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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(2): 455-460, 2024 Mar 20.
Artículo en Zh | MEDLINE | ID: mdl-38645853

RESUMEN

Objective: To construct a deep learning-based target detection method to help radiologists perform rapid diagnosis of lesions in the CT images of patients with novel coronavirus pneumonia (NCP) by restoring detailed information and mining local information. Methods: We present a deep learning approach that integrates detail upsampling and attention guidance. A linear upsampling algorithm based on bicubic interpolation algorithm was adopted to improve the restoration of detailed information within feature maps during the upsampling phase. Additionally, a visual attention mechanism based on vertical and horizontal spatial dimensions embedded in the feature extraction module to enhance the capability of the object detection algorithm to represent key information related to NCP lesions. Results: Experimental results on the NCP dataset showed that the detection method based on the detail upsampling algorithm improved the recall rate by 1.07% compared with the baseline model, with the AP50 reaching 85.14%. After embedding the attention mechanism in the feature extraction module, 86.13% AP50, 73.92% recall, and 90.37% accuracy were achieved, which were better than those of the popular object detection models. Conclusion: The feature information mining of CT images based on deep learning can further improve the lesion detection ability. The proposed approach helps radiologists rapidly identify NCP lesions on CT images and provides an important clinical basis for early intervention and high-intensity monitoring of NCP patients.


Asunto(s)
Algoritmos , COVID-19 , Aprendizaje Profundo , Neumonía Viral , SARS-CoV-2 , Tomografía Computarizada por Rayos X , Humanos , COVID-19/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Neumonía Viral/diagnóstico por imagen , Infecciones por Coronavirus/diagnóstico por imagen , Infecciones por Coronavirus/diagnóstico , Pandemias , Betacoronavirus
2.
Am J Hematol ; 98(2): 309-321, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36591789

RESUMEN

There has been little consensus on how to quantitatively assess immune reconstitution after hematopoietic stem cell transplantation (HSCT) as part of the standard of care. We retrospectively analyzed 11 150 post-transplant immune profiles of 1945 patients who underwent HSCT between 2012 and 2020. 1838 (94.5%) of the cases were allogeneic HSCT. Using the training set of patients (n = 729), we identified a composite immune signature (integrating neutrophil, total lymphocyte, natural killer, total T, CD4+ T, and B cell counts in the peripheral blood) during days 91-180 after allogeneic HSCT that was predictive of early mortality and moreover simplified it into a formula for a Composite Immune Risk Score. When we verified the Composite Immune Risk Score in the validation (n = 284) and test (n = 391) sets of patients, a high score value was found to be associated with hazard ratios (HR) of 3.64 (95% C.I. 1.55-8.51; p = .0014) and 2.44 (95% C.I., 1.22-4.87; p = .0087), respectively, for early mortality. In multivariate analysis, a high Composite Immune Risk Score during days 91-180 remained an independent risk factor for early mortality after allogeneic HSCT (HR, 1.80; 95% C.I., 1.28-2.55; p = .00085). In conclusion, the Composite Immune Risk Score is easy to compute and could identify the high-risk patients of allogeneic HSCT who require targeted effort for prevention and control of infection.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Humanos , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Modelos de Riesgos Proporcionales , Linfocitos B , Factores de Riesgo
3.
Phytother Res ; 37(12): 5700-5723, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37748788

RESUMEN

Galangin is an important flavonoid with natural activity, that is abundant in galangal and propolis. Currently, various biological activities of galangin have been disclosed, including anti-inflammation, antibacterial effect, anti-oxidative stress and aging, anti-fibrosis, and antihypertensive effect. Based on the above bioactivities, more and more attention has been paid to the role of galangin in neurodegenerative diseases, rheumatoid arthritis, osteoarthritis, osteoporosis, skin diseases, and cancer. In this paper, the natural sources, pharmacokinetics, bioactivities, and therapeutic potential of galangin against various diseases were systematically reviewed by collecting and summarizing relevant literature. In addition, the molecular mechanism and new preparation of galangin in the treatment of related diseases are also discussed, to broaden the application prospect and provide reference for its clinical application. Furthermore, it should be noted that current toxicity and clinical studies of galangin are insufficient, and more evidence is needed to support its possibility as a functional food.


