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1.
Heliyon ; 10(11): e32590, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38961936

RESUMO

Model-based learning and teaching are vital for addressing real-world challenges and are gaining research traction. This study, employing CiteSpace, analyses 583 articles, uncovering trends in authors, regions, and highly cited documents. Noteworthy focuses include learning achievements, technical support, and teaching approaches. Keyword analysis emphasises thinking cultivation and interdisciplinary integration. The study discusses current and future developments in modelling and modelling education research, particularly in learning evaluation and teacher professional development. Offering an international perspective, this analysis provides stakeholders with valuable insights. In summary, model-based learning's growth and influence are evident in the identified trends and future directions, guiding the field toward effective teaching strategies and solving complex problems. This research contributes to the broader understanding of modelling education's dynamics, facilitating informed decision-making for educators and policymakers.

3.
Bioorg Chem ; 151: 107619, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39024806

RESUMO

Two rare 8-hydroxysteroid glycosides (6-7), and their downstream metabolites (1-5) with an unprecedented 6/6/5/5/5-pentacyclic scaffold, together with seven known analogues (8-14) were isolated from the twigs and leaves of Strophanthus divaricatus. Their structures were fully assigned by analysis of the spectroscopic and ECD data, NMR calculations, X-ray crystallographic study, and chemical methods. In addition, the inhibitory effects of 1-14 on liver and lung cancer cell lines were evaluated, and preliminary structure-activity relationship was discussed. Data-independent acquisition (DIA)-based quantitative proteomic analysis and biological verification of H1299 cells suggested that this family of compounds may play an anticancer role by suppressing both DNA damage response (DDR) and mTOR/S6K signaling pathways.

4.
J Immunol ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984862

RESUMO

Teleost IgM+ B cells can phagocytose, like mammalian B1 cells, and secrete Ag-specific IgM, like mammalian B2 cells. Therefore, teleost IgM+ B cells may have the functions of both mammalian B1 and B2 cells. To support this view, we initially found that grass carp (Ctenopharyngodon idella) IgM+ plasma cells (PCs) exhibit robust phagocytic ability, akin to IgM+ naive B cells. Subsequently, we sorted grass carp IgM+ PCs into two subpopulations: nonphagocytic (Pha-IgM+ PCs) and phagocytic IgM+ PCs (Pha+IgM+ PCs), both of which demonstrated the capacity to secrete natural IgM with LPS and peptidoglycan binding capacity. Remarkably, following immunization of grass carp with an Ag, we observed that both Pha-IgM+ PCs and Pha+IgM+ PCs could secrete Ag-specific IgM. Furthermore, in vitro concatenated phagocytosis experiments in which Pha-IgM+ PCs from an initial phagocytosis experiment were sorted and exposed again to beads confirmed that these cells also have phagocytic capabilities, thereby suggesting that all teleost IgM+ B cells have phagocytic potential. Additionally, we found that grass carp IgM+ PCs display classical phenotypic features of macrophages, providing support for the hypothesis that vertebrate B cells evolved from ancient phagocytes. These findings together reveal that teleost B cells are a primitive B cell type with functions reminiscent of both mammalian B1 and B2 cells, providing insights into the origin and evolution of B cells in vertebrates.

