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1.
Front Endocrinol (Lausanne) ; 15: 1426380, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38978623

RESUMEN

Diabetes, a multifaceted metabolic disorder, poses a significant global health burden with its increasing prevalence and associated complications, such as diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, and diabetic angiopathy. Recent studies have highlighted the intricate interplay between N6-methyladenosine (m6A) and non-coding RNAs (ncRNAs) in key pathways implicated in these diabetes complications, like cell apoptosis, oxidative stress, and inflammation. Thus, understanding the mechanistic insights into how m6A dysregulation impacts the expression and function of ncRNAs opens new avenues for therapeutic interventions targeting the m6A-ncRNAs axis in diabetes complications. This review explores the regulatory roles of m6A modifications and ncRNAs, and stresses the role of the m6A-ncRNA axis in diabetes complications, providing a therapeutic potential for these diseases.


Asunto(s)
Adenosina , Complicaciones de la Diabetes , ARN no Traducido , Humanos , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , ARN no Traducido/genética , Animales , Estrés Oxidativo
2.
Front Immunol ; 15: 1397716, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38873605

RESUMEN

Background: To evaluate the methodological quality, report quality, and evidence quality of meta-analysis (MA) and systematic review (SR) on the efficacy of probiotics in the treatment of rheumatoid arthritis (RA). Methods: Databases were used to identify eligible SRs/MAs until February 12, 2024. The methodological quality of the studies was assessed using AMSTAR-2 tool, the quality of the literature reports was scored using PRISMA checklists, and the quality of the evidence was graded using GRADE system. Results: Seven reviews including 21 outcomes were included. Methodological quality of the included reviews was of general low, and the entries with poor scores were 2, 4, and 7. By PRISMA checklists, there were some reporting deficiencies, and quality problems were mainly reflected in the reporting registration and protocol, comprehensive search strategy and additional analysis. GRADE results elevated the quality of evidence to be low or very low overall. Conclusions: Probiotics may have a therapeutic effect on RA, based on the evidence provided by the SRs/MAs in this overview. Nevertheless, there is still a lack of conclusive evidence due to methodological limitations in the included research. To make trustworthy judgments regarding the efficacy of probiotics in the treatment of RA, more large-scale, high-quality randomized controlled trials are still required.


Asunto(s)
Artritis Reumatoide , Probióticos , Revisiones Sistemáticas como Asunto , Probióticos/uso terapéutico , Artritis Reumatoide/terapia , Humanos , Resultado del Tratamiento , Metaanálisis como Asunto
3.
Biomed Chromatogr ; 38(8): e5925, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38837800

RESUMEN

The rapid and accurate detection of illegal adulteration of chemical drugs into dietary supplements is a big challenge in the food chemistry field. Detection of compounds without a standard reference is even more difficult; however, this is a common situation. Here in this study, a novel "standard-free detection of adulteration" (SFDA) method was proposed and phosphodiesterase-5 inhibitor derivatives were used as an example to figure out the possibility and reliability of this SFDA method. After analysis by quadrupole coupled time of flight-tandem mass spectrometry detection and multivariable statistics, six common fragment ions were chosen to indicate whether adulteration was present or not, while 20 characteristic fragment ions indicated whether adulteration was by nitrogen-containing heterocycles or by anilines. Furthermore, the quantitative methods were conducted by high-performance liquid chromatography-tandem mass spectrometry. In a word, this strategy allows for a quick determination of dietary supplement adulteration without any need for standard materials, improving the efficacy of food safety testing.


Asunto(s)
Suplementos Dietéticos , Contaminación de Medicamentos , Citrato de Sildenafil , Espectrometría de Masas en Tándem , Suplementos Dietéticos/análisis , Citrato de Sildenafil/análisis , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Reproducibilidad de los Resultados , Límite de Detección , Modelos Lineales , Inhibidores de Fosfodiesterasa 5/análisis
4.
Theor Appl Genet ; 137(7): 170, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38913206

