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1.
Nat Cancer ; 5(9): 1427-1447, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39242942

RESUMEN

Prostate cancer (PCa) exhibits significant geoethnic disparities as reflected by distinct variations in the cancer genome and disease progression. Here, we perform a comprehensive proteogenomic characterization of localized high-risk PCa utilizing paired tumors and nearby tissues from 125 Chinese male patients, with the primary objectives of identifying potential biomarkers, unraveling critical oncogenic events and delineating molecular subtypes with poor prognosis. Our integrated analysis highlights the utility of GOLM1 as a noninvasive serum biomarker. Phosphoproteomics analysis reveals the crucial role of Ser331 phosphorylation on FOXA1 in regulating FOXA1-AR-dependent cistrome. Notably, our proteomic profiling identifies three distinct subtypes, with metabolic immune-desert tumors (S-III) emerging as a particularly aggressive subtype linked to poor prognosis and BCAT2 catabolism-driven PCa progression. In summary, our study provides a comprehensive resource detailing the unique proteomic and phosphoproteomic characteristics of PCa molecular pathogenesis and offering valuable insights for the development of diagnostic and therapeutic strategies.


Asunto(s)
Biomarcadores de Tumor , Factor Nuclear 3-alfa del Hepatocito , Neoplasias de la Próstata , Proteogenómica , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Proteogenómica/métodos , Factor Nuclear 3-alfa del Hepatocito/genética , Factor Nuclear 3-alfa del Hepatocito/metabolismo , China , Pronóstico , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Pueblo Asiatico/genética , Persona de Mediana Edad , Fosforilación , Anciano , Regulación Neoplásica de la Expresión Génica , Pueblos del Este de Asia
2.
Acta Biomater ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39278301

RESUMEN

The regulation of intracellular ionic homeostasis to trigger antigen-specific immune responses has attracted extensive interest in tumor therapy. In this study, we developed a dual-pathway nanoreactor, Au-Cu2-xSe@ZIF-8@P18 NPs (ACS-Z-P NPs), which targets danger-associated molecular patterns (DAMPs) and releases Zn2+ and reactive oxygen species (ROS) within the tumor microenvironment (TME). Zn2+ released from the metal-organic frameworks (MOFs) was deposited in the cytoplasm, leading to aberrant transcription levels of intracellular zinc-regulated proteins and DNA damage, thereby inducing pyroptosis and immunogenic cell death (ICD) dependent on caspase1/gasdermin D (GSDMD) pathway. Furthermore, upon laser irradiation, ACS-Z-P NPs could break through the limitations of inherent defects of immunosuppression in TME, enhance ROS generation through a Fenton-like reaction cascade, which subsequently triggered the activation of inflammatory vesicles and the release of damage-associated molecular patterns (DAMPs). This cascade effect led to the amplification of pyroptosis and immunogenic cell death (ICD), thereby remodeling the immunosuppressed TME. Consequently, this process improved dendritic cell (DC) antigen presentation and augmented anti-tumor T-cell responses, effectively initiating antigen-specific immune responses and further enhancing pyroptosis and ICD. This study explores the therapeutic properties of these mechanisms in detail. STATEMENT OF SIGNIFICANCE: The synthesized Au-Cu2-xSe@ZIF-8@P18 nanoparticles (ACS-Z-Ps) can effectively enhance the body's immune response by regulating zinc ion levels within cells. This regulation leads to abnormal levels of zinc-regulated protein transcription and DNA damage, which induces cellular pyroptosis. As a result, antigen presentation to dendritic cells (DCs) is improved, and anti-tumor T-cell responses are enhanced. The ACS-Z-P NPs overcome the limitations of ROS deficiency and immunosuppression in the tumor microenvironment by using H2O2 in the tumor microenvironment through a Fenton-like reaction. This leads to an increased production of ROS and O2, remodeling of the immunosuppressed tumor microenvironment, and enhanced induction of cell pyroptosis and immunogenic cell death. ACS-Z-P NPs targeted B16 cells using the photosensitizer P18 in combination with PDT treatment. This approach significantly inhibited the proliferation of B16 cells and effectively inhibited tumor growth.

