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1.
EMBO Mol Med ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164471

RESUMEN

While whole genome sequencing (WGS) of cell-free DNA (cfDNA) holds enormous promise for detection of molecular residual disease (MRD), its performance is limited by WGS error rate. Here we introduce AccuScan, an efficient cfDNA WGS technology that enables genome-wide error correction at single read-level, achieving an error rate of 4.2 × 10-7, which is about two orders of magnitude lower than a read-centric de-noising method. The application of AccuScan to MRD demonstrated analytical sensitivity down to 10-6 circulating variant allele frequency at 99% sample-level specificity. AccuScan showed 90% landmark sensitivity (within 6 weeks after surgery) and 100% specificity for predicting relapse in colorectal cancer. It also showed 67% sensitivity and 100% specificity in esophageal cancer using samples collected within one week after surgery. When AccuScan was applied to monitor immunotherapy in melanoma patients, the circulating tumor DNA (ctDNA) levels and dynamic profiles were consistent with clinical outcomes. Overall, AccuScan provides a highly accurate WGS solution for MRD detection, empowering ctDNA detection at parts per million range without requiring high sample input or personalized reagents.

2.
J Int Soc Sports Nutr ; 21(1): 2393368, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39166753

RESUMEN

BACKGROUND: As a relatively novel approach to enhancing skeletal muscle health, mixed protein supplementation has shown similar responses to whey protein. However, no previous studies have examined its impact on golf swing performance. This study aimed to examine the effect of mixed protein supplementation on the swing performance and muscle strength of casual golfers. METHODS: Sixty participants with a handicap of less than 20 were recruited and randomly assigned to a double-blind, placebo-controlled study design. The participants were divided into two groups: a mixed protein group (MG, n = 30), and a placebo control group (CG, n = 30). They were instructed to ingest either a supplement containing casein calcium, whey protein, and isolated pea protein, or a placebo, once daily for 8 weeks. Pre- and posttests consisted of anthropometric measurements, muscle strength (isokinetic knee and trunk strength, and handgrip strength), 2-minute push-ups, balance, and golf swing performance using a driver and 7-iron. RESULTS: After the 8-week supplementation period, ANCOVA, using baseline values as covariates, revealed significant differences for driver distance (p = .004) and driver ball speed (p < .001). MG significantly increased driver distance by 5.17 ± 12.8 m (p = .046), driver ball speed by 1.36 ± 2.87 m/s (p = .021). Additionally, significantly improvements were observed in hand grip strength (+2.12 ± 3.47 kg, p = .004), two-minute push-ups (+4.89 ± 8.14 reps, p = .004), and balance score (-0.37 ± 0.69 min, p = .009). No significant differences were observed in body composition parameters (p > .05). CONCLUSION: The intake of a mixed protein containing both animal and plant proteins had positive effects on golf performance and muscle function. Therefore, mixed proteins may represent a safe and effective approach to enhancing skeletal muscle health in golf players.


Asunto(s)
Rendimiento Atlético , Suplementos Dietéticos , Golf , Fuerza Muscular , Músculo Esquelético , Proteína de Suero de Leche , Humanos , Golf/fisiología , Método Doble Ciego , Fuerza Muscular/efectos de los fármacos , Fuerza Muscular/fisiología , Masculino , Proteína de Suero de Leche/administración & dosificación , Proteína de Suero de Leche/farmacología , Rendimiento Atlético/fisiología , Músculo Esquelético/fisiología , Músculo Esquelético/efectos de los fármacos , Adulto , Caseínas/administración & dosificación , Caseínas/farmacología , Adulto Joven , Proteínas de Guisantes/administración & dosificación , Fenómenos Fisiológicos en la Nutrición Deportiva , Proteínas en la Dieta/administración & dosificación , Femenino , Fuerza de la Mano/fisiología
3.
Complement Ther Clin Pract ; 57: 101887, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39084129

