RESUMEN

Introduction: RNA interference (RNAi) stands as a widely employed gene interference technology, with small interfering RNA (siRNA) emerging as a promising tool for cancer treatment. However, the inherent limitations of siRNA, such as easy degradation and low bioavailability, hamper its efficacy in cancer therapy. To address these challenges, this study focused on the development of a nanocarrier system (HLM-N@DOX/R) capable of delivering both siRNA and doxorubicin for the treatment of breast cancer. Methods: The study involved a comprehensive investigation into various characteristics of the nanocarrier, including shape, diameter, Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), encapsulation efficiency, and drug loading. Subsequently, in vitro and in vivo studies were conducted on cytotoxicity, cellular uptake, cellular immunofluorescence, lysosome escape, and mouse tumor models to evaluate the efficacy of the nanocarrier in reversing tumor multidrug resistance and anti-tumor effects. Results: The results showed that HLM-N@DOX/R had a high encapsulation efficiency and drug loading capacity, and exhibited pH/redox dual responsive drug release characteristics. In vitro and in vivo studies showed that HLM-N@DOX/R inhibited the expression of P-gp by 80%, inhibited MDR tumor growth by 71% and eliminated P protein mediated multidrug resistance. Conclusion: In summary, HLM-N holds tremendous potential as an effective and targeted co-delivery system for DOX and P-gp siRNA, offering a promising strategy for overcoming MDR in breast cancer.

Asunto(s)

Neoplasias de la Mama , Doxorrubicina , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Liposomas , ARN Interferente Pequeño , Animales , Doxorrubicina/farmacología , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/administración & dosificación , Femenino , Liposomas/química , Ratones , Resistencia a Antineoplásicos/efectos de los fármacos , Humanos , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/química , ARN Interferente Pequeño/farmacocinética , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Células MCF-7 , Ratones Endogámicos BALB C , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Nanopartículas/química , Liberación de Fármacos , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/farmacocinética , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

Clear cell renal cell carcinoma (ccRCC) demonstrates enhanced glycolysis, critically contributing to tumor development. Programmed death-ligand 1 (PD-L1) aids tumor cells in evading T-cell-mediated immune surveillance. Yet, the specific mechanism by which glycolysis influences PD-L1 expression in ccRCC is not fully understood. Our research identified that the glycolysis-related gene (GRG) HK3 has a unique correlation with PD-L1 expression. HK3 has been identified as a key regulator of O-GlcNAcylation in ccRCC. O-GlcNAcylation exists on the serine 900 (Ser900) site of EP300 and can enhance its stability and oncogenic activity by preventing ubiquitination. Stably expressed EP300 works together with TFAP2A as a co-transcription factor to promote PD-L1 transcription and as an acetyltransferase to stabilize PD-L1 protein. Furthermore, ccRCC exhibits interactive dynamics with tumor-associated macrophages (TAMs). The uridine 5'-diphospho-N-acetylglucosamine (UDP-GlcNAc), which serves as a critical substrate for the O-GlcNAcylation process, facilitates TAMs polarization. In ccRCC cells, HK3 expression is influenced by IL-10 secreted by M2 TAMs. Our study elucidates that HK3-mediated O-GlcNAcylation of EP300 is involved in tumor immune evasion. This finding suggests potential strategies to enhance the efficacy of immune checkpoint blockade therapy.

Asunto(s)

Antígeno B7-H1 , Carcinoma de Células Renales , Proteína p300 Asociada a E1A , Hexoquinasa , Neoplasias Renales , Humanos , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/genética , Proteína p300 Asociada a E1A/metabolismo , Antígeno B7-H1/metabolismo , Hexoquinasa/metabolismo , Hexoquinasa/genética , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Neoplasias Renales/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Animales , Evasión Inmune , Macrófagos Asociados a Tumores/metabolismo , Glucólisis , Ratones

RESUMEN

Aims: This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms. Methods: We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes. Results: Signal transducer and activator of transcription 3 (STAT3) was notably expressed in both conditions. Single-cell analysis pinpointed specific cells with high STAT3 expression, and microRNA (miRNA)-125a-5p emerged as a potential regulator. Experiments confirmed the crucial role of STAT3 in osteoclast differentiation and muscle proliferation. Conclusion: STAT3 has emerged as a key gene in both POMP and sarcopenia. This insight positions STAT3 as a potential common therapeutic target, possibly improving management strategies for these age-related diseases.

