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1.
Front Immunol ; 15: 1362642, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38745649

RESUMEN

Hyperuricaemia (HUA) is a metabolic disorder characterised by high blood uric acid (UA) levels; moreover, HUA severity is closely related to the gut microbiota. HUA is also a risk factor for renal damage, diabetes, hypertension, and dyslipidaemia; however, current treatments are associated with detrimental side effects. Alternatively, Fangyukangsuan granules are a natural product with UA-reducing properties. To examine their efficacy in HUA, the binding of small molecules in Fangyukangsuan granules to xanthine oxidase (XOD), a key factor in UA metabolism, was investigated via molecular simulation, and the effects of oral Fangyukangsuan granule administration on serum biochemical indices and intestinal microorganisms in HUA-model rats were examined. Overall, 24 small molecules in Fangyukangsuan granules could bind to XOD. Serum UA, creatinine, blood urea nitrogen, and XOD levels were decreased in rats treated with Fangyukangsuan granules compared to those in untreated HUA-model rats. Moreover, Fangyukangsuan granules restored the intestinal microbial structure in HUA-model rats. Functional analysis of the gut microbiota revealed decreased amino acid biosynthesis and increased fermentation of pyruvate into short-chain fatty acids in Fangyukangsuan granule-treated rats. Together, these findings demonstrate that Fangyukangsuan granules have anti-hyperuricaemic and regulatory effects on the gut microbiota and may be a therapeutic candidate for HUA.


Asunto(s)
Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Hiperuricemia , Ácido Úrico , Animales , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Ratas , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Masculino , Ácido Úrico/sangre , Xantina Oxidasa/metabolismo , Ratas Sprague-Dawley
2.
Can Liver J ; 7(2): 273-285, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38746866

RESUMEN

Background: Prior to the COVID-19 pandemic, Alberta was on track to meet national HCV elimination targets by 2030. However, it is unclear how the pandemic has affected progress. Here, we aim to assess the impact of first-wave COVID-19 restrictions on Alberta HCV testing trends. Methods: HCV testing information was extracted from the provincial public health laboratory from 2019 to 2022. HCV antibody and RNA testing were categorized into (1) number ordered, (2) number positive, and (3) percent positivity, and stratified by HCV history status. Testing trends were evaluated across locations engaging high-risk individuals and priority demographics. An interrupted time-series analysis was used to identify average monthly testing rates before, during, and after first-wave COVID-19 restrictions. Results: Overall, HCV testing trends were significantly affected by COVID-19 restrictions in April 2020. Average monthly rates decreased by 98.39 antibody tests ordered per 100,000 among individuals without an HCV history and by 1.78 RNA tests ordered per 100,000 among those with an HCV history. While antibody and RNA testing trends started to rebound in the follow-up period relative to pre-restriction period, testing levels in the follow-up period remained below pre-restriction levels for all groups, except for addiction/recovery centres and emergency room/acute care facilities, which increased. Conclusions: If rates are to return to pre-restriction levels and elimination goals are to be met, more work is needed to engage individuals in HCV testing. As antibody testing rates are rebounding, reengaging those with a history of HCV for viral load monitoring and treatment should be prioritized.