RESUMEN

The timely degradation of tapetum, the innermost somatic anther cell layer in flowering plants, is critical for pollen development. Although several genes involved in tapetum development have been characterized, the molecular mechanisms underlying tapetum degeneration remain elusive. Here, we showed that mutation in Abnormal Degraded Tapetum 1 (ADT1) resulted in overaccumulation of Reactive Oxygen Species (ROS) and abnormal anther development, causing earlier tapetum Programmed Cell Death (PCD) and pollen abortion. ADT1 encodes a nuclear membrane localized protein, which is strongly expressed in the developing microspores and tapetal cells during early anther development. Moreover, ADT1 could interact with metallothionein MT2b, which was related to ROS scavenging and cell death regulation. These findings indicate that ADT1 is required for proper timing of tapetum PCD by regulating ROS homeostasis, expanding our understanding of the regulatory network of male reproductive development in rice.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Mutación , Oryza , Proteínas de Plantas , Polen , Especies Reactivas de Oxígeno , Oryza/genética , Oryza/crecimiento & desarrollo , Oryza/metabolismo , Polen/crecimiento & desarrollo , Polen/genética , Especies Reactivas de Oxígeno/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Muerte Celular , Flores/crecimiento & desarrollo , Flores/genética , Apoptosis
5.
PeerJ ; 12: e17519, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903882

RESUMEN

Houttuynia cordata Thunb., also known as Yuxingcao in Chinese, occupies a pivotal role in Asian traditional medicine and cuisine. The aerial parts and underground stems of H. cordata exhibit remarkable chemical diversity, particularly in essential oil. Nevertheless, the mechanisms regulating essential oil biosynthesis in H. cordata remain unclear. In this study, we present a quantitative overview of the proteomes across four tissues (flower, stem, leaf, and underground stem) of H. cordata, achieved through the application of the isobaric tag for relative and absolute quantitation (iTRAQ). Our research findings indicate that certain crucial ribosomal proteins and their interactions may significantly impact the production of essential oils in H. cordata. These results offer novel insights into the roles of ribosomal proteins and their associations in essential oil biosynthesis across various organisms of H. cordata.


Asunto(s)
Houttuynia , Aceites Volátiles , Proteómica , Proteínas Ribosómicas , Houttuynia/metabolismo , Houttuynia/química , Aceites Volátiles/metabolismo , Proteínas Ribosómicas/metabolismo , Proteómica/métodos , Proteínas de Plantas/metabolismo , Proteoma/metabolismo
6.
Toxicol Appl Pharmacol ; 486: 116951, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38705401

RESUMEN

Cardiac lipotoxicity is a prevalent consequence of lipid metabolism disorders occurring in cardiomyocytes, which in turn precipitates the onset of heart failure. Mimetics of brain-derived neurotrophic factor (BDNF), such as 7,8-dihydroxyflavone (DHF) and 7,8,3'-trihydroxyflavone (THF), have demonstrated significant cardioprotective effects. However, it remains unclear whether these mimetics can protect cardiomyocytes against lipotoxicity. The aim of this study was to examine the impact of DHF and THF on the lipotoxic effects induced by palmitic acid (PA), as well as the concurrent mitochondrial dysfunction. H9c2 cells were subjected to treatment with PA alone or in conjunction with DHF or THF. Various factors such as cell viability, lactate dehydrogenase (LDH) release, death ratio, and mitochondrial function including mitochondrial membrane potential (MMP), mitochondrial-derived reactive oxygen species (mito-SOX) production, and mitochondrial respiration were assessed. PA dose-dependently reduced cell viability, which was restored by DHF or THF. Additionally, both DHF and THF decreased LDH content, death ratio, and mito-SOX production, while increasing MMP and regulating mitochondrial oxidative phosphorylation in cardiomyocytes. Moreover, DHF and THF specifically activated Akt signaling. The protective effects of DHF and THF were abolished when an Akt inhibitor was used. In conclusion, BDNF mimetics attenuate PA-induced injury in cardiomyocytes by alleviating mitochondrial impairments through the activation of Akt signaling.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Flavonas , Potencial de la Membrana Mitocondrial , Miocitos Cardíacos , Ácido Palmítico , Proteínas Proto-Oncogénicas c-akt , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Ácido Palmítico/toxicidad , Ácido Palmítico/farmacología , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ratas , Línea Celular , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Flavonas/farmacología , Supervivencia Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Especies Reactivas de Oxígeno/metabolismo
7.
Front Oncol ; 14: 1398968, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38817899