RESUMEN

BACKGROUND: To summarize the clinical experience of intracranial aneurysm clipping in the treatment of ruptured intracranial aneurysms in the second trimester of pregnancy. METHODS: A case of ruptured middle cerebral aneurysm in the second trimester of pregnancy was reported. Craniotomy and aneurysm clipping were performed at 24 weeks of pregnancy, and fetal preservation was continued after the operation. RESULTS: The prognosis of the parturient was good and the skull was missing on the operative side. A healthy baby boy was delivered by cesarean section 2 months after the operation, and skull repair was performed 4 months after the operation. During the follow-up for 1 year, the mother and son were healthy and no obvious sequelae were found. CONCLUSION: Ruptured intracranial aneurysm hemorrhage in mid-pregnancy is a rare and critical case. Summarizing the corresponding clinical experience will help to have a reference plan for the next time when facing a similar situation, and it will help to treat critically ill patients. The treatment of ruptured intracranial aneurysm in mid-pregnancy requires multidisciplinary collaboration, and cranial aneurysm clamping + fertility preservation can reduce the impact of radiation on the fetus and improve the prognosis for both the mother and the fetus.

Asunto(s)

Aneurisma Roto , Aneurisma Intracraneal , Segundo Trimestre del Embarazo , Humanos , Embarazo , Femenino , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/complicaciones , Aneurisma Roto/cirugía , Aneurisma Roto/complicaciones , Adulto , Complicaciones Cardiovasculares del Embarazo/cirugía , Complicaciones Cardiovasculares del Embarazo/terapia , Craneotomía/métodos , Cesárea

RESUMEN

The recent acceleration of industrialization and urbanization has brought significant attention to N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6-PPDQ), an emerging environmental pollutant from tire wear, due to its long-term effects on the environment and organisms. Recent studies suggest that 6-PPDQ can disrupt neurotransmitter synthesis and release, impact receptor function, and alter signaling pathways, potentially causing oxidative stress, inflammation, and apoptosis. This review investigates the potential neurotoxic effects of prolonged 6-PPDQ exposure, the mechanisms underlying its cytotoxicity, and the associated health risks. We emphasize the need for future research, including precise exposure assessments, identification of individual differences, and development of risk assessments and intervention strategies. This article provides a comprehensive overview of 6-PPDQ's behavior, impact, and neurotoxicity in the environment, highlighting key areas and challenges for future research.

Asunto(s)

Contaminantes Ambientales , Síndromes de Neurotoxicidad , Humanos , Contaminantes Ambientales/toxicidad , Síndromes de Neurotoxicidad/etiología , Animales , Estrés Oxidativo/efectos de los fármacos , Fenilendiaminas/toxicidad , Medición de Riesgo , Exposición a Riesgos Ambientales/efectos adversos , Apoptosis/efectos de los fármacos

RESUMEN

The relationship between different ribonucleic acids (RNAs) and tumor immunity has been widely investigated. However, a systematic description of tumor immune-related RNAs in different tumors is still lacking. We collected the relationship of tumor immune-related RNAs from the published literature and presented them in a user-friendly interface, "ImmRNA" (http://www.immrna.cn/), to provide a resource to study immune-RNA-cancer regulatory relations. The ImmRNA contains 49 996 curated entries. Each entry includes gene symbols, gene types, target genes, downstream effects, functions, immune cells, and other information. By rearranging and reanalyzing the data, our dataset contains the following key points: (i) providing the links between RNAs and the immune in cancers, (ii) displaying the downstream effects and functions of RNAs, (iii) listing immune cells and immune pathways related to RNA function, (iv) showing the relationship between RNAs and prognostic outcomes, and (v) exhibiting the experimental methods described in the article. ImmRNA provides a valuable resource for understanding the functions of tumor immune-related RNAs. Database URL:  http://www.immrna.cn/.

