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1.
Food Chem ; 463(Pt 4): 141455, 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39362094

RESUMEN

This study focused on unlocking the potential of Jinhua ham-derived peptides (JHP) for enhancing saltiness. JHP (<3 kDa) was obtained through ultrafiltration and desalting, reducing the salt content by 96 %. Four peptide fractions (JHP-P1/P2/P3/P4) were isolated using Sephadex G-25 gel filtration and anion-exchange chromatography. Sensory evaluation and electronic tongue analysis revealed that JHP-P2 (0.5 mg/mL) exhibited the highest saltiness which could replace four-fold NaCl salinity. Three peptides (DL, FMSALF, and HVRRK) identified by UPLC-QTOF-MS/MS were simulated with salty taste receptors ENaC/TMC4. Results indicated that Ser84 and Phe89 of ENaC and Asn404 and Lys567 of TMC4 are crucial for peptide docking related to salty taste. Molecular dynamics simulations showed that the three peptides bind to the TMC4 and ENaC through van der Waals forces, electrostatic interactions, and hydrogen bonds. These findings establish a robust theoretical foundation for salt reduction strategies and provide novel insights into the potential applications of Jinhua ham.

2.
Front Plant Sci ; 15: 1439747, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39363917

RESUMEN

Drought stress inhibits oat growth and yield. The application of fulvic acid (FA) can improve the drought resistance of oats, but the corresponding molecular mechanism of FA-mediated drought resistance remains unclear. Here, we studied the effects of FA on the drought tolerance of oat leaves through physiological, transcriptomic, and metabolomics analyses, and identified FA-induced genes and metabolites related to drought tolerance. Physiological analysis showed that under drought stress, FA increased the relative water and chlorophyll contents of oat leaves, enhanced the activity of antioxidant enzymes (SOD, POD, PAL, CAT and 4CL), inhibited the accumulation of malondialdehyde (MDA), hydrogen peroxide (H2O2) and dehydroascorbic acid (DHA), reduced the degree of oxidative damage in oat leaves, improved the drought resistance of oats, and promoted the growth of oat plants. Transcriptome and metabolite analyses revealed 652 differentially expressed genes (DEGs) and 571 differentially expressed metabolites (DEMs) in FA-treated oat leaves under drought stress. These DEGs and DEMs are involved in a variety of biological processes, such as phenylspropanoid biosynthesis and glutathione metabolism pathways. Additionally, FA may be involved in regulating the role of DEGs and DEMs in phenylpropanoid biosynthesis and glutathione metabolism under drought stress. In conclusion, our results suggest that FA promotes oat growth under drought stress by attenuating membrane lipid peroxidation and regulating the antioxidant system, phenylpropanoid biosynthesis, and glutathione metabolism pathways in oat leaves. This study provides new insights into the complex mechanisms by which FA improves drought tolerance in crops.

3.
Biodivers Data J ; 12: e133971, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39399759

RESUMEN

Background: According to the Species Catalogue of China, Tibet, China, has more than 1,000 species of bryophytes, showing its remarkably high biodiversity. Amongst them, the Polytrichaceae is one of the largest family, with six genera and 25 species, one subspecies and two varieties reported previously. New information: Based on a field survey and specimen identification, the following species have been newly recorded in the bryoflora of Tibet, namely Oligotrichumobtusatum Broth., Pogonatumcontortum (Menzies ex Brid.) Lesq. and Polytrichumsphaerothecium (Besch.) Müll. Hal.

4.
J Agric Food Chem ; 72(39): 21763-21771, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39315455

RESUMEN

Effectively controlling ice recrystallization (IR) during the frozen storage of food remains highly challenging. Inspired by the structural characteristics of antifreeze proteins in nature, silk fibroin (SF) derived from silk fibers has been developed. Through dual validation using the "splat" assay and "sucrose sandwich" assay, the IR inhibition activity of SF at various concentrations was confirmed, revealing that its regular alternating hydrophilic/hydrophobic domains endow SF with the potential to inhibit the axial growth of single ice crystal and significantly reduce the average maximum crystal size by approximately 67%. Additionally, the quality stability of frozen muscle foods treated with SF was comprehensively evaluated. In stark contrast to traditional commercial antifreeze agents (4% sucrose and 4% sorbitol), prepared steaks with the addition of 2% SF maintained rich juiciness and excellent color acceptability over a three-month frozen storage period. Thus, SF holds promise as a potential protective agent for frozen muscle foods, enhancing their quality during storage.