RESUMEN

OBJECTIVE: To diminish the negative influence of sarcopenia on senior adults, the study aimed to investigate the association between adherence to 24-h movement behavior guidelines (physical activity, sedentary behavior, sleep duration) and the risk of sarcopenia among individuals aged ≥55 years in five low- and middle-income countries (LMICs). METHODS: A total of 16,503 adults aged ≥55 years were included in this cross-sectional study. The study utilized data from Global Aging and Adult Health Survey (SAGE). Participants reported their information about physical activity, sedentary behavior, and sleep duration using the questionnaire. Sarcopenia was identified as low skeletal muscle mass with a diminished gait speed or weakened handgrip strength. Multiple logistic regression models were used to investigate the association between adherence to 24-h movement behavior guidelines and the risk of sarcopenia. RESULTS: Merely 32.73 % of participants met all three 24-h movement behavior guidelines (physical activity, less sedentary behavior, sleep). Meeting all three guidelines (p < 0.01) was significantly associated with a lower risk of sarcopenia. Meeting physical activity only (p < 0.05), or meeting both physical activity and sedentary behaivor (p < 0.05), or meeting both physical activity and sleep duration (p < 0.01) guidelines were also associated with a reduced risk of sarcopenia. Moreover, adults aged 65+ years who adhered to 24-h movement behavior guidelines exhibited a significantly reduced risk of developing sarcopenia. CONCLUSION: The findings suggest that the adherence to 24-h movement behavior guidelines for regular physical activity, limited sedentary behavior, and sufficient sleep duration was associated with a reduced risk of sarcopenia in adults aged ≥55 years in five LMICs.

4.
Ann Geriatr Med Res ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39021131

RESUMEN

Background: Sarcopenia is a muscle wasting condition that affects elderly individuals. It can lead to changes in movement patterns, which can increase the risk of falls and other injuries. Methods: Elderly women participants aged ≥65 years who could walk independently were recruited and classified into two groups based on knee extension strength (KES). Participants with low KES scores were assigned to the possible sarcopenia group (PSG, n=7) and an 8-week exercise intervention was implemented. Healthy seniors with high KES scores were classified as the reference group (RG, n=4), and a 3-week exercise intervention was conducted. Kinematic movement data were recorded during the intervention period. All participants' exercise repetitions were used in the data analysis (number of data points =1,128). Results: The PSG showed significantly larger movement patterns in knee rotation during wide squats compared to the RG, attributed to weakened lower limb strength. The voting classifier, trained on the movement patterns from wide squats, determined that significant differences in overall movement patterns between the two groups persisted until the end of the exercise intervention. However, after the exercise intervention, significant improvements in lower limb strength in the PSG resulted in reduced knee rotation ROM and Max, thereby stabilizing movements and eliminating significant differences with the RG. Conclusions: This study suggests that exercise interventions can modify the movement patterns in elderly individuals with possible sarcopenia. These findings provide fundamental data for developing an exercise management system that remotely tracks and monitors the movement patterns of older adults during exercise activities.

