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1.
Clin Oral Investig ; 28(7): 368, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38862733

RESUMO

OBJECTIVES: The aims of this clinical study were to investigate success rate, vital pulp survival rate, tooth survival rate and patient-reported masticatory ability by evaluating the pain symptoms and signs of the cracked teeth as well as Index of Eating Difficulty (IED) and Oral Health Impact Profile-14 (OHIP-14) questionnaire after cracked teeth were restored with occlusal veneers. MATERIALS AND METHODS: 27 cracked teeth of 24 patients with cold and/or biting pains without spontaneous/nocturnal pains were recruited in this study. The cracked teeth were restored with occlusal veneers fabricated by lithium disilicate ceramic. Cold test and biting test were used to evaluate pain signs. IED and OHIP-14 questionnaire were used to evaluate masticatory ability. FDI criteria was used to evaluate restorations. The paired Wilcoxon test was used to analyze significant differences of detection rate of pain signs, OHIP scores and IED grade before and after restorations. Kaplan-Meier survival curve was used to describe the success rate, vital pulp survival rate, and tooth survival rate. RESULTS: 27 cracked teeth were restored with occlusal veneers with average of 22.4-month follow-up. Two cracked teeth had pulpitis and pain signs of the other cracked teeth completely disappeared. OHIP total scores were significantly reduced after treatment. Scores of 'pain', 'occlusal discomfort', 'uncomfortable to eat', 'diet unsatisfactory' and 'interrupted meals' reduced significantly after treatment. After treatment, IED grades of 25 vital teeth were significantly lower than those before treatment. FDI scores of 25 restorations except for 2 teeth with pulpitis were no greater than 2. The 12 months accumulated pulp survival rate of the cracked teeth was 92.6%. The 12 months accumulated tooth survival rate was 100%. The success rate at the latest recall was 92.6%. CONCLUSION: Occlusal veneer restorations with success rate of 92.6% and the same pulp survival rate might be an effective restoration for treating the cracked teeth. CLINICAL RELEVANCE: The occlusal veneer restorations might be an option for treating the cracked teeth when cracks only involve enamel and dentin, not dental pulp.


Assuntos
Síndrome de Dente Quebrado , Facetas Dentárias , Humanos , Feminino , Masculino , Adulto , Seguimentos , Síndrome de Dente Quebrado/terapia , Resultado do Tratamento , Inquéritos e Questionários , Pessoa de Meia-Idade , Medição da Dor , Porcelana Dentária , Restauração Dentária Permanente/métodos , Mastigação/fisiologia
2.
Acc Chem Res ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833580

RESUMO

ConspectusOver the past two decades, we have developed a series of pincer-type transition metal complexes capable of activating strong covalent bonds through a mode of reactivity known as metal-ligand cooperation (MLC). In such systems, an incoming substrate molecule simultaneously interacts with both the metal center and ligand backbone, with one part of the molecule reacting at the metal center and another part at the ligand. The majority of these complexes feature pincer ligands with a pyridine core, and undergo MLC through reversible dearomatization/aromatization of this pyridine moiety. This MLC platform has enabled us to perform a variety of catalytic dehydrogenation, hydrogenation, and related reactions, with high efficiency and selectivity under relatively mild conditions.In a typical catalytic complex that operates through MLC, the cooperative ligand remains coordinated to the metal center throughout the entire catalytic process, and this complex is the only catalytic species involved in the reaction. As part of our ongoing efforts to develop new catalytic systems featuring MLC, we have recently introduced the concept of transient cooperative ligand (TCL), i.e., a ligand that is capable of MLC when coordinated to a metal center, but the coordination of which is reversible rather than permanent. We have thus far employed thiol(ate)s as TCLs, in conjunction with an acridanide-based ruthenium(II)-pincer catalyst, and this has resulted in remarkable acceleration and inhibition effects in various hydrogenation and dehydrogenation reactions. A cooperative thiol(ate) ligand can be installed in situ by the simple addition of an appropriate thiol in an amount equivalent to the catalyst, and this has been repeatedly shown to enable efficient bond activation by MLC without the need for other additives, such as base. The use of an ancillary thiol ligand that is not fixed to the pincer backbone allows the catalytic system to benefit from a high degree of tunability, easily implemented by varying the added thiol. Importantly, thiols are coordinatively labile enough under typical catalytic conditions to leave a meaningful portion of the catalyst in its original unsaturated form, thereby allowing it to carry out its own characteristic catalytic activity. This generates two coexisting catalyst populations─one that contains a thiol(ate) ligand and another that does not─and this may lead to different catalytic outcomes, namely, enhancement of the original catalytic activity, inhibition of this activity, or the occurrence of diverging reactivities within the same catalytic reaction mixture. These thiol effects have enabled us to achieve a series of unique transformations, such as thiol-accelerated base-free aqueous methanol reforming, controlled stereodivergent semihydrogenation of alkynes using thiol as a reversible catalyst inhibitor, and hydrogenative perdeuteration of C═C bonds without using D2, enabled by a combination of thiol-induced acceleration and inhibition. We have also successfully realized the unprecedented formation of thioesters through dehydrogenative coupling of alcohols and thiols, as well as the hydrogenation of organosulfur compounds, wherein the cooperative thiol serves as a reactant or product. In this Account, we present an overview of the TCL concept and its various applications using thiols.

