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1.
BMC Med Imaging ; 24(1): 162, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38956470

RESUMO

BACKGROUND: The image quality of computed tomography angiography (CTA) images following endovascular aneurysm repair (EVAR) is not satisfactory, since artifacts resulting from metallic implants obstruct the clear depiction of stent and isolation lumens, and also adjacent soft tissues. However, current techniques to reduce these artifacts still need further advancements due to higher radiation doses, longer processing times and so on. Thus, the aim of this study is to assess the impact of utilizing Single-Energy Metal Artifact Reduction (SEMAR) alongside a novel deep learning image reconstruction technique, known as the Advanced Intelligent Clear-IQ Engine (AiCE), on image quality of CTA follow-ups conducted after EVAR. MATERIALS: This retrospective study included 47 patients (mean age ± standard deviation: 68.6 ± 7.8 years; 37 males) who underwent CTA examinations following EVAR. Images were reconstructed using four different methods: hybrid iterative reconstruction (HIR), AiCE, the combination of HIR and SEMAR (HIR + SEMAR), and the combination of AiCE and SEMAR (AiCE + SEMAR). Two radiologists, blinded to the reconstruction techniques, independently evaluated the images. Quantitative assessments included measurements of image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), the longest length of artifacts (AL), and artifact index (AI). These parameters were subsequently compared across different reconstruction methods. RESULTS: The subjective results indicated that AiCE + SEMAR performed the best in terms of image quality. The mean image noise intensity was significantly lower in the AiCE + SEMAR group (25.35 ± 6.51 HU) than in the HIR (47.77 ± 8.76 HU), AiCE (42.93 ± 10.61 HU), and HIR + SEMAR (30.34 ± 4.87 HU) groups (p < 0.001). Additionally, AiCE + SEMAR exhibited the highest SNRs and CNRs, as well as the lowest AIs and ALs. Importantly, endoleaks and thrombi were most clearly visualized using AiCE + SEMAR. CONCLUSIONS: In comparison to other reconstruction methods, the combination of AiCE + SEMAR demonstrates superior image quality, thereby enhancing the detection capabilities and diagnostic confidence of potential complications such as early minor endleaks and thrombi following EVAR. This improvement in image quality could lead to more accurate diagnoses and better patient outcomes.


Assuntos
Artefatos , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares , Humanos , Estudos Retrospectivos , Feminino , Angiografia por Tomografia Computadorizada/métodos , Idoso , Masculino , Procedimentos Endovasculares/métodos , Pessoa de Meia-Idade , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aprendizado Profundo , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Stents , Correção Endovascular de Aneurisma
2.
Animals (Basel) ; 14(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38998024

RESUMO

This study aimed to investigate the effects of bile acids (BAs) supplementation on fatty liver hemorrhagic syndrome (FLHS), production performance, and physiological and quality characteristics of laying hen eggs. Sixty Sanhuang laying hens, aged 28 weeks, were randomly allocated to six dietary treatments over a 4-week period, including the control (CON) group (feeding basal diet), the high-fat diet (HFD)-treated group (basal diet containing 10% soybean oil), and HFD supplemented with 0.01% and 0.02% of chenodeoxycholic acid (CDCA) or hyodeoxycholic acid (HDCA) groups. Production performance, egg quality, liver morphology, serum biochemical indexes, antioxidant capacity, proinflammatory cytokines, and intestinal microbiota were evaluated. The average body weight in 0.01% CDCA was larger than in the HFD group (p < 0.05). Eggshell Thickness in the CON group was greater than in the HFD, 0.01% CDCA, and HDCA groups (p < 0.05). Albumen height in the 0.02% HDCA group was higher than the HFD group (p < 0.05). Eggshell weight in the HFD group was less than the CON group (p < 0.05). Haugh unit (HU) in the HDCA group was larger than the HFD group (p < 0.05). Albumen weight in the 0.02% HDCA group was greater than the CON and HFD groups (p < 0.05). In the HFD group, the levels of triglyceride (TG), total cholesterol (TC), and low-density lipo-protein cholesterol (LDL-C) were surpassing the other groups (p < 0.05). The levels of catalase (CAT) and total superoxide dismutase (T-SOD) in the HFD group was smaller than the other groups (p < 0.05). The level of malondialdehyde (MDA) in the HFD group was higher than in the other groups (p < 0.05). Tumor necrosis factor-α (TNF-α) levels were larger in the HFD group than in the other groups (p < 0.05). The 16S rRNA sequencing analysis indicated significant variations in the relative abundance of specific bacterial populations among the different treatment groups. The treatment and CON groups exhibited a higher presence of bacteria that inhibit host energy absorption or promote intestinal health such as Firmicutes, Bacteroidetes, and Ruminococcus, whereas the HFD group showed an increased prevalence of potentially pathogenic or deleterious bacteria, such as Desulfovibrio spp. In conclusion, the supplementation of BAs in poultry feed has been demonstrated to effectively mitigate the detrimental effects of FLHS in laying hens. This intervention regulates lipid metabolism, bolsters antioxidant defenses, reduces inflammation, and modulates the gut microbiota, offering a novel perspective on the application of BAs in the poultry industry.