3.
JMIR Public Health Surveill ; 10: e51279, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38669075

RESUMEN

BACKGROUND: The COVID-19 pandemic rapidly changed the landscape of clinical practice in the United States; telehealth became an essential mode of health care delivery, yet many components of telehealth use remain unknown years after the disease's emergence. OBJECTIVE: We aim to comprehensively assess telehealth use and its associated factors in the United States. METHODS: This cross-sectional study used a nationally representative survey (Health Information National Trends Survey) administered to US adults (≥18 years) from March 2022 through November 2022. To assess telehealth adoption, perceptions of telehealth, satisfaction with telehealth, and the telehealth care purpose, we conducted weighted descriptive analyses. To identify the subpopulations with low adoption of telehealth, we developed a weighted multivariable logistic regression model. RESULTS: Among a total of 6252 survey participants, 39.3% (2517/6252) reported telehealth use in the past 12 months (video: 1110/6252, 17.8%; audio: 876/6252, 11.6%). The most prominent reason for not using telehealth was due to telehealth providers failing to offer this option (2200/3529, 63%). The most common reason for respondents not using offered telehealth services was a preference for in-person care (527/578, 84.4%). Primary motivations to use telehealth were providers' recommendations (1716/2517, 72.7%) and convenience (1516/2517, 65.6%), mainly for acute minor illness (600/2397, 29.7%) and chronic condition management (583/2397, 21.4%), yet care purposes differed by age, race/ethnicity, and income. The satisfaction rate was predominately high, with no technical problems (1829/2517, 80.5%), comparable care quality to that of in-person care (1779/2517, 75%), and no privacy concerns (1958/2517, 83.7%). Younger individuals (odd ratios [ORs] 1.48-2.23; 18-64 years vs ≥75 years), women (OR 1.33, 95% CI 1.09-1.61), Hispanic individuals (OR 1.37, 95% CI 1.05-1.80; vs non-Hispanic White), those with more education (OR 1.72, 95% CI 1.03-2.87; at least a college graduate vs less than high school), unemployed individuals (OR 1.25, 95% CI 1.02-1.54), insured individuals (OR 1.83, 95% CI 1.25-2.69), or those with poor general health status (OR 1.66, 95% CI 1.30-2.13) had higher odds of using telehealth. CONCLUSIONS: To our best knowledge, this is among the first studies to examine patient factors around telehealth use, including motivations to use, perceptions of, satisfaction with, and care purpose of telehealth, as well as sociodemographic factors associated with telehealth adoption using a nationally representative survey. The wide array of descriptive findings and identified associations will help providers and health systems understand the factors that drive patients toward or away from telehealth visits as the technology becomes more routinely available across the United States, providing future directions for telehealth use and telehealth research.


Asunto(s)
COVID-19 , Telemedicina , Telemedicina/estadística & datos numéricos , Estados Unidos , Encuestas de Atención de la Salud , Estudios Transversales , Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Demografía/estadística & datos numéricos
4.
Cancer Lett ; 591: 216882, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38636893

RESUMEN

Super enhancers (SEs) are genomic regions comprising multiple closely spaced enhancers, typically occupied by a high density of cell-type-specific master transcription factors (TFs) and frequently enriched in key oncogenes in various tumors, including neuroblastoma (NB), one of the most prevalent malignant solid tumors in children originating from the neural crest. Cyclin-dependent kinase 5 regulatory subunit-associated protein 3 (CDK5RAP3) is a newly identified super-enhancer-driven gene regulated by master TFs in NB; however, its function in NB remains unclear. Through an integrated study of publicly available datasets and microarrays, we observed a significantly elevated CDK5RAP3 expression level in NB, associated with poor patient prognosis. Further research demonstrated that CDK5RAP3 promotes the growth of NB cells, both in vitro and in vivo. Mechanistically, defective CDK5RAP3 interfered with the UFMylation system, thereby triggering endoplasmic reticulum (ER) phagy. Additionally, we provide evidence that CDK5RAP3 maintains the stability of MEIS2, a master TF in NB, and in turn, contributes to the high expression of CDK5RAP3. Overall, our findings shed light on the molecular mechanisms by which CDK5RAP3 promotes tumor progression and suggest that its inhibition may represent a novel therapeutic strategy for NB.

5.
NPJ Digit Med ; 7(1): 78, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594408

RESUMEN

The development of diagnostic tools for skin cancer based on artificial intelligence (AI) is increasing rapidly and will likely soon be widely implemented in clinical use. Even though the performance of these algorithms is promising in theory, there is limited evidence on the impact of AI assistance on human diagnostic decisions. Therefore, the aim of this systematic review and meta-analysis was to study the effect of AI assistance on the accuracy of skin cancer diagnosis. We searched PubMed, Embase, IEE Xplore, Scopus and conference proceedings for articles from 1/1/2017 to 11/8/2022. We included studies comparing the performance of clinicians diagnosing at least one skin cancer with and without deep learning-based AI assistance. Summary estimates of sensitivity and specificity of diagnostic accuracy with versus without AI assistance were computed using a bivariate random effects model. We identified 2983 studies, of which ten were eligible for meta-analysis. For clinicians without AI assistance, pooled sensitivity was 74.8% (95% CI 68.6-80.1) and specificity was 81.5% (95% CI 73.9-87.3). For AI-assisted clinicians, the overall sensitivity was 81.1% (95% CI 74.4-86.5) and specificity was 86.1% (95% CI 79.2-90.9). AI benefitted medical professionals of all experience levels in subgroup analyses, with the largest improvement among non-dermatologists. No publication bias was detected, and sensitivity analysis revealed that the findings were robust. AI in the hands of clinicians has the potential to improve diagnostic accuracy in skin cancer diagnosis. Given that most studies were conducted in experimental settings, we encourage future studies to further investigate these potential benefits in real-life settings.