3.
Poult Sci ; 103(8): 103789, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38833740

RESUMO

This study aimed to improve the eating quality of yellow-feathered broiler chicks by feeding them corn-soybean meal diets supplemented with 250, 500, and 1,000 mg/kg quercetin. we examined the impact of varying doses of dietary quercetin on the sensory quality of chicken breast meat as well as on the antioxidant enzymes, antioxidant-related signaling molecules, structure and thermal stability of myofibrillar protein (MPs), and microstructure of myogenic fibers in the meat during 24 h of postslaughter aging. Additionally, we investigated the potential correlations among antioxidant capacity, MP structure, and meat quality parameters. The results indicated that dietary supplementations with 500 and 1,000 mg/kg quercetin improved the physicochemical properties and eating quality of yellow-feathered broiler chicken breast meat during 12 to 24 h postslaughter. Additionally, quercetin improved the postslaughter oxidative stress status and reduced protein and lipid oxidation levels. It also increased hydrogen bonding interactions and α-helix content during 6 to 12 h postslaughter and decreased ß-sheet content during 12 to 24 h postslaughter in chicken breast MP. This resulted in improved postslaughter MP structure and thermal stability. The correlation results indicated that the enhancement of antioxidant capacity and MP structure enhanced the physicochemical and edible qualities of yellow-feathered broiler chicken breast meat. In conclusion, the current findings suggest that dietary supplementation with quercetin is an ideal approach for improving the eating quality of chicken meat, thereby broadening our understanding of theoretical and technological applications for improving the quality of chicken.

4.
J Dairy Sci ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38825138

RESUMO

Products of lipolysis released during digestion positively affect the metabolism of newborns. In contrast to the 3-layer biological membranes covering human milk (HM) fat, the lipid droplets in infant milk formula (IMF) are covered by a single membrane composed of casein and whey proteins. To reduce the differences in lipid structure between IMF and HM, studies have used milk fat globule membrane (MFGM) components such as milk polar lipids (MPL) to prepare emulsions mimicking HM fat globules However, few studies have elucidated the effect of membrane proteins (MP) on lipid digestion in infants. In this study, 3 kinds of emulsions were prepared: One with MPL as the interfaced of lipid droplets (RE-1), one with membrane protein concentrate (MPC) (RE-2) as the interface of lipid droplets, and one with both MPL and MPC (1:2) as the co-interface of lipid droplets (RE-3). The interfacial coverage of the emulsions was confirmed by measuring the contents of MPL and MPC at the lipid droplet interface, and by confocal laser scanning microscopy analyzed. By controlling the homogenization intensity, the specific surface area of lipid droplets was controlled at the same level among the 3 emulsions. The stability constants of the emulsions varied, and RE-1 was the most stable. During simulated in vitro infant gastrointestinal digestion, the amount of free fatty acids (FFA) released from the lipid droplets was significantly higher from those with MPC at the interface (RE-2, RE-3) than from that with MPL at the interface (RE-1). The amount of FFA released at the end of intestinal digestion of RE-1, RE-2, and RE-3 was 255.00 ± 3.54 µmol,328.75 ± 5.30 µmol, 298.50 ± 9.19 µmol, respectively. Compared with the lipid droplets in RE-2, those with MPL at the interface (RE-1, RE-3) released more unsaturated fatty acids (USFAs) during digestion. The emulsifying activity index was highest in RE-3 (MPL and MPC co-interface). The presence of MPL at the emulsion interface increased the release of USFAs, while the presence of MPC increased the release of FFA. These results show that both MPL and MP are indispensable in the construction of MFGM. Understanding their effects on digestion can provide new strategies for the development of infant foods.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38843077

