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OBJECTIVE: To explore the mechanism underlying the therapeutic effect of Bufei Yishen Formula III combined with exercise rehabilitation (ECC-BYF III + ER) on chronic obstructive pulmonary disease (COPD) and further identify hub genes. MATERIALS AND METHODS: Gene Set Enrichment Analysis was used to identify the COPD-associated pathways and reversal pathways after ECC-BYF III + ER treatment. Protein-protein interaction network analysis and cytoHubba were used to identify the hub genes. These genes were verified using independent datasets, molecular docking and quantitative real-time polymerase chain reaction experiment. RESULTS: Using the high-throughput sequencing data of COPD rats from our laboratory, 49 significantly disturbed pathways were identified in COPD model compared with control group via gene set enrichment analysis (false discovery rate < 0.05). The 34 pathways were reversed after ECC-BYF III + ER treatment. In the 2306 genes of these 34 pathways, 121 of them were differentially expressed in COPD rats compared with control samples. A protein-protein interaction network comprising 111 nodes and 274 edges was created, and 34 candidate genes were identified. Finally, seven COPD hub genes (Il1b, Ccl2, Cxcl1, Apoe, Ccl7, Ccl12, and Ccl4) were well identified and verified in independent COPD rat data from our laboratory and the public dataset GSE178513. The area under the receiver operating characteristic curve values ranged from 0.86 to 1 and from 0.67 to 1, respectively. The reliability of the mentioned genes, which can bind to the active ingredients of ECC-BYF III through molecular docking, were further verified through qRT-PCR experiments. CONCLUSION: Thirty-four COPD-related pathways and seven hub genes that may be regulated by ECC-BYF III + ER were identified and well verified. The findings of this study may provide insights into the treatment and mechanism underlying COPD.
GSEA method can circumvent the limitations of the preacquisition of DEGs for ORA and is suitable for small sample data.34 COPD-related pathways that can be regulated by ECC-BYF III + ER were identified.Seven COPD hub genes were identified and well verified in independent RNA-seq data and PCR experiment, and they may play a crucial role in TCM treatment.
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Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Mapas de Interacción de Proteínas , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Ratas , Masculino , Modelos Animales de Enfermedad , Terapia por Ejercicio/métodos , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Terapia CombinadaRESUMEN
With the increasingly intense academic competition, the stressors faced by doctoral students are gradually escalating. Based on the Job Demands-Resources Model, this study proposed a moderated moderation to explore how hindrance research stressors affect doctoral students' research creativity. Explicitly, the present study investigates whether the relationship between hindrance research stressors and research creativity is contingent on inclusive mentoring style and academic resilience. By analyzing the survey data from 538 valid questionnaire responses of doctoral students in China, this study has revealed that hindrance research stressors negatively relate to doctoral students' research creativity, and inclusive mentoring style from academic supervisors can mitigate the negative impact of hindrance research stressors on the research creativity of doctoral students. Furthermore, academic resilience strengthens the moderating effect of inclusive mentoring style. Specifically, it buffers the negative impact of hindrance research stressors on research creativity among doctoral students who receive high inclusive mentoring, but not among those with low levels of inclusive mentoring. These findings emphasize that effective strategies to enhance the research creativity of doctoral students who encounter hindrance stressors may require the joint consideration of contextual and personal resources.