Asunto(s)
Cristalización , Fibroínas , Conservación de Alimentos , Almacenamiento de Alimentos , Congelación , Hielo , Fibroínas/química , Animales , Conservación de Alimentos/métodos , Bombyx/química , Carne/análisis , Porcinos , Humanos
5.
Nat Commun ; 15(1): 6524, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107278

RESUMEN

Sequence-based genetic testing identifies causative variants in ~ 50% of individuals with developmental and epileptic encephalopathies (DEEs). Aberrant changes in DNA methylation are implicated in various neurodevelopmental disorders but remain unstudied in DEEs. We interrogate the diagnostic utility of genome-wide DNA methylation array analysis on peripheral blood samples from 582 individuals with genetically unsolved DEEs. We identify rare differentially methylated regions (DMRs) and explanatory episignatures to uncover causative and candidate genetic etiologies in 12 individuals. Using long-read sequencing, we identify DNA variants underlying rare DMRs, including one balanced translocation, three CG-rich repeat expansions, and four copy number variants. We also identify pathogenic variants associated with episignatures. Finally, we refine the CHD2 episignature using an 850 K methylation array and bisulfite sequencing to investigate potential insights into CHD2 pathophysiology. Our study demonstrates the diagnostic yield of genome-wide DNA methylation analysis to identify causal and candidate variants as 2% (12/582) for unsolved DEE cases.


Asunto(s)
Variaciones en el Número de Copia de ADN , Metilación de ADN , Epilepsia , Humanos , Metilación de ADN/genética , Femenino , Niño , Masculino , Epilepsia/genética , Epilepsia/diagnóstico , Variaciones en el Número de Copia de ADN/genética , Preescolar , Proteínas de Unión al ADN/genética , Adolescente , Pruebas Genéticas/métodos , Lactante
6.
Int J Biol Macromol ; 278(Pt 2): 134762, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39151845

RESUMEN

In this study, oregano essential oil (OEO)-loaded soluble soybean polysaccharide (SSPS) -nisin nanoparticles (ONSNPs) were formulated through electrostatic attraction-driven and hydrophobic interactions utilizing SSPS, nisin, and OEO as raw materials. ONSNPs were integrated into polyvinyl alcohol (PVA) and soybean protein isolate (SPI) matrices to create composite pads (PS-ONSNPs) by physically cross-linked using a simple freeze-thaw cycling process. The effects of ONSNPs content on the structure and physicochemical properties were evaluated. The results revealed that strong intermolecular interactions between ONSNPs and the PS matrices affected the crystallinity, microstructure, and thermal stability of the pads. Upon incorporating 5 % to 15 % ONSNPs, the structure of composite pads became denser, and the mechanical properties and water resistance were enhanced. Concurrently, the PS-ONSNPs pads facilitated the protection and controlled release of OEO. Furthermore, ONSNPs significantly improved the antioxidant activity of the pads and effectively inhibited the growth of Staphylococcus aureus and Escherichia coli. The prepared PS-ONSNPs 15 % pad was applied to storage experiments of fresh pork, which could extend the shelf life of meat to 10-12 days under 4 °C storage conditions. Therefore, the composite pad devised in this research holds promise as a viable option for intelligent active packaging of fresh meat.


Asunto(s)
Antioxidantes , Conservación de Alimentos , Nanopartículas , Alcohol Polivinílico , Proteínas de Soja , Alcohol Polivinílico/química , Antioxidantes/química , Antioxidantes/farmacología , Nanopartículas/química , Animales , Proteínas de Soja/química , Conservación de Alimentos/métodos , Porcinos , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Nisina/química , Nisina/farmacología , Carne de Cerdo , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antibacterianos/farmacología , Antibacterianos/química , Aceites Volátiles/química , Aceites Volátiles/farmacología
7.
Food Chem ; 459: 140298, 2024 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-39018616

RESUMEN

Research conducted previously has demonstrated that apoptosis significantly influences the chicken quality. While ROS are acknowledged as significant activators of apoptosis, the precise mechanism by which they influence muscle cell apoptosis in the post-mortem remains unclear. In this study, chicken samples were treated with rosemarinic acid and H2O2 to induce varying ROS levels, and the ROS-triggered apoptosis mechanism in chicken muscle cells in post-mortem was analyzed. The TUNEL results revealed that elevated ROS levels in chicken were associated with a greater degree of muscle cell apoptosis. Western-blot results suggested that sarcoplasmic ROS could initiate apoptosis through the mitochondrial pathway by activating the MAPK-JNK signaling pathway. Moreover, TEM and shear force results demonstrated that muscle cell apoptosis initiates myofiber fragmentation and structural damage to sarcomeres, ultimately reducing chicken tenderness. This study enhances our understanding of post-mortem muscle cell apoptosis, providing valuable insights for regulating chicken quality.