5.
Complement Ther Clin Pract ; 57: 101878, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38959563

RESUMEN

BACKGROUND: Researchers have investigated the physical and psychosocial advantages of Taekwondo for older adults. However, prior studies of Taekwondo's impact on physical function and psychological well-being in this demographic have produced inconsistent findings. Thus, this systematic review aimed to assess how Taekwondo practice affects the physical function and psychological well-being of older adults. METHODS: We systematically searched PubMed, EMBASE, CINAHL, SPORTDiscus, Scopus, Korea Education and Research Information Service, Korean Studies Information Service System, Korean National Assembly Library, Research Information Sharing Service, National Digital Science Library, and China National Knowledge Infrastructure from their inception to December 2023. Two reviewers independently selected and extracted data from each study. We calculated effect sizes using a random-effects model with a 95 % confidence interval (CI) and evaluated study quality using the Physiotherapy Evidence Database scale. RESULTS: This review included ten studies with 227 participants aged 66.1-73.6 years. The meta-analysis revealed significant enhancements in cognitive function [Korean Version of Mini-Mental State Examination, standard mean difference (SMD) = 0.700, 95 % CI (0.364-1.037), I2 = 0 %, p < .001], blood indicators [ß-amyloid, SMD = 0.613, 95 % CI (0.103-1.123), I2 = 34.920 %, p < .05; brain-derived neurotrophic factor, SMD = 0.566, 95 % CI (0.166-0.966), I2 = 0 %, p < .01; high-density lipoprotein cholesterol, SMD = 0.677, 95 % CI (0.357-0.966), I2 = 0 %, p < .001; low-density lipoprotein cholesterol, SMD = 0.809, 95 % CI (0.376-1.242), I2 = 42.621 %, p < .001; and total cholesterol, SMD = 0.979, 95 % CI (0.603-1.356), I2 = 22.221 %, p < .001], and physical function [lean body mass, SMD = 0.465, 95 % CI (0.109-0.821), I2 = 0 %, p < .05, and handgrip strength, SMD = 0.929, 95 % CI (0.194-1.663), I2 = 48.217 %, p < .05]. CONCLUSIONS: This meta-analysis indicates that Taekwondo training is a beneficial therapy with protective effects on cognitive function, physical function, and body composition in older adults. These findings highlight its potential significance in cognitive rehabilitation and physiological health promotion among this demographic population.

6.
Heliyon ; 10(12): e32687, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38988584

RESUMEN

Background: Patients with colorectal cancer commonly experience disturbances in coagulation homeostasis. Activation of the coagulation system contributes to cancer-associated thrombosis as the second risk factor for death in cancer patients. This study intended to discover coagulation-related genes and construct a risk model for colorectal cancer patients' prognosis. Methods: Coagulation-related genes were identified by searching coagulation-related pathways in the Molecular Signatures Database. Transcriptomic data and clinical data were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus datasets. Univariate Cox and backward stepwise regression were utilized to identify prognosis-related genes and construct a predictive risk model for the training cohort. Next, survival analysis determines the risk model's predictive power, correlation with clinicopathological characteristics, and nomogram. Additionally, we characterized the variances in immune cell infiltration, somatic mutations, immune checkpoint molecules, biological functions, and drug sensitivity between the high- and low-score patients. Result: Eight hundred forty-five genes were obtained by searching the theme term "coagulation" after de-duplication. After univariate regression analysis, 69 genes correlated with prognosis were obtained from the Cancer Genome Atlas dataset. A signature consisting of 17 coagulation-related genes was established through backward stepwise regression. The Kaplan-Meier curve indicated a worse prognosis for high-score patients. Time-dependent receiver operating characteristic curve analysis demonstrated high accuracy in predicting overall survival. Further, the results were validated by two independent datasets (GSE39582 and GSE17536). Combined with clinicopathological characteristics, the risk model was proven to be an independent prognostic factor to predict poor pathological status and worse prognosis. Furthermore, high-score patients had significantly higher stromal cell infiltration. Low-score patients were associated with high infiltration of resting memory CD4+ T cells, activated CD4+ T cells, and T follicular helper cells. The low-score patients exhibited increased expression of immune checkpoint genes, and this might be relevant to their better prognosis. High-score patients exhibited lower IC50 values of Paclitaxel, Rapamycin, Temozolomide, Cyclophosphamide, etc. The differential signaling pathways mainly involve the calcium signaling pathway and the neuroactive ligand-receptor interaction. Lastly, a nomogram was constructed and showed a good prediction. Conclusion: The prognostic signature of 17 coagulation-related genes had significant prognostic value for colorectal cancer patients. We expect to improve treatment modalities and benefit more patients through research on molecular features.