3.
Int J Biol Macromol ; : 135929, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39322151

RESUMEN

Rheumatoid arthritis, characterized by the abnormal proliferation of synovial cells and extensive macrophage infiltration, is a chronic inflammatory disease. Molecular hydrogen, known for its antioxidant properties, has shown promise in eliminating reactive oxygen species. However, the low solubility and bioavailability of hydrogen limit the effectiveness of this therapy. To overcome these issues, we developed a novel yolk-shell heterostructure, H-AAZS (Au/Ag@ZnS modified hyaluronic acid), utilizing a hydrothermal cation exchange process. Through ion doping, semiconductor hybridization, and Schottky barriers in H-AAZS, photocatalysis for hydrogen generation has been successfully implemented using 660 nm laser irradiation. Additionally, the H-AAZS demonstrate the capacity for mild photothermal therapy, inducing apoptosis in synovial cells with Au's hot electrons with 660 nm laser irradiation. This strategy not only improves the abnormal proliferation of synovial cells but also avoids the exacerbation of inflammation caused by thermal stimulation. Both in vitro and in vivo experiments validate the synergistic effects of hydrogen production mediated anti-inflammatory responses, macrophage polarization and photothermal therapy. Therefore, this work represents a significant advancement as it ingeniously harnesses photocatalysis to modulate the synovial microenvironment while mitigating the side effects associated with photothermal therapy. This nanocrystal provides new and valuable insights into the potential treatment of Rheumatoid arthritis.

4.
ACS Nano ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259947

RESUMEN

Sensorineural hearing loss (SNHL) represents a significant clinical challenge, predominantly attributed to oxidative stress-related mechanisms. In this work, we report an innovative antioxidant strategy for mitigating SNHL, utilizing synthetically engineered allomelanin nanoparticles (AMNPs). Empirical evidence elucidates AMNPs' profound capability in free radical neutralization, substantiated by a significant decrement in reactive oxygen species (ROS) levels within HEI-OC1 auditory cells exposure to cisplatin or hydrogen peroxide (H2O2). Comparative analyses reveal that AMNPs afford protection against cisplatin-induced and noise-induced auditory impairments, mirroring the effect of dexamethasone (DEX), a standard pharmacological treatment for acute SNHL. AMNPs exhibit notable cytoprotective properties for auditory hair cells (HCs), effectively preventing ototoxicity from cisplatin or H2O2 exposure, as confirmed by both in vitro assays and cultured organ of Corti studies. Further in vivo research corroborates AMNPs' ability to reverse auditory brainstem response (ABR) threshold shifts resulting from acoustic injury, concurrently reducing HCs loss, ribbon synapse depletion, and spiral ganglion neuron degeneration. The therapeutic benefits of AMNPs are attributed to mitigating oxidative stress and inflammation within the cochlea, with transcriptome analysis indicating downregulated gene expression related to these processes post-AMNPs treatment. The pronounced antioxidative and anti-inflammatory effects of AMNPs position them as a promising alternative to DEX for SNHL treatment.

5.
Medicine (Baltimore) ; 103(36): e39627, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39252223

RESUMEN

Periodontitis and diabetes mellitus exhibit a bidirectional relationship. This narrative review descriptively outlines the role of chlorhexidine in the periodontal treatment of diabetic patients, focusing on its antimicrobial mechanisms against microbial communities and its antiplaque effects. Although chlorhexidine is proven to be effective in combating microbial presence and improving gingivitis with substantial supporting evidence, its impact on glycemic control and insulin resistance in diabetic patients remains contentious. Additionally, the effectiveness of chlorhexidine as an adjunctive chemotherapeutic in the periodontal treatment of gestational diabetes has not yet been studied, highlighting a gap in research that necessitates further prospective studies and randomized controlled trials. Considering the interconnection between periodontal inflammation and glycemic levels, this article finally advocates for collaborative care between dental and medical professionals to manage periodontitis in diabetic patients effectively.