6.
RSC Adv ; 14(16): 11323-11333, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38595724

RESUMEN

Silicon-carbon composites have been recognized as some of the most promising anode candidates for advancing new-generation lithium-ion batteries (LIBs). The development of high-efficiency silicon/graphene anodes through a simple and cost-effective preparation route is significant. Herein, by using micron silicon as raw material, we designed a mesoporous composite of silicon/alumina/reduced graphene oxide (Si/Al2O3/RGO) via a two-step ball milling combined annealing process. Commercial Al2O3 nanoparticles are introduced as an interlayer due to the toughening effect, while RGO nanosheets serve as a conductive and elastic coating to protect active submicron silicon particles during lithium alloying/dealloying reactions. Owing to the rational porous structure and dual protection strategy, the core/shell structured Si/Al2O3/RGO composite is efficient for Li+ storage and demonstrates improved electrical conductivity, accelerated charge transfer and electrolyte diffusion, and especially high structural stability upon charge/discharge cycling. As a consequence, Si/Al2O3/RGO yields a high discharge capacity of 852 mA h g-1 under a current density of 500 mA g-1 even after 200 cycles, exhibiting a high capacity retention of ∼85%. Besides, Si/Al2O3/RGO achieves excellent cycling reversibility and superb high-rate capability with a stable specific capacity of 405 mA h g-1 at 3000 mA g-1. Results demonstrate that the Al2O3 interlayer is synergistic with the indispensable RGO nanosheet shells, affording more buffer space for silicon cores to alleviate the mechanical expansion and thus stabilizing active silicon species during charge/discharge cycles. This work provides an alternative low-cost approach to achieving high-capacity silicon/carbon composites for high-performance LIBs.

7.
Nat Med ; 30(4): 1154-1165, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38627560

RESUMEN

Building trustworthy and transparent image-based medical artificial intelligence (AI) systems requires the ability to interrogate data and models at all stages of the development pipeline, from training models to post-deployment monitoring. Ideally, the data and associated AI systems could be described using terms already familiar to physicians, but this requires medical datasets densely annotated with semantically meaningful concepts. In the present study, we present a foundation model approach, named MONET (medical concept retriever), which learns how to connect medical images with text and densely scores images on concept presence to enable important tasks in medical AI development and deployment such as data auditing, model auditing and model interpretation. Dermatology provides a demanding use case for the versatility of MONET, due to the heterogeneity in diseases, skin tones and imaging modalities. We trained MONET based on 105,550 dermatological images paired with natural language descriptions from a large collection of medical literature. MONET can accurately annotate concepts across dermatology images as verified by board-certified dermatologists, competitively with supervised models built on previously concept-annotated dermatology datasets of clinical images. We demonstrate how MONET enables AI transparency across the entire AI system development pipeline, from building inherently interpretable models to dataset and model auditing, including a case study dissecting the results of an AI clinical trial.


Asunto(s)
Inteligencia Artificial , Médicos , Humanos , Aprendizaje
8.
Ying Yong Sheng Tai Xue Bao ; 35(2): 543-554, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38523113

RESUMEN

Under the context of global climate change and growing population, irrigation and fertilization have become important ways to ensure food production, with consequences on water cycling, energy flow, and materials cycling in terrestrial ecosystems. In the land surface model (LSM), coupling irrigation and fertilization schemes are of great importance for clearly understanding the land-atmosphere interactions to ensure food security. We reviewed the expression methods of three key parameters, namely, the applied method, usage, and time in the parameterization process of irrigation and fertilization (nitrogen fertilizer) in LSM. We found that the ways to irrigate and ferti-lize in LSM are different from the ways used in actual practice due to the limitation of the high resolution of spatio-temporal data, which makes it difficult to understand the actual influences of irrigation and fertilization on grain yield, environment, and local climate. Finally, we proposed future works: 1) taking the differences of crop water demand into account and making the different irrigation thresholds for different crops to properly evaluate the total and intensity of water consumption of different crops; 2) using the field records and the regional grid data of fertilization and irrigation developed in recent years to develop parameterized schemes that are more in line with actual agricultural operations, which can accurately reveal their economic, ecological, and climatic effects; 3) developing fertilization diagnosis scheme considering crop type, phenological stage, and soil basic fertility as the supplementary scheme in LSM, to improve the applicability and simulation accuracy of LSM in the areas without nitrogen fertilizer data.


