurements of the incident photon-to-current collection efficiency and photocurrent. The OPV cell using 3 wt% DHDCNQI exhibited a high PCE of 3.29% due to the high charge separation efficiency, good compatibility and low trap site effect.


Assuntos
Luz , Nitrilas/química , Semicondutores
10.
J Craniofac Surg ; 25(2): e164-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24621759

RESUMO

Temporalis fascia has been used widely as a interposition graft for mucosal rotation flap in nasal septal perforation repair. However, the exact role of temporalis fascia in healing process has not yet been clarified. For the pedicle of rotation flap has been considered as a major vehicle for nutrition distribution, the role of temporalis fascia has been devaluated. In this study, we experienced small nasal septal perforation repairs using free mucosal graft not having pedicles but covered by temporalis fascia. Three patients with small nasal septal perforations not larger than 1 × 1 cm were included. In 2 patients, the perforations were repaired using free composite grafts from the inferior turbinate mucosa covered by continuous temporalis fascia not divided, and the surgical results were successful with complete healings. In 1 patient, however, the temporalis fascia was divided into 2 parts to better fit the shape of the perforation, and the graft failed to survive. These surgical results suggest that the temporalis fascia might have an important role in healing process of nasal septal defect and could be used as a beneficial options for small mucosal defect repair surgeries using free mucosal grafts.


Assuntos
Fáscia/transplante , Retalhos de Tecido Biológico , Mucosa Nasal/transplante , Perfuração do Septo Nasal/cirurgia , Adulto , Idoso , Sobrevivência de Enxerto , Humanos , Pessoa de Meia-Idade , Septo Nasal/cirurgia , Estudos Retrospectivos , Conchas Nasais
11.
J Mater Chem B ; 12(21): 5238-5247, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38699788

RESUMO

This study introduces a thermally responsive smart hydrogel with enhanced electrical properties achieved through volume switching. This advancement was realized by incorporating multiscale liquid metal particles (LMPs) into the PNIPAM hydrogel during polymerization, using their inherent elasticity and conductivity when deswelled. Unlike traditional conductive additives, LMPs endow the PNIPAM hydrogel with a remarkably consistent volume switching ratio, significantly enhancing electrical switching. This is attributed to the minimal nucleation effect of LMPs during polymerization and their liquid-like behavior, like vacancies in the polymeric hydrogel under compression. The PNIPAM/LMP hydrogel exhibits the highest electrical switching, with an unprecedented switch of 6.1 orders of magnitude. Even after repeated swelling/deswelling cycles that merge some LMPs and increase the conductivity when swelled, the hydrogel consistently maintains an electrical switch exceeding 4.5 orders of magnitude, which is still the highest record to date. Comprehensive measurements reveal that the hydrogel possesses robust mechanical properties, a tissue-like compression modulus, biocompatibility, and self-healing capabilities. These features make the PNIPAM/LMP hydrogel an ideal candidate for long-term implantable bioelectronics, offering a solution to the mechanical mismatch with dynamic human tissues.


Assuntos
Resinas Acrílicas , Condutividade Elétrica , Hidrogéis , Hidrogéis/química , Resinas Acrílicas/química , Temperatura , Materiais Biocompatíveis/química , Metais/química , Tamanho da Partícula , Animais
12.
J Nanosci Nanotechnol ; 13(3): 2012-5, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23755640

RESUMO

In previous work, we have reported that a P3HT:PCBM-based organic photovoltaic cell using a thermally evaporated DMDCNQI buffer layer shows a high power conversion efficiency. In the present work, we have fabricated organic photovoltaic cells consisting of ITO/PEDOT:PSS/P3HT:PCBM:DMDCNQI/DMDCNQI/Al using an all-solution process. A thin, uniform DMDCNQI film was obtained in a methanol solution with high solubility and low viscosity. The prepared device shows a high power conversion efficiency of 2.9%. In particular, a maximum external quantum efficiency of 81% was obtained.


Assuntos
Teoria Quântica , Soluções Tampão , Espectrofotometria
13.
Sci Rep ; 13(1): 14983, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37696881

RESUMO

As both the industry and academia become more focused on biomass-based smart materials, they are attracting a lot of attention. There has been a significant effort in the field of polyurethane (PU) synthesis to replace polyols used in synthesis with bio-derived polyols. Bio-derived polyols have limited application potential for bio-based PU due to their low functionality. Here, we reported castor oil (CO) based multifunctional polyols prepared by grafting thiols such as 1-mercaptoethanol or α-thioglycerol via a facile thiol-ene click reaction method (coded as COM and COT, respectively). Subsequently, bio-based shape memory polyurethanes (SMPU) crosslinked with prepared polyols were synthesized using a 2-step prepolymer method. By confirming the functionality of the synthesized polyols, it was determined that COT has an OH value of 380 mg KOH/g, which is approximately three times that of CO. The successful synthesis of SMPUs was confirmed through chemical structural analysis. It was also proved that the phase separation between the soft and hard segments was limited due to the increase in crosslinking density. As compared to SMPU crosslinked with CO, the mechanical strength of SMPU crosslinked with COT was improved by 80%, while the elongation was decreased by about 26%. As a result of shape memory behavior analysis, it was confirmed that the outstanding SMPU can be synthesized using CO-based multifunctional polyols.