RESUMEN

Objective: The study aimed to build and validate a competitive risk nomogram to predict the cumulative incidence of hepatocellular carcinoma (HCC) for patients with hepatitis B virus (HBV)-related cirrhosis. Methods: A total of 1401 HBV-related cirrhosis patients were retrospectively enrolled from January 1, 2011 to December 31, 2014. Application of 20 times imputation dealt with missing data using multiple imputation by chained equations (MICE). The patients were randomly divided into a training set (n = 1017) and a validation set (n = 384) at a ratio of 3:1. A prediction study was carried out using a competing risk model, where the event of interest was HCC and the competing events were death and liver transplantation, and subdistribution hazard ratios (sHRs) with 95% CIs were reported. The multivariate competing risk model was constructed and validated. Results: There was a negligible difference between the original database and the 20 imputed datasets. At the end of follow-up, the median follow-up time was 69.9 months (interquartile range: 43.8-86.6). There were 31.5% (442/1401) of the patients who developed HCC, with a 5-year cumulative incidence of 22.9 (95%CI, 20.8%-25.2%). The univariate and multivariate competing risk regression and construction of the nomogram were performed in 20 imputed training datasets. Age, sex, antiviral therapy history, hepatitis B e antigen, alcohol drinking history, and alpha-fetoprotein levels were included in the nomogram. The area under receiver operating characteristic curve values at 12, 24, 36, 60, and 96 months were 0.68, 0.69, 0.70, 0.68, and 0.80, and the Brier scores were 0.30, 0.25, 0.23, 0.21, and 0.20 in the validation set. According to the cumulative incidence function, the nomogram effectively screened out high-risk HCC patients from low-risk patients in the presence of competing events (Fine-Gray test p < 0.001). Conclusion: The competitive risk nomogram was allowed to be used for predicting HCC risk in individual patients with liver cirrhosis, taking into account both the association between risk factors and HCC and the modifying effect of competition events on this association.

8.
Anal Chim Acta ; 1311: 342735, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38816164

RESUMEN

BACKGROUND: In reversed-phase liquid chromatography, the C18 alkyl bonded phase, as the primary stationary phase, is widely used in pharmaceutical and food analysis. The phenyl bonded phase often serves as a complementary choice to the C18 phase to enhance the separation performance of specific categories of compounds. However, both C18 and the currently available phenyl bonded phase chromatography columns show room for further optimization in improving the separation efficiency of specific compound classes, such as dihydroflavonoids. Additionally, the potential role and impact of introducing phosphorus groups into chromatographic stationary phases have not been fully explored, indicating a promising direction for research. RESULTS: In the present work, we prepared a novel phenyl stationary phase by bonding 9-oxa-10-phosphaphenanthrene 10-oxide onto silica gel. The obtained material was characterized by scanning electron microscopy, fourier transforms infrared spectroscopy, and elemental analysis. The results show that 9-oxa-10-phosphaphenanthrene 10-oxide was successfully bonded on the silica surface with a load of 3.90 %. Further chromatographic characterization in high-performance liquid chromatography exhibited high column efficiency (40,792 plates m-1 for the determination of biphenyl) and good stability (RSD of 0.28 %∼5.38 %). Moreover, we made a detailed study of the column separation mechanism by nuclear magnetic resonance spectroscopy titration experiment. Comparing to commercial phenyl column, the proposed stationary phase showed shorter retention time and higher throughput. In addition, the stationary phase has a strong ability to separate multiple types of compounds, which provides a new strategy for the separation of complex samples, such as active ingredients in traditional Chinese medicine. SIGNIFICANCE: We have developed a novel phenyl column and conducted a comprehensive examination of its chromatographic performance, demonstrating excellent separation capabilities and high efficiency for both nonpolar and moderately polar aromatic compounds. Additionally, we explored the impact of phosphorus-containing groups on the separation performance of chromatographic stationary phases.

9.
Front Public Health ; 12: 1399704, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737855

RESUMEN

Background: Fruits are essential for health, yet their consumption in children is inadequate, with unclear influencing factors. Methods: A cross-sectional study was conducted among students in grades 3-12 in Beijing, China, from September 2020 to June 2021. Fruit consumption in children was surveyed using a self-administered food frequency questionnaire. Additionally, children's food and nutrition literacy and family food environments were assessed using the "Food and Nutrition Literacy Questionnaire for Chinese School-age Children" and the "Family Food Environment Questionnaire for Chinese School-age Children," respectively. Results: Out of 10,000 participating children, 62.5% consumed fruit daily, with a lower frequency among boys (59.3%) compared to girls (65.8%), and among senior students (48.6%) compared to junior (63.6%) and primary students (71.2%). Fruit consumption was positively associated with other healthy foods (vegetables, whole grains, etc.) and negatively with unhealthy foods (sugared soft drinks). Children with higher food and nutrition literacy consumed fruits daily more frequently (82.4% vs. 59.9%, ORs = 2.438, 95%CI: 2.072-2.868). A significant positive correlation was found between children's fruit consumption and a healthy family food environment (66.4% vs. 50.2%, OR = 1.507, 95%CI: 1.363-1.667). Conclusion: The results indicate that individual food and nutrition literacy and family food environment are key positive predictors of children's fruit consumption. Future interventions should focus on educating children and encouraging parents to foster supportive family environments.