Asunto(s)

Neoplasias , Humanos , Neoplasias/genética , Neoplasias/inmunología , Bases de Datos Genéticas , Bases de Datos de Ácidos Nucleicos , ARN Neoplásico/genética , ARN Neoplásico/inmunología , ARN/genética , ARN/inmunología

RESUMEN

Ameliorating microglia-mediated neuroinflammation is a crucial strategy in developing new drugs for neurodegenerative diseases. Plant compounds are an important screening target for the discovery of drugs for the treatment of neurodegenerative diseases. However, due to the spatial complexity of phytochemicals, it becomes particularly important to evaluate the effectiveness of compounds while avoiding the mixing of cytotoxic substances in the early stages of compound screening. Traditional high-throughput screening methods suffer from high cost and low efficiency. A computational model based on machine learning provides a novel avenue for cytotoxicity determination. In this study, a microglia cytotoxicity classifier was developed using a machine learning approach. First, we proposed a data splitting strategy based on the molecule murcko generic scaffold, under this condition, three machine learning approaches were coupled with three kinds of molecular representation methods to construct microglia cytotoxicity classifier, which were then compared and assessed by the predictive accuracy, balanced accuracy, F1-score, and Matthews Correlation Coefficient. Then, the recursive feature elimination integrated with support vector machine (RFE-SVC) dimension reduction method was introduced to molecular fingerprints with high dimensions to further improve the model performance. Among all the microglial cytotoxicity classifiers, the SVM coupled with ECFP4 fingerprint after feature selection (ECFP4-RFE-SVM) obtained the most accurate classification for the test set (ACC of 0.99, BA of 0.99, F1-score of 0.99, MCC of 0.97). Finally, the Shapley additive explanations (SHAP) method was used in interpreting the microglia cytotoxicity classifier and key substructure smart identified as structural alerts. Experimental results show that ECFP4-RFE-SVM have reliable classification capability for microglia cytotoxicity, and SHAP can not only provide a rational explanation for microglia cytotoxicity predictions, but also offer a guideline for subsequent molecular cytotoxicity modifications.

RESUMEN

Dairy products are a significant source of iodine, and their contribution to iodine intake must be evaluated regularly. However, there is a lack of data on iodine intake from dairy products in China. Through a cross-sectional study, we determined the iodine content of dairy products in the Chinese diet and estimated iodine intake among Chinese children. Intake records for 30 consecutive days were used to investigate the consumption of dairy products by 2009 children from Yunnan and Liaoning Provinces. The iodine contents of 266 dairy products with high intake frequency were determined using inductively coupled plasma-mass spectrometry (ICP-MS). We then calculated the iodine intake and contribution of dairy products and explored the related factors of dairy iodine intake through a generalized linear mixed model. Ultra-high-temperature (UHT) sterilized milk accounted for 78.7% of the total dairy products, with an iodine content of 23.0 µg/100 g. The dairy product intake rate of children in China was 83.6%, with an average daily intake of 143.1 g. The median iodine intake from milk and dairy was 26.8 µg/d, 41.5% of the estimated average recommendation (EAR) for younger children and 31.8% of the EAR for older children. The daily milk iodine intake of children in Yunnan Province was 9.448 µg/day lower than that of children in Liaoning Province (p < 0.001), and the daily iodine intake of children in rural areas was 17.958 µg/day lower than that of children in urban areas (p < 0.001). Chinese dairy products were rich in iodine, and the content of iodine was intermediate to that reported in Europe and the USA. However, children's daily intake of milk iodine was lower than that of children in other developed countries due to the lower daily intake of dairy products, especially those in rural areas.

Asunto(s)

Productos Lácteos , Dieta , Yodo , Yodo/análisis , Yodo/administración & dosificación , Humanos , Productos Lácteos/análisis , China , Estudios Transversales , Masculino , Femenino , Niño , Preescolar , Dieta/estadística & datos numéricos , Leche/química , Animales , Lactante