3.
Food Res Int ; 188: 114501, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823874

RESUMO

This study investigated the effects of different pickle brines and glycine additions on biogenic amine formation in pickle fermentation. The results showed that the brines with higher biogenic amine content led to the production of more biogenic amines in the simulated pickle fermentation system. This was related to the abundance of biogenic amine-producing microorganisms in the microbial communities of the brines. Metagenome analysis of the brines and metatranscriptome analysis of the fermentation systems showed that putrescine was primarily from Lactobacillus, Oenococcus, and Pichia, while histamine and tyramine were primarily from Lactobacillus and Tetragenococcus. Addition of glycine significantly reduced the accumulation of biogenic amines in the simulated pickle fermentation system by as much as 70 %. The addition of glycine had no inhibitory effect on the amine-producing microorganisms, but it down-regulated the transcription levels of the genes for enzymes related to putrescine synthesis in Pichia, Lactobacillus, and Oenococcus, as well as the histidine decarboxylase genes in Lactobacillus and Tetragenococcus. Catalytic reaction assay using crude solutions of amino acid decarboxylase extracted from Lactobacillus brevis showed that the addition of glycine inhibited 45 %-55 % of ornithine decarboxylase and tyrosine decarboxylase activities. This study may provide a reference for the study and control of the mechanism of biogenic amine formation in pickle fermentation.


Assuntos
Aminas Biogênicas , Fermentação , Glicina , Glicina/metabolismo , Aminas Biogênicas/metabolismo , Sais , Putrescina/metabolismo , Tiramina/metabolismo , Microbiologia de Alimentos , Lactobacillus/metabolismo , Lactobacillus/genética , Alimentos Fermentados/microbiologia , Pichia/metabolismo , Pichia/genética
4.
Sci Rep ; 14(1): 12270, 2024 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806611

RESUMO

The prognosis for patients with colorectal cancer (CRC) remains worse than expected due to metastasis, recurrence, and resistance to chemotherapy. Colorectal cancer stem cells (CRCSCs) play a vital role in tumor metastasis, recurrence, and chemotherapy resistance. However, there are currently no prognostic markers based on CRCSCs-related genes available for clinical use. In this study, single-cell transcriptome sequencing was employed to distinguish cancer stem cells (CSCs) in the CRC microenvironment and analyze their properties at the single-cell level. Subsequently, data from TCGA and GEO databases were utilized to develop a prognostic risk model for CRCSCs-related genes and validate its diagnostic performance. Additionally, functional enrichment, immune response, and chemotherapeutic drug sensitivity of the relevant genes in the risk model were investigated. Lastly, the key gene RPS17 in the risk model was identified as a potential prognostic marker and therapeutic target for further comprehensive studies. Our findings provide new insights into the prognostic treatment of CRC and offer novel perspectives for a systematic and comprehensive understanding of CRC development.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais , Células-Tronco Neoplásicas , RNA-Seq , Análise de Célula Única , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Análise de Célula Única/métodos , Prognóstico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral/genética , Transcriptoma , Perfilação da Expressão Gênica , Análise de Sequência de RNA/métodos
5.
Artigo em Inglês | MEDLINE | ID: mdl-38809741