Asunto(s)
Frutas , Humanos , Femenino , Masculino , Estudios Transversales , Niño , Encuestas y Cuestionarios , Conducta Alimentaria , Beijing , Adolescente , China , Estudiantes/estadística & datos numéricos , Alfabetización en Salud/estadística & datos numéricos , Familia
10.
J Control Release ; 370: 626-642, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38734314

RESUMEN

Severe nephrotoxicity and infusion-related side effects pose significant obstacles to the clinical application of Amphotericin B (AmB) in life-threatening systemic fungal infections. In pursuit of a cost-effective and safe formulation, we have introduced multiple phenylboronic acid (PBA) moieties onto a linear dendritic telodendrimer (TD) scaffold, enabling effective AmB conjugation via boronate chemistry through a rapid, high yield, catalysis-free and dialysis-free "Click" drug loading process. Optimized AmB-TD prodrugs self-assemble into monodispersed micelles characterized by small particle sizes and neutral surface charges. AmB prodrugs sustain drug release in circulation, which is accelerated in response to the acidic pH and Reactive Oxygen Species (ROS) in the infection and inflammation. Prodrugs mitigate the AmB aggregation status, reduce cytotoxicity and hemolytic activity compared to Fungizone®, and demonstrate superior antifungal activity to AmBisome®. AmB-PEG5kBA4 has a comparable maximum tolerated dose (MTD) to AmBisome®, while over 20-fold increase than Fungizone®. A single dose of AmB-PEG5kBA4 demonstrates superior efficacy to Fungizone® and AmBisome® in treating systemic fungal infections in both immunocompetent and immunocompromised mice.


Asunto(s)
Anfotericina B , Antifúngicos , Fungemia , Profármacos , Animales , Anfotericina B/administración & dosificación , Anfotericina B/farmacología , Anfotericina B/química , Anfotericina B/farmacocinética , Profármacos/administración & dosificación , Profármacos/química , Profármacos/farmacología , Antifúngicos/administración & dosificación , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/uso terapéutico , Humanos , Fungemia/tratamiento farmacológico , Nanopartículas/química , Liberación de Fármacos , Micelas , Ratones , Femenino , Química Clic , Candida albicans/efectos de los fármacos , Polietilenglicoles/química , Polietilenglicoles/administración & dosificación
11.
J Food Sci ; 89(6): 3569-3576, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38745380

RESUMEN

This study aims to investigate the impact of four key factors, namely, temperature, water source, metal ion, and pH, on the stability of molecular chirality of dihydromyricetin (DMY) and proposed effective strategies for configuration protection. The findings reveal that temperatures exceeding 80°C could accelerate the racemization process of DMY, with a significant increase in racemization observed at 100°C. In addition, DMY exhibited heightened stability in ultrapure water as compared to various water sources, including pure water-1, pure water-2, mineral water, and running water. Notably, the presence of Fe2+ displayed an inhibitory effect on the racemization of DMY, whereas Mg2+, Ca2+, and Mn2+ showed a substantial promotional effect. Additionally, acidic conditions (pH < 5.0) were found to be protective for maintaining the stability of DMY, whereas alkaline conditions (pH > 9.0) were observed to be detrimental. Meanwhile, we first identified the presence of another pair of DMY isomers in this work.


Asunto(s)
Flavonoles , Flavonoles/farmacología , Flavonoles/química , Concentración de Iones de Hidrógeno , Estereoisomerismo , Agua/química , Temperatura , Isomerismo , Té/química
12.
Ann Diagn Pathol ; 72: 152321, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38759563