Asunto(s)
Apoptosis , Pollos , Especies Reactivas de Oxígeno , Animales , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Carne/análisis , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Células Musculares/metabolismo , Células Musculares/citología , Cambios Post Mortem , Músculo Esquelético/metabolismo , Músculo Esquelético/citología , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/farmacología
8.
Food Chem ; 460(Pt 1): 140386, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39029367

RESUMEN

In promoting healthy diet, developing animal fat substitutes for meat products has been a prominent trend in food science. In this study, Prinsepia utilis Royle protein (PuRP) with amphiphilic property was extracted from waste oil pomace. High internal phase emulsions (HIPEs) were prepared with a 75% oil phase and stabilized with 2% (w/v) PuRP due to their excellent elastic-gel property. Furthermore, the PuRP-HIPEs were used to substitute animal fat in low-fat meatballs. Below 100 mM ionic strength, the uniformly distributed PuRP-HIPEs exhibited an approximate Gaussian size distribution with an average particle size of about 100 µm. The PuRP-HIPEs exhibited good thermodynamic stability and improved the texture of meatballs. Additionally, the PuRP-HIPEs significantly increased the mobile water content in steamed meatballs, resulting in better water retention and distribution than the free-fat and lard-added meatballs. Overall, the PuRP-HIPEs could substitute 100% animal fat in meatballs and maintain their cooking characteristics.


Asunto(s)
Emulsiones , Sustitutos de Grasa , Productos de la Carne , Emulsiones/química , Animales , Productos de la Carne/análisis , Sustitutos de Grasa/química , Sustitutos de Grasa/análisis , Tamaño de la Partícula , Culinaria , Proteínas de Plantas/química , Escarabajos/química
9.
JAMA Netw Open ; 7(7): e2419771, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38954412

RESUMEN

Importance: Current research in epigenetic age acceleration (EAA) is limited to non-Hispanic White individuals. It is imperative to improve inclusivity by considering racial and ethnic minorities in EAA research. Objective: To compare non-Hispanic Black with non-Hispanic White survivors of childhood cancer by examining the associations of EAA with cancer treatment exposures, potential racial and ethnic disparity in EAA, and mediating roles of social determinants of health (SDOH). Design, Setting, and Participants: In this cross-sectional study, participants were from the St Jude Lifetime Cohort, which was initiated in 2007 with ongoing follow-up. Eligible participants included non-Hispanic Black and non-Hispanic White survivors of childhood cancer treated at St Jude Children's Research Hospital between 1962 and 2012 who had DNA methylation data. Data analysis was conducted from February 2023 to May 2024. Exposure: Three treatment exposures for childhood cancer (chest radiotherapy, alkylating agents, and epipodophyllotoxin). Main Outcomes and Measures: DNA methylation was generated from peripheral blood mononuclear cell-derived DNA. EAA was calculated as residuals from regressing Levine or Horvath epigenetic age on chronological age. SDOH included educational attainment, annual personal income, and the socioeconomic area deprivation index (ADI). General linear models evaluated cross-sectional associations of EAA with race and ethnicity (non-Hispanic Black and non-Hispanic White) and/or SDOH, adjusting for sex, body mass index, smoking, and cancer treatments. Adjusted least square means (ALSM) of EAA were calculated for group comparisons. Mediation analysis treated SDOH as mediators with average causal mediation effect (ACME) calculated for the association of EAA with race and ethnicity. Results: Among a total of 1706 survivors including 230 non-Hispanic Black survivors (median [IQR] age at diagnosis, 9.5 [4.3-14.3] years; 103 male [44.8%] and 127 female [55.2%]) and 1476 non-Hispanic White survivors (median [IQR] age at diagnosis, 9.3 [3.9-14.6] years; 766 male [51.9%] and 710 female [48.1%]), EAA was significantly greater among non-Hispanic Black survivors (ALSM = 1.41; 95% CI, 0.66 to 2.16) than non-Hispanic White survivors (ALSM = 0.47; 95% CI, 0.12 to 0.81). Among non-Hispanic Black survivors, EAA was significantly increased among those exposed to chest radiotherapy (ALSM = 2.82; 95% CI, 1.37 to 4.26) vs those unexposed (ALSM = 0.46; 95% CI, -0.60 to 1.51), among those exposed to alkylating agents (ALSM = 2.33; 95% CI, 1.21 to 3.45) vs those unexposed (ALSM = 0.95; 95% CI, -0.38 to 2.27), and among those exposed to epipodophyllotoxins (ALSM = 2.83; 95% CI, 1.27 to 4.40) vs those unexposed (ALSM = 0.44; 95% CI, -0.52 to 1.40). The association of EAA with epipodophyllotoxins differed by race and ethnicity (ß for non-Hispanic Black survivors, 2.39 years; 95% CI, 0.74 to 4.04 years; ß for non-Hispanic White survivors, 0.68; 95% CI, 0.05 to 1.31 years) and the difference was significant (1.77 years; 95% CI, 0.01 to 3.53 years; P for interaction = .049). Racial and ethnic disparities in EAA were mediated by educational attainment (