Asunto(s)
Riego Agrícola , Fertilizantes , Riego Agrícola/métodos , Agricultura/métodos , Ecosistema , Nitrógeno/análisis , Suelo , Agua
9.
Nat Commun ; 15(1): 2038, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38448448

RESUMEN

Hypertrophic scar (HS) considerably affects the appearance and causes tissue dysfunction in patients. The low bioavailability of 5-fluorouracil poses a challenge for HS treatment. Here we show a separating microneedle (MN) consisting of photo-crosslinked GelMA and 5-FuA-Pep-MA prodrug in response to high reactive oxygen species (ROS) levels and overexpression of matrix metalloproteinases (MMPs) in the HS pathological microenvironment. In vivo experiments in female mice demonstrate that the retention of MN tips in the tissue provides a slowly sustained drug release manner. Importantly, drug-loaded MNs could remodel the pathological microenvironment of female rabbit ear HS tissues by ROS scavenging and MMPs consumption. Bulk and single cell RNA sequencing analyses confirm that drug-loaded MNs could reverse skin fibrosis through down-regulation of BCL-2-associated death promoter (BAD), insulin-like growth factor 1 receptor (IGF1R) pathways, simultaneously regulate inflammatory response and keratinocyte differentiation via up-regulation of toll-like receptors (TOLL), interleukin-1 receptor (IL1R) and keratinocyte pathways, and promote the interactions between fibroblasts and keratinocytes via ligand-receptor pair of proteoglycans 2 (HSPG2)-dystroglycan 1(DAG1). This study reveals the potential therapeutic mechanism of drug-loaded MNs in HS treatment and presents a broad prospect for clinical application.


Asunto(s)
Cicatriz Hipertrófica , Humanos , Animales , Femenino , Ratones , Conejos , Cicatriz Hipertrófica/tratamiento farmacológico , Especies Reactivas de Oxígeno , Disponibilidad Biológica , Diferenciación Celular , Metaloproteinasas de la Matriz
11.
J Proteome Res ; 23(4): 1272-1284, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38470452

RESUMEN

Gestational diabetes mellitus (GDM) with intrauterine hyperglycemia induces a series of changes in the placenta, which have adverse effects on both the mother and the fetus. The aim of this study was to investigate the changes in the placenta in GDM and its gender differences. In this study, we established an intrauterine hyperglycemia model using ICR mice. We collected placental specimens from mice before birth for histological observation, along with tandem mass tag (TMT)-labeled proteomic analysis, which was stratified by sex. When the analysis was not segregated by sex, the GDM group showed 208 upregulated and 225 downregulated proteins in the placenta, primarily within the extracellular matrix and mitochondria. Altered biological processes included cholesterol metabolism and oxidative stress responses. After stratification by sex, the male subgroup showed a heightened tendency for immune-related pathway alterations, whereas the female subgroup manifested changes in branched-chain amino acid metabolism. Our study suggests that the observed sex differences in placental protein expression may explain the differential impact of GDM on offspring.


Asunto(s)
Diabetes Gestacional , Hiperglucemia , Humanos , Embarazo , Femenino , Masculino , Ratones , Animales , Placenta/metabolismo , Proteómica , Ratones Endogámicos ICR , Diabetes Gestacional/genética , Diabetes Gestacional/metabolismo , Hiperglucemia/genética
12.
J Colloid Interface Sci ; 663: 1074-1086, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38331692

RESUMEN

Drug-resistant biofilm infection is an extremely serious clinical problem, that easily leads to failure of antibiotic treatment. Although gold nanoparticles (AuNPs) as photothermal agents have been widely used in biofilm eradication, there are still challenges to be addressed, such as insignificantly redshifted absorption and slow assembly process of aggregated AuNPs. Herein, we developed an acidity-activated dispersion-to-aggregation transition to enhance the accumulation of self-complementary zwitterionic peptide-decorated AuNPs for photothermal eradication of drug-resistant biofilm infections. AuNPs were decorated with self-complementary zwitterionic peptides (ZP1 and ZP2) coupled with pH-sensitive anhydride (DMA) and pH-insensitive anhydride (SA), respectively. ZP2-decorated AuNPs with DMA modification (AuNP@ZP2(DMA)) exhibited prolonged blood circulation and enhanced accumulation in acidic biofilm microenvironment. Moreover, the electrostatic attraction between self-complementary ligands drove AuNPs to form closely packed aggregates with strong near-infrared absorption, leading to in vivo photoacoustic imaging ability and photothermal effect against drug-resistant bacteria and fungus, as well as microbial biofilms. AuNP@ZP2(DMA) with longer charge domains and a polyethylene glycol oligomer spacer showed greater photothermal antimicrobial and biofilm resistance in vitro and in vivo. This study develops an innovative acidity-activated AuNP photothermal agent, which provides an effective approach for treatment of biofilm infections.