5.
JAMA Oncol ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990578

RESUMO

Importance: There has been an increasing trend of using noncigarette products, including waterpipe tobacco (WTP), worldwide. While cigarette smoking is a well-established risk factor for numerous cancers, little is known about the association between WTP smoking and cancer mortality. Objective: To assess the association between WTP smoking and risk of cancer mortality in Vietnam. Design, Setting, and Participants: This cohort study was based on data from the Hanoi Prospective Cohort Study, an ongoing study with a median (range) follow-up of 11.0 (0.1-11.6) years for participants aged 15 years or older in Northern Vietnam from 2007 through 2019. Data were analyzed from June 1 to September 1, 2023. Exposures: Tobacco smoking and WTP smoking statuses. Main Outcomes and Measures: Overall and site-specific cancer mortality. Cox proportional regression models were used to calculate the hazard ratio (HR) and 95% CIs for the associations between WTP smoking alone, cigarette smoking alone, and dual WTP and cigarette smoking and the risk of cancer death. Results: A total of 554 cancer deaths were identified among the 39 401 study participants (mean [SD] age, 40.4 [18.8] years; 20 616 females [52.3%]). In multivariable models, compared with never smokers, ever smokers had a significantly increased risk of cancer mortality (HR, 1.87; 95% CI, 1.48-2.35). Exclusive WTP smokers had the highest risk of cancer mortality compared with never smokers (HR, 2.66; 95% CI, 2.07-3.43). Risk of cancer mortality was higher for dual smokers of WTP and cigarettes (HR, 2.06; 95% CI, 1.53-2.76) than for exclusive cigarette smokers (HR, 1.86; 95% CI, 1.41-2.45). As most smokers (95.6% [8897 of 9312]) were male, these patterns were more apparent in male participants. Compared with never smokers, exclusive WTP smoking among males was associated with an elevated risk of death from liver cancer (HR, 3.92; 95% CI, 2.25-6.85), lung cancer (HR, 3.49; 95% CI, 2.08-5.88), nasopharyngeal carcinoma (HR, 2.79; 95% CI, 1.27-6.12), and stomach cancer (HR, 4.11; 95% CI, 2.04-8.27). For exclusive WTP smokers, the risk of cancer mortality was highest among those who smoked 11 to 15 sessions per day (HR, 3.42; 95% CI, 2.03-5.75), started smoking at age 26 to 30 years (HR, 4.01; 95% CI, 2.63-6.11), smoked for 9 to 20 years (HR, 4.04; 95% CI, 2.16-7.56), and smoked 61 to 160 sessions annually (HR, 3.68; 95% CI, 2.38-5.71). For males, the risk of cancer death was lower for those who had quit smoking for more than 10 years, compared with those who quit smoking within 1 year (HR, 0.27; 95% CI, 0.11-0.66; P for trend < .001). Conclusion and Relevance: In this cohort study in Vietnam, WTP smoking alone or in combination with cigarette smoking was associated with an increased risk of cancer death due to liver cancer, lung cancer, nasopharyngeal carcinoma, and stomach cancer. A tailored program to control WTP smoking is warranted in Vietnam and low- and middle-income countries with a high prevalence of smoking and modest resources to address smoking-related issues.

6.
Heliyon ; 10(13): e33590, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39035544

RESUMO

To comprehensively assess the impact of K-12 engineering education research (K-12 EER) and provide insights to stakeholders and policymakers, this study uses the scientometric analysis software CiteSpace to evaluate recent advances in K-12 EER. A search of 885 articles from the Web of Science Core Collection was conducted. This study analyzed publication trends, authors, countries, and research institutions to determine the trajectory of the K-12 EER. In addition, keyword co-occurrence and clustering maps were generated to identify major hotspots, and keyword burst detection was used to demonstrate development trends. The analysis reveals that global interest in the K-12 EER is growing, and the results are accumulating rapidly. However, cooperation between universities, institutions, experts, and scholars must be strengthened. Current significant topics in K-12 EER focus on the practical form of engineering education, its impact on learners, the centrality of engineering design, and teachers' professional development. Research frontiers primarily revolve around the nature of engineering. Future research efforts should promote the systematic integration of K-12 engineering education through the learning process, develop comprehensive measurement tools to assess its impact on learners, and expand research on teachers' professional development in K-12 engineering education.

7.
Proc Natl Acad Sci U S A ; 121(25): e2312415121, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38875149

RESUMO

Plants rely on immune receptor complexes at the cell surface to perceive microbial molecules and transduce these signals into the cell to regulate immunity. Various immune receptors and associated proteins are often dynamically distributed in specific nanodomains on the plasma membrane (PM). However, the exact molecular mechanism and functional relevance of this nanodomain targeting in plant immunity regulation remain largely unknown. By utilizing high spatiotemporal resolution imaging and single-particle tracking analysis, we show that myosin XIK interacts with remorin to recruit and stabilize PM-associated kinase BOTRYTIS-INDUCED KINASE 1 (BIK1) within immune receptor FLAGELLIN SENSING 2 (FLS2)-containing nanodomains. This recruitment facilitates FLS2/BIK1 complex formation, leading to the full activation of BIK1-dependent defense responses upon ligand perception. Collectively, our findings provide compelling evidence that myosin XI functions as a molecular scaffold to enable a spatially confined complex assembly within nanodomains. This ensures the presence of a sufficient quantity of preformed immune receptor complex for efficient signaling transduction from the cell surface.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Imunidade Inata , Miosinas , Imunidade Vegetal , Proteínas Serina-Treonina Quinases , Arabidopsis/imunologia , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Membrana Celular/metabolismo , Miosinas/metabolismo , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais
8.
Cancers (Basel) ; 16(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38893190