RESUMEN

Retroperitoneal Ewing sarcomas (RES) are very rare and mostly described in case reports. The purpose of this study was to retrospectively analyze the clinicopathology, molecular characteristics, biological behavior, and therapeutic information of 13 cases of primary RES with immunohistochemical staining, fluorescence in situ hybridization, RT-PCR and NGS sequencing detection techniques. The thirteen patients included eight males and five females with a mean age of 34 years. Morphologically, the tumors were comprised of small round or epithelial-like cells with vacuolated cytoplasm (6/13,46 %) arranged in diffuse, nested (8/13,62 %) and perivascular (7/13,54 %) patterns. Unusual morphologic patterns, such as meningioma-like swirling structures and sieve-like structures were relatively novel findings. Immunohistochemical studies showed CD99 (12/13; 92 %), CD56 (11/13; 85 %), NKX2.2 (9/13; 69 %), PAX7 (10/11;91 %) and CD117(6/9;67 %) to be positive.12 cases (92 %) demonstrated EWSR1 rearrangement and 3 cases displayed EWSR1::FLI1 fusion by FISH. ERCC4 splice-site variant, a novel pathogenic variant, was discovered for the first time via RNA sequencing. With a median follow-up duration of 14 months (6 to 79 months), 8/13 (62 %) patients died, while 5/13(38 %) survived. Three cases recurred, and five patients developed metastasis to the liver (2 cases), lung (2 cases) and bone (1 case). RES is an aggressive, high-grade tumor, prone to multiple recurrences and metastases, with distinctive morphologic, immunohistochemical, and molecular genetic features. ERCC4 splicing mutation, which is a novel pathogenic variant discovered for the first time, with possible significance for understanding the disease, as well as the development of targeted drugs.


Asunto(s)
Proteína Homeobox Nkx-2.2 , Proteína EWS de Unión a ARN , Neoplasias Retroperitoneales , Sarcoma de Ewing , Humanos , Sarcoma de Ewing/genética , Sarcoma de Ewing/patología , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/metabolismo , Masculino , Femenino , Adulto , Neoplasias Retroperitoneales/genética , Neoplasias Retroperitoneales/patología , Neoplasias Retroperitoneales/diagnóstico , Estudios Retrospectivos , Persona de Mediana Edad , Adulto Joven , Adolescente , Proteína EWS de Unión a ARN/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Hibridación Fluorescente in Situ/métodos , Reordenamiento Génico , Inmunohistoquímica/métodos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Fusión Oncogénica/genética , Niño , Proteínas Nucleares , Proteínas de Homeodominio , Proteínas de Pez Cebra
13.
Front Microbiol ; 15: 1356171, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38601928

RESUMEN

Introduction: By implementing small-scale and efficient fertilization techniques, it is possible to enhance the activity of microorganisms, thereby improving soil carbon sequestration and ecological value in agriculture. Methods: In this study, field experiments were conducted using various types of fertilizers: organic fertilizer, microbial fungal fertilizer, composite fertilizer, and an unfertilized control (CK). Additionally, different dosages of compound fertilizers were applied, including 0.5 times compound fertilizers, constant compound fertilizers, 1.5 times compound fertilizers and CK. Using advanced technologies such as Illumina MiSeq high-throughput sequencing, PICRUSt2 prediction, Anosim analysis, redundancy analysis, canonical correlation analysis, and correlation matrix, soil organic carbon (SOC) content and components, bacterial diversity, metabolic functions, and interaction mechanisms were examined in different fields. Results and Discussion: The results showed pronounced effects of various fertilization modes on SOC and the bacterial community, particularly in the topsoil layer (0-20 cm). Organic fertilizer treatments increased the richness and diversity of bacterial communities in the soil. However, conventional doses and excessive application of compound fertilizers reduced the diversity of soil bacterial communities and SOC content. Additionally, different fertilization treatments led to an increase in easily oxidizable organic carbon (EOC) contents. Interestingly, the relationship between SOC components and soil bacteria exhibited inconsistency. EOC was positively correlated with the bacterial diversity index. Additionally, Chloroflexi exhibited a negative correlation with both SOC and its components. The influence of metabolismon primary metabolic functions on the content of SOC components in the soil was more notable. It included seven types of tertiary functional metabolic pathways significantly correlated with SOC components (p < 0.05). Purpose and Significance: These findings enhance the understanding of the relative abundance of bacterial communities, particularly those related to the carbon cycle, by adjusting agricultural fertilization patterns. This adjustment serves as a reference for enhancing carbon sinks and reducing emissions in agricultural soils.