Asunto(s)
Antiinfecciosos Locales , Clorhexidina , Periodontitis , Humanos , Clorhexidina/uso terapéutico , Clorhexidina/administración & dosificación , Periodontitis/tratamiento farmacológico , Periodontitis/complicaciones , Antiinfecciosos Locales/uso terapéutico , Antiinfecciosos Locales/administración & dosificación , Complicaciones de la Diabetes/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológico
6.
J Nanobiotechnology ; 22(1): 526, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39217372

RESUMEN

The programmed cell death (PCD) pathway removes functionally insignificant, infection-prone, or potentially tumorigenic cells, underscoring its important role in maintaining the stability of the internal environment and warding off cancer and a host of other diseases. PCD includes various forms, such as apoptosis, copper death, iron death, and cellular pyroptosis. However, emerging solid-state electron-mediated Z-scheme heterostructured semiconductor nanomaterials with high electron-hole (e-h+) separation as a new method for inducing PCD have not been well studied. We synthesize the Bi2S3-Bi2O3-Au-PEG nanorods (BB-A-P NRs) Z-scheme heterostructured semiconductor has a higher redox capacity and biocompatibility. Firstly, the BB-A-P NRs are excited by near-infrared (NIR) light, which mimics the action of catalase by supplying oxygen (O2) and converting it to a single-linear state of oxygen (1O2) via e-h+ transfer. Secondly, they react with hydrogen peroxide (H2O2) and water (H2O) in tumor to produce hydroxyl radicals (•OH), inducing apoptosis. Intriguingly, the Caspase-1/Gasdermin D (GSDMD)-dependent conventional pyroptosis pathway induced cellular pyroptosis activated by apoptosis and reactive oxygen species (ROS) which causes the intense release of damage associated molecular patterns (DAMPs), leading to the inflammatory death of tumor cells. This, in turn, activates the immunological environment to achieve immunogenic cell death (ICD). BB-A-P enables computed tomography imaging, which allows for visualization of the treatment. BB-A-P activated dual PCD can be viewed as an effective mode of cell death that coordinates the intracellular environment, and the various pathways are interrelated and mutually reinforcing which shows promising therapeutic effects and provides a new strategy for eliminating anoxic tumors.


Asunto(s)
Apoptosis , Semiconductores , Animales , Apoptosis/efectos de los fármacos , Ratones , Línea Celular Tumoral , Electrones , Humanos , Melanoma/patología , Nanotubos/química , Nanoestructuras/química , Especies Reactivas de Oxígeno/metabolismo , Peróxido de Hidrógeno , Bismuto/química , Piroptosis/efectos de los fármacos , Oro/química
7.
bioRxiv ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39149271

RESUMEN

Spatial genomic technologies include imaging- and sequencing-based methods (1-3). An emerging subcategory of sequencing-based methods relies on a surface coated with coordinate-associated DNA barcodes, which are leveraged to tag endogenous nucleic acids or cells in an overlaid tissue section (4-7). However, the physical registration of DNA barcodes to spatial coordinates is challenging, necessitating either high density printing of coordinate-specific oligonucleotides or in situ sequencing/probing of randomly deposited, oligonucleotide-bearing beads. As a consequence, the surface areas available to sequencing-based spatial genomic methods are constrained by the time, labor, cost, and instrumentation required to either print, synthesize or decode a coordinate-tagged surface. To address this challenge, we developed SCOPE (Spatial reConstruction via Oligonucleotide Proximity Encoding), an optics-free, DNA microscopy (8) inspired method. With SCOPE, the relative positions of randomly deposited beads on a 2D surface are inferred from the ex situ sequencing of chimeric molecules formed from diffusing "sender" and tethered "receiver" oligonucleotides. As a first proof-of-concept, we apply SCOPE to reconstruct an asymmetric "swoosh" shape resembling the Nike logo (16.75 × 9.25 mm). Next, we use a microarray printer to encode a "color" version of the Snellen eye chart for visual acuity (17.18 × 40.97 mm), and apply SCOPE to achieve optics-free reconstruction of individual letters. Although these are early demonstrations of the concept and much work remains to be done, we envision that the optics-free, sequencing-based quantitation of the molecular proximities of DNA barcodes will enable spatial genomics in constant experimental time, across fields of view and at resolutions that are determined by sequencing depth, bead size, and diffusion kinetics, rather than the limitations of optical instruments or microarray printers.