RESUMO

PURPOSE: To assess the association of a polygenic risk score (PRS) for functional genetic variants with the risk of developing breast cancer. METHODS: Summary data-based Mendelian randomization (SMR) and heterogeneity in dependent instruments (HEIDI) were used to identify breast cancer risk variants associated with gene expression and DNA methylation levels. A new SMR-based PRS was computed from the identified variants (functional PRS) and compared to an established 313-variant breast cancer PRS (GWAS PRS). The two scores were evaluated in 3560 breast cancer cases and 3383 non-cancer controls and also in a prospective study (n = 10,213) comprising 418 cases. RESULTS: We identified 149 variants showing pleiotropic association with breast cancer risk (eQTLHEIDI > 0.05 = 9, mQTLHEIDI > 0.05 = 165). The discriminatory ability of the functional PRS (AUCcontinuous [95% CI]: 0.540 [0.526 to 0.553]) was found to be lower than that of the GWAS PRS (AUCcontinuous [95% CI]: 0.609 [0.596 to 0.622]). Even when utilizing 457 distinct variants from both the functional and GWAS PRS, the combined discriminatory performance remained below that of the GWAS PRS (AUCcontinuous, combined [95% CI]: 0.561 [0.548 to 0.575]). A binary high/low-risk classification based on the 80th centile PRS in controls revealed a 6% increase in cases using the GWAS PRS compared to the functional PRS. The functional PRS identified an additional 12% of high-risk cases but also led to a 13% increase in high-risk classification among controls. Similar findings were observed in the SCHS prospective cohort, where the GWAS PRS outperformed the functional PRS, and the highest-performing PRS, a combined model, did not significantly improve over the GWAS PRS. CONCLUSIONS: While this study identified potentially functional variants associated with breast cancer risk, their inclusion did not substantially enhance the predictive accuracy of the GWAS PRS.

9.
JAMA Dermatol ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865150

RESUMO

A woman in her 30s presented with mildly itchy skin nodules in the vulvar region for 1 year, which occurred during pregnancy and increased gradually in size and number without any treatments. What is your diagnosis?

10.
Nat Methods ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907114

RESUMO

Advances in spatial omics technologies now allow multiple types of data to be acquired from the same tissue slice. To realize the full potential of such data, we need spatially informed methods for data integration. Here, we introduce SpatialGlue, a graph neural network model with a dual-attention mechanism that deciphers spatial domains by intra-omics integration of spatial location and omics measurement followed by cross-omics integration. We demonstrated SpatialGlue on data acquired from different tissue types using different technologies, including spatial epigenome-transcriptome and transcriptome-proteome modalities. Compared to other methods, SpatialGlue captured more anatomical details and more accurately resolved spatial domains such as the cortex layers of the brain. Our method also identified cell types like spleen macrophage subsets located at three different zones that were not available in the original data annotations. SpatialGlue scales well with data size and can be used to integrate three modalities. Our spatial multi-omics analysis tool combines the information from complementary omics modalities to obtain a holistic view of cellular and tissue properties.

11.
Hepatol Commun ; 8(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38934706

RESUMO

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in people with obesity. We aimed to study the association of body mass index (BMI) with clinical outcomes in patients with MASLD. METHODS: A retrospective cohort of 32,900 patients with MASLD, identified through the International Classification of Diseases-9 and 10 codes within the electronic health records of a large US-based health system, with a mean follow-up of 5.5 years (range: 1-15 y), was stratified into 6 BMI categories, <25, 25-<30, 30-<40, 40-<50, and ≥50 kg/m2. RESULTS: The risk of liver decompensation and extrahepatic obesity-associated cancers had a J-shaped profile (both ps for linear and quadratic terms <0.05). Compared to patients with BMI 25-<30 kg/m2, the adjusted HRs (95% CIs) for liver decompensation of patients with BMI <25 and BMI ≥50 kg/m2 were 1.44 (1.17-1.77) and 2.27 (1.66-3.00), respectively. The corresponding figures for obesity-associated extrahepatic cancer were 1.15 (0.97-1.36) and 1.29 (1.00-1.76). There was an inverse association for BMI with liver transplantation and non-obesity-associated cancer (both ps for linear terms <0.05), but no association with HCC or all types of cancers combined. A similar J-shaped association between BMI and all-cause mortality was observed; adjusted HRs (95% CIs) for BMI <25 and ≥50 kg/m2 were 1.51 (1.32-1.72) and 3.24 (2.67-3.83), respectively, compared with BMI 25-<30 kg/m2 (both ps for linear and quadratic terms <0.001). CONCLUSIONS: Patients with MASLD and very severe obesity (BMI ≥50 kg/m2) had the highest risk, exceeding that of patients with lean MASLD, for developing liver decompensation, obesity-associated extrahepatic cancers, or dying from any cause.