14.
Front Biosci (Landmark Ed) ; 29(4): 136, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38682184

RESUMEN

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder characterized by aberrant amyloid precursor protein (APP) cleavage, pathological aggregations of beta-amyloid (Aß) that make up Aß plaques and hyperphosphorylation of Tau that makes up neurofibrillary tangles (NFTs). Although progress has been made in research on AD, the fundamental causes of this disease have not been fully elucidated. Recent studies have shown that vascular dysfunction especially the loss of pericytes plays a significant role in the onset of AD. Pericytes play a variety of important roles in the nervous system including the regulation of the cerebral blood flow (CBF), the formation and maintenance of the blood-brain barrier (BBB), angiogenesis, and the clearance of toxic substances from the brain. Pericytes participate in the transport of Aß through various receptors, and Aß acts on pericytes to cause them to constrict, detach, and die. The loss of pericytes elevates the levels of Aß1-40 and Aß1-42 by disrupting the integrity of the BBB and reducing the clearance of soluble Aß from the brain interstitial fluid. The aggravated deposition of Aß further exacerbates pericyte dysfunction, forming a vicious cycle. The combined influence of these factors eventually results in the loss of neurons and cognitive decline. Further exploration of the interactions between pericytes and Aß is beneficial for understanding AD and could lead to the identification of new therapeutic targets for the prevention and treatment of AD. In this review, we explore the characterization of pericytes, interactions between pericytes and other cells in the neurovascular unit (NVU), and the physiological functions of pericytes and dysfunctions in AD. This review discusses the interactions between pericytes and Aß, as well as current and further strategies for preventing or treating AD targeting pericytes.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Barrera Hematoencefálica , Pericitos , Pericitos/metabolismo , Enfermedad de Alzheimer/metabolismo , Humanos , Péptidos beta-Amiloides/metabolismo , Barrera Hematoencefálica/metabolismo , Animales , Encéfalo/metabolismo
15.
Cell Signal ; 118: 111144, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38493883

RESUMEN

Diabetic nephropathy (DN) is a serious complication of diabetes that causes glomerular sclerosis and end-stage renal disease, leading to ascending morbidity and mortality in diabetic patients. Excessive accumulation of aberrantly modified proteins or damaged organelles, such as advanced glycation end-products, dysfunctional mitochondria, and inflammasomes is associated with the pathogenesis of DN. As one of the main degradation pathways, autophagy recycles toxic substances to maintain cellular homeostasis and autophagy dysregulation plays a crucial role in DN progression. MicroRNA (miRNA) and long non-coding RNA (lncRNA) are non-coding RNA (ncRNA) molecules that regulate gene expression and have been implicated in both physiological and pathological conditions. Recent studies have revealed that autophagy-regulating miRNA and lncRNA have been involved in pathological processes of DN, including renal cell injury, mitochondrial dysfunction, inflammation, and renal fibrosis. This review summarizes the role of autophagy in DN and emphasizes the modulation of miRNA and lncRNA on autophagy during disease progression, for the development of promising interventions by targeting these ncRNAs in this disease.


Asunto(s)
Diabetes Mellitus , Nefropatías Diabéticas , MicroARNs , ARN Largo no Codificante , Humanos , Nefropatías Diabéticas/patología , MicroARNs/genética , ARN Largo no Codificante/genética , Riñón/patología , Autofagia/genética
16.
Eur J Pediatr ; 183(5): 2353-2363, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38429545

RESUMEN

There are increasing reports of neurological manifestation in children with coronavirus disease 2019 (COVID-19). However, the frequency and clinical outcomes of in hospitalized children infected with the Omicron variant are unknown. The aim of this study was to describe the clinical characteristics, neurological manifestations, and risk factor associated with poor prognosis of hospitalized children suffering from COVID-19 due to the Omicron variant. Participants included children older than 28 days and younger than 18 years. Patients were recruited from December 10, 2022 through January 5, 2023. They were followed up for 30 days. A total of 509 pediatric patients hospitalized with the Omicron variant infection were recruited into the study. Among them, 167 (32.81%) patients had neurological manifestations. The most common manifestations were febrile convulsions (n = 90, 53.89%), viral encephalitis (n = 34, 20.36%), epilepsy (n = 23, 13.77%), hypoxic-ischemic encephalopathy (n = 9, 5.39%), and acute necrotizing encephalopathy (n = 6, 3.59%). At discharge, 92.81% of patients had a good prognosis according to the Glasgow Outcome Scale (scores ≥ 4). However, 7.19% had a poor prognosis. Eight patients died during the follow-up period with a cumulative 30-day mortality rate of 4.8% (95% confidence interval (CI) 1.5-8.1). Multivariate analysis revealed that albumin (odds ratio 0.711, 95% CI 0.556-0.910) and creatine kinase MB (CK-MB) levels (odds ratio 1.033, 95% CI 1.004-1.063) were independent risk factors of poor prognosis due to neurological manifestations. The area under the curve for the prediction of poor prognosis with albumin and CK-MB was 0.915 (95%CI 0.799-1.000), indicating that these factors can accurately predict a poor prognosis.          Conclusion: In this study, 32.8% of hospitalized children suffering from COVID-19 due to the Omicron variant infection experienced neurological manifestations. Baseline albumin and CK-MB levels could accurately predict poor prognosis in this patient population. What is Known: • Neurological injury has been reported in SARS-CoV-2 infection; compared with other strains, the Omicron strain is more likely to cause neurological manifestations in adults. • Neurologic injury in adults such as cerebral hemorrhage and epilepsy has been reported in patients with Omicron variant infection. What is New: • One-third hospitalized children with Omicron infection experience neurological manifestations, including central nervous system manifestations and peripheral nervous system manifestations. • Albumin and CK-MB combined can accurately predict poor prognosis (AUC 0.915), and the 30-day mortality rate of children with Omicron variant infection and neurological manifestations was 4.8%.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/mortalidad , COVID-19/complicaciones , COVID-19/diagnóstico , Masculino , Femenino , Niño , Pronóstico , Factores de Riesgo , Preescolar , Lactante , Adolescente , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/virología , Hospitalización/estadística & datos numéricos , Recién Nacido , China/epidemiología , Niño Hospitalizado/estadística & datos numéricos
17.
Acta Biomater ; 178: 147-159, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38447811