Asunto(s)
Flavonoides , Estrés Oxidativo , Flavonoides/farmacología , Flavonoides/uso terapéutico
4.
Int J Mol Sci ; 24(18)2023 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-37762063

RESUMEN

Obesity is the basis of numerous metabolic diseases and has become a major public health issue due to its rapidly increasing prevalence. Nevertheless, current obesity therapeutic strategies are not sufficiently effective, so there is an urgent need to develop novel anti-obesity agents. Naturally occurring saponins with outstanding bio-activities have been considered promising drug leads and templates for human diseases. Cyclosiversioside F (CSF) is a paramount multi-functional saponin separated from the roots of the food-medicinal herb Astragali Radix, which possesses a broad spectrum of bioactivities, including lowering blood lipid and glucose, alleviating insulin resistance, relieving adipocytes inflammation, and anti-apoptosis. Recently, the therapeutic potential of CSF in obesity and relevant disorders has been gradually explored and has become a hot research topic. This review highlights the role of CSF in treating obesity and obesity-induced complications, such as diabetes mellitus, diabetic nephropathy, cardiovascular and cerebrovascular diseases, and non-alcoholic fatty liver disease. Remarkably, the underlying molecular mechanisms associated with CSF in disease therapy have been partially elucidated, especially PI3K/Akt, NF-κB, MAPK, apoptotic pathway, TGF-ß, NLRP3, Nrf-2, and AMPK, with the aim of promoting the development of CSF as a functional food and providing references for its clinical application in obesity-related disorders therapy.

5.
Int J Mol Sci ; 24(6)2023 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-36982912

RESUMEN

Heart failure (HF) is the most common complication following myocardial infarction, closely associated with ventricular remodeling. Aconitum carmichaelii Debx., a traditional Chinese herb, possesses therapeutic effects on HF and related cardiac diseases. However, its effects and mechanisms on HF-associated cardiac diseases are still unclear. In the present study, a water extraction of toasted Aconitum carmichaelii Debx. (WETA) was verified using UPLC-Q/TOF-MS. The heart function of HF rats was assessed by echocardiography and strain analysis, and myocardial injury was measured by serum levels of CK-MB, cTnT, and cTnI. The pathological changes of cardiac tissues were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and Masson's trichrome staining. Additionally, the levels of inflammation-related genes and proteins and components related to vascular remodeling were detected by RT-qPCR, Western blot, and immunofluorescence. WETA significantly inhibited the changes in echocardiographic parameters and the increase in heart weight, cardiac infarction size, the myonecrosis, edema, and infiltration of inflammatory cells, collagen deposition in heart tissues, and also mitigated the elevated serum levels of CK-MB, cTnT, and cTnI in ISO-induced rats. Additionally, WETA suppressed the expressions of inflammatory genes, including IL-1ß, IL-6, and TNF-α and vascular injury-related genes, such as VCAM1, ICAM1, ANP, BNP, and MHC in heart tissues of ISO-induced HF rats, which were further confirmed by Western blotting and immunofluorescence. In summary, the myocardial protective effect of WETA was conferred through inhibiting inflammatory responses and abnormal vascular remodeling in ISO-treated rats.


Asunto(s)
Aconitum , Insuficiencia Cardíaca , Infarto del Miocardio , Ratas , Animales , Remodelación Vascular , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/metabolismo , Corazón , Infarto del Miocardio/patología , Inflamación
6.
Opt Express ; 30(15): 28170-28181, 2022 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-36236970

RESUMEN

Doppler-free spectroscopy of 40Ca+ on the transition 3D3/2 → 4P1/2 known as the frequency standard for repumping beam of Calcium ion trap was performed by means of optogalvanic detection. This reference signal was applied to measure the frequency stability of laser locked to the resonance of an ultra-low expansion (ULE) glass made cavity. Lamb dip spectrum fitting of this Calcium ion spectra revealed that the long-term drift of our laser system is below 2 MHz per hour. A simple setup for frequency locking of dual colour of lasers at 866 nm and 780 nm was also demonstrated. Consistencies of the frequency difference between these two lasers were measured less than 2 MHz in a hour after stabilizing both lasers to the cavity.

