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1.
Restor Dent Endod ; 49(2): e13, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38841385

RESUMO

Chronic osteomyelitis with proliferative periostitis, known as Garre's osteomyelitis, is a type of osteomyelitis characterized by a distinctive gross thickening of the periosteum of bones. Peripheral reactive bone formation can be caused by mild irritation or infection. Garre's osteomyelitis is usually diagnosed in children and young adults, and the mandible is more affected than the maxilla. The following is a case report of a 12-year-old female patient with Garre's osteomyelitis of the mandible due to an infection of a root canal-treated tooth. Without surgical intervention, the patient's symptoms were relieved through nonsurgical root canal re-treatment with long-term calcium hydroxide placement. A cone-beam computed tomography image obtained 6 months after treatment completion displayed complete healing of the periapical lesion and resolution of the peripheral reactive buccal bone. Due to the clinical features of Garre's osteomyelitis, which is characterized by thickening of the periosteum, it can be mistaken for other diseases such as fibrous dysplasia. It is important to correctly diagnose Garre's osteomyelitis based on its distinctive clinical features to avoid unnecessary surgical intervention, and it can lead to minimally invasive treatment options.

2.
Sci Rep ; 14(1): 13926, 2024 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886498

RESUMO

This split-mouth blinded randomized controlled study compared the efficacy of a desensitizing agent with oxalate/resin polymer and a universal adhesive containing mesoporous bioactive glass (MBG) for dentin hypersensitivity (DH) relief, using Schiff sensitivity score (SSS) and visual analog scale (VAS). Split quadrants containing teeth with DH were treated with either MS Coat ONE or Hi-Bond Universal with MBG as the functional additive. Assessments at baseline, immediately post-application, and at 1- and 2-week follow-ups used standardized stimulus protocols (air, cold, and acid). The SSS difference was the primary outcome, while the VAS difference was the secondary outcome. A mixed linear effect model performed statistical analysis. Immediate DH reduction occurred in response to air stimuli, with a significant decrease in Group HB than in Group MS (p = 0.0178). Cold stimulus reduction exhibited a gradual cumulative effect, with consistently greater reductions in Group HB than in Group MS (p ≤ 0.0377). Both groups effectively managed acidic stimuli, with no significant differences (p > 0.05). The VAS scores decreased gradually over the follow-up period (p < 0.0001). This study highlights the differential efficacy of treatments for various DH triggers and recommends specific approaches based on different stimulus types. The universal adhesive containing MBG demonstrated DH relief potential, promising efficacy identical to or superior to that of a dedicated desensitizing agent. Further research exploring the long-term efficacy and underlying mechanisms is warranted. The universal adhesive containing MBG can be adopted as an in-office desensitizing agent for DH relief. The desensitizing efficacy of universal adhesive matches or surpasses dedicated agents for air and cold stimuli.


Assuntos
Dessensibilizantes Dentinários , Sensibilidade da Dentina , Humanos , Sensibilidade da Dentina/tratamento farmacológico , Feminino , Masculino , Dessensibilizantes Dentinários/uso terapêutico , Adulto , Vidro/química , Resultado do Tratamento , Cerâmica/química , Cimentos Dentários/química , Cimentos Dentários/uso terapêutico , Adulto Jovem , Pessoa de Meia-Idade , Porosidade
3.
Nat Commun ; 15(1): 4166, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755146

RESUMO

Failure of proper ventricular trabeculation is often associated with congenital heart disease. Support from endocardial cells, including the secretion of extracellular matrix and growth factors is critical for trabeculation. However, it is poorly understood how the secretion of extracellular matrix and growth factors is initiated and regulated by endocardial cells. We find that genetic knockout of histone deacetylase 3 in the endocardium in mice results in early embryo lethality and ventricular hypotrabeculation. Single cell RNA sequencing identifies significant downregulation of extracellular matrix components in histone deacetylase 3 knockout endocardial cells. Secretome from cultured histone deacetylase 3 knockout mouse cardiac endothelial cells lacks transforming growth factor ß3 and shows significantly reduced capacity in stimulating cultured cardiomyocyte proliferation, which is remarkably rescued by transforming growth factor ß3 supplementation. Mechanistically, we identify that histone deacetylase 3 knockout induces transforming growth factor ß3 expression through repressing microRNA-129-5p. Our findings provide insights into the pathogenesis of congenital heart disease and conceptual strategies to promote myocardial regeneration.