RESUMEN

Wound infection commonly causes delayed healing, especially in the setting of chronic wounds. Local release of antibiotics is considered a viable approach to treat chronic wounds. We have developed a versatile telodendrimer (TD) platform for efficient loading of charged antibiotic molecules via a combination of multivalent and synergistic charge and hydrophobic interactions. The conjugation of TD in biocompatible hydrogel allows for topical application to provide sustained antibiotic release. Notably, a drug loading capacity as high as 20 % of the drug-to-resin dry weight ratio can be achieved. The payload content (PC) and release profile of the various antibiotics can be optimized by fine-tuning TD density and valency in hydrogel based on the charge and hydrophobic features of the drug, e.g., polymyxin B (PMB), gentamycin (GM), and daptomycin (Dap), for effective infection control. We have shown that hydrogel with moderately reduced TD density demonstrates a more favorable release profile than hydrogel with higher TD density. Antibiotics loaded in TD hydrogel have comparable antimicrobial potency and reduced cytotoxicity compared to the free antibiotics due to a prolonged, controlled drug release profile. In a mouse model of skin and soft tissue infection, the subcutaneous administration of PMB-loaded TD hydrogel effectively eliminated the bacterial burden. Overall, these results suggest that engineerable TD hydrogels have great potential as a topical treatment to control infection for wound healing. STATEMENT OF SIGNIFICANCE: Wound infection causes a significant delay in the wound healing process, which results in a significant financial and resource burden to the healthcare system. PEGA-telodendrimer (TD) resin hydrogel is an innovative and versatile platform that can be fine-tuned to efficiently encapsulate different antibiotics by altering charged and hydrophobic structural moieties. Additionally, this platform is advantageous as the TD density in the resin can also be fine-tuned to provide the desired antibiotic payload release profile. Sustained antibiotics release through optimization of TD density provides a prolonged therapeutic window and reduces burst release-induced cytotoxicity compared to conventional antibiotics application. Studies in a preclinical mouse model of bacteria-induced skin and soft tissue infection demonstrated promising therapeutic efficacy as evidenced by effective infection control and prolonged antibacterial efficacy of antibiotics-loaded PEGA-TD resin. In conclusion, the PEGA-TD resin platform provides a highly customizable approach for effective antibiotics release with significant potential for topical application to treat various bacterial wound infections to promote wound healing.


Asunto(s)
Resinas Acrílicas , Polietilenglicoles , Infecciones de los Tejidos Blandos , Infección de Heridas , Ratones , Animales , Antibacterianos/uso terapéutico , Hidrogeles/química , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infección de Heridas/tratamiento farmacológico , Control de Infecciones
18.
AJNR Am J Neuroradiol ; 45(4): 444-452, 2024 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-38485196