Asunto(s)
Supervivientes de Cáncer , Epigénesis Genética , Factores Socioeconómicos , Humanos , Femenino , Masculino , Estudios Transversales , Supervivientes de Cáncer/estadística & datos numéricos , Niño , Neoplasias/genética , Neoplasias/etnología , Adolescente , Población Blanca/estadística & datos numéricos , Población Blanca/genética , Negro o Afroamericano/estadística & datos numéricos , Negro o Afroamericano/genética , Metilación de ADN , Adulto , Etnicidad/estadística & datos numéricos , Determinantes Sociales de la Salud/estadística & datos numéricos
10.
J Sci Food Agric ; 104(12): 7704-7712, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38860511

RESUMEN

BACKGROUND: Cold chain distribution with multiple links maintains low temperatures to ensure the quality of meat products, whereas temperature fluctuations during this are often disregarded by the industry. The present study simulated two distinct temperatures cold chain distribution processes. Quality indicators and high-throughput sequencing were employed to investigate the effects of temperature fluctuations on the quality and microbial diversity of beef meatballs during cold chain distribution. RESULTS: Quality indicators revealed that temperature fluctuations during simulated cold chain distribution significantly (P < 0.05) exacerbated the quality deterioration of beef meatballs. High-throughput sequencing demonstrated that temperature fluctuations affected the diversity and structure of microbial community. Lower microbial species abundance and higher microbial species diversity were observed in the temperature fluctuations group. Proteobacteria and Pseudomonas were identified as the dominant phylum and genus in beef meatballs, respectively, exhibiting faster growth rates and greater relative abundance under temperature fluctuations. CONCLUSION: The present study demonstrates that temperature fluctuations during simulated cold chain distribution can worsen spoilage and shorten the shelf life of beef meatballs. It also offers certain insights into the spoilage mechanism and preservation of meat products during cold chain distribution. © 2024 Society of Chemical Industry.


Asunto(s)
Bacterias , Frío , Almacenamiento de Alimentos , Productos de la Carne , Bovinos , Animales , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Bacterias/crecimiento & desarrollo , Productos de la Carne/microbiología , Productos de la Carne/análisis , Microbiología de Alimentos , Microbiota , Conservación de Alimentos/métodos , Temperatura , Biodiversidad
11.
Nat Aging ; 4(8): 1053-1063, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38867059

RESUMEN

Chronological aging correlates with epigenetic modifications at specific loci, calibrated to species lifespan. Such 'epigenetic clocks' appear conserved among mammals, but whether they are cell autonomous and restricted by maximal organismal lifespan remains unknown. We used a multilifetime murine model of repeat vaccination and memory T cell transplantation to test whether epigenetic aging tracks with cellular replication and if such clocks continue 'counting' beyond species lifespan. Here we found that memory T cell epigenetic clocks tick independently of host age and continue through four lifetimes. Instead of recording chronological time, T cells recorded proliferative experience through modification of cell cycle regulatory genes. Applying this epigenetic profile across a range of human T cell contexts, we found that naive T cells appeared 'young' regardless of organism age, while in pediatric patients, T cell acute lymphoblastic leukemia appeared to have epigenetically aged for up to 200 years. Thus, T cell epigenetic clocks measure replicative history and can continue to accumulate well-beyond organismal lifespan.