RESUMO

This study proposes a neural-network (NN)-based adaptive fixed-time control method for a two-degree-of-freedom (2-DOF) nonlinear helicopter system with input quantization and output constraints. First, a hysteresis quantizer is employed to mitigate chattering during signal quantization, and adaptive variables are utilized to eliminate errors in the quantization process. Subsequently, the system uncertainties are approximated using a radial basis function NN. Simultaneously, a logarithmic barrier Lyapunov function (BLF) is constructed to prevent the system outputs from violating the constraint boundaries. Based on a rigorous Lyapunov stability analysis and the fixed-time stability criterion, the signals of the closed-loop system are proven to be bounded within a fixed time. Finally, numerical simulations and experiments verified the feasibility of the proposed method.

6.
Org Lett ; 26(15): 3208-3212, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38597783

RESUMO

Herein, we report a catalyst-free reaction of cyclobutanone oximes with chlorophosphines (R2PCl), which forms a fragile C═N-O-PR2 species that undergoes N-O homolysis, fragmentation, and radical-radical coupling, leading to the formation of cyano-containing phosphine oxides in good yields. The reaction features an in situ activation of cyclobutanone oximes for radical generation, in which R2PCl plays a dual role as both an activator and a reactant.

7.
Clin Nutr ; 43(6): 1224-1239, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38643738

RESUMO

BACKGROUND: Probiotic administration is a promising therapy for improving conditions in NAFLD patients. This network meta-analysis aimed to compare and estimate the relative effects of probiotic interventions and identify the optimal probiotic species for the treatment of NAFLD (Nonalcoholic fatty liver disease) patients. METHODS: The PubMed, Web of Science, Embase, and Cochrane databases were searched from inception to 29 January 2024 to identify RCTs that were published in English. The GRADE framework was used to assess the quality of evidence contributing to each network estimate. RESULTS: A total of 35 RCTs involving 2212 NAFLD patients were included in the analysis. For primary outcomes, Lactobacillus + Bifidobacterium + Streptococcus exhibited the highest probability of being the finest probiotic combination in terms of enhancing acceptability as well as reducing AST (SMD: -1.95 95% CI: -2.90, -0.99), ALT (SMD = -1.67, 95% CI: -2.48, -0.85), and GGT levels (SMD = -2.17, 95% CI: -3.27, -1.06). In terms of the secondary outcomes, Lactobacillus + Bifidobacterium + Streptococcus was also the best probiotic combination for reducing BMI (SMD = -0.45, 95% CI: -0.86, -0.04), LDL levels (SMD = -0.45, 95% CI: -0.87, -0.02), TC levels (SMD = -1.09, 95% CI: -1.89, -0.29), and TNF-α levels (SMD = -1.73, 95% CI: -2.72, -0.74). CONCLUSION: This network meta-analysis revealed that Lactobacillus + Bifidobacterium + Streptococcus may be the most effective probiotic combination for the treatment of liver enzymes, lipid profiles, and inflammation factors. These findings can be used to guide the development of a probiotics-based treatment guideline for NAFLD since there are few direct comparisons between different therapies.


Assuntos
Lactobacillus , Metanálise em Rede , Hepatopatia Gordurosa não Alcoólica , Probióticos , Probióticos/administração & dosagem , Probióticos/uso terapêutico , Humanos , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Bifidobacterium , Streptococcus , Resultado do Tratamento
8.
Water Res ; 256: 121588, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38636120

RESUMO

So far, little has been known about how the combined collection systems of sewage and rainfall runoff (CCSs) affect emerging contaminants in river water. To fill up the knowledge gap, this study was conducted to investigate the spatial distributions of three natural estrogens (NEs, i.e., estrone (E1), 17ß-estradiol (E2) and estriol (E3)) and their conjugates (C-NEs) in the Pearl River in the wet and dry seasons. Results showed that the respective average concentrations of NEs and C-NEs at different locations alongside the Pearl River in the wet season were 7.3 and 1.8 times those in the dry season. Based on estrogen equivalence (EEQ), the average estimated EEQ level in the Pearl River waters in the wet season was nearly 10 times that in the dry season. These seemed to imply that the CCSs in the wet season not only cause untreated sewage into the receiving water body, but greatly decrease the removal efficiency of NEs and C-NEs in wastewater treatment plant. Furthermore, the estimated annual loads of E1, E2, and E3 to the Pearl River in the wet season accounted for about 88.6 %, 100 %, and 99.3 % of the total annual loads. Consequently, this work for the first time demonstrated that the CCSs in cities with high precipitation are unfavorable for controlling of emerging contaminants.