Assuntos
Índice de Massa Corporal , Obesidade Mórbida , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Adulto , Idoso , Fatores de Risco , Fígado Gorduroso/complicações , Fígado Gorduroso/mortalidade , Estados Unidos/epidemiologia , Transplante de Fígado
13.
Phys Chem Chem Phys ; 26(24): 17075-17082, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38842020

RESUMO

The topological and magnetic properties induced by topological defects in graphene have attracted attention. Here, we study a novel topological defect structure for graphene nanoribbons interspersed with C558-line defects along the armchair boundary, which possesses topological properties and is tritopic. Using strain engineering to regulate the magnitude of hopping at defects, the position of the energy level can be easily changed to achieve a topological phase transition. We also discuss the local magnetic moment and the ferromagnetic ground state in the context of line defects. This leads to spin polarization of the whole system. Finally, when C558 graphene nanoribbons are controlled by a nonlocal exchange magnetic field, spin-polarized quantum conductivity occurs near the Fermi level. Consequently, spin filtering can be achieved by varying the incident energy of the electrons. Our results provide new insights into realizing topological and spin electronics in low-dimensional quantum devices.

14.
Heliyon ; 10(11): e32288, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38912485

RESUMO

Liver cancer is a heterogeneous disease characterized by poor responses to standard therapies and therefore unfavourable clinical outcomes. Understanding the characteristics of liver cancer and developing novel therapeutic strategies are imperative. Ferroptosis, a type of programmed cell death induced by lipid peroxidation, has emerged as a potential target for treatment. Naringenin, a natural compound that modulates lipid metabolism by targeting AMPK, shows promise in enhancing the efficacy of ferroptosis inducers. In this study, we utilized liver cancer cell lines and xenograft mice to explore the synergistic effects of naringenin in combination with ferroptosis inducers, examining both phenotypic outcomes and molecular mechanisms. Our study results indicate that the use of naringenin at non-toxic doses to hepatocytes can significantly enhance the anticancer effects of ferroptosis inducers (erastin, RSL3, and sorafenib). The combination index method confirmed a synergistic effect between naringenin and ferroptosis inducers. In comparison to naringenin or ferroptosis inducers alone, the combined therapy caused more robust lipid peroxidation and hence more severe ferroptotic damage to cancer cells. The inhibition of aerobic glycolysis mediated by the AMPK-PGC1α signalling axis is the key to naringenin's effect on reducing ferroptosis resistance in liver cancer, and the synergistic cytotoxic effect of naringenin and ferroptosis inducers on cancer cells was reversed after pretreatment with an AMPK inhibitor or a PGC1α inhibitor. Taken together, these findings suggest that naringenin could boost cancer cell sensitivity to ferroptosis inducers, which has potential clinical translational value.

15.
Nanomicro Lett ; 16(1): 209, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842597

RESUMO

With the development of science and technology, the scale of industrial production continues to grow, and the types and quantities of gas raw materials used in industrial production and produced during the production process are also constantly increasing. These gases include flammable and explosive gases, and even contain toxic gases. Therefore, it is very important and necessary for gas sensors to detect and monitor these gases quickly and accurately. In recent years, a new two-dimensional material called MXene has attracted widespread attention in various applications. Their abundant surface functional groups and sites, excellent current conductivity, tunable surface chemistry, and outstanding stability make them promising for gas sensor applications. Since the birth of MXene materials, researchers have utilized the efficient and convenient solution etching preparation, high flexibility, and easily functionalize MXene with other materials to prepare composites for gas sensing. This has opened a new chapter in high-performance gas sensing materials and provided a new approach for advanced sensor research. However, previous reviews on MXene-based composite materials in gas sensing only focused on the performance of gas sensing, without systematically explaining the gas sensing mechanisms generated by different gases, as well as summarizing and predicting the advantages and disadvantages of MXene-based composite materials. This article reviews the latest progress in the application of MXene-based composite materials in gas sensing. Firstly, a brief summary was given of the commonly used methods for preparing gas sensing device structures, followed by an introduction to the key attributes of MXene related to gas sensing performance. This article focuses on the performance of MXene-based composite materials used for gas sensing, such as MXene/graphene, MXene/Metal oxide, MXene/Transition metal sulfides (TMDs), MXene/Metal-organic framework (MOF), MXene/Polymer. It summarizes the advantages and disadvantages of MXene composite materials with different composites and discusses the possible gas sensing mechanisms of MXene-based composite materials for different gases. Finally, future directions and inroads of MXenes-based composites in gas sensing are presented and discussed.