8.
FASEB J ; 38(15): e23864, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39109513

RESUMEN

Little is known about the blood-feeding physiology of arbovirus vector Aedes aegypti although this type of mosquito is known to transmit infectious diseases dengue, Zika, yellow fever, and chikungunya. Blood feeding in the female A. aegypti mosquito is essential for egg maturation and for transmission of disease agents between human subjects. Here, we identify the A. aegypti sulfakinin receptor gene SKR from the A. aegypti genome and show that SKR is expressed at different developmental stages and in varied anatomical localizations in the adult mosquito (at three days after eclosion), with particularly high expression in the CNS. Knockingdown sulfakinin and sulfakinin receptor gene expression in the female A. aegypti results in increased blood meal intake, but microinjection in the thorax of the sulfakinin peptide 1 and 2 both inhibits dose dependently blood meal intake (and delays the time course of blood intake), which is reversible with receptor antagonist. Sulfakinin receptor expressed ectopically in mammalian cells CHO-K1 responds to sulfakinin stimulation with persistent calcium spikes, blockable with receptor antagonist. These data together suggest that activation of the Gq protein-coupled (i.e., calcium-mobilizing) sulfakinin receptor inhibits blood meal intake in female A. aegypti mosquitoes and could serve as a strategic node for the future control of A. aegypti mosquito reproduction/population and disease transmission.


Asunto(s)
Aedes , Receptores Acoplados a Proteínas G , Animales , Aedes/metabolismo , Aedes/genética , Femenino , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Células CHO , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Cricetulus , Conducta Alimentaria/fisiología , Mosquitos Vectores
9.
Adv Sci (Weinh) ; : e2406523, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39166413

RESUMEN

The inefficient delivery of herbicides causes unpleasant side effects on the ecological environment. Protoporphyrinogen oxidase (PPO)-inhibiting herbicides rely on the presence of external light to exert the activities and thus their performance in the field is extremely susceptible to the light environment. Here, taking acifluorfen (ACI) as a model PPO-inhibiting herbicide to enhance efficacy by boosting the utilization rate of sunlight, amphiphilic cationic CDs (CPC-CDs) from cetylpyridinium chloride (CPC) as a precursor, is first prepared as a supplementary light source generator, and subsequently co-assembled with ACI through non-covalent bond interactions to obtain the stable fluorescent nanoparticles (ACI@CPC-CDs). ACI@CPC-CDs with fascinating physicochemical properties can penetrate the leaves of weeds through the stomata and undergo a long-distance transport in the cell intervals. Under low light intensity, CPC-CDs can be applied as the internal light source to promote the formation of more singlet oxygen to damage the leaf cell membrane, consequently improving the herbicidal activity of ACI. Moreover, the safety evaluation of ACI@CPC-CDs demonstrates no risk to non-target organisms and the environment. Therefore, this work offers a promising strategy for the efficient delivery of light-dependent PPO-inhibiting herbicides and opens new insights into the application of CDs in the development of sustainable agriculture.

10.
MedComm (2020) ; 5(8): e654, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39040848

RESUMEN

Liver fibrosis can cause hepatitis B virus (HBV)-associated hepatocellular carcinoma. Menstrual blood-derived mesenchymal stem cells (MenSCs) can ameliorate liver fibrosis through paracrine. Single-cell RNA sequencing (scRNA-seq) may be used to explore the roadmap of activated hepatic stellate cell (aHSC) inactivation to target liver fibrosis. This study established HBV transgenic (HBV-Tg) mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis and demonstrated that MenSCs migrated to the injured liver to improve serological indices and reduce fibrotic accumulation. RNA-bulk analysis revealed that MenSCs mediated extracellular matrix accumulation and cell adhesion. Liver parenchymal cells and nonparenchymal cells were identified by scRNA-seq in the control, CCl4, and MenSC groups, revealing the heterogeneity of fibroblasts/HSCs. A CellChat analysis revealed that diminished intercellular adhesion molecule (ICAM) signaling is vital for MenSC therapy. Specifically, Icam1 in aHSCs acted on Itgal/Itgb2 and Itgam/Itgb2 in neutrophils, causing decreased adhesion. The expression of Itgal, Itgam, and Itgb2 was higher in CCl4 group than in the control group and decreased after MenSC therapy in neutrophil clusters. The Lcn2, Pglyrp1, Wfdc21, and Mmp8 had high expression and may be potential targets in neutrophils. This study highlights interacting cells, corresponding molecules, and underlying targets for MenSCs in treating HBV-associated liver fibrosis.