Asunto(s)
Senescencia Celular , Epigénesis Genética , Animales , Humanos , Ratones , Senescencia Celular/genética , Senescencia Celular/inmunología , Envejecimiento/inmunología , Envejecimiento/genética , Linfocitos T/inmunología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Células T de Memoria/inmunología , Células T de Memoria/metabolismo , Ratones Endogámicos C57BL , Masculino , Senescencia de Células T
12.
Int J Biol Macromol ; 271(Pt 1): 132402, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38754662

RESUMEN

In this paper, the effects of chitosan film containing star anise essential oil nanofiltration (CFSAO) and superchilled (SC) temperature on the changes of physicochemical and microbiological indexes of rabbit meat patties within 15 days of storage were studied. The total aerobic bacteria counts, malondialdehyde content, protein carbonyl content, total sulfhydryl content, and metmyoglobin content continued to grow throughout the entire experimental period, and the maximum absorption peak at the soret region of myoglobin gradually decreased. Along with the storage time extended, the brightness and redness of rabbit meat significantly decreased (P < 0.05), while the yellowness significantly increased (P < 0.05). The results of storage experiments showed that chitosan composite films and SC temperature had good inhibition on lipid oxidation, myoglobin oxidation and degradation, sulfhydryl content reduction, and microbial growth of rabbit meat after 15 days of storage, and could slow down the change of rabbit meat color.


Asunto(s)
Quitosano , Embalaje de Alimentos , Almacenamiento de Alimentos , Carne , Aceites Volátiles , Animales , Quitosano/química , Quitosano/farmacología , Conejos , Embalaje de Alimentos/métodos , Aceites Volátiles/química , Aceites Volátiles/farmacología , Carne/microbiología , Almacenamiento de Alimentos/métodos , Mioglobina/metabolismo , Mioglobina/química , Conservación de Alimentos/métodos , Calidad de los Alimentos
13.
J Sci Food Agric ; 104(12): 7668-7677, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38767345

RESUMEN

BACKGROUND: The steam processing characteristics of chicken are a key factor in the simplicity and versatility of steamed chicken dishes. The aim of this study was to investigate in depth the changes in tenderness and water retention of marinated chicken at different slow steaming endpoint temperatures, and to further explore the effect of the evolution of protein conformations on the water status. RESULTS: The results showed that chicken samples' shear force peaked at 80 °C and decreased rapidly at 90 °C. As the steaming endpoint temperature increased between 50 and 90 °C, T21, T22, moisture content and centrifugal loss decreased, but P21, P22 and myofibril water-holding capacity showed regular changes. The electrophoretic bands and protein conformation changes showed that protein in marinated chicken underwent different degrees of denaturation, degradation and aggregation. And at 70 °C, with an increase of hydrophobic groups and crosslinking of disulfide bonds as well as an increase in the number of denatured sarcoplasmic proteins, the intermolecular network was enhanced, thus affecting the water retention. CONCLUSION: Water status of chicken meat heated at different steaming temperatures is closely related to the evolution of protein conformations. The present study serves as a robust theoretical foundation for enhancing the quality of steamed chicken products at an industrial scale. © 2024 Society of Chemical Industry.


Asunto(s)
Pollos , Culinaria , Carne , Vapor , Agua , Animales , Agua/análisis , Agua/química , Carne/análisis , Calor , Temperatura , Manipulación de Alimentos/métodos
14.
aBIOTECH ; 5(1): 116, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38576438

RESUMEN

[This corrects the article DOI: 10.1007/s42994-023-00119-3.].