RESUMEN

BACKGROUND: A favorable regenerative microenvironment is essential for peripheral nerve regeneration. Neural tissue-specific extracellular matrix (ECM) is a natural material that helps direct cell behavior and promote axon regeneration. Both bone marrow-derived mesenchymal stem cells (BMSCs) and adipose-derived mesenchymal stem cells (ADSCs) transplantation are effective in repairing peripheral nerve injury (PNI). However, there is no study that characterizes the in vivo microenvironmental characteristics of these two MSCs for the early repair of PNI when combined with neural tissue-derived ECM materials, i.e., acellular nerve allograft (ANA). METHODS: In order to investigate biological characteristics, molecular mechanisms of early stage, and effectiveness of ADSCs- or BMSCs-injected into ANA for repairing PNI in vivo, a rat 10 mm long sciatic nerve defect model was used. We isolated primary BMSCs and ADSCs from bone marrow and adipose tissue, respectively. First, to investigate the in vivo response characteristics and underlying molecular mechanisms of ANA combined with BMSCs or ADSCs, eighty-four rats were randomly divided into three groups: ANA group, ANA+BMSC group, and ANA+ADSC group. We performed flow cytometry, RT-PCR, and immunofluorescence staining up to 4 weeks postoperatively. To further elucidate the underlying molecular mechanisms, changes in long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) were systematically investigated using whole transcriptome sequencing. We then constructed protein-protein interaction networks to find 10 top ranked hub genes among differentially expressed mRNAs. Second, in order to explore the effectiveness of BMSCs and ADSCs on neural tissue-derived ECM materials for repairing PNI, sixty-eight rats were randomized into four groups: ANA group, ANA+BMSC group, ANA+ADSC group, and AUTO group. In the ANA+BMSC and ANA+ADSC groups, ADSCs/BMSCs were equally injected along the long axis of the 10-mm ANA. Then, we performed histological and functional assessments up to 12 weeks postoperatively. RESULTS: The results of flow cytometry and RT-PCR showed that ANA combined with BMSCs exhibited more significant immunomodulatory effects, as evidenced by the up-regulation of interleukin (IL)-10, down-regulation of IL-1ß and tumor necrosis factor-alpha (TNF-α) expression, promotion of M1-type macrophage polarization to M2-type, and a significant increase in the number of regulatory T cells (Tregs). ANA combined with ADSCs exhibited more pronounced features of pro-myelination and angiogenesis, as evidenced by the up-regulation of myelin-associated protein gene (MBP and MPZ) and angiogenesis-related factors (TGF-ß, VEGF). Moreover, differentially expressed genes from whole transcriptome sequencing results further indicated that ANA loaded with BMSCs exhibited notable immunomodulatory effects and ANA loaded with ADSCs was more associated with angiogenesis, axonal growth, and myelin formation. Notably, ANA infused with BMSCs or ADSCs enhanced peripheral nerve regeneration and motor function recovery with no statistically significant differences. CONCLUSIONS: This study revealed that both ANA combined with BMSCs and ADSCs enhance peripheral nerve regeneration and motor function recovery, but their biological characteristics (mainly including immunomodulatory effects, pro-vascular regenerative effects, and pro-myelin regenerative effects) and underlying molecular mechanisms in the process of repairing PNI in vivo are different, providing new insights into MSC therapy for peripheral nerve injury and its clinical translation.

Asunto(s)

Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Ratas Sprague-Dawley , Ingeniería de Tejidos , Animales , Ratas , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Ingeniería de Tejidos/métodos , Traumatismos de los Nervios Periféricos/terapia , Traumatismos de los Nervios Periféricos/metabolismo , Trasplante de Células Madre Mesenquimatosas/métodos , Nervio Ciático/lesiones , Nervio Ciático/metabolismo , Masculino , Tejido Adiposo/citología , Tejido Adiposo/metabolismo

RESUMEN

The emulsification activity of myosin plays a significant role in affecting quality of emulsified meat products. High-density lipoprotein (HDL) possesses strong emulsification activity and stability due to its structural characteristics, suggesting potential for its utilization in developing functional emulsified meat products. In order to explore the effect of HDL addition on emulsification stability, rheological properties and structural features of myosin (MS) emulsions, HDL-MS emulsion was prepared by mixing soybean oil with isolated HDL and MS, with pH adjustments ranging from 3.0 to 11.0. The results found that emulsification activity and stability in two emulsion groups consistently improved as pH increased. Under identical pH, HDL-MS emulsion exhibited superior emulsification behavior as compared to MS emulsion. The HDL-MS emulsion under pH of 7.0-11.0 formed a viscoelastic protein layer at the interface, adsorbing more proteins and retarding oil droplet diffusion, leading to enhanced oxidative stability, compared to the MS emulsion. Raman spectroscopy analysis showed more flexible conformational changes in the HDL-MS emulsion. Microstructural observations corroborated these findings, showing a more uniform distribution of droplet sizes in the HDL-MS emulsion with smaller particle sizes. Overall, these determinations suggested that the addition of HDL enhanced the emulsification behavior of MS emulsions, and the composite emulsions demonstrated heightened responsiveness under alkaline conditions. This establishes a theoretical basis for the practical utilization of HDL in emulsified meat products.