11.
Front Public Health ; 12: 1385166, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38962779

RESUMEN

Background: Healthy aging is crucial to the quality of life of older adults, of which mental health is an essential part. Physical exercise strongly affects their mental health and can alleviate psychological problems to a certain extent. Nevertheless, the correlation between physical exercise and the mental health of older adults individuals, as well as the underlying mechanism by which physical exercise impacts mental health, remains rather ambiguous. Methods: We utilized multiple linear regression models to investigate the relationship between physical activity and mental health in 3,240 persons aged 60 and up. The propensity score matching (PSM) method was used to assess the robustness of the regression results. In addition, sequential recursive models were employed to investigate the mediating role of social competence in the link between physical activity and mental health. Results and discussion: We discovered a strong favorable association between physical exercise and mental health, which was mediated by social competence. Furthermore, the effect of physical exercise on mental health differed across older persons from various socioeconomic backgrounds. Conclusion: Older adults should strengthen their understanding of the role of physical exercise. Sports organizations that serve older adults by providing resources and services to help them maintain physical fitness and by hosting sports activities and competitions according to their needs should be established.


Asunto(s)
Ejercicio Físico , Salud Mental , Habilidades Sociales , Humanos , Masculino , Anciano , Femenino , Ejercicio Físico/psicología , Persona de Mediana Edad , Calidad de Vida , Anciano de 80 o más Años , Encuestas y Cuestionarios
12.
J Craniomaxillofac Surg ; 52(9): 1024-1029, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39025694

RESUMEN

Salivary collection (SC) following surgery for oral cancer represents an underreported and unrecognized complication. Our study aimed to evaluate the efficacy of parotideomasseteric fascia flap (PFF) in preventing postoperative SC, comparing its effectiveness with other conventional methods. Between November 2019 and January 2023, 221 patients diagnosed with oral squamous cell carcinoma (OSCC) undergoing wide tumor ablation and neck dissection at Xiangya Hospital were included in the study. Patients were randomly allocated into four groups based on different intraoperative techniques to assess the preventive efficacy of PFF against SC. The incidence of SC in the PFF group was only 5.9%, which was significantly lower than the other three groups (p < 0.05). Among the 221 patients, the highest SC incidence occurred in buccal cancer cases (19.6%). However, in the PFF group, the incidence was not significantly different (9.5%; p > 0.05). Univariate analysis revealed a higher SC incidence associated with advanced clinical T stage (p = 0.02), N(+) stage (p = 0.01), low average serum albumin (SA) level (p = 0.00), and a large parotid wound (p = 0.00). In multivariate analysis, only average SA (p = 0.01; odds ratio [OR] 4.104; 95% CI 0.921-11.746) emerged as the most prevalent factor predisposing to SC. The utilization of PFF demonstrated a notable reduction in the incidence of postoperative SC, establishing it as a safe, effective, and convenient method for patients undergoing radical ablation for OSCC.


Asunto(s)
Fascia , Neoplasias de la Boca , Complicaciones Posoperatorias , Colgajos Quirúrgicos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de la Boca/cirugía , Complicaciones Posoperatorias/prevención & control , Fascia/trasplante , Anciano , Glándula Parótida/cirugía , Adulto , Disección del Cuello/métodos , Incidencia , Saliva
13.
Colloids Surf B Biointerfaces ; 242: 114077, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39003849

RESUMEN

The off-target loss of pesticide formulations caused by volatilization and leaching has reduced effective utilization and increased risks to the ecological environment and human health. Self-assembly of pesticides has been widely concerned due to the improved bioactivity and environmental compatibility. Herbicidal ionic liquids (HILs) could effectively decrease off-target loss and increase efficacy and environmental safety by improving the physicochemical properties of herbicides. Herein, HILs were prepared by pairing dicamba with quaternary ammonium salts containing different alkyl chain lengths and aromatic groups and subsequently self-assembled into spherical nanoparticles (HIL NPs) via electrostatic interaction and hydrophobic effect. Compared with dicamba, the obtained HIL NPs with an average particle size of 6-55 nm exhibited improved physicochemical properties, including high zeta potential values (+20.3 to +27.8 mV), low volatilization rate (2.4-3.9 %) and surface tension (22.83-33.07 mN m-1), decreased contact angle (32.25-41.55°) and leaching potential (76.2-86.5 %), and high soil adsorption (12.1-23.8 %), suggesting low risks to the environment. The control efficacy against Amaranthus retroflexus of HIL3 NPs pairing dicamba with octadecyl-trimethyl ammonium chloride was better than that of dicamba sodium salt at different concentrations. Therefore, the ionic liquid self-assembly developed by a facile and green preparation approach to reduce the volatility and leaching of pesticides would have enormous potential in sustainable agriculture.