7.
Mol Neurobiol ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38951469

RESUMEN

Gliomas are common brain tumors. Despite extensive research, the 5-year survival rate of glioma remains low. Many studies have reported that circular RNAs (circRNAs) play a role in promoting the malignant progression of glioma; however, the role of circ_0059914 in this process remains unclear. In this study, we aimed to investigate the function and underlying mechanism of circ_0059914 in glioma. Western blotting and qRT-PCR were used to determine the levels of circ_0059914, miR-1249, VEGFA, N-cadherin, vimentin, Snail, and EIF4A3. EDU and colony formation assays were conducted to evaluate cell proliferation. Transwell assays were used to explore cell migration and invasion and tube formation assays were used to analyze angiogenesis. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were used to explore the relationship between EIF4A3, circ_0059914, miR-1249, and VEGFA. A xenograft tumor assay was performed to determine the role of circ_0059914 in vivo. Circ_0059914 expression was upregulated in gliomas. Knockdown of gliomal circ_0059914 expression reduced the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), angiogenesis, and growth of glioma cells in vivo. Circ_0059914 sponged miR-1249, and miR-1249 inhibition reversed the circ_0059914 knockdown-mediated effects in glioma cells. VEGFA was found to be a target gene of miR1249; overexpression of VEGFA reversed the effect of miR-1249 up-regulation in glioma. Finally, EIF4A3 increased the expression of circ_0059914. EIF4A3-induced circ_0059914 expression plays a role in promoting glioma via the miR-1249/VEGFA axis.

8.
Sci Rep ; 14(1): 14565, 2024 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-38914603

RESUMEN

Sarcopenic obesity (SO) is characterized by concomitant sarcopenia and obesity and presents a high risk of disability, morbidity, and mortality among older adults. However, predictions based on sequential neural network SO studies and the relationship between physical fitness factors and SO are lacking. This study aimed to develop a predictive model for SO in older adults by focusing on physical fitness factors. A comprehensive dataset of older Korean adults participating in national fitness programs was analyzed using sequential neural networks. Appendicular skeletal muscle/body weight was defined as SO using an anthropometric equation. Independent variables included body fat (BF, %), waist circumference, systolic and diastolic blood pressure, and various physical fitness factors. The dependent variable was a binary outcome (possible SO vs normal). We analyzed hyperparameter tuning and stratified K-fold validation to optimize a predictive model. The prevalence of SO was significantly higher in women (13.81%) than in men, highlighting sex-specific differences. The optimized neural network model and Shapley Additive Explanations analysis demonstrated a high validation accuracy of 93.1%, with BF% and absolute grip strength emerging as the most influential predictors of SO. This study presents a highly accurate predictive model for SO in older adults, emphasizing the critical roles of BF% and absolute grip strength. We identified BF, absolute grip strength, and sit-and-reach as key SO predictors. Our findings underscore the sex-specific nature of SO and the importance of physical fitness factors in its prediction.


Asunto(s)
Redes Neurales de la Computación , Obesidad , Aptitud Física , Sarcopenia , Humanos , Sarcopenia/epidemiología , Sarcopenia/fisiopatología , Masculino , Femenino , Obesidad/epidemiología , Obesidad/fisiopatología , Obesidad/complicaciones , República de Corea/epidemiología , Anciano , Fuerza de la Mano/fisiología , Persona de Mediana Edad , Anciano de 80 o más Años
9.
J Sports Med Phys Fitness ; 64(9): 857-862, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38842371

RESUMEN

BACKGROUND: Alterations caused by face masks on physiological responses vary among different population groups. This study aimed to investigate whether physically active and sedentary individuals respond differently to face mask use during exercise. METHODS: Sixteen healthy college students were divided into two groups: Physically active group (N.=10; 26.50±2.80 years) and Sedentary group (N.=6; 26.33±2.81 years). They performed three maximal cardiopulmonary exercise test (CPET)s following the Bruce protocol: one without a face mask (NON), one with a surgical mask (SUR) and one with a cloth mask (CLO). Cardiorespiratory parameters and heart rate were monitored continuously during the test. Blood pressure, oxygen saturation and lactate level were measured immediately before and after exertion. RESULTS: Significant differences were found between the Physically active and the Sedentary group in peak VO2 (VO2peak) in NON (P=0.030). However, this difference disappeared when the face masks were used. Furthermore, VO2/kg (P=0.002) and METs (P=0.002) decreased significantly at the respiratory compensation point (RCP) only in the Physically active group with face masks. No significant differences were found between the two groups for exercise time, lactate level and dyspnea (P>0.05). CONCLUSIONS: The decrease in exercise tolerance and cardiorespiratory responses, particularly VO2peak, due to face mask use was greater in physically active individuals compared to sedentary individuals. Population group characteristics should be considered when adapting face masks to daily life.