Asunto(s)
Oro , Nanopartículas del Metal , Oro/farmacología , Oro/química , Nanopartículas del Metal/química , Antibacterianos/farmacología , Antibacterianos/química , Biopelículas , Anhídridos/farmacología
13.
Biochem Biophys Res Commun ; 704: 149638, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38422899

RESUMEN

BACKGROUND: Pheochromocytoma (PCC) is a rare neuroendocrine tumor. Angiogenesis is primary contributing factor for tumorigenesis. Cytochrome c oxidase 4I2 (COX4I2) has been confirmed to take part in the progression of cancer. Hypoxia-inducible factor 1A (HIF1A) is the main regulatory factor for the steady-state response of hypoxia, involved in metabolism and angiogenesis. In this study, we intended to explore the functions of COX4I2 in PCC and the effect mechanism between HIF1A and COX4I2. MATERIALS AND METHODS: The RNA-sequencing and immunohistochemistry tested COX4I2 expression in highly vascular PCC. Small interfering RNA (siRNA) was used to reduce the mRNA expression of COX4I2, and a small molecule inhibitor was utilized to reduce the protein expression of HIF1A. Culturing cells in 1% O2environment was performed to activate HIF1A. Western blot was applied to quantify the expression of target genes at the protein levels. The supernatant from PCC cells and fibroblasts acted as the conditioned medium. We conducted the tube formation and transwell assays in human vascular endothelial cells (HUVECs) to determine angiogenesis, the binding of COX4I2 promoter and HIF1A was evaluated by the dual luciferase reporter assay. RESULTS: COX4I2 had been rigorously shown to be overexpressed in highly vascular PCC. Knockdown of COX4I2 in PCC cells (MPC) did not significantly impact angiogenesis, while knockdown of COX4I2 in fibroblast (3T3) notably inhibited angiogenesis. RNA sequencing suggested that the expression of 11 vascular markers, such as CD34 and angiogenesis associated pathways in 3T3, decreased with knockdown of COX4I2. HIF1A had been shown to enhance the mRNA expression of COX4I2 through transcriptional regulation. Activation and inhibition of HIF1A resulted in upregulation and downregulation of COX4I2, respectively. The HIF1A inhibitor demonstrated a reduction in angiogenesis. CONCLUSION: COX4I2 is overexpressed in highly vascular PCC and contributes to angiogenesis in fibroblasts. Mechanistically, HIF1A transcriptional regulation enhances COX4I2 and its effects on angiogenesis in PCC. COX4I2 might serve as a vascular marker and represent a potential target for vascular therapy.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Feocromocitoma , Humanos , Complejo IV de Transporte de Electrones/genética , Complejo IV de Transporte de Electrones/metabolismo , Feocromocitoma/genética , Células Endoteliales/metabolismo , Angiogénesis , ARN Interferente Pequeño/genética , Neoplasias de las Glándulas Suprarrenales/genética , Hipoxia/genética , ARN Mensajero/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo
14.
Cancer Cell Int ; 24(1): 81, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38383388

RESUMEN

BACKGROUND: Acute myeloid leukemia (AML) is a malignancy of the hematopoietic system, and childhood AML accounts for about 20% of pediatric leukemia. ANP32B, an important nuclear protein associated with proliferation, has been found to regulate hematopoiesis and CML leukemogenesis by inhibiting p53 activity. However, recent study suggests that ANP32B exerts a suppressive effect on B-cell acute lymphoblastic leukemia (ALL) in mice by activating PU.1. Nevertheless, the precise underlying mechanism of ANP32B in AML remains elusive. RESULTS: Super enhancer related gene ANP32B was significantly upregulated in AML patients. The expression of ANP32B exhibited a negative correlation with overall survival. Knocking down ANP32B suppressed the proliferation of AML cell lines MV4-11 and Kasumi-1, along with downregulation of C-MYC expression. Additionally, it led to a significant decrease in H3K27ac levels in AML cell lines. In vivo experiments further demonstrated that ANP32B knockdown effectively inhibited tumor growth. CONCLUSIONS: ANP32B plays a significant role in promoting tumor proliferation in AML. The downregulation of ANP32B induces cell cycle arrest and promotes apoptosis in AML cell lines. Mechanistic analysis suggests that ANP32B may epigenetically regulate the expression of MYC through histone H3K27 acetylation. ANP32B could serve as a prognostic biomarker and potential therapeutic target for AML patients.