Asunto(s)
Dicamba , Herbicidas , Líquidos Iónicos , Tamaño de la Partícula , Líquidos Iónicos/química , Líquidos Iónicos/farmacología , Herbicidas/química , Herbicidas/farmacología , Dicamba/química , Dicamba/farmacología , Nanopartículas/química , Propiedades de Superficie , Electricidad Estática , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/farmacología , Adsorción
14.
IUBMB Life ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38873890

RESUMEN

Parecoxib, a well-recognized nonsteroidal anti-inflammatory drug, has been reported to possess anticancer properties in various tumor types. In this work, we aimed to investigate the potential anticancer effects of parecoxib on hepatocellular carcinoma (HCC) cells. To assess the impact of parecoxib on HCC cell proliferation, we employed Cell Counting Kit-8, colony formation, and 5-ethynyl-2'-deoxyuridine assays. Hoechst/propidium iodide (PI) double staining and flow cytometry were performed to evaluate apoptosis and cell cycle analysis. Wound healing and transwell assays were utilized to assess cell migration and invasion. Tube formation assay was employed to analyze angiogenesis. Protein levels were determined using western blotting, and mRNA expression levels were assessed using quantitative real-time polymerase chain reaction (PCR). A xenograft mouse model was used to confirm the antitumor effects of parecoxib on HCC tumors in vivo. Our data demonstrated that parecoxib effectively inhibited the proliferation of HCC cells in a dose- and time-dependent manner. In addition, parecoxib induced cell cycle arrest in the G2 phase and promoted apoptosis. Moreover, parecoxib hindered tumor migration and invasion by impeding the epithelial-mesenchymal transition process. Further investigation showed that parecoxib could significantly suppress angiogenesis through the inhibition of extracellular signal-regulated kinase (ERK)-vascular endothelial growth factor (VEGF) axis. Notably, treatment with the ERK activator phorbol myristate acetate upregulated the expression of matrix metalloproteinase (MMP)-2, MMP-9, and VEGF and reversed the function of parecoxib in HCC cells. Besides, parecoxib displayed its antitumor efficacy in vivo. Collectively, our results suggest that parecoxib ameliorates HCC progression by regulating proliferation, cell cycle, apoptosis, migration, invasion, and angiogenesis through the ERK-VEGF/MMPs signaling pathway.

15.
iScience ; 27(6): 109979, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38832007

RESUMEN

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized by the Warburg effect, and the dynamic interplay between cancer cells and mitochondria. The role of cancer stem cells (CSCs) in treatment resistance and the regulatory influence of non-coding RNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are studied. The chapter emphasizes future directions, encompassing advancements in immunotherapy, strategies to counter adaptive resistance, integration of artificial intelligence for predictive modeling, and the identification of biomarkers for personalized treatment. The comprehensive exploration of these hallmarks provides a foundation for innovative therapeutic approaches, aiming to navigate the complex landscape of cancer resistance and enhance patient outcomes.

16.
Sci Total Environ ; 943: 173821, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38866165

RESUMEN

Nanoformulations of pesticides are an effective way to increase utilization efficiency and alleviate the adverse impacts on the environments caused by conventional pesticide formulations. However, the complex preparation process, high cost, and potential environmental risk of nanocarriers severely restricted practical applications of carrier-based pesticide nanoformulations in agriculture. Herein, carrier-free self-assembled nanoparticles (FHA-PRO NPs) based on fenhexamid (FHA) and prochloraz (PRO) were developed by a facile co-assembly strategy to improve utilization efficiency and reduce toxicity to aquatic organism of pesticides. The results showed that noncovalent interactions between negatively charged FHA and positively charged PRO led to core-shell structured nanoparticles arranged in an orderly manner dispersing in aqueous solution with a diameter of 256 nm. The prepared FHA-PRO NPs showed a typical pH-responsive release profile and exhibited excellent physicochemical properties including low surface tension and high max retention. The photostability of FHA-PRO NPs was improved 2.4 times compared with free PRO. The FHA-PRO NPs displayed superior fungicidal activity against Sclerotinia sclerotiorum and Botrytis cinerea and longer duration against Sclerotinia sclerotiorum on potted rapeseed plants. Additionally, the FHA-PRO NPs reduced the acute toxicity of PRO to zebrafish significantly. Therefore, this work provided a promising strategy to develop nanoformulations of pesticides with stimuli-responsive controlled release characteristics for precise pesticide delivery.