Assuntos
Monitoramento Ambiental , Estrogênios , Chuva , Rios , Esgotos , Poluentes Químicos da Água , Rios/química , China , Estrogênios/análise , Esgotos/química , Poluentes Químicos da Água/análise , Estações do Ano , Estrona/análise , Estradiol/análise
9.
Braz J Med Biol Res ; 57: e12951, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38511766

RESUMO

The incidences of periodontitis and osteoporosis are rising worldwide. Observational studies have shown that periodontitis is associated with increased risk of osteoporosis. We performed a Mendelian randomization (MR) study to genetically investigate the causality of periodontitis on osteoporosis. We explored the causal effect of periodontitis on osteoporosis by MR analysis. A total of 9 single nucleotide polymorphisms (SNP) were related to periodontitis. The primary approach in this MR analysis was the inverse variance-weighted (IVW) method. Simple median, weighted median, and penalized weighted median were used to analyze sensitivity. The fixed-effect IVW model and random-effect IVW model showed no significant causal effect of genetically predicted periodontitis on the risk of osteoporosis (OR=1.032; 95%CI: 0.923-1.153; P=0.574; OR=1.032; 95%CI: 0.920-1.158; P=0.588, respectively). Similar results were observed in simple mode (OR=1.031; 95%CI: 0.780-1.361, P=0.835), weighted mode (OR=1.120; 95%CI: 0.944-1.328, P=0.229), simple median (OR=1.003; 95%CI: 0.839-1.197, P=0.977), weighted median (OR=1.078; 95%CI: 0.921-1.262, P=0.346), penalized weight median (OR 1.078; 95%CI: 0.919-1.264, P=0.351), and MR-Egger method (OR=1.360; 95%CI: 0.998-1.853, P=0.092). There was no heterogeneity in the IVW and MR-Egger analyses (Q=7.454, P=0.489 and Q=3.901, P=0.791, respectively). MR-Egger regression revealed no evidence of a pleiotropic influence through genetic variants (intercept: -0.004; P=0.101). The leave-one-out sensitivity analysis indicated no driven influence of any individual SNP on the association between periodontitis and osteoporosis. The Mendelian randomization analysis did not show a significant detrimental effect of periodontitis on the risk of osteoporosis.


Assuntos
Osteoporose , Periodontite , Humanos , Análise da Randomização Mendeliana , Osteoporose/genética , Nonoxinol , Periodontite/genética , Polimorfismo de Nucleotídeo Único/genética
10.
Sci Total Environ ; 926: 172071, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38554960

RESUMO

Natural estrogen conjugates play important roles in municipal wastewater treatment plant (WWTP), but their deconjugation potentials are poorly understood. This work is the first to investigate the relationships between the enzyme activities of arylsulfatase/ß-glucuronidase and deconjugation potentials of natural estrogen conjugates. This work led to three important findings. First, the enzyme activity of ß-glucuronidase in sewage is far higher than that of arylsulfatase, while their corresponding activities in activated sludge were similar. Second, a model based on ß-glucuronidase could successfully predict the deconjugation potentials of natural estrogen glucuronide conjugates in sewage. Third, the enzyme activity of arylsulfatase in sewage was too low to lead to evident deconjugation of sulfate conjugates, which means that the deconjugation rate of estrogen sulfates can be regarded as zero. By comparing their theoretical removal based on enzyme activity and on-site investigation, it is reasonable to conclude that reverse deconjugation of estrogen conjugates (i.e., conjugation of natural estrogens to form conjugated estrogens) likely exist in WWTP, which explains well why natural estrogen conjugates cannot be effectively removed in WWTP. Meanwhile, this work provides new insights how to improve the removal performance of WWTP on natural estrogen conjugates. SYNOPSIS: This work is the first to show how arylsulfatase/ß-glucuronidase could affect deconjugation of natural estrogen conjugates and possible way to enhance their removal in wastewater treatment plant.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Esgotos , Poluentes Químicos da Água/análise , Estrogênios , Arilsulfatases , Glucuronidase
11.
Cancer Cell ; 42(3): 325-327, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38402608

RESUMO

Dozens of compounds that rescue tumor-associated mutant p53 have been reported. Xiao et al. perform 10 assays to evaluate effectiveness of the mutant p53-rescue compounds side-by-side but do not detect reliable rescue in any assay for the evaluated compounds, except for ATO and its analog PAT.