RESUMO

OBJECTIVES: To evaluate the association between psychosocial stress (PS) trajectories and pubertal outcomes of girls and boys in a Chinese cohort (2015-2022). METHODS: Pubertal outcomes of 732 girls and 688 boys were physically examined every 6 months. Stressful life events were repeatedly assessed 7 times. Group-Based Trajectory Model was fitted for the optimum trajectories of total PS and PS from 5 sources. Cox model adjusted for age, BMI and socioeconomic factors was used to evaluate the association. RESULTS: Compared to the "low, gradual decline" trajectory, the "moderate, gradual decline" trajectory of total PS was associated with late menarche (HR: 0.816, 95% CI: 0.677-0.983), late pubic hair development (HR: 0.729, 95% CI: 0.609-0.872) and late axillary hair development (HR: 0.803, 95% CI: 0.661 - 0.975) in girls. Girls following the "high, rise then decline" trajectory of PS from family life demonstrated delayed axillary hair development (HR: 0.752, 95% CI: (0.571-0.990). As for boys, the "high, rise then decline" trajectory of PS from academic adaptation (HR: 0.670, 95% CI: 0.476 - 0.945) and life adaptation (HR: 0.642, 95% CI: 0.445 - 0.925) was associated with late axillary hair development. Boys in the "moderate, gradual decline" trajectory of PS from peer relationship was at risk of early testicular development (HR: 1.353, 95% CI: 1.108 - 1.653). CONCLUSIONS: Chronic PS may be associated with delayed onset of several pubertal signs in both girls and boys. It may also accelerate testicular development of boys, indicating its varying impact on pubertal timing during early and later stages.

6.
Sci Rep ; 14(1): 12990, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844779

RESUMO

The main purpose of this article is to investigate the qualitative behavior and traveling wave solutions of the fractional stochastic Kraenkel-Manna-Merle equations, which is commonly used to simulate the zero conductivity nonlinear propagation behavior of short waves in saturated ferromagnetic materials. Firstly, fractional stochastic Kraenkel-Manna-Merle equations are transformed into ordinary differential equations by using the traveling wave transformation. Secondly, the phase portraits, sensitivity analysis, and Poincaré sections of the two-dimensional dynamic system and its perturbation system of ordinary differential equations are drawn. Finally, the traveling wave solutions of fractional stochastic Kraenkel-Manna-Merle equations are obtained based on the analysis theory of planar dynamical system. Moreover, the obtained three-dimensional graphs of random solutions, two-dimensional graphs of random solutions, and three-dimensional graphs of deterministic solutions are drawn.

7.
Eur J Med Res ; 29(1): 323, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867262

RESUMO

BACKGROUND: Abdominal aortic aneurysm (AAA) is a highly lethal cardiovascular disease. The aim of this research is to identify new biomarkers and therapeutic targets for the treatment of such deadly diseases. METHODS: Single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithms were used to identify distinct immune cell infiltration types between AAA and normal abdominal aortas. Single-cell RNA sequencing data were used to analyse the hallmark genes of AAA-associated macrophage cell subsets. Six macrophage-related hub genes were identified through weighted gene co-expression network analysis (WGCNA) and validated for expression in clinical samples and AAA mouse models. We screened potential therapeutic drugs for AAA through online Connectivity Map databases (CMap). A network-based approach was used to explore the relationships between the candidate genes and transcription factors (TFs), lncRNAs, and miRNAs. Additionally, we also identified hub genes that can effectively identify AAA and atherosclerosis (AS) through a variety of machine learning algorithms. RESULTS: We obtained six macrophage hub genes (IL-1B, CXCL1, SOCS3, SLC2A3, G0S2, and CCL3) that can effectively diagnose abdominal aortic aneurysm. The ROC curves and decision curve analysis (DCA) were combined to further confirm the good diagnostic efficacy of the hub genes. Further analysis revealed that the expression of the six hub genes mentioned above was significantly increased in AAA patients and mice. We also constructed TF regulatory networks and competing endogenous RNA networks (ceRNA) to reveal potential mechanisms of disease occurrence. We also obtained two key genes (ZNF652 and UBR5) through a variety of machine learning algorithms, which can effectively distinguish abdominal aortic aneurysm and atherosclerosis. CONCLUSION: Our findings depict the molecular pharmaceutical network in AAA, providing new ideas for effective diagnosis and treatment of diseases.