Asunto(s)
Fungicidas Industriales , Imidazoles , Nanopartículas , Contaminantes Químicos del Agua , Nanopartículas/toxicidad , Nanopartículas/química , Animales , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/toxicidad , Imidazoles/química , Imidazoles/toxicidad , Fungicidas Industriales/toxicidad , Fungicidas Industriales/química , Pez Cebra , Organismos Acuáticos/efectos de los fármacos , Plaguicidas/toxicidad , Plaguicidas/química , Botrytis/efectos de los fármacos , Ascomicetos/efectos de los fármacos
17.
Proc Natl Acad Sci U S A ; 121(24): e2321758121, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38830093

RESUMEN

Impulsivity is a personality construct frequently employed to explain and predict important human behaviors. Major inconsistencies in its definition and measurement, however, have led some researchers to call for an outright rejection of impulsivity as a psychological construct. We address this highly unsatisfactory state with a large-scale, preregistered study (N = 1,676) in which each participant completed 48 measures of impulsivity derived from 10 self-report scales and 10 behavioral tasks and reported frequencies of seven impulsivity-related behaviors (e.g., impulsive buying and social media usage); a subsample (N = 196) then completed a retest session 3 mo later. We found that correlations between self-report measures were substantially higher than those between behavioral tasks and between self-report measures and behavioral tasks. Bifactor analysis of these measures exacted one general factor of impulsivity I, akin to the general intelligence factor g, and six specific factors. Factor I was related mainly to self-report measures, had high test-retest reliability, and could predict impulsivity-related behaviors better than existing measures. We further developed a scale named the adjustable impulsivity scale (AIMS) to measure I. AIMS possesses excellent psychometric properties that are largely retained in shorter versions and could predict impulsivity-related behaviors equally well as I. These findings collectively support impulsivity as a stable, measurable, and predictive trait, indicating that it may be too early to reject it as a valid and useful psychological construct. The bifactorial structure of impulsivity and AIMS, meanwhile, significantly advance the conceptualization and measurement of construct impulsivity.


Asunto(s)
Conducta Impulsiva , Humanos , Masculino , Femenino , Adulto , Autoinforme , Personalidad , Adulto Joven , Adolescente , Reproducibilidad de los Resultados , Persona de Mediana Edad
18.
Sci Total Environ ; 945: 173927, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38901584

RESUMEN

The ubiquity and persistence of organophosphate esters (OPEs) and heavy metal (HMs) pose global environmental risks. This study explored tris(2-chloroisopropyl)phosphate (TCPP) biomineralization coupled to lead (Pb2+) biostabilization driven by denitrifying bacteria (DNB). The domesticated DNB achieved synergistic bioremoval of TCPP and Pb2+ in the batch bioreactor (efficiency: 98 %).TCPP mineralized into PO43- and Cl-, and Pb2+ precipitated with PO43-. The TCPP-degrading/Pb2+-resistant DNB: Achromobacter, Pseudomonas, Citrobacter, and Stenotrophomonas, dominated the bacterial community, and synergized TCPP biomineralization and Pb2+ biostabilization. Metagenomics and metaproteomics revealed TCPP underwent dechlorination, hydrolysis, the TCA cycle-based dissimilation, and assimilation; Pb2+ was detoxified via bioprecipitation, bacterial membrane biosorption, EPS biocomplexation, and efflux out of cells. TCPP, as an initial donor, along with NO3-, as the terminal acceptor, formed a respiratory redox as the primary energy metabolism. Both TCPP and Pb2+ can stimulate phosphatase expression, which established the mutual enhancements between their bioconversions by catalyzing TCPP dephosphorylation and facilitating Pb2+ bioprecipitation. TCPP may alleviate the Pb2+-induced oxidative stress by aiding protein phosphorylation. 80 % of Pb2+ converted into crystalized pyromorphite. These results provide the mechanistic foundations and help develop greener strategies for synergistic bioremediation of OPEs and HMs.