7.
Phytother Res ; 36(4): 1545-1575, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35253930

RESUMEN

Quercitrin is a naturally available type of flavonoid that commonly functions as the dietary ingredient and supplement. So far, a wide spectrum of bioactivities of quercitrin have been revealed, including antioxidative stress, antiinflammation, anti-microorganisms, immunomodulation, analgesia, wound healing, and vasodilation. Based on these various pharmacological activities, increasing studies have focused on the potency of quercitrin in diverse diseases in recent years, such as bone metabolic diseases, gastrointestinal diseases, cardiovascular and cerebrovascular diseases, and others. In this paper, by collecting and summarizing publications from the recent years, the natural sources, pharmacological activities and roles in various diseases, pharmacokinetics, structure-activity relationship, as well as the toxicity of quercitrin were systematically reviewed. In addition, the underlying molecular mechanisms of quercitrin in treating related diseases, the dose-effect relationships, and the novel preparations were discussed on the purpose of broadening the application prospect of quercitrin as functional food and providing reference for its clinical application. Notably, clinical studies of quercitrin are insufficient at present, further high-quality studies are needed to firmly establish the clinical efficacy of quercitrin.


Asunto(s)
Flavonoides , Quercetina , Antioxidantes/metabolismo , Antioxidantes/farmacología , Flavonoides/farmacología , Estrés Oxidativo , Quercetina/análogos & derivados , Quercetina/química , Quercetina/farmacología
8.
Zhongguo Zhong Yao Za Zhi ; 47(17): 4574-4582, 2022 Sep.
Artículo en Zh | MEDLINE | ID: mdl-36164862

RESUMEN

Carthamus tinctorius is proved potent in treating ischemic stroke. Flavonoids, such as safflower yellow, hydroxysafflor yellow A(HSYA), nicotiflorin, safflower yellow B, and kaempferol-3-O-rutinoside, are the main substance basis of C. tinctorius in the treatment of ischemic stroke, and HSYA is the research hotspot. Current studies have shown that C. tinctorius can prevent and treat ischemic stroke by reducing inflammation, oxidative stress, and endoplasmic reticulum stress, inhibiting neuronal apoptosis and platelet aggregation, as well as increasing blood flow. C. tinctorius can regulate the pathways including nuclear factor(NF)-κB, mitogen-activated protein kinase(MAPK), signal transducer and activator of transcription protein 3(STAT3), and NF-κB/NLR family pyrin domain containing 3(NLRP3), and inhibit the activation of cyclooxygenase-2(COX-2)/prostaglandin D2/D prostanoid receptor pathway to alleviate the inflammatory development during ischemic stroke. Additionally, C. tinctorius can relieve oxidative stress injury by inhibiting oxidation and nitrification, regulating free radicals, and mediating nitric oxide(NO)/inducible nitric oxide synthase(iNOS) signals. Furthermore, mediating the activation of Janus kinase 2(JAK2)/STAT3/suppressor of cytokine signaling 3(SOCS3) signaling pathway and phosphoinositide 3-kinase(PI3 K)/protein kinase B(Akt)/glycogen synthase kinase-3ß(GSK3ß) signaling pathway and regulating the release of matrix metalloproteinase(MMP) inhibitor/MMP are main ways that C. tinctorius inhibits neuronal apoptosis. In addition, C. tinctorius exerts the therapeutic effect on ischemic stroke by regulating autophagy and endoplasmic reticulum stress. The present study reviewed the molecular mechanisms of C. tinctorius in the treatment of ischemic stroke to provide references for the clinical application of C. tinctorius.