14.
RSC Adv ; 13(32): 22315-22324, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37497093

RESUMO

To enhance the crack propagation and initiation properties and heat deflection temperature of poly(lactic acid) (PLA), PLA/poly(1,4-cyclohexanedimethylene isosorbide terephthalate) (PEICT) blend systems were prepared and glass fibers (GF) were incorporated as reinforcements. Due to high shear force during extrusion and injection molding the length of GF was reduced and was oriented towards the flow direction. Although the reinforcing effect of the GF deviated from the theoretical values calculated by the Halpin-Tsai equation, both tensile and flexural properties were greatly enhanced with increasing GF content. Dynamic mechanical and thermal testing showed improved storage modulus throughout the entire temperature range showing outstanding reinforcing ability. By incorporating GF into the PLA/PEICT blend, the crack propagation and initiation properties were enhanced compared to pristine PLA. Such an increase in crack propagation properties was the result of enhanced modulus with the added GF. Moreover, because of the increased modulus, the heat deflection temperatures of the GF reinforced blends were drastically increased showing a value of 91.4 °C at 20 wt% GF loading. The high performance reached by the biomass-based composites developed in this research shows great possibility of replacing these conventional petroleum-based polymer systems.

15.
J Am Heart Assoc ; 12(18): e030022, 2023 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-37721166

RESUMO

Background Triglyceride and glucose (TyG) index and TyG-related indices combined with obesity-related markers are considered important markers of insulin resistance. We aimed to examine the association between the TyG index and modified TyG indices with new-onset hypertension and their predictive ability stratified by sex. Methods and Results We analyzed data from 5414 Korean Genome and Epidemiology Study participants aged 40 to 69 years. Multiple Cox proportional hazard regression analyses were conducted to estimate the hazard ratio (HR) and 95% CI for new-onset hypertension according to sex-specific tertile groups after confounder adjustments. To evaluate the predictive performance of these indices for new-onset hypertension, we calculated Harrell's C-index (95% CI). Over a 9.5-year follow-up period, 1014 men and 1012 women developed new-onset hypertension. Compared with the lowest tertile (T) group, the adjusted HR and 95% CI for new-onset hypertension in T3 for TyG, TyG-body mass index, TyG-waist circumference, and TyG-waist-to-height ratio were 1.16 (0.95-1.40), 1.11 (0.84-1.48), 1.77 (1.38-2.27), and 1.68 (1.33-2.13) in men and 1.37 (1.13-1.66), 1.55 (1.16-2.06), 1.43 (1.15-1.79), and 1.64 (1.30-2.07) in women, respectively. The C-indices of TyG-waist-to-height ratio for new-onset hypertension were significantly higher than those of TyG and TyG-body mass index in both men and women. Conclusions TyG and TyG-body mass index were significantly associated with new-onset hypertension only in women. TyG-waist circumference and TyG-waist-to-height ratio were significantly associated with new-onset hypertension in both men and women. A sex-specific approach is required when using TyG and modified TyG indices to identify individuals at risk of incident hypertension.


Assuntos
Povo Asiático , Hipertensão , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Massa Corporal , Glucose , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Triglicerídeos , Adulto
16.
Cell Death Dis ; 14(2): 81, 2023 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-36737605

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. TNBC patients typically exhibit unfavorable outcomes due to its rapid growth and metastatic potential. Here, we found overexpression of CCN3 in TNBC patients. We identified that CCN3 knockdown diminished cancer stem cell formation, metastasis, and tumor growth in vitro and in vivo. Mechanistically, ablation of CCN3 reduced activity of the EGFR/MAPK pathway. Transcriptome profiling revealed that CCN3 induces glycoprotein nonmetastatic melanoma protein B (GPNMB) expression, which in turn activates the EGFR pathway. An interrogation of the TCGA dataset further supported the transcriptional regulation of GPNMB by CCN3. Finally, we showed that CCN3 activates Wnt signaling through a ligand-dependent or -independent mechanism, which increases microphthalmia-associated transcription factor (MITF) protein, a transcription factor inducing GPNMB expression. Together, our findings demonstrate the oncogenic role of CCN3 in TNBC, and we propose CCN3 as a putative therapeutic target for TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Receptores ErbB/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Fatores de Transcrição , Neoplasias de Mama Triplo Negativas/patologia
17.
ACS Appl Mater Interfaces ; 15(32): 38335-38345, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37539960

RESUMO

Functional amyloid fibers are crucial in melanogenesis, but their roles are incompletely understood. In particular, their relationship with intrinsic spin characters of melanin remains unexplored. Here, we show that adding an amyloid scaffold greatly augments the spin density in synthetic melanin. It also brings about concurrent alterations in water dispersibility, bandgaps, and radical scavenging properties of the synthetic melanin, which facilitates its applications in solar water remediation and protection of human keratinocytes from UV irradiation. This work provides implications in the unrevealed role of functional amyloid in melanogenesis and in the origin of the superiority of natural melanin toward its synthetic variants in terms of the spin-related properties.