16.
Carcinogenesis ; 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38302114

RESUMEN

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy originating from T progenitor cells. It accounts for 15% of childhood and 25% of adult ALL cases. GNE-987 is a novel chimeric molecule developed using proteolysis-targeting chimeras (PROTAC) technology for targeted therapy. It consists of a potent inhibitor of the bromodomain and extraterminal (BET) protein, as well as the E3 ubiquitin ligase Von Hippel-Lindau (VHL), which enables the effective induction of proteasomal degradation of BRD4. Although GNE-987 has shown persistent inhibition of cell proliferation and apoptosis, its specific anti-tumor activity in T-ALL remains unclear. In this study, we aimed to investigate the molecular mechanisms underlying the anti-tumor effect of GNE-987 in T-ALL. To achieve this, we employed technologies including RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and CUT&Tag. The degradation of BET proteins, specifically BRD4, by GNE-987 has a profound impact on T-ALL cell. In in vivo experiments, sh-BRD4 lentivirus reduced T-ALL cell proliferation and invasion, extending the survival time of mice. The RNA-seq and CUT&Tag analyses provided further insights into the mechanism of action of GNE-987 in T-ALL. These analyses revealed that GNE-987 possesses the ability to suppress the expression of various genes associated with superenhancers (SEs), including lymphoblastic leukemia 1 (LCK). By targeting these SE-associated genes, GNE-987 effectively inhibits the progression of T-ALL. Importantly, SE-related oncogenes like LCK were identified as critical targets of GNE-987. Based on these findings, GNE-987 holds promise as a potential novel candidate drug for the treatment of T-ALL.

17.
J Endourol ; 38(3): 262-269, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38205660

RESUMEN

Purpose: To evaluate functional outcomes of robot-assisted ureteroplasty with labial mucosa grafting for long proximal ureteral stenosis (LPUS) in children and adolescents. Methods: Included in this study were 15 patients who underwent robot-assisted ureteroplasty with labial mucosal grafting in our center between July 2017 and September 2021. The left affected stenotic ureter was repaired using labial mucosal grafting. If the ureter was simply strictured but not obliterated, the ureter was spatulated longitudinally along the ventral side and the labial mucosa graft was interposed and anastomosed in a continuous manner. Faced with the obliterated segment, it was excised and the spatulated portion re-anastomosed with a pelvic flap as the dorsal wall. The labial mucosa graft was placed as the ventral wall. The preoperative clinical data and follow-up outcomes were collected and evaluated. Results: Labial mucosa graft onlay ureteroplasty was well performed in all the 15 patients with no occurrence of intraoperative complications or surgical conversion. Five patients underwent an onlay ureteroplasty, and 10 patients underwent a dorsally augmented pelvic flap anastomotic ureteroplasty. The mean (range) stricture length was 7.1 (3-10) cm. The mean operative time was 371.2 (216-480) minutes, and the median blood loss was 40 mL. At the median follow-up of 35 months (range 12-58 months), the overall success rate was 93.3%. Conclusions: Labial mucosa grafting appears to be safe and feasible for repairing long ureteral strictures in pediatric and adolescent patients. Our experience may provide beneficial references and conveniences to solve complex problems in LPUS. This study was approved by the institutional review board, and written informed consent was obtained from each participant (ethics number: 2017-30).