Asunto(s)

Emulsiones , Lipoproteínas HDL , Miosinas , Reología , Emulsiones/química , Concentración de Iones de Hidrógeno , Lipoproteínas HDL/química , Miosinas/química , Productos de la Carne/análisis , Tamaño de la Partícula , Aceite de Soja/química , Viscosidad , Espectrometría Raman

RESUMEN

Myofibrillar proteins are crucial for gel formation in processed meat products such as sausages and meat patties. Freeze-thaw cycles can alter protein properties, impacting gel stability and product quality. This study aims to investigate the potential of thawed drip and its membrane-separated components as potential antifreeze agents to retard denaturation, oxidation and gel deterioration of myofibrillar proteins during freezing-thawing cycles of pork patties. The thawed drip and its membrane-separated components of > 10 kDa and < 10 kDa, along with deionized water, were added to minced pork at 10 % mass fraction and subjected to increasing freeze-thaw cycles. Results showed that the addition of thawed drip and its membrane separation components inhibited denaturation and structural changes of myofibrillar proteins, evidenced by reduced surface hydrophobicity and carbonyl content, increased free sulfhydryl groups, protein solubility and α-helix, as compared to the deionized water group. Correspondingly, improved gel properties including water-holding capacity, textural parameters and denser network structure were observed with the addition of thawed drip and its membrane separation components. Denaturation and oxidation of myofibrillar proteins were positively correlated with gel deterioration during freezing-thawing cycles. We here propose a role of thawed drip and its membrane separation components as cryoprotectants against myofibrillar protein gel deterioration during freeze-thawing cycles.

Asunto(s)

Congelación , Geles , Proteínas Musculares , Miofibrillas , Animales , Geles/química , Porcinos , Proteínas Musculares/química , Miofibrillas/química , Manipulación de Alimentos/métodos , Desnaturalización Proteica , Productos de la Carne/análisis , Interacciones Hidrofóbicas e Hidrofílicas , Solubilidad , Agua/química , Oxidación-Reducción

RESUMEN

Postmenopausal osteoporosis is a prevalent metabolic bone disorder characterized by a decrease in bone mineral density and deterioration of bone microstructure. Despite the high prevalence of this disease, no effective treatment for osteoporosis has been developed. Exercise has long been considered a potent anabolic factor that promotes bone mass via upregulation of myokines secreted by skeletal muscle, exerting long-term osteoprotective effects and few side effects. Irisin was recently identified as a novel myokine that is significantly upregulated by exercise and could increase bone mass. However, the mechanisms underlying exercise-induced muscle-bone crosstalk remain unclear. Here, we identified that polyunsaturated fatty acids (arachidonic acid and docosahexaenoic acid) are increased in skeletal muscles following a 10-week treadmill exercise programme, which then promotes the expression and release of FNDC5/irisin. In osteoblasts, irisin binds directly to Cav1, which recruits and interacts with AMP-activated protein kinase α (AMPKα) to activate the AMPK pathway. Nrf2 is the downstream target of the AMPK pathway and increases the transcription of HMOX1 and Fpn. HMOX1 is involved in regulating the cell cycle and promotes the proliferation of osteoblasts. Moreover, upregulation of Fpn in osteoblasts enhanced iron removal, thereby suppressing ferroptosis in osteoblasts. Additionally, we confirmed that myotube-derived exosomes are involved in the transportation of irisin and enter osteoblasts through caveolae-mediated endocytosis. In conclusion, our findings highlight the crucial role of irisin, present in myotube-derived exosomes, as a crucial regulator of exercise-induced protective effects on bone, which provides novel insights into the mechanisms underlying exercise-dependent treatment of osteoporosis.