16.
Phytochemistry ; 224: 114163, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38815883

RESUMO

Stereochemical investigations on the twigs and leaves of Solanum erianthum afforded five pairs of lignanamide enantiomers and a previously undescribed phenolic amide (3). Particularly, two pairs of previously undescribed lignanamide racemates (1a/1b-2a/2b) represent the first case of natural products that feature an unreported 5/5-fused N/O-biheterocyclic core. Their structures, including the absolute configurations, were determined unambiguously by using spectroscopic analyses and electronic circular dichroism calculations. A speculative biogenetic pathway for 1-3 was proposed. Interestingly, these lignanamides exhibited enantioselective antiplasmodial activities against drug-sensitive Plasmodium falciparum 3D7 strain and chloroquine-resistant Plasmodium falciparum Dd2 strain, pointing out that chirality plays an important role in drug development.


Assuntos
Antimaláricos , Folhas de Planta , Plasmodium falciparum , Solanum , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/química , Antimaláricos/farmacologia , Antimaláricos/isolamento & purificação , Folhas de Planta/química , Solanum/química , Estereoisomerismo , Estrutura Molecular , Lignanas/química , Lignanas/farmacologia , Lignanas/isolamento & purificação , Amidas/química , Amidas/farmacologia , Amidas/isolamento & purificação , Relação Estrutura-Atividade , Testes de Sensibilidade Parasitária
17.
Fish Shellfish Immunol ; 150: 109621, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38740230

RESUMO

This study aims to explore the effects of supplementing cholesterol in plant-based feed on intestinal barriers (including physical barrier, chemical barrier, immune barrier, biological barrier) of GIFT strain tilapia (Oreochromis niloticus). Four isonitrogenous and isolipidic diets were prepared as follows: plant-based protein diet (Con group) containing corn protein powder, soybean meal, cottonseed meal, and rapeseed meal, with the addition of cholesterol at a level of 0.6 % (C0.6 % group), 1.2 % (C1.2 % group), and 1.8 % (C1.8 % group), respectively. A total of 360 fish (mean initial weight of (6.08 ± 0.12) g) were divided into 12 tanks with 30 fish per tank, each treatment was set with three tanks and the feeding period lasted 9 weeks. Histological analysis revealed that both the C0.6 % and C1.2 % groups exhibited a more organized intestinal structure, with significantly increased muscle layer thickness compared to the Con group (P < 0.05). Furthermore, in the C1.2 % group, there was a significant up-regulation of tight junction-related genes (claudin-14, occludin, zo-1) compared to the Con group (P < 0.05). 5-ethynyl-2'-deoxyuridine staining results also demonstrated a notable enhancement in intestinal cell proliferation within the C1.2 % group (P < 0.05). Regarding the intestinal chemical barrier, trypsin and lipase activities were significantly elevated in the C1.2 % group (P < 0.05), while hepcidin gene expression was considerably down-regulated in this group but up-regulated in the C1.8 % group (P < 0.05). In terms of the intestinal immune barrier, inflammation-related gene expression levels (tnf-α, il-1ß, caspase 9, ire1, perk, atf6) were markedly reduced in the C1.2 % group (P < 0.05). Regarding the intestinal biological barrier, the composition of the intestinal microbiota indicated that compared to the Con group, both the 0.6 % and 1.2 % groups showed a significant increase in Shannon index (P < 0.05). Additionally, there was a significant increase in the abundance of Firmicutes and Clostridium in the C1.2 % group (P < 0.05). In summary, supplementation of 1.2 % cholesterol in the plant-based diet exhibits the potential to enhance intestinal tight junction function and improve the composition of intestinal microbiota, thereby significantly promoting tilapia's intestinal health.