Assuntos
Aneurisma da Aorta Abdominal , Perfilação da Expressão Gênica , Macrófagos , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/diagnóstico , Humanos , Animais , Macrófagos/metabolismo , Camundongos , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Modelos Animais de Doenças , Transcriptoma , Biomarcadores/metabolismo
8.
J Lipid Res ; : 100579, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880128

RESUMO

Sterol-regulatory element binding proteins (SREBPs) are a conserved transcription factor family governing lipid metabolism. When cellular cholesterol level is low, SREBP2 is transported from the endoplasmic reticulum to the Golgi apparatus where it undergoes proteolytic activation to generate a soluble N-terminal fragment, which drives the expression of lipid biosynthetic genes. Malfunctional SREBP activation is associated with various metabolic abnormalities. In this study, we find that overexpression of the active nuclear form SREBP2 (nSREBP2) causes caspase-dependent lytic cell death in various types of cells. These cells display typical pyroptotic and necrotic signatures, including plasma membrane ballooning and release of cellular contents. However, this phenotype is independent of the gasdermin family proteins or mixed lineage kinase domain-like (MLKL). Transcriptomic analysis identifies that nSREBP2 induces expression of p73, which further activates caspases. Through whole-genome CRISPR-Cas9 screening, we find that Pannexin-1 (PANX1) acts downstream of caspases to promote membrane rupture. Caspase-3 or 7 cleaves PANX1 at the C-terminal tail and increases permeability. Inhibition of pore-forming activity of PANX1 alleviates lytic cell death. PANX1 can mediate gasdermins and MLKL-independent cell lysis during TNF-induced or chemotherapeutic reagents (doxorubicin or cisplatin)-induced cell death. Together, this study uncovers a noncanonical function of SREBPs as a potentiator of programmed cell death and suggests that PANX1 can directly promote lytic cell death independent of gasdermins and MLKL.

9.
PLoS One ; 19(6): e0304689, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38875285

RESUMO

To explore cost-effective and efficient phytoremediation strategies, this study investigated the distinct roles of earthworm activity and mucus in enhancing Cd phytoextraction from soils contaminated by Festuca arundinacea, focusing on the comparative advantages of selective leaf harvesting versus traditional whole-plant harvesting methods. Our study employed a horticultural trial to explore how earthworm activity and mucus affect Festuca arundinacea' s Cd phytoremediation in soils using control, earthworm, and mucus treatments to examine their respective effects on plant growth and Cd distribution. Earthworm activity increased the dry weight of leaves by 13.5% and significantly increased the dry weights of declining and senescent leaves, surpassing that of the control by more than 40%. Earthworm mucus had a similar, albeit less pronounced, effect on plant growth than earthworm activity. This study not only validated the significant role of earthworm activity in enhancing Cd phytoextraction by Festuca arundinacea, with earthworm activity leading to over 85% of Cd being allocated to senescent tissues that comprise only approximately 20% of the plant biomass, but also highlighted a sustainable and cost-effective approach to phytoremediation by emphasizing selective leaf harvesting supported by earthworm activity. By demonstrating that earthworm mucus alone can redistribute Cd with less efficiency compared to live earthworms, our findings offer practical insights into optimizing phytoremediation strategies and underscore the need for further research into the synergistic effects of biological agents in soil remediation processes.


Assuntos
Biodegradação Ambiental , Cádmio , Festuca , Muco , Oligoquetos , Folhas de Planta , Poluentes do Solo , Animais , Oligoquetos/metabolismo , Oligoquetos/fisiologia , Cádmio/metabolismo , Folhas de Planta/metabolismo , Festuca/metabolismo , Poluentes do Solo/metabolismo , Muco/metabolismo , Biomassa , Solo/química
10.
Transl Psychiatry ; 14(1): 251, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858375