Asunto(s)

Caveolina 1 , Proliferación Celular , Exosomas , Fibronectinas , Osteoblastos , Caveolina 1/metabolismo , Osteoblastos/metabolismo , Fibronectinas/metabolismo , Exosomas/metabolismo , Humanos , Animales , Ratones , Músculo Esquelético/metabolismo , Femenino

RESUMEN

BACKGROUND: While many studies have established a positive correlation between adolescents' internet addiction and mental health problems, most of these studies have overlooked the internal heterogeneity of Internet addiction. This study aims to identify latent profiles among adolescents based on their Internet addiction and to examine the differences in aggression, depression, and anxiety across these profiles. METHODS: We conducted a survey involving 7422 adolescents and administered the Young's Internet Addiction Test, Aggression Behavior Questionnaire, Patient Health Questionnaire-9, and Generalized Anxiety Disorder Scale. Latent profile analysis was utilized to categorize Internet addiction profiles among adolescents. Associations between Internet addiction profiles and related factors were examined using the Bolck-Croon-Hagenaars method. RESULTS: Latent profile analysis suggested four profiles of Internet addiction, which were labeled: Regular, Risk, Low Internet addiction, and Internet addiction. The Internet addiction profile showed higher levels of aggression, depression, and anxiety than the Low Internet addiction profile. The Low Internet addiction profile had higher levels of aggression, depression, and anxiety than the Risk profile. The Risk profile demonstrated higher levels of aggression, depression, and anxiety when compared to the Regular profile. LIMITATIONS: Limitations include the cross-sectional design and the self-report measures. CONCLUSIONS: The identified Internet addiction profiles offer differential predictions for aggression, depression, and anxiety. These results underscore the significance of employing latent profile analysis when exploring the associations between Internet addiction and mental health issues.

Asunto(s)

Agresión , Ansiedad , Depresión , Trastorno de Adicción a Internet , Humanos , Adolescente , Agresión/psicología , Masculino , Trastorno de Adicción a Internet/epidemiología , Trastorno de Adicción a Internet/psicología , Femenino , Depresión/epidemiología , Depresión/psicología , Ansiedad/epidemiología , Ansiedad/psicología , Estudios Transversales , Encuestas y Cuestionarios , Conducta Adictiva/psicología , Conducta Adictiva/epidemiología , Conducta del Adolescente/psicología , Internet , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/psicología , Análisis de Clases Latentes

RESUMEN

The utilization of metallic nanoparticles in bio-nanofabrication holds significant potential in the field of applied research. The current study applied and compared integrated ultrasonic-microwave-assisted extraction (US/MICE), ultrasonic extraction (USE), microwave-assisted extraction (MICE), and maceration (MAE) to extract total phenolic content (TPC). In addition, the study examined the antioxidant activity of Commiphora gileadensis (Cg) leaf. The results demonstrated that the TPC of US/MICE exhibited the maximum value at 59.34 ± 0.007 mg GAE/g DM. Furthermore, at a concentration of 10 µg/mL, TPC displayed a significant scavenging effect on DPPH (56.69 %), with an EC50 (6.48 µg/mL). Comprehensive metabolite profiling of the extract using UPLC-qTOF-MS/MS was performed to identify active agents. A total of 64 chromatographic peaks were found, out of which 60 were annotated. The most prevalent classes of metabolites found were polyphenols (including flavonoids and lignans), organic compounds and their derivatives, amides and amines, terpenes, and fatty acid derivatives. Transmission electron microscopy (TEM) revealed the aggregate size of the synthesized nanoparticles and the spherical shape of C. gileadensis-mediated silver nanoparticles (Cg-AgNPs). The nanoparticles had a particle size ranging from 7.7 to 42.9 nm. The Cg-AgNPs exhibited more inhibition zones against S. aureus and E. coli. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Cg-extract, AgNPs, and Cg-AgNPs were also tested. This study demonstrated the feasibility of using combined ultrasonic-microwave-assisted extraction to separate and extract chemicals from C. gileadensis on a large scale. These compounds have potential use in the pharmaceutical industry. Combining antibacterial and biocompatible properties in materials is vital for designing new materials for biomedical applications. Additionally, the results showed that the biocompatibility of the Ag-NPs using C. gileadensis extracts demonstrated outstanding antibacterial properties.