Assuntos
Endocárdio , Histona Desacetilases , Camundongos Knockout , MicroRNAs , Miócitos Cardíacos , Animais , Endocárdio/metabolismo , Camundongos , MicroRNAs/metabolismo , MicroRNAs/genética , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Miócitos Cardíacos/metabolismo , Fator de Crescimento Transformador beta3/metabolismo , Fator de Crescimento Transformador beta3/genética , Proliferação de Células , Miocárdio/metabolismo , Células Endoteliais/metabolismo , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/patologia , Matriz Extracelular/metabolismo , Feminino
4.
Nat Commun ; 15(1): 2991, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582753

RESUMO

All-solid-state batteries using Si as the anode have shown promising performance without continual solid-electrolyte interface (SEI) growth. However, the first cycle irreversible capacity loss yields low initial Coulombic efficiency (ICE) of Si, limiting the energy density. To address this, we adopt a prelithiation strategy to increase ICE and conductivity of all-solid-state Si cells. A significant increase in ICE is observed for Li1Si anode paired with a lithium cobalt oxide (LCO) cathode. Additionally, a comparison with lithium nickel manganese cobalt oxide (NCM) reveals that performance improvements with Si prelithiation is only applicable for full cells dominated by high anode irreversibility. With this prelithiation strategy, 15% improvement in capacity retention is achieved after 1000 cycles compared to a pure Si. With Li1Si, a high areal capacity of up to 10 mAh cm-2 is attained using a dry-processed LCO cathode film, suggesting that the prelithiation method may be suitable for high-loading next-generation all-solid-state batteries.

5.
Pharmacol Ther ; 257: 108638, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38548089

RESUMO

Congenital heart disease is the most common birth defect worldwide. Defective cardiac myogenesis is either a major presentation or associated with many types of congenital heart disease. Non-myocardial tissues, including endocardium and epicardium, function as a supporting hub for myocardial growth and maturation during heart development. Recent research findings suggest an emerging role of epigenetics in nonmyocytes supporting myocardial development. Understanding how growth signaling pathways in non-myocardial tissues are regulated by epigenetic factors will likely identify new disease mechanisms for congenital heart diseases and shed lights for novel therapeutic strategies for heart regeneration.


Assuntos
Cardiopatias Congênitas , Miocárdio , Humanos , Miocárdio/metabolismo , Coração , Pericárdio , Transdução de Sinais , Cardiopatias Congênitas/metabolismo , Regeneração , Epigênese Genética , Miócitos Cardíacos
6.
bioRxiv ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-37886504