RESUMO

This research aimed to devise and assess a mobile game therapy software for children with Attention-Deficit/Hyperactivity Disorder (ADHD), as well as evaluating its suitability and effectiveness in improving the cognitive ability of typically developing children. The study encompassed 55 children diagnosed with ADHD and 55 neurotypical children. Initial assessments involved ADHD-related scales, computerized tests for information processing, and physiological-psychological evaluations. After a 4-week home-based game intervention, participants underwent re-evaluation using baseline measures and provided feedback on treatment satisfaction. Considering the small proportion of study participants who dropped out, data was analyzed using both the Intention-to-Treat (ITT) analysis and the Per-protocol (PP) analysis. The trial was registered at ClinicalTrials.gov (NCT06181747). In ITT analysis, post-intervention analysis using linear mixed models indicated that the ADHD group improved significantly more than the neurotypical group particularly in Continuous Performance Test (CPT) accuracy (B = -23.92, p < 0.001) and reaction time (B = 86.08, p < 0.01), along with enhancements in anti-saccade (B = -10.65, p < 0.05) and delayed-saccade tasks (B = 0.34, p < 0.05). A reduction in parent-rated SNAP-IV scores was also observed (B = 0.43, p < 0.01). In PP analysis, paired-sample t-tests suggested that the ADHD group had significant changes pre- and post-intervention, in terms of CPT Accuracy (t = -7.62, p < 0.01), Anti-saccade task Correct Rate (t = -3.90, p < 0.01) and SNAP-IV scores (t = -4,64, p < 0.01). However, no significant changes post-intervention were observed in the neurotypical group. Survey feedback highlighted a strong interest in the games across both groups, though ADHD participants found the game more challenging. Parents of ADHD children reported perceived benefits and a willingness to continue the game therapy, unlike the neurotypical group's parents. The findings advocated for the integration of serious video games as a complementary tool in ADHD treatment strategies, demonstrating the potential to augment attentional abilities and alleviate clinical symptoms. However, a randomized controlled trial (RCT) is needed to further verify its efficacy.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estudos de Viabilidade , Jogos de Vídeo , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Criança , Masculino , Feminino , Aplicativos Móveis , Resultado do Tratamento
11.
Plant Cell Environ ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712996

RESUMO

For trees originating from boreal and temperate regions, the dormancy-to-active transition, also known as bud dormancy release and bud break, are crucial processes that allow trees to reactive growth in the spring. The molecular mechanisms underlying these two processes remain poorly understood. Here, through integrative multiomics analysis of the transcriptome, DNA methylome, and proteome, we gained insights into the reprogrammed cellular processes associated with bud dormancy release and bud break. Our findings revealed multilayer regulatory landscapes governing bud dormancy release and bud break regulation, providing a valuable reference framework for future functional studies. Based on the multiomics analysis, we have determined a novel long intergenic noncoding RNA named Phenology Responsive Intergenic lncRNA 1 (PRIR1) plays a role in the activation of bud break. that the molecular mechanism of PRIR1 has been preliminary explored, and it may partially promote bud break by activating its neighbouring gene, EXORDIUM LIKE 5 (PtEXL5), which has also been genetically confirmed as an activator for bud break. This study has revealed a lncRNA-mediated regulatory mechanism for the control of bud break in Populus, operating independently of known regulatory pathways.

12.
Technol Cancer Res Treat ; 23: 15330338241252423, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38752261

RESUMO

OBJECTIVES: Circular RNAs (circRNAs) serve a crucial regulatory role in ovarian cancer (OC). Circular RNA ArfGAP with FG repeats 1 (circAGFG1) has been shown to be involved in promoting the progression of several cancers, containing triple-negative breast cancer, esophageal cancer and colorectal cancer. However, the function of circAGFG1 in OC is unclear. METHODS: Quantitative real-time reverse transcription PCR (RT-qPCR) was conducted to determine the expression levels of circAGFG1 and miR-409-3p. The proliferation and metastasis of cells were determined by colony formation assays, EdU assays, transwell assays and wound healing assays. In addition, a dual-luciferase reporter assay was performed to validate the mechanism between circAGFG1, miR-409-3p, and ZEB1. RESULTS: Our data suggested that circAGFG1 was significantly overexpressed in OC tissues compared to normal ovarian epithelial tissues. Overexpression of circAGFG1 was correlated with intraperitoneal metastasis, tumor recurrence and advanced stage. Additionally, circAGFG1 overexpression revealed a poor prognosis in OC patients. Knockdown of circAGFG1 suppressed the proliferation, invasion and migration of OC cells. Mechanistically, circAGFG1 acted as a sponge of miR-409-3p to enhance the expression level of zinc finger E-box binding homeobox 1 (ZEB1), thereby conferring OC cell proliferation, invasion and migration. Importantly, re-expression of ZEB1 effectively reversed the effects of circAGFG1 knockdown on OC cells. CONCLUSIONS: In summary, our study indicated that circAGFG1 may act as a prognostic biomarker and potential therapeutic target for patients with OC.