15.
Cancer Discov ; 14(8): 1403-1417, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-38593228

RESUMEN

Childhood cancer survivorship studies generate comprehensive datasets comprising demographic, diagnosis, treatment, outcome, and genomic data from survivors. To broadly share this data, we created the St. Jude Survivorship Portal (https://survivorship.stjude.cloud), the first data portal for sharing, analyzing, and visualizing pediatric cancer survivorship data. More than 1,600 phenotypic variables and 400 million genetic variants from more than 7,700 childhood cancer survivors can be explored on this free, open-access portal. Summary statistics of variables are computed on-the-fly and visualized through interactive and customizable charts. Survivor cohorts can be customized and/or divided into groups for comparative analysis. Users can also seamlessly perform cumulative incidence and regression analyses on the stored survivorship data. Using the portal, we explored the ototoxic effects of platinum-based chemotherapy, uncovered a novel association between mental health, age, and limb amputation, and discovered a novel haplotype in MAGI3 strongly associated with cardiomyopathy specifically in survivors of African ancestry. Significance: The St. Jude Survivorship Portal is the first data portal designed to share and explore clinical and genetic data from childhood cancer survivors. The portal provides both open- and controlled-access features and will fulfill a wide range of data sharing needs of the survivorship research community and beyond. See co-corresponding author Xin Zhou discuss this research article, published simultaneously at the AACR Annual Meeting 2024: https://vimeo.com/932617204/7d99fa4958.


Asunto(s)
Supervivientes de Cáncer , Genómica , Neoplasias , Humanos , Niño , Genómica/métodos , Neoplasias/genética , Difusión de la Información , Masculino , Femenino , Adolescente , Supervivencia
16.
J Cancer Surviv ; 18(4): 1154-1167, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38635100

RESUMEN

PURPOSE: Childhood cancer survivors are at risk for cardiac dysfunction and impaired physical performance, though underlying cellular mechanisms are not well studied. In this cross-sectional study, we examined the association between peripheral blood mitochondrial DNA copy number (mtDNA-CN, a proxy for mitochondrial function) and markers of performance impairment and cardiac dysfunction. METHODS: Whole-genome sequencing, validated by quantitative polymerase chain reaction, was used to estimate mtDNA-CN in 1720 adult survivors of childhood cancer (48.5% female; mean age = 30.7 years, standard deviation (SD) = 9.0). Multivariable logistic regression was performed to evaluate the associations between mtDNA-CN and exercise intolerance, walking inefficiency, and abnormal global longitudinal strain (GLS), adjusting for treatment exposures, age, sex, and race and ethnicity. RESULTS: The prevalence of exercise intolerance, walking inefficiency, and abnormal GLS among survivors was 25.7%, 10.7%, and 31.7%, respectively. Each SD increase of mtDNA-CN was associated with decreased odds of abnormal GLS (adjusted odds ratio (OR) = 0.88, p = 0.04) but was not associated with exercise intolerance (OR = 1.02, p = 0.76) or walking inefficiency (OR = 1.06, p = 0.46). Alkylating agent exposure was associated with increased odds of exercise intolerance (OR = 2.25, p < 0.0001), walking inefficiency (OR = 2.37, p < 0.0001), and abnormal GLS (OR = 1.78, p = 0.0002). CONCLUSIONS: Increased mtDNA-CN is associated with decreased odds of abnormal cardiac function in childhood cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: These findings demonstrate a potential role for mtDNA-CN as a biomarker of early cardiac dysfunction in this population.


Asunto(s)
Supervivientes de Cáncer , ADN Mitocondrial , Neoplasias , Caminata , Humanos , Femenino , Masculino , Supervivientes de Cáncer/estadística & datos numéricos , Adulto , Estudios Transversales , Neoplasias/genética , ADN Mitocondrial/genética , Variaciones en el Número de Copia de ADN , Adulto Joven , Tolerancia al Ejercicio , Niño , Adolescente , Mitocondrias , Cardiopatías/etiología , Cardiopatías/genética
17.
Blood ; 143(18): 1816-1824, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38457360

RESUMEN

ABSTRACT: Rituximab (RTX) and other monoclonal antibodies (mAbs) that bind directly to malignant cells are of great clinical value but are not effective for all patients. A major mechanism of action of RTX is antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells. Prior in vitro studies in our laboratory demonstrated that T cells contribute to maintaining the viability and cytotoxic potential of NK cells activated by anti-CD20-coated target B cells. Here, we conducted studies using a novel mouse model and clinical correlative analysis to assess whether T-cell help contribute to RTX-mediated NK-cell ADCC in the tumor microenvironment (TME) in vivo. A humanized mouse model was developed using Raji lymphoma cells and normal donor peripheral blood mononuclear cells that allows for control of T-cell numbers in the lymphoma TME. In this model, NK-cell viability and CD16 and CD25 expression dropped after RTX in the absence of T cells but increased in the presence of T cells. RTX therapy was more effective when T cells were present and was ineffective when NK cells were depleted. In patients with indolent lymphoma, fine needle aspirates were obtained before and ∼1 week after treatment with a RTX-containing regimen. There was a strong correlation between CD4+ T cells as well as total T cells in the pretherapy TME and an increase in NK-cell CD16 and CD25 expression after RTX. We conclude that T-cell help in the TME enhances RTX-mediated NK-cell viability and ADCC.