RESUMO

BACKGROUND: Trabeculation, a key process in early heart development, is the formation of myocardial trabecular meshwork. The failure of trabeculation often leads to embryonic lethality. Support from endocardial cells, including the secretion of extracellular matrix (ECM) and growth factors is critical for trabeculation; however, it is unknown how the secretion of ECM and growth factors is initiated and regulated by endocardial cells. METHODS: Various cellular and mouse models in conjunction with biochemical and molecular tools were employed to study the role of histone deacetylase 3 (HDAC3) in the developing endocardium. RESULTS: We found that genetic deletion of Hdac3 in endocardial cells in mice resulted in early embryo lethality presenting as a hypotrabeculation cardiac phenotype. Single cell RNA sequencing identified several ECM components including collagens that were significantly downregulated in Hdac3 knockout (KO) endocardial cells. When cultured with supernatant from Hdac3 KO mouse cardiac endothelial cells (MCECs), wild-type mouse embryonic cardiomyocytes showed decreased proliferation, suggesting that growth signaling from Hdac3 KO MCECs is disrupted. Subsequent transcriptomic analysis revealed that transforming growth factor ß3 (TGFß3) was significantly downregulated in Hdac3 KO MCECs and Hdac3 cardiac endothelial KO hearts. Mechanistically, we identified that microRNA (miR)-129-5p was significantly upregulated in Hdac3 KO MCECs and Hdac3 cardiac endothelial KO hearts. Overexpression of miR-129-5p repressed Tgfß3 expression in wild-type MCECs, whereas knockdown of miR-129-5p restored Tgfß3 expression in Hdac3 KO MCECs. CONCLUSION: Our findings reveal a critical signaling pathway in which endocardial HDAC3 promotes trabecular myocardium growth by stimulating TGFß signaling through repressing miR-129-5p, providing novel insights into the etiology of congenital heart disease and conceptual strategies to promote myocardial regeneration.

7.
Small ; 20(23): e2308771, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38152967

RESUMO

The study presents the binder-free synthesis of mixed metallic organic frameworks (MMOFs) supported on a ternary metal oxide (TMO) core as an innovative three-dimensional (3D) approach to enhance electron transport and mass transfer during the electrochemical charge-discharge process, resulting in high-performance hybrid supercapacitors. The research demonstrates that the choice of organic linkers can be used to tailor the morphology of these MMOFs, thus optimizing their electrochemical efficiency. Specifically, a NiCo-MOF@NiCoO2@Ni electrode, based on terephthalic linkers, exhibits highly ordered porosity and a vast internal surface area, achieving a maximum specific capacity of 2320 mC cm-2, while maintaining excellent rate capability and cycle stability. With these performances, the hybrid supercapacitor (HSC) achieves a maximum specific capacitance of 424.6 mF cm-2 (specific capacity 653.8 mC cm-2) and 30.7 F cm-3 with energy density values of 10.1 mWh cm-3 at 167.4 mW cm-3 (139.8 µWh cm-2 at 2310 µW cm-2), which are higher than those of previously reported MMOFs based electrodes. This research introduces a novel approach for metal organic framework based HSC electrodes, diverging from the traditional emphasis on metal ions, in order to achieve the desired electrochemical performance.

8.
Odontology ; 2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38102366

RESUMO

We aimed to evaluate the screw-in force, torque generation, and performance of three nickel-titanium (NiTi) glide-path files with different rotational kinetics. ProTaper Ultimate Slider (PULS) and HyFlex EDM Glide-path (HEDG) files were used for canal shaping with constant rotation (CON) or the alternative rotation technique (ART). In the ART mode, the NiTi file was periodically rotated at a speed of 1.5 times faster than that in the CON mode. WaveOne Gold Glider was used with reciprocating motion (WOGG_RCP). Sixty J-shaped resin blocks were assigned to five groups: PULS_CON, PULS_ART, HEDG_CON, HEDG_ART, and WOGG_RCP (n = 12). Glide-path preparation was performed using an automated pecking device. During glide-path preparation, the screw-in force and clockwise and counterclockwise torques were recorded and the number of pecking motions required to reach the working length was determined. The centering ratio was calculated after glide-path preparation using stereomicroscopic images. Data were analyzed using one-way analysis of variance with the Games-Howell post hoc test and the Kruskal-Wallis test with Bonferroni correction. PULS_ART generated a lower maximum screw-in force than PULS_CON. The average number of pecking motions required to reach the working length by HEDG_ART was lower than that by HEDG_CON. The mean centering ratios of PULS_CON and HEDG_CON were - 0.04 and - 0.06, respectively, while those of PULS_ART, HEDG_ART, and WOGG_RCP were 0.09, 0.01, and 0.08, respectively. The ART mode reduced the screw-in force of PULS and enabled faster glide-path preparation with the HEDG file.