Assuntos
Ração Animal , Ciclídeos , Dieta , Intestinos , Animais , Ciclídeos/imunologia , Ração Animal/análise , Dieta/veterinária , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Colesterol na Dieta/administração & dosagem , Colesterol na Dieta/efeitos adversos , Doenças dos Peixes/imunologia , Suplementos Nutricionais/análise , Distribuição Aleatória , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Dieta Baseada em Plantas
19.
Eur J Med Chem ; 272: 116478, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38718624

RESUMO

Metallodrugs exhibiting distinct mechanisms of action compared with cisplatin hold promise for overcoming cisplatin resistance and improving the efficacy of anticancer drugs. In this study, a new series of rhodium (Rh)(III) complexes containing tris(triphenylphosphine)rhodium(I) chloride [(TPP)3RhCl] (TPP = triphenylphosphine, TPP=O = triphenylphosphine oxide) and 8-hydroxyquinoline derivatives (H-XR1-H-XR4), namely [Rh(XR1)2(TPP)Cl]·(TPP=O) (Yulin Normal University-1a [YNU-1a]), [Rh(XR2)2(TPP)Cl] (YNU-1b), [Rh(XR3)2(TPP)Cl] (YNU-1c), and [Rh(XR4)2(TPP)Cl] (YNU-1d), was synthesized and characterized via X-ray diffraction, mass spectrometry and IR. The cytotoxicity of the compounds YNU-1a-YNU-1d in Hep-G2 and HCC1806 human cancer cell lines and normal HL-7702 cell line was evaluated. YNU-1c exhibited cytotoxicity and selectivity in HCC1806 cells (IC50 = 0.13 ± 0.06 µM, selectivity factor (SF) = 384.6). The compounds YNU-1b and YNU-1c, which were selected for mechanistic studies, induced the activation of apoptotic pathways and mitophagy. In addition, these compounds released cytochrome c, cleaved caspase-3/pro-caspase-3 and downregulated the levels of mitochondrial respiratory chain complexes I/IV (M1 and M4) and ATP. The compound YNU-1c, which was selected for in vivo experiments, exhibited tumor growth inhibition (58.9 %). Importantly, hematoxylin and eosin staining and TUNEL revealed that HCC1806 tumor tissues exhibited significant apoptotic characteristics. YNU-1a-YNU-1d compounds are promising drug candidates that can be used to overcome cisplatin resistance.


Assuntos
Antineoplásicos , Proliferação de Células , Complexos de Coordenação , Ensaios de Seleção de Medicamentos Antitumorais , Mitofagia , Oxiquinolina , Ródio , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Ródio/química , Ródio/farmacologia , Oxiquinolina/química , Oxiquinolina/farmacologia , Oxiquinolina/síntese química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Animais , Relação Estrutura-Atividade , Proliferação de Células/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Estrutura Molecular , Compostos Organofosforados/farmacologia , Compostos Organofosforados/química , Compostos Organofosforados/síntese química , Relação Dose-Resposta a Droga , Apoptose/efeitos dos fármacos , Camundongos , Linhagem Celular Tumoral
20.
Eur J Oncol Nurs ; 70: 102549, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692158

RESUMO

OBJECTIVE: To evaluate the effectiveness of Orem's self-care model in preparing hospitals for the discharge of patients with colorectal cancer who undergo enterostomy. METHODS: 92 patients with enterostomy were recruited between February 2022 and February 2023 from a general tertiary hospital. The participants were assigned to either the intervention group or the control group randomly. The intervention group received Orem's self-care program and a three-month follow-up, whereas the control group received only routine care and a three-month follow-up. Discharge readiness, self-care ability, and stoma-quality-of-life data were collected at hospital discharge (T1), 30 days (T2), and 90 days (T3) after discharge. RESULTS: The intervention group had substantially higher discharge readiness (knowledge, p < 0.001; coping ability, p = 0.006; personal status, p = 0.001; expected support, p = 0.021; total score, p < 0.001), better self-care ability at T1 (self-care knowledge, p < 0.001; self-care skills, p = 0.010), better total quality of life (QoL) at T1, T2, and T3 (p < 0.001; p = 0.006; p = 0.014); better stoma management and daily routine at T1 (p = 0.004; p < 0.001); and better daily routine at T2 (p = 0.009) than the control group. CONCLUSIONS: The designed discharge readiness program based on Orem's self-care could promote effective patient discharge readiness, self-care knowledge, self-care skills, and QoL. TRIAL REGISTRATION: The trial number ChiCTR2200056302 registered on ClinicalTrials.gov.


Assuntos
Neoplasias Colorretais , Enterostomia , Alta do Paciente , Qualidade de Vida , Autocuidado , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Neoplasias Colorretais/cirurgia , Adulto , Adaptação Psicológica
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