Asunto(s)
Citotoxicidad Celular Dependiente de Anticuerpos , Células Asesinas Naturales , Rituximab , Microambiente Tumoral , Rituximab/farmacología , Rituximab/uso terapéutico , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Animales , Citotoxicidad Celular Dependiente de Anticuerpos/efectos de los fármacos , Humanos , Ratones , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Línea Celular Tumoral , Ratones SCID , Linfoma/inmunología , Linfoma/tratamiento farmacológico , Linfoma/patología , Linfoma/terapia , Femenino
18.
Int J Biol Macromol ; 265(Pt 1): 130713, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38471612

RESUMEN

Rapeseed-derived peptides (RPPs) can maintain the homeostasis of human blood glucose by inhibiting Dipeptidyl Peptidase-IV (DPP-IV) and activating the calcium-sensing receptor (CaSR). However, these peptides are susceptible to hydrolysis in the gastrointestinal tract. To enhance the therapeutic potential of these peptides, we developed a chitosan/sodium alginate-based nanocarrier to encapsulate two RPP variants, rapeseed-derived cruciferin peptide (RCPP) and rapeseed-derived napin peptide (RNPP). A convenient three-channel device was employed to prepare chitosan (CS)/sodium alginate (ALG)-RPPs nanoparticles (CS/ALG-RPPs) at a ratio of 1:3:1 for CS, ALG, and RPPs. CS/ALG-RPPs possessed optimal encapsulation efficiencies of 90.7 % (CS/ALG-RNPP) and 91.4 % (CS/ALG-RCPP), with loading capacities of 15.38 % (CS/ALG-RNPP) and 16.63 % (CS/ALG-RCPP) at the specified ratios. The electrostatic association between CS and ALG was corroborated by zeta potential and near infrared analysis. 13C NMR analysis verified successful RPPs loading, with CS/ALG-RNPP displaying superior stability. Pharmacokinetics showed that both nanoparticles were sustained release and transported irregularly (0.43 < n < 0.85). Compared with the control group, CS/ALG-RPPs exhibited significantly increased glucose tolerance, serum GLP-1 (Glucagon-like peptide 1) content, and CaSR expression which play pivotal roles in glucose homeostasis (*p < 0.05). These findings proposed that CS/ALG-RPPs hold promise in achieving sustained release within the intestinal epithelium, thereby augmenting the therapeutic efficacy of targeted peptides.


Asunto(s)
Brassica napus , Quitosano , Nanopartículas , Humanos , Quitosano/química , Portadores de Fármacos/química , Preparaciones de Acción Retardada , Brassica napus/metabolismo , Alginatos/química , Nanopartículas/química , Glucosa , Péptidos
20.
Nat Cancer ; 5(5): 731-741, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38553617

RESUMEN

Survivors of childhood cancer may experience accelerated biological aging, resulting in premature frailty and death. We used seven measures of biological age in the St. Jude Lifetime (SJLIFE) Cohort to compare biological age acceleration between the SJLIFE Cohort and the third United States National Health and Nutrition Examination Survey controls, explore trajectories of biological age according to cancer treatment and type, and test associations of biological age acceleration with frailty and death (mean follow-up of 26.5 years) among survivors. Survivors of cancer aged 5% faster per year and measured, on average, 0.6-6.44 years biologically older compared to controls and 5-16 years biologically older compared to age-matched individuals at the population level. Survivors treated with hematopoietic cell transplant and vinca alkaloid chemotherapy evidenced the fastest trajectories of biological aging. Biologically, older and faster-aging survivors consistently and robustly had a higher risk of frailty and died earlier than those with slower biological aging, suggesting a potential opportunity to intervene on excess aging.


Asunto(s)
Supervivientes de Cáncer , Fragilidad , Neoplasias , Humanos , Supervivientes de Cáncer/estadística & datos numéricos , Masculino , Femenino , Adulto , Neoplasias/mortalidad , Neoplasias/terapia , Adolescente , Adulto Joven , Estudios de Cohortes , Niño , Persona de Mediana Edad , Envejecimiento , Encuestas Nutricionales , Causas de Muerte
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