9.
J Endod ; 49(12): 1660-1667, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37774945

RESUMO

INTRODUCTION: Osteolectin is a secreted glycoprotein of the C-type lectin domain superfamily, expressed in bone tissues and is reported as a novel osteogenic factor that promotes bone regeneration. However, the effect of osteolectin on human dental pulp cells (hDPCs) has not been reported. Therefore, we aimed to investigate the odontoblastic differentiation of osteolectin in hDPCs and further attempt to reveal its underlying mechanism. METHODS: Cytotoxicity assays were used to detect the cytotoxicity of osteolectin. The odontoblastic differentiation of hDPCs and its underlying mechanisms were measured by the alkaline phosphatase (ALP) activity, mineralized spots formation, and the gene and protein expression of odontoblastic differentiation through ALP staining, Alizarin red S staining, quantitative real-time polymerase chain reaction, and Western blot analysis, respectively. RESULTS: WST-1 assay showed osteolectin at concentrations below 300 ng/ml was noncytotoxic and safe for hDPCs. The following experiment demonstrated that osteolectin could increase ALP activity, accelerate the mineralization process, and up-regulate the odontogenic differentiation markers in both gene and protein levels (P < .05). Osteolectin stimulated the phosphorylation of ERK, JNK, and Protein kinase B (AKT) in hDPCs. Extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK), and AKT inhibitors decreased ALP activity and mineralization capacity and suppressed the expression of dentin sialophosphoprotein and dentin matrix protein-1. CONCLUSION: Osteolectin can promote odontoblastic differentiation of hDPCs, and the whole process may stimulate ERK, JNK, and AKT signaling pathways by increasing p-ERK, p-JNK, and p-AKT signals.


Assuntos
Proteínas da Matriz Extracelular , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas da Matriz Extracelular/farmacologia , Polpa Dentária , Diferenciação Celular , Transdução de Sinais , Odontoblastos , Fosfatase Alcalina/metabolismo , Células Cultivadas , Proliferação de Células , Fosfoproteínas
10.
Bio Protoc ; 13(17): e4802, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37719080

RESUMO

Congenital heart disease (CHD) is often associated with myogenic defects. During heart development, cardiomyocyte growth requires essential cues from extrinsic factors such as insulin-like growth factor 2 (IGF-2). To determine whether and how growth factors account for embryonic cardiomyocyte proliferation, isolation followed by culturing of embryonic cardiomyocytes can be utilized as a useful tool for heart developmental studies. Current protocols for isolating cardiomyocytes from the heart do not include a cardiomyocyte-specific reporter to distinguish cardiomyocytes from other cell types. To optimize visualization of cardiomyocyte proliferation, our protocol utilizes a Tnnt2-promoter-driven H2B-GFP knock-in mouse model (TNNT2H2B-GFP/+) for in vitro visualization of nuclear-tagged cardiomyocyte-specific fluorescence. A cardiomyocyte-specific genetic reporter paired with an effective proliferation assay improves the reproducibility of mechanistic studies by increasing the accuracy of cell identification, proliferated cell counting, and cardiomyocyte tracking. Key features • This protocol refines previous methods of cardiomyocyte isolation to specifically target embryonic cardiomyocytes. • UsesH2B-GFP/+cardiomyocyte reporters as identified by Yan et al. (2016). • Traces cell proliferation with Phospho-Histone 3 (p-H3) assay. • Has applications in assessing the role of growth factors in cardiomyocyte proliferation.