Assuntos
Neoplasias , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/genética , Mutação
12.
Braz. j. med. biol. res ; 57: e12951, fev.2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1550148

RESUMO

Abstract The incidences of periodontitis and osteoporosis are rising worldwide. Observational studies have shown that periodontitis is associated with increased risk of osteoporosis. We performed a Mendelian randomization (MR) study to genetically investigate the causality of periodontitis on osteoporosis. We explored the causal effect of periodontitis on osteoporosis by MR analysis. A total of 9 single nucleotide polymorphisms (SNP) were related to periodontitis. The primary approach in this MR analysis was the inverse variance-weighted (IVW) method. Simple median, weighted median, and penalized weighted median were used to analyze sensitivity. The fixed-effect IVW model and random-effect IVW model showed no significant causal effect of genetically predicted periodontitis on the risk of osteoporosis (OR=1.032; 95%CI: 0.923-1.153; P=0.574; OR=1.032; 95%CI: 0.920-1.158; P=0.588, respectively). Similar results were observed in simple mode (OR=1.031; 95%CI: 0.780-1.361, P=0.835), weighted mode (OR=1.120; 95%CI: 0.944-1.328, P=0.229), simple median (OR=1.003; 95%CI: 0.839-1.197, P=0.977), weighted median (OR=1.078; 95%CI: 0.921-1.262, P=0.346), penalized weight median (OR 1.078; 95%CI: 0.919-1.264, P=0.351), and MR-Egger method (OR=1.360; 95%CI: 0.998-1.853, P=0.092). There was no heterogeneity in the IVW and MR-Egger analyses (Q=7.454, P=0.489 and Q=3.901, P=0.791, respectively). MR-Egger regression revealed no evidence of a pleiotropic influence through genetic variants (intercept: -0.004; P=0.101). The leave-one-out sensitivity analysis indicated no driven influence of any individual SNP on the association between periodontitis and osteoporosis. The Mendelian randomization analysis did not show a significant detrimental effect of periodontitis on the risk of osteoporosis.

13.
Materials (Basel) ; 17(2)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38255440

RESUMO

Thermoplastic polyurethane (TPU) composites with eutectic gallium (Ga) and indium (In) (eGaIn) fillings of 0 wt%-75 wt% were prepared using the electrostatic spinning method. Field emission scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared (FTIR) spectroscopy were used to characterize the eGaIn NDs/TPU composites. To evaluate their X-ray shielding properties, Phy-X/PSD and WinXCom were employed to calculate the mass attenuation coefficients, linear attenuation coefficients, half-value layers, tenth value layers, mean free paths, and adequate atomic numbers of the eGaIn NDs/TPU composites. The SEM results indicated that the eGaIn nanodroplets were evenly distributed throughout the TPU fibers, and the flowable eGaIn was well-suited for interfacial compatibility with the TPU. A comparison of the eGaIn NDs/TPU composites with different content levels showed that the composite with 75 wt% eGaIn had the highest µm at all the evaluated energies, indicating a superior ability to attenuate X-rays. This non-toxic, lightweight, and flexible composite is a potential material for shielding against medical diagnostic X-rays.