Asunto(s)

Antibacterianos , Commiphora , Nanopartículas del Metal , Microondas , Extractos Vegetales , Hojas de la Planta , Plata , Ondas Ultrasónicas , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Plata/química , Commiphora/química , Nanopartículas del Metal/química , Hojas de la Planta/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Cromatografía Líquida de Alta Presión , Pruebas de Sensibilidad Microbiana , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Fitoquímicos/farmacología , Fitoquímicos/química , Fitoquímicos/aislamiento & purificación , Técnicas de Química Sintética

RESUMEN

Lung cancer is a dangerous disease that is lacking in an ideal therapy. Here, we evaluated the anti-lung cancer effect in nude mice of a fully human single-chain antibody (scFv) against the associated antigen 7 transmembrane receptor (Ts7TMR), which is also called G protein-coupled receptor, between A549 cells and Trichinella spiralis (T. spiralis). Our data showed that anti-Ts7TMR scFv could inhibit lung cancer growth in a dose-dependent manner, with a tumour inhibition rate of 59.1%. HE staining did not reveal any obvious tissue damage. Mechanistically, immunohistochemical staining revealed that the scFv down-regulated the expression of PCNA and VEGF in tumour tissues. Overall, this study found that anti-Ts7TMR scFv could inhibit A549 lung cancer growth by suppressing cell proliferation and angiogenesis, which may provide a new strategy for treating lung cancer.

Asunto(s)

Neoplasias Pulmonares , Anticuerpos de Cadena Única , Trichinella spiralis , Animales , Humanos , Ratones , Células A549 , Proliferación Celular/efectos de los fármacos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Ratones Desnudos , Neovascularización Patológica/inmunología , Antígeno Nuclear de Célula en Proliferación/inmunología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Anticuerpos de Cadena Única/inmunología , Anticuerpos de Cadena Única/farmacología , Trichinella spiralis/inmunología , Factor A de Crecimiento Endotelial Vascular/inmunología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

Cellulose is used widely in antimicrobial packaging due to its abundance in nature, biodegradability, renewability, non-toxicity, and low cost. However, how efficiently and rapidly it imparts high antimicrobial activity to cellulose-based packaging materials remains a challenge. In this work, Ag NPs were deposited on the surface of carboxymethyl cellulose/starch/N'N Methylenebisacrylamide film using ultrasonic radiation. Morphology and structure analysis of as-prepared films were conducted, and the antibacterial effects under different ultrasonic times and reductant contents were investigated. These results showed that Ag NPs were distributed uniformly on the film surface under an ultrasonic time of 45 min. The size of Ag NPs changes as the reducing agent content decreases. The composite film demonstrated a slightly better antibacterial effect against E. coli than against S. aureus. Therefore, this work can provide valuable insights for the research on antimicrobial packaging.

RESUMEN

CFAP58 is a testis-enriched gene that plays an important role in the sperm flagellogenesis of humans and mice. However, the effect of CFAP58 on bull semen quality and the underlying molecular mechanisms involved in spermatogenesis remain unknown. Here, we identified two single-nucleotide polymorphisms (rs110610797, A>G and rs133760846, G>T) and one indel (g.-1811_ g.-1810 ins147bp) in the promoter of CFAP58 that were significantly associated with semen quality of bulls, including sperm deformity rate and ejaculate volume. Moreover, by generating gene knockout mice, we found for the first time that the loss of Cfap58 not only causes severe defects in the sperm tail, but also affects the manchette structure, resulting in abnormal sperm head shaping. Cfap58 deficiency causes an increase in spermatozoa apoptosis. Further experiments confirmed that CFAP58 interacts with IFT88 and CCDC42. Moreover, it may be a transported cargo protein that plays a role in stabilizing other cargo proteins, such as CCDC42, in the intra-manchette transport/intra-flagellar transport pathway. Collectively, our findings reveal that CFAP58 is required for spermatogenesis and provide genetic markers for evaluating semen quality in cattle.