11.
ACS Omega ; 8(26): 23799-23805, 2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37426240

RESUMO

Li-S batteries have received significant attention owing to their high energy density, nontoxicity, low cost, and eco-friendliness. However, the dissolution of lithium polysulfide during the charge/discharge process and its extremely low electron conductivity hinder practical applications of Li-S batteries. Herein, we report a sulfur-infiltrated carbon cathode material with a spherical morphology and conductive polymer coating. The material was produced via a facile polymerization process that forms a robust nanostructured layer and physically prevents the dissolution of lithium polysulfide. The thin double layer composed of carbon and poly(3,4-ethylenedioxythiophene) provides sufficient space for sulfur storage and effectively prevents the elution of polysulfide during continuous cycling, thereby playing an essential role in increasing the sulfur utilization rate and significantly improving the electrochemical performance of the battery. Sulfur-infiltrated hollow carbon spheres with a conductive polymer layer demonstrate a stable cycle life and reduced internal resistance. The as-fabricated battery demonstrated an excellent capacity of 970 mA h g-1 at 0.5 C and a stable cycle performance, exhibiting ∼78% of the initial discharge capacity after 50 cycles. This study provides a promising approach to significantly improve the electrochemical performance of Li-S batteries and render them as valuable and safe energy devices for large-scale energy storage systems.

12.
Gynecol Oncol ; 174: 21-27, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37146436

RESUMO

OBJECTIVE: Surgical margin status in women undergoing surgery for early-stage cervical cancer is an important prognostic factor. We sought to determine whether close (<3 mm) and positive surgical margins are associated with surgical approach and survival. METHODS: This is a national retrospective cohort study of cervical cancer patients treated with radical hysterectomy. Patients with stage IA1/LVSI-Ib2(FIGO 2018) with lesions up to 4 cm at 11 Canadian institutions from 2007 to 2019 were included. Surgical approach included robotic/laparoscopic (LRH), abdominal (ARH) or combined laparoscopic-assisted vaginal/vaginal (LVRH) radical hysterectomy. Recurrence free survival(RFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Chi-square and log-rank tests were used to compare groups. RESULTS: 956 patients met inclusion criteria. Surgical margins were as follows: negative (87.0%), positive (0.4%) or close <3 mm (6.8%), missing (5.8%). Most patients had squamous histology (46.9%); 34.6% had adenocarcinomas and 11.3% adenosquamous. Most were stage IB (75.1%) and 24.9% were IA. Mode of surgery included: LRH(51.8%), ARH (39.2%), LVRH (8.9%). Predictive factors for close/positive margins included stage, tumour diameter, vaginal involvement and parametrial extension. Surgical approach was not associated with margin status (p = 0.27). Close/positive margins were associated with a higher risk of death on univariate analysis (HR = non calculable for positive and HR = 1.83 for close margins, p = 0.017), but not significant for OS when adjusted for stage, histology, surgical approach and adjuvant treatment. There were 7 recurrences in patients with close margins (10.3%, p = 0.25). 71.5% with positive/close margins received adjuvant treatment. In addition, MIS was associated with a higher risk of death (OR = 2.39, p = 0.029). CONCLUSION: Surgical approach was not associated to close or positive margins. Close surgical margins were associated with a higher risk of death. MIS was associated with worse survival, suggesting that margin status may not be the driver of worse survival in these cases.


Assuntos
Laparoscopia , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Estudos Retrospectivos , Margens de Excisão , Intervalo Livre de Doença , Estadiamento de Neoplasias , Canadá/epidemiologia , Histerectomia
13.
Small ; 19(29): e2300551, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37052488

RESUMO

Carbon-based electrocatalysts with both high activity and high stability are desirable for use in Zn-air batteries. However, the carbon corrosion reaction (CCR) is a critical obstacle in rechargeable Zn-air batteries. In this study, a cost-effective carbon-based novel material is reported with a high catalytic effect and good durability for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), prepared via a simple graphitization process. In situ growth of graphene is utilized in a 3D-metal-coordinated hydrogel by introducing a catalytic lattice of transition metal alloys. Due to the direct growth of few-layer graphene on the metal alloy decorated 3d-carbon network, greatly reduced CCR is observed in a repetitive OER test. As a result, an efficient bifunctional electrocatalytic performance is achieved with a low ΔE value of 0.63 V and good electrochemical durability for 83 h at a current density of 10 mA cm-2 in an alkaline media. Moreover, graphene-encapsulated transition metal alloys on the nitrogen-doped carbon supporter exhibit an excellent catalytic effect and good durability in a Zn-air battery system. This study suggests a straightforward way to overcome the CCR of carbon-based materials for an electrochemical catalyst with wide application in energy conversion and energy storage devices.