14.
Ecotoxicol Environ Saf ; 272: 116004, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38290315

RESUMO

Hepatotoxicity is frequently observed following acute cadmium (Cd) exposure in chicken. Oxidative stress and subsequent inflammation are regarded as the main reasons for cadmium-induced liver injury. NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome-induced pyroptosis is involved in various inflammatory diseases, including liver injury. Poultry are more susceptible to harmful effects of heavy metals. However, the mechanism of cadmium-induced liver injury in chicken is still elusive. In this study, the effect of cadmium on chicken liver cells and the underlying mechanisms were investigated. The results showed mitochondria was damaged and excessive reactive oxygen species (ROS) were generated in chicken liver cell line LMH after cadmium exposure. Furthermore, cadmium-induced NLRP3 inflammasome activation and the cell membrane rupture indicated LMH cells pyroptosis. The ROS scavengers, acetylcysteine (NAC) and Mito-TEMPO prevented pyroptosis in LMH cells, suggesting that ROS were responsible for the activation of the NLRP3 inflammasome induced by cadmium. Additionally, anti-oxidative transcription factor Nrf2 was inhibited after cadmium exposure, explaining the excessive ROS generation. In summary, our study showed that cadmium leads to ROS generation by inducing mitochondrial damage and inhibiting Nrf2 activity, which promotes NLRP3 inflammasome activation and eventually induces pyroptosis in LMH cells.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Piroptose , Cádmio/toxicidade , Galinhas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2 , Inflamação/induzido quimicamente
15.
Front Med ; 18(2): 357-374, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38157193

RESUMO

p53 is mutated in half of cancer cases. However, no p53-targeting drugs have been approved. Here, we reposition decitabine for triple-negative breast cancer (TNBC), a subtype with frequent p53 mutations and extremely poor prognosis. In a retrospective study on tissue microarrays with 132 TNBC cases, DNMT1 overexpression was associated with p53 mutations (P = 0.037) and poor overall survival (OS) (P = 0.010). In a prospective DEciTabinE and Carboplatin in TNBC (DETECT) trial (NCT03295552), decitabine with carboplatin produced an objective response rate (ORR) of 42% in 12 patients with stage IV TNBC. Among the 9 trialed patients with available TP53 sequencing results, the 6 patients with p53 mutations had higher ORR (3/6 vs. 0/3) and better OS (16.0 vs. 4.0 months) than the patients with wild-type p53. In a mechanistic study, isogenic TNBC cell lines harboring DETECT-derived p53 mutations exhibited higher DNMT1 expression and decitabine sensitivity than the cell line with wild-type p53. In the DETECT trial, decitabine induced strong immune responses featuring the striking upregulation of the innate immune player IRF7 in the p53-mutated TNBC cell line (upregulation by 16-fold) and the most responsive patient with TNBC. Our integrative studies reveal the potential of repurposing decitabine for the treatment of p53-mutated TNBC and suggest IRF7 as a potential biomarker for decitabine-based treatments.


Assuntos
Decitabina , Fator Regulador 7 de Interferon , Mutação , Neoplasias de Mama Triplo Negativas , Proteína Supressora de Tumor p53 , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/imunologia , Feminino , Decitabina/uso terapêutico , Decitabina/farmacologia , Proteína Supressora de Tumor p53/genética , Pessoa de Meia-Idade , Estudos Retrospectivos , Fator Regulador 7 de Interferon/genética , Carboplatina/uso terapêutico , Carboplatina/farmacologia , Linhagem Celular Tumoral , Adulto , DNA (Citosina-5-)-Metiltransferase 1/genética , Estudos Prospectivos , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Antimetabólitos Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
16.
Rev. bras. med. esporte ; 30: e2023_0091, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1529921

RESUMO

ABSTRACT Introduction: In ice hockey games, the team's performance is influenced by many contextual factors, and understanding playing styles allows to reveal how key performance indicators vary under different situations. Objective: This research aims to explore the playing styles of elite ice-hockey teams and to identify key performance aspects under different final goal difference situations. Methods: This article analyzed compared the match performance of 31 National Hockey League teams during 1271 matches considering their playing styles and final goal difference. Results: The principal component analysis obtained 8 performance components describing the technical-tactical styles of the teams. The subsequent analysis found that there was significant difference between three match outcomes in unfavorable state, major penalties, puck possession maintaining ability, shot defending ability, aggressive performance (p<0.001; = 0.007-0.273). Conclusions: Higher-ranked teams winning the unbalanced games showed better performance in shot defending ability and aggressive performance. Lower-ranked teams losing in unbalanced games kept less possession of the puck and were more likely to be shorthanded (p<0.05, ES=0.131-1.410). The study demonstrates how playing styles can be used to contextualize key determinants from ice hockey games. Level of evidence I; Therapeutic Studies Investigating the Results of Treatment.