Assuntos
Movimento Celular , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Neoplasias Ovarianas , RNA Circular , Homeobox 1 de Ligação a E-box em Dedo de Zinco , Humanos , Feminino , MicroRNAs/genética , RNA Circular/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/mortalidade , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Prognóstico , Camundongos , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Transição Epitelial-Mesenquimal/genética
13.
Technol Cancer Res Treat ; 23: 15330338241248576, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38693824

RESUMO

Background: Acute myeloid leukemia (AML) is a type of blood cancer characterized by excessive growth of immature myeloid cells. Unfortunately, the prognosis of pediatric AML remains unfavorable. It is imperative to further our understanding of the mechanisms underlying leukemogenesis and explore innovative therapeutic approaches to enhance overall disease outcomes for patients with this condition. Methods: Quantitative reverse-transcription PCR was used to quantify the expression levels of microRNA (miR)-133a and miR-135a in 68 samples from 59 pediatric patients with AML. Dual-luciferase reporter transfection assay, Cell Counting Kit-8 assay, and western blot analysis were used to investigate the functions of miR-133a and miR-135a. Results: Our study found that all-trans-retinoic acid (ATRA) promoted the expression of miR-133a and miR-135a in AML cells, inhibited caudal type homeobox 2 (CDX2) expression, and subsequently inhibited the proliferation of AML cells. Additionally, miR-133a and miR-135a were highly expressed in patients with complete remission and those with better survival. Conclusions: miR-133a and miR-135a may play an antioncogenic role in pediatric AML through the ATRA-miRNA133a/135a-CDX2 pathway. They hold promise as potentially favorable prognostic indicators and novel therapeutic targets for pediatric AML.


Assuntos
Biomarcadores Tumorais , Leucemia Mieloide Aguda , MicroRNAs , Tretinoína , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Biomarcadores Tumorais/genética , Diferenciação Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/metabolismo , MicroRNAs/genética , Prognóstico , Tretinoína/farmacologia , Tretinoína/uso terapêutico
14.
Oncol Lett ; 28(1): 311, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38784604

RESUMO

[This retracts the article DOI: 10.3892/ol.2022.13268.].

15.
Mol Psychiatry ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724566

RESUMO

Psychiatric disorders are highly heritable yet polygenic, potentially involving hundreds of risk genes. Genome-wide association studies have identified hundreds of genomic susceptibility loci with susceptibility to psychiatric disorders; however, the contribution of these loci to the underlying psychopathology and etiology remains elusive. Here we generated deep human brain proteomics data by quantifying 11,608 proteins across 268 subjects using 11-plex tandem mass tag coupled with two-dimensional liquid chromatography-tandem mass spectrometry. Our analysis revealed 788 cis-acting protein quantitative trait loci associated with the expression of 883 proteins at a genome-wide false discovery rate <5%. In contrast to expression at the transcript level and complex diseases that are found to be mainly influenced by noncoding variants, we found protein expression level tends to be regulated by non-synonymous variants. We also provided evidence of 76 shared regulatory signals between gene expression and protein abundance. Mediation analysis revealed that for most (88%) of the colocalized genes, the expression levels of their corresponding proteins are regulated by cis-pQTLs via gene transcription. Using summary data-based Mendelian randomization analysis, we identified 4 proteins and 19 genes that are causally associated with schizophrenia. We further integrated multiple omics data with network analysis to prioritize candidate genes for schizophrenia risk loci. Collectively, our findings underscore the potential of proteome-wide linkage analysis in gaining mechanistic insights into the pathogenesis of psychiatric disorders.