Asunto(s)

Análisis de Semen , Semen , Humanos , Bovinos , Masculino , Animales , Ratones , Cabeza del Espermatozoide , Espermatozoides , Ratones Noqueados

RESUMEN

In this study, a combination of whey protein (hydrophilic coating) and polydopamine (crosslinking agent) was used to improve the stability and functionality of quercetin-loaded zein nanoparticles. There are two key benefits of the core-shell nanoparticles formed. First, the ability of the polydopamine to bind to both zein and whey protein facilitates the formation of a stable core-shell structure, thereby protecting quercetin from any pro-oxidants in the aqueous surroundings. Second, neutral and hydrophilic whey proteins were used for the surface coating of the nanoparticles to further enhance the sustained and slow release of quercetin, facilitating its sustained release into the body at a slow and steady rate. The results of this study will promote the innovative development of precise nutritional delivery systems for zein and provide a theoretical basis for the design and development of dietary supplements based on hydrophobic food nutrient molecules.

Asunto(s)

Interacciones Hidrofóbicas e Hidrofílicas , Indoles , Nanopartículas , Polímeros , Zeína , Zeína/química , Indoles/química , Polímeros/química , Nanopartículas/química , Proteína de Suero de Leche/química , Quercetina/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos

RESUMEN

This study investigated impact of high-density lipoprotein (HDL) on thermal aggregation and gelling behavior of myosin in relation to varied pHs. Results revealed that HDL modified myosin structure before and after heating, with distinct effects observed at varied pH. Under pH 5.0, both myosin and HDL-MS exhibited larger aggregates and altered microstructure; at pH 7.0 and 9.0, HDL inhibited myosin aggregation, resulting in enhanced solubility, reduced turbidity and particle size. Comparative analysis of surface hydrophobicity, free sulfhydryl groups and secondary structure highlighted distinct thermal aggregation behavior between MS and HDL-MS, with the latter showing inhibitory effects under neutral or alkaline conditions. Gelation behavior was enhanced at pH 7.0 with maximum strength, hardness, water-holding capacity and rheological properties. Under acidic pH, excessive protein aggregation resulted in increased whiteness and rough microstructure with granular aggregates. Under alkaline pH, gel network structure was weaker, possibly due to higher thermal stability of protein molecules. Scanning electron microscopy revealed expanded HDL protein particles at pH 7.0, accounting for decreased gel strength and altered rheological properties compared with myosin gel. Overall, the results indicated a positive role of HDL at varied pH in regulating thermal aggregation of myosin and further impacting heat-induced gel characteristics.

Asunto(s)

Geles , Calor , Lipoproteínas HDL , Miosinas , Agregado de Proteínas , Reología , Concentración de Iones de Hidrógeno , Miosinas/química , Miosinas/metabolismo , Lipoproteínas HDL/química , Geles/química , Interacciones Hidrofóbicas e Hidrofílicas , Solubilidad , Animales , Tamaño de la Partícula

RESUMEN

To effectively inhibit the retrogradation of staple foods, the effects of maltotetraose-forming amylase(G4-amylase) on the short and long-term retrogradation of different staple starches such as rice starch (RS), wheat starch (WS), potato starch (PS) were studied. The results indicated that G4-amylase decreased the content of amylose. Amylose contents (21.09%) of WSG4 were higher than that (14.82%) of RSG4 and (13.13%) of PSG4. WS had the most obvious change in the chain length distribution of amylopectin. A chains decreased by 18.99% and the B1 chains decreased by 12.08% after G4-amylase treatment. Compared to RS (662 cP) and WS (693 cP), the setback viscosity of RSG4 (338 cP) and WSG4 (385 cP) decreased. Compared to RS (0.41), WS (0.45), and PS (0.51), the long-term retrogradation rate of RSG4 (0.33), WSG4 (0.31), and PSG4 (0.38) significantly reduced. It indicated that G4-amylase significantly inhibited the long-term retrogradation of WS, followed by RS and PS.

Asunto(s)

Amilasas , Maltosa/análogos & derivados , Oryza , Solanum tuberosum , Almidón , Triticum , Almidón/química , Amilasas/química , Amilasas/metabolismo , Triticum/química , Viscosidad , Solanum tuberosum/química , Oryza/química , Amilosa/química , Amilosa/análisis , Maltosa/química , Biocatálisis