Asunto(s)
Prueba de Esfuerzo , Ejercicio Físico , Frecuencia Cardíaca , Máscaras , Consumo de Oxígeno , Conducta Sedentaria , Humanos , Adulto , Frecuencia Cardíaca/fisiología , Masculino , Consumo de Oxígeno/fisiología , Ejercicio Físico/fisiología , Femenino , Adulto Joven , Ácido Láctico/sangre , Presión Sanguínea/fisiología , Saturación de Oxígeno/fisiología , Capacidad Cardiovascular/fisiología
10.
Chemistry ; : e202400874, 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38853144

RESUMEN

MXenes, a class of two-dimensional transition metal carbides, nitrides, and carbonitrides, have garnered significant attention due to their remarkable potential for energy storage, electrocatalysis, and gas separation applications. The fabrication processes of MXene involve building up the MXene structure from constituent elements and the selective elimination of M-A bonds from the precursor MAX. However, considerable efforts are still required to design and develop efficient MXene-based technologies. This review article aims to briefly analyse the synthesis methods employed for MXene production, ranging from direct synthesis and conventional chemical wet etching approach to the more recent molten salt etching technique. The review highlights the advancements made in achieving precise control over the terminal groups, which is paramount for tailoring the properties of MXenes for specific applications. Furthermore, the potential of MXene-based materials for carbon capture applications, particularly in developing advanced adsorbents, is emphasized. The in-depth examination of MXene synthesis techniques and their implications for carbon capture applications provides a solid foundation for developing and optimizing these promising materials.

11.
J Alzheimers Dis ; 99(1): 345-362, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38669527

RESUMEN

Background: Alzheimer-associated neuronal thread protein (AD7c-NTP) has been demonstrated to have high diagnostic accuracy in differentiating Alzheimer's disease (AD) patients from healthy individuals. However, it is yet unclear whether exercise can lower the level of AD7c-NTP in urine among active Korean elderly. Objective: To assess the effect of exercise on AD7c-ntp levels in urine and cognitive function among active Korean elderly. Methods: In total, 40 Korean elderly (≥65 years) were divided into Active Control group (CG, n = 10), Aerobic exercise group (AG, n = 18), and combined Resistance/Aerobic exercise group (RAG, n = 12). A total of 12 weeks of exercise intervention was implemented. At week 0 and 12, cognitive performance (Korean Mini-Mental State Examination, Korean-Color Word Stroop test), grip strength, and body composition (muscle mass and body fat percentage) were measured. Also, a morning urine sample was obtained from each subject. The level of AD7c-NTP was measured using competitive enzyme-linked immunosorbent assay (ELISA). Results: After 12 weeks of exercise intervention, there was a significant difference of AD7c-NTP levels between RAG and CG (p = 0.026), AG and CG (p = 0.032), respectively. Furthermore, the AD7c-NTP levels in urine showed negative correlation with K-MMSE scores (r = -0.390, p = 0.013) and grip strength (r = -0.376, p = 0.017), among all participants after exercise intervention. Conclusions: This is the first study to investigate urine biomarker through exercise intervention. In future stuides, participants who have low cognitive function and low activity levels need to be recruited to observe more significant 'Exercise' effect.