Asunto(s)
Robótica , Uréter , Obstrucción Ureteral , Humanos , Adolescente , Niño , Uréter/cirugía , Constricción Patológica/cirugía , Estudios Retrospectivos , Obstrucción Ureteral/cirugía , Mucosa Bucal/trasplante , Resultado del Tratamiento
18.
J Robot Surg ; 18(1): 3, 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38175361

RESUMEN

To report our institutional experience and the medium-term outcomes of utilizing robotic-assisted laparoscopic surgery (RALS) in patients with Wilms' tumor (WT). The robotic surgical interventions include nephron-sparing surgery (RAL-NSS), radical nephrectomy (RAL-RN), and nephrectomy with inferior vena cava thrombectomy (RAL-N-IVCT). We retrospectively collected medical records of WT patients who underwent RALS in our center between August 2019 and February 2022. Patients' baseline demographics, preoperative parameters, and perioperative/postoperative data were recorded and analyzed. Follow-up results were collected to evaluate the oncological outcomes. A total of 12 patients (13 sides) with a median age of 30 (IQR: 19.5-45.5) months were included. All operations were successfully completed without conversion. Seven patients received preoperative chemotherapy. Distribution of surgical interventions was as follows: five patients underwent RAL-RN, five received RAL-NSS, one with bilateral WT underwent concurrent RAL-RN and RAL-NSS, and one received RAL-RN-IVCT post preoperative chemotherapy. Postoperative chemotherapy was conducted in ten patients. The estimated intraoperative blood loss was 27 ± 4.0 ml for the RAL-NSS group, 41.67 ± 12.13 ml for the RAL-RN group, and 350 ml for the RAL-RN-IVCT groups, respectively. The median perioperative serum creatinine levels were 32.5 (IQR: 30.75-39.5) µmol/l preoperatively and 35 (IQR: 31.75-38.5) µmol/l postoperatively, which showed no significant difference. No positive lymph nodes were detected. Postoperative chemotherapy was performed according to the tumor volume and pathological findings. The median follow-up time was 17.5 (15.8-22.3) months. During this interval, neither distant metastasis nor recurrence was identified. Based on our medium-term follow-up observations, RAL-NSS, RAL-RN, and RAL-RN-IVCT exhibit promising feasibility and safety profiles in the therapeutic landscape of WT.


Asunto(s)
Neoplasias Renales , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Tumor de Wilms , Niño , Humanos , Lactante , Preescolar , Procedimientos Quirúrgicos Robotizados/métodos , Estudios Retrospectivos , Tumor de Wilms/cirugía , Neoplasias Renales/cirugía
19.
Int J Biol Macromol ; 257(Pt 1): 128636, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38065459

RESUMEN

Injectable hydrogel has attracted appealing attention for skin wound treatment. Although multifunctional injectable hydrogels can be prepared by introducing bioactive ingredients with antibacterial and anti-inflammatory capabilities, their preparation remains complicated. Herein, a polyphenol-based supramolecular injectable hydrogel (PBSIH) based on polyphenol gallic acid and biological macromolecule sodium alginate is developed as a wound dressing to accelerate wound healing. We show that such PBSIH can be rapidly formed within 15 s by mixing the sodium alginate and gallic acid solutions based on the hydrogen bonding and hydrophobic interactions. The PBSIH shows excellent cytocompatibility, antibacterial, and antioxidant properties, which enhance infected wound healing by inhibiting bacterial infection and alleviating inflammation after treatment of 11 days. Moreover, we show that the preparative strategies of injectable supramolecular hydrogels can be extended to other polyphenols, including protocatechuic and tannic acids. This study provides a facile yet highly effective method to design injectable polyphenol- sodium alginate hydrogel for wound dressing based on naturally bioactive ingredients.


Asunto(s)
Hidrogeles , Cicatrización de Heridas , Antiinflamatorios/farmacología , Antibacterianos/farmacología , Alginatos , Ácido Gálico/farmacología , Vehículos Farmacéuticos , Polifenoles/farmacología
20.
Small ; 20(16): e2308469, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38032176

RESUMEN

Triboelectric nanogenerators (TENGs) have manifested a remarkable potential for harvesting environmental energy and have the prospects to be utilized for various uses, for instance, self-powered sensing devices, flexible wearables, and marine corrosion protection. However, the potential for further development of TENGs is restricted on account of their low output power that in turn is determined by their surface charge density. The current review majorly focuses on the selection and optimization of triboelectric materials. Subsequently, various methods capable of enhancing the surface charge density of TENGs, including environmental regulation, charge excitation, charge pumping, electrostatic breakdown, charge trapping, and liquid-solid structure are comprehensively reviewed. Lastly, the review is concluded by highlighting the existing challenges in enhancing the surface charge density of TENGs and exploring potential opportunities for future research endeavors in this area.

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