14.
Sci Rep ; 13(1): 5271, 2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-37002263

RESUMO

The 4-week double-blind clinical trial to manage dentin hypersensitivity (DH) using different desensitizing toothpastes was conducted. 53 participants with DH were enrolled in this trial. The participants were randomized into 3 groups: Group N; no active ingredient-containing toothpaste (Pleasia fluoride-free), Group SC; a toothpaste containing strontium chloride (Sensodyne Original), and Group TP; a toothpaste containing tricalcium phosphate (Vussen S). They were instructed to brush their teeth manually for 3 min, 3 times per day for 4 weeks with the allocated toothpastes, and were assessed at baseline (0), 2, and 4 weeks, respectively. Schiff sensitivity score was recorded to 3 different stimuli (air-blast, cold, and acid) at each assessment. Overall DH was also assessed using a visual analog scale (VAS). The longer participants used the toothpastes, the greater reduction in DH in all groups to the three stimuli. Group TP demonstrated significant reduction of DH compared to group N for air-blast and cold stimuli. Group TP showed significantly lower VAS than group N and SC. Tricalcium phosphate containing toothpaste used in this trial was most useful to reduce DH. It can be one of the treatment options that alleviate DH.


Assuntos
Dessensibilizantes Dentinários , Sensibilidade da Dentina , Humanos , Cremes Dentais/uso terapêutico , Fluoreto de Sódio/uso terapêutico , Sensibilidade da Dentina/tratamento farmacológico , Resultado do Tratamento , Dessensibilizantes Dentinários/uso terapêutico , Arginina/uso terapêutico , Método Duplo-Cego , Fluoretos/uso terapêutico
15.
Surg Oncol ; 48: 101922, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36924642

RESUMO

OBJECTIVES: The landscape of early-stage endometrial cancer treatment has changed dramatically over the last decade. The aim of this study is to provide a real-world view of the impact sentinel lymph node (SLN) biopsy has had on both clinical practice and patient outcomes. We describe detection and recurrence rates, as well as our experience in managing low volume lymph node disease. METHODS: We conducted an international, multicenter retrospective cohort study of 1012 patients with apparent early-stage endometrial cancer. Eligible patients underwent primary surgical staging and SLN biopsy in one of three large academic tertiary cancer centers in Canada or the Republic of Korea between 2015 and 2019. Demographic, surgical, clinicopathologic and recurrence data were collected through chart review. RESULTS: A total of 1012 patients were included. Overall SLN detection rate for all tracer types was 94.1% and recurrence rate was 5.3%. Higher FIGO stage (III vs. I/II) was associated with failed bilateral mapping (OR 2.27, 95%CI 1.14-4.52). We identified seven patients with micrometastases and 12 with isolated tumor cells, of which only one patient with micrometastases recurred at 17 months. Recurrence rates based on risk groups were 2.1%, 5.3%, 8.1%, and 9.9% for low, intermediate, high-intermediate, and high risk, respectively. CONCLUSION: SLN biopsy is safe and feasible. Detection rates are high, regardless of which tracer type is used and recurrence rates are low, especially in low and intermediate risk disease. Patients with low volume metastases appear to have low risk of recurrence, but replication of our findings by large prospective studies are needed to elucidate their clinical importance.