Asunto(s)
Cognición , Ejercicio Físico , Humanos , Masculino , Femenino , Anciano , Cognición/fisiología , Ejercicio Físico/fisiología , República de Corea , Proteínas del Tejido Nervioso/orina , Terapia por Ejercicio/métodos , Enfermedad de Alzheimer/orina , Enfermedad de Alzheimer/diagnóstico , Biomarcadores/orina , Pruebas Neuropsicológicas
13.
Behav Sci (Basel) ; 14(3)2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38540467

RESUMEN

BACKGROUND: Regular physical activity is an effective means to enhance university students' subjective well-being. However, current research needs to understand how physical activity enhances the subjective well-being of Chinese university students. Therefore, the study investigated the mechanism of physical activity's impact on university students' subjective well-being and the mediating roles of cognitive reappraisal and resilience in this mechanism. METHODS: The physical activity scale, subjective well-being scale, cognitive reappraisal scale and resilience scale were used to investigate 1350 university students, and the relationship between physical activity, cognitive reappraisal, resilience and university students' subjective well-being was verified through correlation analysis, regression analysis and a Bootstrap method. RESULTS: (1) There is a significant positive correlation between physical activity, cognitive reappraisal, resilience and university students' subjective well-being (p < 0.01); (2) physical activity, cognitive reappraisal and resilience all have a significant positive effects on university students' subjective well-being (p < 0.01); (3) cognitive reappraisal and resilience have significant mediating roles in the process of physical activity affecting university students' well-being, with mediating-effect values of 0.052 and 0.285; (4) the chain-mediating role of cognitive reappraisal and resilience in the process of physical activity affecting university students' well-being is significant, with the chain-mediating effect value of 0.062. CONCLUSION: Promoting university students' participation in physical activity not only directly enhances university students' subjective well-being but also indirectly improves university students' subjective well-being through cognitive reappraisal and resilience.

14.
medRxiv ; 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38260271

RESUMEN

While whole genome sequencing (WGS) of cell-free DNA (cfDNA) holds enormous promise for molecular residual disease (MRD) detection, its performance is limited by WGS error rate. Here we introduce AccuScan, an efficient cfDNA WGS technology that enables genome-wide error correction at single read level, achieving an error rate of 4.2×10 -7 , which is about two orders of magnitude lower than a read-centric de-noising method. When applied to MRD detection, AccuScan demonstrated analytical sensitivity down to 10 -6 circulating tumor allele fraction at 99% sample level specificity. In colorectal cancer, AccuScan showed 90% landmark sensitivity for predicting relapse. It also showed robust MRD performance with esophageal cancer using samples collected as early as 1 week after surgery, and predictive value for immunotherapy monitoring with melanoma patients. Overall, AccuScan provides a highly accurate WGS solution for MRD, empowering circulating tumor DNA detection at parts per million range without high sample input nor personalized reagents. One Sentence Summary: AccuScan showed remarkable ultra-low limit of detection with a short turnaround time, low sample requirement and a simple workflow for MRD detection.

15.
Clin Chem Lab Med ; 62(1): 168-177, 2024 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-37678194

RESUMEN

OBJECTIVES: Cancer morbidity and mortality can be reduced if the cancer is detected early. Cell-free DNA (cfDNA) fragmentomics emerged as a novel epigenetic biomarker for early cancer detection, however, it is still at its infancy and requires technical improvement. We sought to apply a single-strand DNA sequencing technology, for measuring genetic and fragmentomic features of cfDNA and evaluate the performance in detecting multiple cancers. METHODS: Blood samples of 364 patients from six cancer types (colorectal, esophageal, gastric, liver, lung, and ovarian cancers) and 675 healthy individuals were included in this study. Circulating tumor DNA mutations, cfDNA fragmentomic features and a set of protein biomarkers were assayed. Sensitivity and specificity were reported by cancer types and stages. RESULTS: Circular Ligation Amplification and sequencing (CLAmp-seq), a single-strand DNA sequencing technology, yielded a population of ultra-short fragments (<100 bp) than double-strand DNA preparation protocols and reveals a more significant size difference between cancer and healthy cfDNA fragments (25.84 bp vs. 16.05 bp). Analysis of the subnucleosomal peaks in ultra-short cfDNA fragments indicates that these peaks are regulatory element "footprints" and correlates with gene expression and cancer stages. At 98 % specificity, a prediction model using ctDNA mutations alone showed an overall sensitivity of 46 %; sensitivity reaches 60 % when protein is added, sensitivity further increases to 66 % when fragmentomics is also integrated. More improvements observed for samples representing earlier cancer stages than later ones. CONCLUSIONS: These results suggest synergistic properties of protein, genetic and fragmentomics features in the identification of early-stage cancers.