16.
Foods ; 13(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38731730

RESUMO

This study aimed to investigate the changes in proteins and volatile flavor compounds that occur in bacon during low-temperature smoking (LTS) and identify potential correlations between these changes. To achieve this, a combination of gas chromatography-mass spectrometry and proteomics was employed. A total of 42 volatile flavor compounds were identified in the bacon samples, and, during LTS, 11 key volatile flavor compounds with variable importance were found at a projection value of >1, including 2',4'-dihydroxyacetophenone, 4-methyl-2H-furan-5-one, Nonanal, etc. In total, 2017 proteins were quantified at different stages of LTS; correlation coefficients and KEGG analyses identified 27 down-regulated flavor-related proteins. Of these, seven were involved in the tricarboxylic acid (TCA) cycle, metabolic pathways, or amino acid metabolism, and they may be associated with the process of flavor formation. Furthermore, correlation coefficient analysis indicated that certain chemical parameters, such as the contents of free amino acids, carbonyl compounds, and TCA cycle components, were closely and positively correlated with the formation of key volatile flavor compounds. Combined with bioinformatic analysis, the results of this study provide insights into the proteins present in bacon at various stages of LTS. This study demonstrates the changes in proteins and the formation of volatile flavor compounds in bacon during LTS, along with their potential correlations, providing a theoretical basis for the development of green processing methods for Hunan bacon.

17.
FASEB J ; 38(11): e23681, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38814725

RESUMO

Ischemia-reperfusion (IR) injury is primarily characterized by the restoration of blood flow perfusion and oxygen supply to ischemic tissue and organs, but it paradoxically leads to tissue injury aggravation. IR injury is a challenging pathophysiological process that is difficult to avoid clinically and frequently occurs during organ transplantation, surgery, shock resuscitation, and other processes. The major causes of IR injury include increased levels of free radicals, calcium overload, oxidative stress, and excessive inflammatory response. Ghrelin is a newly discovered brain-intestinal peptide with anti-inflammatory and antiapoptotic effects that improve blood supply. The role and mechanism of ghrelin in intestinal ischemia-reperfusion (IIR) injury remain unclear. We hypothesized that ghrelin could attenuate IIR-induced oxidative stress and apoptosis. To investigate this, we established IIR by using a non-invasive arterial clip to clamp the root of the superior mesenteric artery (SMA) in mice. Ghrelin was injected intraperitoneally at a dose of 50 µg/kg 20 min before IIR surgery, and [D-Lys3]-GHRP-6 was injected intraperitoneally at a dose of 12 nmol/kg 20 min before ghrelin injection. We mimicked the IIR process with hypoxia-reoxygenation (HR) in Caco-2 cells, which are similar to intestinal epithelial cells in structure and biochemistry. Our results showed that ghrelin inhibited IIR/HR-induced oxidative stress and apoptosis by activating GHSR-1α. Moreover, it was found that ghrelin activated the GHSR-1α/Sirt1/FOXO1 signaling pathway. We further inhibited Sirt1 and found that Sirt1 was critical for ghrelin-mediated mitigation of IIR/HR injury. Overall, our data suggest that pretreatment with ghrelin reduces oxidative stress and apoptosis to attenuate IIR/HR injury by binding with GHSR-1α to further activate Sirt1.


Assuntos
Apoptose , Proteína Forkhead Box O1 , Grelina , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Receptores de Grelina , Traumatismo por Reperfusão , Sirtuína 1 , Grelina/farmacologia , Grelina/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Sirtuína 1/metabolismo , Animais , Camundongos , Receptores de Grelina/metabolismo , Humanos , Masculino , Proteína Forkhead Box O1/metabolismo , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Células CACO-2
18.
Cancer Control ; 31: 10732748241255212, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38769789