Asunto(s)
Carthamus tinctorius , Chalcona , Flavonoides , Accidente Cerebrovascular Isquémico , Carthamus tinctorius/química , Chalcona/análogos & derivados , Chalcona/farmacología , Chalcona/uso terapéutico , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Flavonoides/farmacología , Flavonoides/uso terapéutico , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Janus Quinasa 2/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Prostaglandina D2 , Proteínas Proto-Oncogénicas c-akt/metabolismo , Quinonas/farmacología
9.
Phytother Res ; 35(8): 4511-4525, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34236105

RESUMEN

Erianin is a small-molecule compound that is isolated from Dendrobium chrysotoxum Lindl. In recent years, it has been found to have evident antitumor activity in various cancers, such as bladder cancer, cervical cancer, and nasopharyngeal carcinoma. In this study, we assessed the effect of erianin on lung cancer in terms of cell growth inhibition and the related mechanism. First, erianin at a concentration of less than 1 nmol/L exhibited cytotoxicity in H1975, A549, LLC lung cancer cells, did not cause marked growth inhibition in normal lung and kidney cells, induced obvious apoptosis and G2/M phase arrest of cells, and inhibited the migration and invasion of lung cancer cells in vitro. Second, in a mouse xenograft model of lewis lung cancer (LLC), oral administration of erianin (50, 35, and 10 mg kg-1  day-1 for 12 days) substantially inhibited nodule growth, reduced the fluorescence counts of lewis cells and the percentage vascularity of tumor tissues, increased the number of apoptotic tumor cells, the thymus indices, up-regulated the levels of interleukin (IL)-2 and tumor necrosis factor-α (TNF-α), decreased IL-10 levels and the spleen index, and enhanced immune function. Lastly, the possible targets of erianin were determined by molecular docking and verified via western blot assay. The results indicated that erianin may achieve the above effects via inhibiting the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in vitro and vivo. Taken together, the results showed that erianin had obvious antitumor effects via inhibiting the PI3K/Akt/mTOR pathway in vitro and vivo and may have potential clinical value for the treatment of lung cancer.


Asunto(s)
Bibencilos/farmacología , Neoplasias Pulmonares , Fenol/farmacología , Transducción de Señal/efectos de los fármacos , Células A549 , Animales , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Dendrobium , Humanos , Pulmón , Neoplasias Pulmonares/tratamiento farmacológico , Ratones , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Serina-Treonina Quinasas TOR
10.
Ecotoxicol Environ Saf ; 138: 71-77, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28012367

RESUMEN

The antioxidation system and accumulation ability of Moso bamboo (Phyllostachys pubescens), which is a valuable remediation material with large biomass and rapid growth rate were studied in hydroponics and pot experiments. In hydroponics experiment, TBARS concentrations and SOD activities decreased with increase of Pb treatments. The activities of POD boost up with elevated Pb treatments, and reached peak level with application of 400µM Pb. Proline concentrations reduced with application of 20µM Pb and then enhanced consistently with application of 100 and 400µM Pb. The biomass of Moso bamboo improved with increase of Pb treatments upto 400mgkg-1, and then decreased with application of each additional increment of Pb in pot experiment. Application of 800mgkg-1 Pb showed significant increase of photosynthetic pigments, however, non significant variation was observed for other treatments. The Pb concentration in roots, stems and leaves attained 523mgkg-1, 303mgkg-1 and 222mgkg-1 respectively with application of 1600mgkg-1 Pb compared with control. Analysis of TEM-EDX revealed that Pb in cell was mostly concentrated in cytoplasm then in cell wall and followed by vacuole. It is concluded that Moso bamboo may be potential remediation species for phytoremediation in low Pb contaminated soils.