Asunto(s)
Ácidos Nucleicos Libres de Células , ADN Tumoral Circulante , Neoplasias , Humanos , Detección Precoz del Cáncer , Mutación , ADN Tumoral Circulante/genética , Neoplasias/diagnóstico , Neoplasias/genética , Biomarcadores de Tumor/genética
16.
Cell Rep ; 42(11): 113362, 2023 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-37938970

RESUMEN

Upregulation of FGL1 helps tumors escape from immune surveillance, and therapeutic antibodies targeting FGL1 have potential as another immune checkpoint inhibitor. However, the underlying mechanism of high FGL1 protein level in cancers is not well defined. Here, we report that FBXO38 interacts with and ubiquitylates FGL1 to negatively regulate its stability and to mediate cancer immune response. Depletion of FBXO38 markedly augments FGL1 abundance, not only suppressing CD8+ T cell infiltration and enhancing immune evasion of tumor but also increasing inflammation in mice. Importantly, we observe a negative correlation of FBXO38 with FGL1 and IL-6 in non-small cell lung cancer specimens. FGL1 and IL-6 levels positively correlate with TNM (tumor, lymph node, metastasis) stages, while FBXO38 and the infiltrating CD8+ T cells negatively correlate with TNM stages. Our study identifies a mechanism regulating FGL1 stability and a target to enhance the immunotherapy and suggests that the combination of anti-FGL1 and anti-IL-6 is a potential therapeutic strategy for cancer immunotherapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Ratones , Linfocitos T CD8-positivos , Inflamación , Interleucina-6 , Ubiquitinación
17.
J Transl Med ; 21(1): 824, 2023 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-37978537

RESUMEN

BACKGROUND: The morbidity of cancer keeps growing worldwide, and among that, the colorectal cancer (CRC) has jumped to third. Existing early screening tests for CRC are limited. The aim of this study was to develop a diagnostic strategy for CRC by plasma metabolomics. METHODS: A targeted amino acids metabolomics method was developed to quantify 32 plasma amino acids in 130 CRC patients and 216 healthy volunteers, to identify potential biomarkers for CRC, and an independent sample cohort comprising 116 CRC subjects, 33 precancerosiss patients and 195 healthy volunteers was further used to validate the diagnostic model. Amino acids-related genes were retrieved from Gene Expression Omnibus and Molecular Signatures Database and analyzed. RESULTS: Three were chosen out of the 32 plasma amino acids examined. The tryptophan / sarcosine / glutamic acid -based receiver operating characteristic (ROC) curve showed the area under the curve (AUC) of 0.955 (specificity 83.3% and sensitivity 96.8%) for all participants, and the logistic regression model were used to distinguish between early stage (I and II) of CRC and precancerosiss patients, which showed superiority to the commonly used carcinoembryonic antigen. The GO and KEGG enrichment analysis proved many alterations in amino acids metabolic pathways in tumorigenesis. CONCLUSION: This altered plasma amino acid profile could effectively distinguish CRC patients from precancerosiss patients and healthy volunteers with high accuracy. Prognostic tests based on the tryptophan/sarcosine/glutamic acid biomarkers in the large population could assess the clinical significance of CRC early detection and intervention.