RESUMEN

BACKGROUND AND PURPOSE: Accelerating the image acquisition speed of MR imaging without compromising the image quality is challenging. This study aimed to evaluate the feasibility of contrast-enhanced (CE) 3D T1WI and CE 3D-FLAIR sequences reconstructed with compressed sensitivity encoding artificial intelligence (CS-AI) for detecting brain metastases (BM) and explore the optimal acceleration factor (AF) for clinical BM imaging. MATERIALS AND METHODS: Fifty-one patients with cancer with suspected BM were included. Fifty participants underwent different customized CE 3D-T1WI or CE 3D-FLAIR sequence scans. Compressed SENSE encoding acceleration 6 (CS6), a commercially available standard sequence, was used as the reference standard. Quantitative and qualitative methods were used to evaluate image quality. The SNR and contrast-to-noise ratio (CNR) were calculated, and qualitative evaluations were independently conducted by 2 neuroradiologists. After exploring the optimal AF, sample images were obtained from 1 patient by using both optimized sequences. RESULTS: Quantitatively, the CNR of the CS-AI protocol for CE 3D-T1WI and CE 3D-FLAIR sequences was superior to that of the CS protocol under the same AF (P < .05). Compared with reference CS6, the CS-AI groups had higher CNR values (all P < .05), with the CS-AI10 scan having the highest value. The SNR of the CS-AI group was better than that of the reference for both CE 3D-T1WI and CE 3D-FLAIR sequences (all P < .05). Qualitatively, the CS-AI protocol produced higher image quality scores than did the CS protocol with the same AF (all P < .05). In contrast to the reference CS6, the CS-AI group showed good image quality scores until an AF of up to 10 (all P < .05). The CS-AI10 scan provided the optimal images, improving the delineation of normal gray-white matter boundaries and lesion areas (P < .05). Compared with the reference, CS-AI10 showed reductions in scan time of 39.25% and 39.93% for CE 3D-T1WI and CE 3D-FLAIR sequences, respectively. CONCLUSIONS: CE 3D-T1WI and CE 3D-FLAIR sequences reconstructed with CS-AI for the detection of BM may provide a more effective alternative reconstruction approach than CS. CS-AI10 is suitable for clinical applications, providing optimal image quality and a shortened scan time.


Asunto(s)
Neoplasias Encefálicas , Sustancia Blanca , Humanos , Inteligencia Artificial , Neoplasias Encefálicas/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Sustancia Gris , Imagenología Tridimensional
19.
BMC Public Health ; 24(1): 723, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38448849

RESUMEN

BACKGROUND: Deep learning (DL), a specialized form of machine learning (ML), is valuable for forecasting survival in various diseases. Its clinical applicability in real-world patients with gastric cancer (GC) has yet to be extensively validated. METHODS: A combined cohort of 11,414 GC patients from the Surveillance, Epidemiology and End Results (SEER) database and 2,846 patients from a Chinese dataset were utilized. The internal validation of different algorithms, including DL model, traditional ML models, and American Joint Committee on Cancer (AJCC) stage model, was conducted by training and testing sets on the SEER database, followed by external validation on the Chinese dataset. The performance of the algorithms was assessed using the area under the receiver operating characteristic curve, decision curve, and calibration curve. RESULTS: DL model demonstrated superior performance in terms of the area under the curve (AUC) at 1, 3, and, 5 years post-surgery across both datasets, surpassing other ML models and AJCC stage model, with AUCs of 0.77, 0.80, and 0.82 in the SEER dataset and 0.77, 0.76, and 0.75 in the Chinese dataset, respectively. Furthermore, decision curve analysis revealed that the DL model yielded greater net gains at 3 years than other ML models and AJCC stage model, and calibration plots at 3 years indicated a favorable level of consistency between the ML and actual observations during external validation. CONCLUSIONS: DL-based model was established to accurately predict the survival rate of postoperative patients with GC.


Asunto(s)
Aprendizaje Profundo , Neoplasias Gástricas , Humanos , Algoritmos , Área Bajo la Curva , Pueblo Asiatico , Neoplasias Gástricas/cirugía , Pueblos de América del Norte
20.
Hortic Res ; 11(1): uhad258, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38298899

RESUMEN

Scutellaria baicalensis Georgi, also known as huang-qin in traditional Chinese medicine, is a widely used herbal remedy due to its anticancer, antivirus, and hepatoprotective properties. The S. baicalensis genome was sequenced many years ago; by contrast, the proteome as the executer of most biological processes of S. baicalensis in the aerial parts, as well as the secondary structure of the roots (xylem, phloem, and periderm), is far less comprehensively characterized. Here we attempt to depict the molecular landscape of the non-model plant S. baicalensis through a multi-omics approach, with the goal of constructing a highly informative and valuable reference dataset. Furthermore, we provide an in-depth characterization dissection to explain the two distinct flavonoid biosynthesis pathways that exist in the aerial parts and root, at the protein and phosphorylated protein levels. Our study provides detailed spatial proteomic and phosphoproteomic information in the context of secondary structures, with implications for the molecular profiling of secondary metabolite biosynthesis in non-model medicinal plants.

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