Asunto(s)
Antioxidantes/metabolismo , Biodegradación Ambiental , Plomo/toxicidad , Poaceae/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Análisis de Varianza , Biomasa , Clorofila/metabolismo , Plomo/metabolismo , Estrés Oxidativo/efectos de los fármacos , Peroxidasa/metabolismo , Hojas de la Planta/metabolismo , Raíces de Plantas/metabolismo , Tallos de la Planta/metabolismo , Poaceae/metabolismo , Contaminantes del Suelo/metabolismo , Superóxido Dismutasa/metabolismo
11.
Z Naturforsch C J Biosci ; 69(9-10): 399-406, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25711041

RESUMEN

A hydroponic culture experiment was conducted to study the effect of copper toxicity on root morphology, ultrastructure, and copper accumulation in Moso bamboo (Phyllostachys pubescens). Root ultrastructure of Moso bamboo was studied by transmission electron microscopy and scanning electron microscopy. Application of 200 µM Cu resulted in an accumulation of 810 mg kg(-1) dry weight and 91 mg kg(-1) dry weight Cu in roots and shoots, respectively. The majority of the plants did not survive the application of 400 µM Cu. Biomass production declined consistently with application of each additional increment of Cu. Root growth was more severely inhibited than shoot growth. Cu adversely affected the root morphology of the plants, however, root surface area and number of root tips increased slightly at low levels of Cu. Root cell ultrastructure and organelles changed significantly under Cu stress, in particular, cell walls, mitochondria, and xylem parenchyma were affected.


Asunto(s)
Cobre/metabolismo , Cobre/toxicidad , Raíces de Plantas/efectos de los fármacos , Poaceae/efectos de los fármacos , Biodegradación Ambiental , Biomasa , Pared Celular/metabolismo , Relación Dosis-Respuesta a Droga , Hidroponía , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Mitocondrias/metabolismo , Raíces de Plantas/ultraestructura , Xilema/metabolismo
12.
Aging Dis ; 15(2): 739-754, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37548945

RESUMEN

Neuroinflammation, characterized by the secretion of abundant inflammatory mediators, pro-inflammatory polarization of microglia, and the recruitment of infiltrating myeloid cells to foci of inflammation, drives or exacerbates the pathological processes of central nervous system disorders, especially in neurodegenerative diseases. Autophagy plays an essential role in neuroinflammatory processes, and the underlaying physiological mechanisms are closely correlated with neuroinflammation-related signals. Inhibition of mTOR and activation of AMPK and FOXO1 enhance autophagy and thereby suppress NLRP3 inflammasome activity and apoptosis, leading to the relief of neuroinflammatory response. And autophagy mitigates neuroinflammation mainly manifested by promoting the polarization of microglia from a pro-inflammatory to an anti-inflammatory state, reducing the production of pro-inflammatory mediators, and up-regulating the levels of anti-inflammatory factors. Notably, epigenetic modifications are intimately associated with autophagy and the onset and progression of various brain diseases. Non-coding RNAs, including microRNAs, circular RNAs and long noncoding RNAs, and histone acetylation have been reported to adjust autophagy-related gene and protein expression to alleviate inflammation in neurological diseases. The present review primarily focuses on the role and mechanisms of autophagy in neuroinflammatory responses, as well as epigenetic modifications of autophagy in neuroinflammation to reveal potential therapeutic targets in central nervous system diseases.


Asunto(s)
Enfermedades Neurodegenerativas , Enfermedades Neuroinflamatorias , Humanos , Epigénesis Genética , Inflamación/genética , Antiinflamatorios/farmacología , Autofagia/genética , Mediadores de Inflamación/farmacología , Enfermedades Neurodegenerativas/genética
13.
Int Urol Nephrol ; 56(10): 3361-3380, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38814370

RESUMEN

BACKGROUND AND OBJECTIVE: Rapid advances in computer vision (CV) have the potential to facilitate the examination, diagnosis, and treatment of diseases of the kidney. The bibliometric study aims to explore the research landscape and evolving research focus of the application of CV in kidney medicine research. METHODS: The Web of Science Core Collection was utilized to identify publications related to the research or applications of CV technology in the field of kidney medicine from January 1, 1900, to December 31, 2022. We analyzed emerging research trends, highly influential publications and journals, prolific researchers, countries/regions, research institutions, co-authorship networks, and co-occurrence networks. Bibliographic information was analyzed and visualized using Python, Matplotlib, Seaborn, HistCite, and Vosviewer. RESULTS: There was an increasing trend in the number of publications on CV-based kidney medicine research. These publications mainly focused on medical image processing, surgical procedures, medical image analysis/diagnosis, as well as the application and innovation of CV technology in medical imaging. The United States is currently the leading country in terms of the quantities of published articles and international collaborations, followed by China. Deep learning-based segmentation and machine learning-based texture analysis are the most commonly used techniques in this field. Regarding research hotspot trends, CV algorithms are shifting toward artificial intelligence, and research objects are expanding to encompass a wider range of kidney-related objects, with data dimensions used in research transitioning from 2D to 3D while simultaneously incorporating more diverse data modalities. CONCLUSION: The present study provides a scientometric overview of the current progress in the research and application of CV technology in kidney medicine research. Through the use of bibliometric analysis and network visualization, we elucidate emerging trends, key sources, leading institutions, and popular topics. Our findings and analysis are expected to provide valuable insights for future research on the use of CV in kidney medicine research.