RESUMEN Introducción: En los juegos de hockey sobre hielo, el rendimiento del equipo está influenciado por varios factores contextuales, y comprender los estilos de juego permite revelar cómo varían los indicadores clave de rendimiento en diferentes situaciones. Objetivo: Esta investigación tiene como objetivo explorar los estilos de juego de los equipos de hockey sobre hielo de élite e identificar aspectos clave del rendimiento en diferentes situaciones de diferencia de gol final. Métodos: El rendimiento del partido de 31 equipos de la Liga Nacional de Hockey durante 1271 partidos fue analizado y comparado, considerando el estilo de juego y la diferencia de gol final. Resultados: El análisis de componentes principales obtuvo 8 componentes de rendimiento que describen los estilos técnico-tácticos de los equipos. El análisis posterior encontró que hubo una diferencia significativa entre tres resultados de partido en estado desfavorable, penalizaciones principales, habilidad para mantener la posesión del disco, habilidad para defender el tiro, desempeño agresivo (p<0,001; = 0,007-0,273). Conclusión: Los equipos de clasificación más alta que ganaron los juegos desequilibrados mostraron un mejor rendimiento en la capacidad de defensa de disparos y en el rendimiento agresivo. Los equipos de clasificación más baja que perdieron en juegos desequilibrados mantuvieron menos posesión del disco y tenían más probabilidades de estar en desventaja numérica (p<0,05, ES=0,131-1,410). El estudio demuestra cómo los estilos de juego pueden utilizarse para contextualizar los determinantes clave de los juegos de hockey sobre hielo. Nivel de Evidencia I; Estudios Terapéuticos que Investigan los Resultados del Tratamiento.


RESUMO Introdução: Nos jogos de hóquei no gelo, o desempenho da equipe é influenciado por vários fatores contextuais, e entender os estilos de jogo permite revelar como os principais indicadores de desempenho variam em diferentes situações. Objetivo: Esta pesquisa tem como objetivo explorar os estilos de jogo das equipes de hóquei no gelo de elite e identificar aspectos-chave de desempenho em diferentes estilos de jogo e a diferença do resultado final. Métodos: O desempenho de partida de 31 equipes da National Hockey League durante 1271 partidas foi analisado e comparado, considerando o estilo de jogo e a diferença de gol final. Resultados: A análise de componentes principais retornou 8 componentes de desempenho, descrevendo os estilos técnico-táticos das equipes. A análise subsequente revelou que houve diferença significativa entre três resultados de jogo em estado desfavorável, penalidades principais, habilidade de manter a posse do disco, habilidade de defender o lance e desempenho agressivo (p<0,001; = 0,007-0,273). Conclusão: As equipes de classificação mais alta que venceram os jogos em desequilíbrio numérico de jogadores apresentaram melhor desempenho na habilidade de defender o lance e no desempenho agressivo. As equipes de classificação mais baixa, que perderam em jogos desequilibrados, mantiveram menos posse do disco e tiveram maior probabilidade de ficar com um jogador a menos (p <0,05, ES = 0,131-1,410). O estudo demonstra como os estilos de jogo podem ser usados para contextualizar os principais determinantes dos jogos de hóquei no gelo. Nível de Evidência I; Estudos Terapêuticos Investigação dos Resultados do Tratamento.

17.
J Med Chem ; 66(24): 16579-16596, 2023 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-38069817

RESUMO

Arsenic trioxide (ATO) targets PML/RARα and leads to miraculous success in treating acute promyelocytic leukemia. Notably, ATO also targets p53, the most frequently mutated protein in cancers, through a similar binding mechanism. However, p53-targeting ATO trials are challenging due to the poor cellular uptake and cancer selectivity of ATO. Here, we analyzed the structure-activity relationship of arsenicals and rationally developed a novel arsenical (designated AcGlcAs) by conjugating arsenic to sulfur atoms and tetraacetyl-ß-d-thioglucose. AcGlcAs exhibited remarkable cellular uptake through a thiol-mediated pathway (maximally 127-fold higher than ATO), thereby potently targeting PML/RARα and mutant p53. Among the 55 tested cell lines, AcGlcAs preferentially killed cancer lines rather than normal lines. In preclinical studies, AcGlcAs significantly extended the survival of mice bearing a xenograft tumor with p53 mutation while showing high plasma stability and oral bioavailability. Thus, AcGlcAs is a potential clinical candidate for precisely treating numerous p53-mutated cancers.