RESUMO

OBJECTIVE: A high number of Non-Small Cell Lung Cancer (NSCLC) patients with brain metastasis who have not had surgery often have a negative outlook. Radiotherapy remains a most common and effective method. Nomograms were developed to forecast the cancer-specific survival (CSS) and overall survival (OS) in NSCLC individuals with nonoperative brain metastases who underwent radiotherapy. METHODS: Information was gathered from the Surveillance, Epidemiology, and End Results (SEER) database about patients diagnosed with NSCLC who had brain metastases not suitable for surgery. Nomograms were created and tested using multivariate Cox regression models to forecast CSS and OS at intervals of 1, 2, and 3 years. RESULTS: The research involved 3413 individuals diagnosed with NSCLC brain metastases who had undergone radiotherapy but had not experienced surgery. These participants were randomly divided into two categories. The analysis revealed that gender, age, ethnicity, marital status, tumor location, tumor laterality, tumor grade, histology, T stage, N stage, chemotherapy, tumor size, lung metastasis, bone metastasis, and liver metastasis were significant independent predictors for OS and CSS. The C-index for the training set for predicting OS was .709 (95% CI, .697-.721), and for the validation set, it was .705 (95% CI, .686-.723), respectively. The C-index for predicting CSS was .710 (95% CI, .697-.722) in the training set and .703 (95% CI, .684-.722) in the validation set, respectively. The nomograms model, as suggested by the impressive C-index, exhibits outstanding differentiation ability. Moreover, the ROC and calibration curves reveal its commendable precision and distinguishing potential. CONCLUSIONS: For the first time, highly accurate and reliable nomograms were developed to predict OS and CSS in NSCLC patients with non-surgical brain metastases, who have undergone radiotherapy treatment. The nomograms may assist in tailoring counseling strategies and choosing the most effective treatment method.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nomogramas , Programa de SEER , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Masculino , Feminino , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/mortalidade , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Idoso , Prognóstico , Adulto
19.
Molecules ; 29(10)2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38792239

RESUMO

The amorphous form of poorly soluble drugs is physically unstable and prone to crystallization, resulting in decreased solubility and bioavailability. However, the conventional accelerated stability test for amorphous drugs is time-consuming and inaccurate. Therefore, there is an urgent need to develop rapid and accurate stability assessment technology. This study used the antitumor drug nilotinib free base as a model drug. The degree of disorder and physical stability in the amorphous form was assessed by applying the pair distribution function (PDF) and principal component analysis (PCA) methods based on powder X-ray diffraction (PXRD) data. Specifically, the assessment conditions, such as the PDF interatomic distance range, PXRD detector type, and PXRD diffraction angle range were also optimized. The results showed that more reliable PCA data could be obtained when the PDF interatomic distance range was 0-15 Å. When the PXRD detector was a semiconductor-type detector, the PDF data obtained were more accurate than other detectors. When the PXRD diffraction angle range was 5-40°, the intermolecular arrangement of the amorphous drugs could be accurately predicted. Finally, the accelerated stability test also showed that under the above-optimized conditions, this method could accurately and rapidly assess the degree of disorder and physical stability in the amorphous form of drugs, which has obvious advantages compared with the accelerated stability test.

20.
Biochem Pharmacol ; 225: 116271, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38723722

RESUMO

Cardiac fibrosis is characterized by abnormal proliferation of cardiac fibroblasts (CFs) and ventricular remodeling, which finally leads to heart failure. Inflammation and oxidative stress play a central role in the development of cardiac fibrosis. CyPA (Cyclophilin A) is a main proinflammatory cytokine secreted under the conditions of oxidative stress. The mechanisms by which intracellular and extracellular CyPA interact with CFs are unclear. Male C57BL/6 J mice received angiotensin Ⅱ (Ang Ⅱ) or vehicle for 4 weeks. Inhibition of CyPA significantly reversed Ang Ⅱ-induced cardiac hypertrophy and fibrosis. Mechanically, TGF-ß (Transforming growth factor-ß) signaling was found to be an indispensable downstream factor of CyPA-mediated myofibroblast differentiation and proliferation. Furthermore, intracellular CyPA and extracellular CyPA activate TGF-ß signaling through NOD-like receptor protein 3 (NLRP3) inflammasome and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, respectively. Pharmacological inhibition of CyPA and its receptor CD147 implemented by Triptolide also attenuated the expression of TGF-ß signaling and cardiac fibrosis in Ang Ⅱ-model. These studies elucidate a novel mechanism by which CyPA promotes TGF-ß and its downstream signaling in CFs and identify CyPA (both intracellular and extracellular) as plausible therapeutic targets for preventing or treating cardiac fibrosis induced by chronic Ang Ⅱ stimulation.


Assuntos
Angiotensina II , Ciclofilina A , Fibrose , Camundongos Endogâmicos C57BL , Transdução de Sinais , Fator de Crescimento Transformador beta , Animais , Angiotensina II/toxicidade , Angiotensina II/farmacologia , Masculino , Fibrose/metabolismo , Camundongos , Ciclofilina A/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Miocárdio/metabolismo , Miocárdio/patologia
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