Asunto(s)
Aminoácidos , Neoplasias Colorrectales , Humanos , Triptófano , Sarcosina , Biomarcadores de Tumor/genética , Metabolómica , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Glutamatos
18.
J Alzheimers Dis ; 95(4): 1709-1722, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37718803

RESUMEN

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia, with its prevalence increasing as the global population ages. AD is a multifactorial and intricate neurodegenerative disease with pathological changes varying from person to person. Because the mechanism of AD is highly controversial, effective treatments remain a distant prospect. Currently, one of the most promising hypotheses posits mitochondrial dysfunction as an early event in AD diagnosis and a potential therapeutic target. OBJECTIVE: Here, we adopted a systems medicine strategy to explore the mitochondria-related mechanisms of AD. Then, its implications for discovering nutrients combatting the disease were demonstrated. METHODS: We employed conditional mutual information (CMI) to construct AD gene dependency networks. Furthermore, the GeneRank algorithm was applied to prioritize the gene importance of AD patients and identify potential anti-AD nutrients targeting crucial genes. RESULTS: The results suggested that two highly interconnected networks of mitochondrial ribosomal proteins (MRPs) play an important role in the regulation of AD pathology. The close association between mitochondrial ribosome dysfunction and AD was identified. Additionally, we proposed seven nutrients with potential preventive and ameliorative effects on AD, five of which have been supported by experimental reports. CONCLUSIONS: Our study explored the important regulatory role of MRP genes in AD, which has significant implications for AD prevention and treatment.

19.
Nutrients ; 15(15)2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37571354

RESUMEN

PURPOSE: The purpose of this study was to investigate the association between moderate to vigorous physical activity (MVPA), sedentary behavior, fruit and vegetable intake, and the risk of sarcopenia among older Chinese adults. METHODS: This cross-sectional study enrolled 5418 older Chinese adults who participated in the Study on Global Aging and Adult Health (SAGE). Participants reported information about their physical activity, sedentary behavior, and dietary habits (fruit and vegetable intake). Sarcopenia was defined as the presence of low skeletal muscle mass and either a slow gait speed or weak handgrip strength. A multiple logistic regression model was employed to determine the relationship between MVPA, sedentary behavior, fruit and vegetable intake, and the risk of sarcopenia. RESULTS: Only 32.63% of participants met all three recommendations (for MVPA, sedentary behavior, and fruit and vegetable intake). Compared with meeting none of the recommendations, meeting all three recommendations was associated with a lower risk of sarcopenia (OR = 0.63, 95% CI = 0.41-0.98). Moreover, meeting the recommendation for sufficient fruit and vegetable intake (OR = 0.69, 95% CI = 0.58-0.83), MVPA and fruit/vegetable intake (OR = 0.67, 95% CI = 0.52-0.86), and sedentary behavior and fruit/vegetable intake (OR = 0.69, 95% CI = 0.48-0.98) was associated with a lower risk of sarcopenia. CONCLUSION: Our findings indicate that in this large representative sample of older Chinese adults, meeting lifestyle recommendations for MVPA, sedentary behavior, and fruit and vegetable intake protected against sarcopenia.


Asunto(s)
Sarcopenia , Verduras , Humanos , Adulto , Persona de Mediana Edad , Anciano , Frutas , Sarcopenia/epidemiología , Sarcopenia/prevención & control , Estudios Transversales , Fuerza de la Mano , Conducta Sedentaria , Pueblos del Este de Asia , Ejercicio Físico/fisiología
20.
Eur Geriatr Med ; 14(5): 1059-1064, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37392358

RESUMEN

PURPOSE: We aimed to determine the best machine learning (ML) regression model for predicting grip strength in adults above 65 years using various independent variables, such as body composition, blood pressure, and physical performance. METHODS: The data comprised 107,290 participants, of whom 33.3% were male and 66.7% were female in Korean National Fitness Award Data from 2009 to 2019. The dependent variable was grip strength, which was calculated as the mean of right and left grip strength values. RESULTS: The results showed that the CatBoost Regressor had the lowest mean squared error (M [Formula: see text] SE:16.659 ± 0.549) and highest R2 value (M [Formula: see text] SE:0.719 ± 0.009) among the seven prediction models tested. The importance of independent variables in facilitating model learning was also determined, with the Figure-of-8 walk test being the most significant. These findings suggest that walking ability and grip strength are closely related, and the Figure-of- 8 walk test is a reasonable indicator of grip strength in older adults. CONCLUSION: The findings of this study can be used to develop more accurate predictive models of grip strength in older adults.

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