Assuntos
Neoplasias do Endométrio , Linfonodo Sentinela , Feminino , Humanos , Biópsia de Linfonodo Sentinela , Linfonodos/patologia , Estudos Retrospectivos , Micrometástase de Neoplasia/patologia , Excisão de Linfonodo , Neoplasias do Endométrio/cirurgia , Neoplasias do Endométrio/patologia , Estadiamento de Neoplasias , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia
16.
Nucleic Acids Res ; 51(6): 2655-2670, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-36727462

RESUMO

Overexpression of androgen receptor (AR) is the primary cause of castration-resistant prostate cancer, although mechanisms upregulating AR transcription in this context are not well understood. Our RNA-seq studies revealed that SMAD3 knockdown decreased levels of AR and AR target genes, whereas SMAD4 or SMAD2 knockdown had little or no effect. ChIP-seq analysis showed that SMAD3 knockdown decreased global binding of AR to chromatin. Mechanistically, we show that SMAD3 binds to intron 3 of the AR gene to promote AR expression. Targeting these binding sites by CRISPRi reduced transcript levels of AR and AR targets. In addition, ∼50% of AR and SMAD3 ChIP-seq peaks overlapped, and SMAD3 may also cooperate with or co-activate AR for AR target expression. Functionally, AR re-expression in SMAD3-knockdown cells partially rescued AR target expression and cell growth defects. The SMAD3 peak in AR intron 3 overlapped with H3K27ac ChIP-seq and ATAC-seq peaks in datasets of prostate cancer. AR and SMAD3 mRNAs were upregulated in datasets of metastatic prostate cancer and CRPC compared with primary prostate cancer. A SMAD3 PROTAC inhibitor reduced levels of AR, AR-V7 and AR targets in prostate cancer cells. This study suggests that SMAD3 could be targeted to inhibit AR in prostate cancer.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Proteína Smad3 , Humanos , Masculino , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Androgênicos/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismo
17.
Curr Oncol ; 30(2): 1977-1985, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36826114

RESUMO

Minimally invasive surgery for the treatment of macroscopic cervical cancer leads to worse oncologic outcomes than with open surgery. Preoperative conization may mitigate the risk of surgical approach. Our objective was to describe the oncologic outcomes in cases of cervical cancer initially treated with conization, and subsequently found to have no residual cervical cancer after hysterectomy performed via open and minimally invasive approaches. This was a retrospective cohort study of surgically treated cervical cancer at 11 Canadian institutions from 2007 to 2017. Cases initially treated with cervical conization and subsequent hysterectomy, with no residual disease on hysterectomy specimen were included. They were subdivided according to minimally invasive (laparoscopic/robotic (MIS) or laparoscopically assisted vaginal/vaginal hysterectomy (LVH)), or abdominal (AH). Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Chi-square and log-rank tests were used to compare between cohorts. Within the total cohort, 238/1696 (14%) had no residual disease on hysterectomy specimen (122 MIS, 103 AH, and 13 VLH). The majority of cases in the cohort were FIGO 2018 stage IB1 (43.7%) and underwent a radical hysterectomy (81.9%). There was no statistical difference between stage, histology, and radical vs simple hysterectomy between the abdominal and minimally invasive groups. There were no significant differences in RFS (5-year: MIS/LVH 97.7%, AH 95.8%, p = 0.23) or OS (5-year: MIS/VLH 98.9%, AH 97.4%, p = 0.10), although event-rates were low. There were only two recurrences. In this large study including only patients with no residual cervical cancer on hysterectomy specimen, no significant differences in survival were seen by surgical approach. This may be due to the small number of events or due to no actual difference between the groups. Further studies are warranted.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias , Canadá , Histerectomia
18.
Artigo em Inglês | MEDLINE | ID: mdl-36749965