Assuntos
Antineoplásicos , Arsenicais , Leucemia Promielocítica Aguda , Humanos , Camundongos , Animais , Proteína Supressora de Tumor p53/metabolismo , Óxidos/farmacologia , Óxidos/metabolismo , Apoptose , Trióxido de Arsênio/farmacologia , Trióxido de Arsênio/metabolismo , Trióxido de Arsênio/uso terapêutico , Arsenicais/farmacologia , Arsenicais/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
18.
Crit Rev Oncol Hematol ; 192: 104192, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37898477

RESUMO

Cancer progression is a dynamic process of continuous evolution, in which genetic diversity and heterogeneity are generated by clonal and subclonal amplification based on random mutations. Traditional cancer treatment strategies have a great challenge, which often leads to treatment failure due to drug resistance. Integrating evolutionary dynamics into treatment regimens may be an effective way to overcome the problem of drug resistance. In particular, a potential treatment is adaptive therapy, which strategy advocates containment strategies that adjust the treatment cycles according to tumor evolution to control the growth of treatment-resistant cells. In this review, we first summarize the shortcomings of traditional tumor treatment methods in evolution and then introduce the theoretical basis and research status of adaptive therapy. By analyzing the limitations of adaptive therapy and exploring possible solutions, we can broaden people's understanding of adaptive therapy and provide new insights and strategies for tumor treatment.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Falha de Tratamento
19.
Nucleic Acids Res ; 51(21): 11549-11567, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-37850662

RESUMO

Parental histone recycling is vital for maintaining chromatin-based epigenetic information during replication, yet its underlying mechanisms remain unclear. Here, we uncover an unexpected role of histone chaperone FACT and its N-terminus of the Spt16 subunit during parental histone recycling and transfer in budding yeast. Depletion of Spt16 and mutations at its middle domain that impair histone binding compromise parental histone recycling on both the leading and lagging strands of DNA replication forks. Intriguingly, deletion of the Spt16-N domain impairs parental histone recycling, with a more pronounced defect observed on the lagging strand. Mechanistically, the Spt16-N domain interacts with the replicative helicase MCM2-7 and facilitates the formation of a ternary complex involving FACT, histone H3/H4 and Mcm2 histone binding domain, critical for the recycling and transfer of parental histones to lagging strands. Lack of the Spt16-N domain weakens the FACT-MCM interaction and reduces parental histone recycling. We propose that the Spt16-N domain acts as a protein-protein interaction module, enabling FACT to function as a shuttle chaperone in collaboration with Mcm2 and potentially other replisome components for efficient local parental histone recycling and inheritance.


Assuntos
Histonas , Proteínas de Saccharomyces cerevisiae , Fatores de Elongação da Transcrição , Cromatina/genética , DNA Helicases/genética , Chaperonas de Histonas/genética , Chaperonas de Histonas/metabolismo , Histonas/metabolismo , Chaperonas Moleculares/genética , Nucleossomos/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Fatores de Elongação da Transcrição/metabolismo , Complexos Multiproteicos/metabolismo
20.
Biomol Ther (Seoul) ; 31(5): 496-514, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37641880

RESUMO

Cold atmospheric plasma (CAP), a redox modulation tool, is capable of inhibiting a wide spectrum of cancers and has thus been proposed as an emerging onco-therapy. However, with incremental successes consecutively reported on the anticancer efficacy of CAP, no consensus has been made on the types of tumours sensitive to CAP due to the different intrinsic characteristics of the cells and the heterogeneous design of CAP devices and their parameter configurations. These factors have substantially hindered the clinical use of CAP as an oncotherapy. It is thus imperative to clarify the tumour types responsive to CAP, the experimental models available for CAP-associated investigations, CAP administration strategies and the mechanisms by which CAP exerts its anticancer effects with the aim of identifying important yet less studied areas to accelerate the process of translating CAP into clinical use and fostering the field of plasma oncology.

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