Asunto(s)
Biodegradación Ambiental , Contaminantes Ambientales , Plomo , Organofosfatos , Organofosfatos/química , Organofosfatos/metabolismo , Retardadores de Llama/metabolismo , Contaminantes Ambientales/química , Contaminantes Ambientales/metabolismo , Desnitrificación , Plomo/química , Plomo/metabolismo , Achromobacter/metabolismo , Pseudomonas/metabolismo , Citrobacter/metabolismo , Stenotrophomonas/metabolismo , Metagenómica , Proteómica , Estrés Oxidativo
19.
BMC Nurs ; 23(1): 402, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886781

RESUMEN

BACKGROUND: Fever is one of the most common clinical symptoms of respiratory diseases in children. Once the child has a fever, parents and caregivers are mainly concerned that the child may have a febrile convulsion. A lack of cognitive ability not only leads to anxiety but also aggravates or delays the time of children's medical treatment and even seriously affects the prognosis because of improper management of fever patients.Therefore, it is necessary to clarify the degree of mastery of knowledge related to febrile convulsions, implement targeted guidance and health education, and ensure that parents and caregivers receive correct and reasonable first aid treatment. The purpose of this study was to translate the Febrile Convulsion Knowledge Scale for Parents/Caregivers into Chinese and to verify its reliability and validity for Chinese parents and caregivers of children. METHODS: The Brislin traditional translation model was used to translate the Febrile Convulsion Knowledge Scale for Parents/Caregivers from English to Chinese, following authorization from the original author of the scale. This involved literal translation, back translation, and cultural adaptation. A convenience sampling method was used to select 402 parents and caregivers of children in the pediatric ward and pediatric infusion clinic of a Grade III hospital in Liaoning Province. The item analysis method was employed to assess item differentiation, while the Delphi method was used to analyze content validity. Scale reliability was evaluated through the calculation of internal consistency and test-retest reliability. Exploratory and confirmatory factor analyses were conducted to explore and verify the underlying factor structure and scale validity. RESULTS: The Chinese version of the Febrile Convulsion Knowledge Scale for Parents/Caregivers consists of 3 dimensions and 8 items. The Cronbach's alpha coefficient was 0.828, with each dimension having coefficients of 0.806, 0.720, and 0.702. The split-half reliability and test-retest reliability were 0.716 and 0.790, respectively. The Chinese version has good reliability. Exploratory factor analysis revealed that the Bartlett sphericity test was 394.52 (p < 0.001) and that the KMO value was 0.802 > 0.600, indicating suitability for factor analysis. Principal component analysis and orthogonal rotation of maximum variance were performed on the data, and items with a load greater than 0.40 within a single factor were selected for inclusion. The resulting three-factor structure explained 70.78% of the total variance. All model fitting indices were within the acceptable range, indicating the good structural validity of the Chinese version. The results of both exploratory and confirmatory factor analyses support this conclusion. CONCLUSIONS: The Chinese version of the Febrile Convulsion Knowledge Scale for Parents/Caregivers has good reliability and validity. It can be used as a tool for clinical pediatric nurses to evaluate the knowledge of parents and caregivers of children with febrile convulsion and provide the basis for the design and implementation of targeted training plans according to the results obtained from the Chinese scale.

20.
Aging Dis ; 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38913050

RESUMEN

This comprehensive review navigates the complex relationship between cellular aging, senescence, and cancer, unraveling the determinants of cellular fate. Beginning with an overview of cellular aging's significance in cancer, the review explores processes, changes, and molecular pathways influencing senescence. The review explores senescence as a dual mechanism in cancer, acting as a suppressor and contributor, focusing on its impact on therapy response. This review highlights opportunities for cancer therapies that target cellular senescence. The review further examines the senescence-associated secretory phenotype and strategies to modulate cellular aging to influence tumor behavior. Additionally, the review highlights the mechanisms of senescence escape in aging and cancer cells, emphasizing their impact on cancer prognosis and resistance to therapy. The article addresses current advances, unexplored aspects, and future perspectives in understanding cellular aging and senescence in cancer.

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