Asunto(s)
Bibliometría , Humanos , Nefrología , Enfermedades Renales , Investigación Biomédica/tendencias , Inteligencia Artificial
14.
Food Chem ; 460(Pt 2): 140614, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39089013

RESUMEN

Migraine as a common neurological disorder still lacks effective therapies. Tetramethylpyrazine (TMP) is the main bioactive component from Ligusticum chuanxiong hort., a traditional edible-medicinal herb. This study aimed to investigate the action of TMP on migraine by metabolomics with mass spectrometry imaging (MSI) analysis and molecular exploring, including random forest model analysis, KEGG enrichment analysis and metabolite-metabolite interaction network analysis. The results indicated that 26 key representative metabolic biomarkers were identified, especially γ-glu-cys, which were highly related to glutathione (GSH) metabolism. MSI found the abundance of eleven endogenous metabolites were modulated by TMP, particularly glucose, the most important energy metabolism molecule, and GSH were increased that maintains intracellular redox balance, which was consistent with activation of Nrf2 signals by TMP. These findings provide insights into the effectiveness of metabolomics integrated with MSI in explaining the metabolic mechanisms of TMP, and afford valuable information for healthy development of TMP in migraine.


Asunto(s)
Espectrometría de Masas , Metabolómica , Trastornos Migrañosos , Pirazinas , Pirazinas/metabolismo , Pirazinas/análisis , Trastornos Migrañosos/metabolismo , Trastornos Migrañosos/tratamiento farmacológico , Humanos , Animales , Ratas , Ligusticum/química , Ligusticum/metabolismo , Biomarcadores/metabolismo , Biomarcadores/análisis , Ratas Sprague-Dawley , Masculino , Glutatión/metabolismo , Medicamentos Herbarios Chinos/metabolismo , Medicamentos Herbarios Chinos/química
15.
Blood Rev ; : 101226, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39164126

RESUMEN

Measurable residual disease (MRD)-testing is used in many haematological cancers to estimate relapse risk and to direct therapy. Sometimes MRD-test results are used for regulatory approval. However, some people including regulators wrongfully believe results of MRD-testing are highly accurate and of proven efficacy in directing therapy. We review MRD-testing technologies and evaluate the accuracy of MRD-testing for predicting relapse and the strength of evidence supporting efficacy of MRD-guided therapy. We show that at the individual level MRD-test results are often an inaccurate relapse predictor. Also, no convincing data indicate that increasing therapy-intensity based on a positive MRD-test reduces relapse risk or improves survival. We caution against adjusting therapy-intensity based solely on results of MRD-testing.