RESUMO

The use of oxygen evolution co-catalysts (OECs) with hematite photoanodes has received much attention because of the potential to reduce surface charge recombination. However, the low surface charge transfer and bulk charge separation rate of hematite are not improved by decorating with OECs, and the intrinsic drawbacks of hematite still limit efficient photoelectrochemical (PEC) water splitting. Here, we successfully overcame the sluggish oxygen evolution reaction performance of hematite for water splitting by inserting zero-dimensional (0D) nanofragmented MXene (NFMX) as a hole transport material between the hematite and the OEC. The 0D NFMX was fabricated from two-dimensional (2D) MXene sheets and deposited onto the surface of a three-dimensional (3D) hematite photoanode via a centrifuge-assisted method without altering the inherent performance of the 2D MXene sheets. Among many OECs, NiFe(OH)x was selected as the OEC to improve hematite PEC performance in our system because of its efficient charge transport behavior and high stability. Because of the great synergy between NFMX and NiFe(OH)x, NiFe(OH)x/NFMX/Fe2O3 achieved a maximum photocurrent density of 3.09 mA cm-2 at 1.23 VRHE, which is 2.78-fold higher than that of α-Fe2O3 (1.11 mA cm-2). Furthermore, the poor stability of MXene in an aqueous solution for water splitting was resolved by uniformly coating it with NiFe(OH)x, after which it showed outstanding stability for 60 h at 1.23 VRHE. This study demonstrates the successful use of NFMX as a hole transport material combined with an OEC for highly efficient water splitting.

19.
IEEE J Transl Eng Health Med ; 11: 145-150, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36816099

RESUMO

Increasingly complex and long-range donor organ allocation routes coupled with implementation of unmanned aerial vehicles (UAVs) have prompted investigations of the conditions affecting organs once packaged for shipment. Our group has previously demonstrated that different modes of organ transport exert unique environmental stressors, in particular vibration. Using a mouse heart transplant model, we demonstrated that vibrational forces exert tangible, cellular effects in the form of cardiomyocyte apoptosis and cytoskeletal derangement. Functionally, these changes translated into accelerated allograft loss. Notably, administration of an apoptosis inhibitor, Z-VAD-FMK, helped to ameliorate the detrimental cellular and functional effects of mechanical vibration in a dose-dependent manner. These findings constitute one of the first reports of the negative impact of transit environment on transplant outcomes, a contributing mechanism underpinning this effect, and a potential agent to prophylax against this process. Given current limitations in measuring donor organ transit environments in situ, further study is required to better characterize the impact of transport environment and to potentially improve the care of donor organs during shipment. Clinical and Translational Impact Statement: We show that apoptosis inhibitor, Z-VAD-FMK, ameliorated transport-related vibrational stress in murine heart transplants, which presents a potential therapeutic or preservation solution additive for future use in transporting donor organs.


Assuntos
Transplante de Coração , Vibração , Animais , Camundongos , Apoptose , Transplante Homólogo , Aloenxertos
20.
BMC Public Health ; 22(1): 2298, 2022 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-36482452

RESUMO

BACKGROUND: Korean government has established various policies to counter the low fertility rate since the mid-2000s, but it still has the lowest fertility rate among OECD member countries. This study investigated the relationship between changes in the Korean fertility rate and policies to encourage fertility. METHODS: This study utilized data of the total fertility rate of 250 local governments between 2014 and 2018, and a casebook of local government birth promotion policies. The dependent variable was fertility rate, and the independent variable was fertility promotion policy. Using SPSS 25.0 and M-plus 8.0 programs, descriptive statistical analysis and latent growth modeling were conducted. An unconditional quadratic function change model was selected as a final model of this study. RESULTS: The average of the initial fertility rate and the linear rate of change in the Korean fertility rate, and the rate of change of the quadratic function were all statistically significant, meaning that the fertility rate of decline increases over time. Also, the linear rate of change and the quadratic function change rate were significant, showing significant differences in the initial level and rate of change of the fertility rate between local governments. Among fertility policies, only the in-kind policy had a significant effect on the initial value of the fertility rate, meaning that the higher the number of in-kind policies, the higher the fertility rate. CONCLUSION: This study is crucial as it examined the changes in the fertility rate of Korean local governments as well as the policy factors affecting the fertility rate at a quantitative level.


Assuntos
Coeficiente de Natalidade , Política Pública , Humanos , Dinâmica Populacional , Demografia , Fertilidade , Países em Desenvolvimento , Economia
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