Assuntos
Amiloide , Amiloide/química , Radicais Livres/química , Melaninas/química , Raios Ultravioleta , Técnicas Eletroquímicas , Citoproteção
18.
Nat Microbiol ; 8(4): 679-694, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36959507

RESUMO

Some viruses restructure host chromatin, influencing gene expression, with implications for disease outcome. Whether this occurs for SARS-CoV-2, the virus causing COVID-19, is largely unknown. Here we characterized the 3D genome and epigenome of human cells after SARS-CoV-2 infection, finding widespread host chromatin restructuring that features widespread compartment A weakening, A-B mixing, reduced intra-TAD contacts and decreased H3K27ac euchromatin modification levels. Such changes were not found following common-cold-virus HCoV-OC43 infection. Intriguingly, the cohesin complex was notably depleted from intra-TAD regions, indicating that SARS-CoV-2 disrupts cohesin loop extrusion. These altered 3D genome/epigenome structures correlated with transcriptional suppression of interferon response genes by the virus, while increased H3K4me3 was found in the promoters of pro-inflammatory genes highly induced during severe COVID-19. These findings show that SARS-CoV-2 acutely rewires host chromatin, facilitating future studies of the long-term epigenomic impacts of its infection.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Cromatina
19.
J Biol Chem ; 286(26): 23093-101, 2011 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-21536672

RESUMO

We previously demonstrated that the receptor for the complement component C1q (gC1qR) is a lipid raft protein that is indispensable for adipogenesis and insulin signaling. Here, we provide the first report that gC1qR is an essential component of lamellipodia in human lung carcinoma A549 cells. Cell-surface gC1qR was concentrated in the lamellipodia along with CD44, monosialoganglioside, actin, and phosphorylated focal adhesion kinase in cells stimulated with insulin, IGF-1, EGF, or serum. The growth factor-induced lamellipodia formation and cell migration were significantly decreased in gC1qR-depleted cells, with a concomitant blunt activation of the focal adhesion kinase and the respective receptor tyrosine kinases. Moreover, the gC1qR-depleted cells exhibited a reduced proliferation rate in culture as well as diminished tumorigenic and metastatic activities in grafted mice. We therefore conclude that cell-surface gC1qR regulates lamellipodia formation and metastasis via receptor tyrosine kinase activation.


Assuntos
Adenocarcinoma/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas de Neoplasias/metabolismo , Pseudópodes/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Animais , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/genética , Feminino , Proteína-Tirosina Quinases de Adesão Focal/genética , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Mitocondriais/genética , Metástase Neoplásica , Proteínas de Neoplasias/genética , Transplante de Neoplasias , Pseudópodes/genética , Pseudópodes/patologia , Transplante Heterólogo
20.
Sci Rep ; 12(1): 14646, 2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36030314

RESUMO

Novel crosslinking bio polyurethane based polymeric solid-solid phase change materials (SSPCM) were synthesized using castor oil (CO) based hyperbranched polyols as crosslinkers. CO-based hyperbranched polyols were synthesized by grafting 1-mercaptoethanol or α-thioglycerol via a thiol-ene click reaction method (coded as COM and COT, respectively). Subsequently, the three SSPCMs were synthesized by a two-step prepolymer method. Polyethylene glycol was used as the phase change material in the SSPCMs, while the CO-based hyperbranched polyols and two types of diisocyanate (hexamethylene diisocyanate (HDI) and 4,4'-diphenylmethane diisocyanate) served as the molecular frameworks. Fourier transform infrared spectroscopy indicated the successful synthesis of the SSPCMs. The solid-solid transition of the prepared SSPCMs was confirmed by X-ray diffraction analysis and polarized optical microscopy. The thermal transition properties of the SSPCMs were analyzed by differential scanning microscopy. The isocyanate and crosslinker types had a significant influence on the phase transition properties. The SSPCM samples prepared using HDI and COT exhibited the highest phase transition enthalpy of 126.5 J/g. The thermal cycling test and thermogravimetric analysis revealed that SSPCMs exhibit outstanding thermal durability. Thus, the novel SSPCMs based on hyperbranched polyols have great potential for application as thermal energy storage materials.

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