16.
Nanoscale ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225229

RESUMEN

Theoretically determining the lowest-energy structure of a cluster has been a persistent challenge due to the inherent difficulty in accurate description of its potential energy surface (PES) and the exponentially increasing number of local minima on the PES with the cluster size. In this work, density-functional theory (DFT) calculations of Co clusters were performed to construct a dataset for training deep neural networks to deduce a deep potential (DP) model with near-DFT accuracy while significantly reducing computational consumption comparable to classic empirical potentials. Leveraging the DP model, a high-efficiency hybrid differential evolution (HDE) algorithm was employed to search for the lowest-energy structures of CoN (N = 11-50) clusters. Our results revealed 38 of these clusters superior to those recorded in the Cambridge Cluster Database and identified diverse architectures of the clusters, evolving from layered structures for N = 11-27 to Marks decahedron-like structures for N = 28-42 and to icosahedron-like structures for N = 43-50. Subsequent analyses of the atomic arrangement, structural similarity, and growth pattern further verified their hierarchical structures. Meanwhile, several highly stable clusters, i.e., Co13, Co19, Co22, Co39, and Co43, were discovered by the energetic analyses. Furthermore, the magnetic stability of the clusters was verified, and a competition between the coordination number and bond length in affecting the magnetic moment was observed. Our study provides high-accuracy and high-efficiency prediction of the optimal structures of clusters and sheds light on the growth trend of Co clusters containing tens of atoms, contributing to advancing the global optimization algorithms for effective determination of cluster structures.

17.
EJHaem ; 5(2): 333-345, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38633121

RESUMEN

ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low-risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low-risk ETV6::RUNX1-positive B-cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome-wide transcriptome and single-nucleotide variants. We found high TIMD4 expression (> 85th-percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR] = 5.07 [1.76, 14.62]; p = 0.03). In an independent validation cohort of low-risk ETV6::RUNX1-positive B-cell ALL (N = 68) high TIMD4 expression at diagnosis had an HR = 4.78 [1.07, 21.36] (p = 0.04) for early relapse. In another validation cohort including 78 children with low-risk ETV6::RUNX1-negative B-cell ALL, high TIMD4 expression at diagnosis had an HR = 3.93 [1.31, 11.79] (p = 0.01). Our results suggest high TIMD4 expression at diagnosis in low-risk B-cell ALL in children might be associated with high risk for early relapse.

18.
Front Pharmacol ; 14: 1265960, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37920216

RESUMEN

Naturally occurring flavonoids have long been utilized as essential templates for the development of novel drugs and as critical ingredients for functional foods. Astragalin (AG) is a natural flavonoid that can be isolated from a variety of familiar edible plants, such as the seeds of green tea, Morus alba L., and Cuscuta chinensis. It is noteworthy that AG has a wide range of pharmacological activities and possesses therapeutic effects against a variety of diseases, covering cancers, osteoarthritis, osteoporosis, ulcerative colitis, mastitis, obesity, diabetes mellitus, diabetic complications, ischemia/reperfusion injury, neuropathy, respiratory diseases, and reproductive system diseases. This article reviewed the natural source and pharmacokinetics of AG and systematically summarized the pharmacological activities and potential mechanisms of AG in treating diverse diseases in order to promote the development of AG as a functional food, in doing so providing references for its clinical application in disease therapy.

19.
Food Chem ; 420: 136101, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37059021

RESUMEN

Natural edible pigments play a paramount part in the food industry. Procyanidin B2 (PB2), one of the most representative naturally occurring edible pigments, is usually isolated from the seeds, fruits, and leaves of lots of common plants, such as grapes, Hawthorn, black soybean, as well as blueberry, and functions as a food additive in daily life. Notably, PB2 has numerous bioactivities and possesses the potential to treat/prevent a wide range of human diseases, such as diabetes mellitus, diabetic complications, atherosclerosis, and non-alcoholic fatty liver disease, and the underlying mechanisms were partially elucidated, including mediating signaling pathways like NF-κB, MAPK, PI3K/Akt, apoptotic axis, and Nrf-2/HO-1. This paper presents a review of the natural sources, bioactivities, and the therapeutic/preventive potential of PB2 and the possible mechanisms, with the aim of promoting the development of PB2 as a functional food and providing references for its clinical application in the treatment of diseases.


Asunto(s)
Biflavonoides , Catequina , Enfermedad del Hígado Graso no Alcohólico , Proantocianidinas , Humanos , Alimentos Funcionales , Fosfatidilinositol 3-Quinasas , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Transducción de Señal
20.
Front Immunol ; 14: 1287048, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37767097

RESUMEN

[This corrects the article DOI: 10.3389/fimmu.2023.1089001.].

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