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BACKGROUND: Established evidences have demonstrated that hypertension was associated with the cognitive impairment. But the associations between the duration of hypertension exposure and cognitive performance are still inconclusive. OBJECTIVES: The objective of this study was to assess the association between the duration of hypertension diagnosis and cognitive performance in older adults by the National Health and Nutrition Examination Survey (2011-2014). METHODS: To evaluate the relationship between the hypertension duration and cognitive performance, we conducted the logistic regression analysis. Furthermore, we also performed the Restricted cubic spline (RCS) analysis to assess the nonlinear relationship between the duration of exposure to hypertension and cognitive performance. RESULTS: Initially, total 19,931 participants were included in this study, and 2928 individuals were enrolled. With the increase of hypertension duration, more risk of cognitive impairment was observed in the Digit Symbol Substitution test (DSST) (OR = 1.012, 1.006-1.019), and a similar trend was observed in Animal Fluency test (AFT) (OR = 1.009,1.003-1.016). The RCS results showed that the hypertension duration pattern was linear associated with the risk of cognitive impairment in DDST (P for non-linearity = 0.758). Meanwhile, subgroups analysis of midlife hypertension, we revealed that linear association with the risk of cognitive impairment in DSST (P for non-linearity = 0.391) and CERAD (P for non-linearity = 0.849) among hypertension diagnose < 55 years populations. CONCLUSION: Collectively, our finding indicates that longer duration of exposure to hypertension worsens the cognition performance, especially for middle-aged hypertension.
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Cognición , Disfunción Cognitiva , Hipertensión , Encuestas Nutricionales , Humanos , Hipertensión/epidemiología , Masculino , Femenino , Anciano , Cognición/fisiología , Disfunción Cognitiva/epidemiología , Persona de Mediana Edad , Estados Unidos/epidemiología , Factores de Tiempo , Anciano de 80 o más Años , Factores de RiesgoRESUMEN
Bioactive peptides, derived from short protein fragments, are recognized for their neuroprotective properties and potential therapeutic applications in treating central nervous system (CNS) diseases. However, a significant challenge for these peptides is their ability to penetrate the blood-brain barrier (BBB). EVSGPGYSPN (EV-10) peptide, a walnut-derived peptide, has demonstrated promising neuroprotective effects in vivo. This study aimed to investigate the transportability of EV-10 across the BBB, explore its capacity to penetrate this barrier, and elucidate the regulatory mechanisms underlying peptide-induced cellular internalization and transport pathways within the BBB. The results indicated that at a concentration of 100 µM and osmotic time of 4 h, the apparent permeability coefficient of EV-10 was Papp = 8.52166 ± 0.58 × 10-6 cm/s. The penetration efficiency of EV-10 was influenced by time, concentration, and temperature. Utilizing Western blot analysis, immunofluorescence, and flow cytometry, in conjunction with the caveolin (Cav)-specific inhibitor M-ß-CD, we confirmed that EV-10 undergoes transcellular transport through a Cav-dependent endocytosis pathway. Notably, the tight junction proteins ZO-1, occludin, and claudin-5 were not disrupted by EV-10. Throughout its transport, EV-10 was localized within the mitochondria, Golgi apparatus, endoplasmic reticulum, lysosomes, endosomes, and cell membranes. Moreover, Cav-1 overexpression facilitated the release of EV-10 from lysosomes. Evidence of EV-10 accumulation was observed in mouse brains using brain slice scans. This study is the first to demonstrate that Cav-1 can facilitate the targeted delivery of walnut-derived peptide to the brain, laying a foundation for the development of functional foods aimed at CNS disease intervention.
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Barrera Hematoencefálica , Juglans , Péptidos , Juglans/química , Juglans/metabolismo , Barrera Hematoencefálica/metabolismo , Animales , Ratones , Péptidos/química , Péptidos/metabolismo , Péptidos/farmacología , Transporte Biológico , Caveolinas/metabolismo , Caveolinas/química , Humanos , Endocitosis , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Nueces/química , Nueces/metabolismoRESUMEN
Increasing research efforts are focused on studying the synthesis and mechanisms of nanomedicine in urologic cancer. We performed a bibliometric study of the literature on nanomedicine in urologic cancer over the last 23 years, focusing on aspects such as researchers, institutions, nations, and keywords. We searched for papers in the Web of Science Core Collection from January 1, 2001, to December 29, 2023. Only reviews and original articles written in English were considered. A total of 2386 papers satisfied the given criteria for inclusion. The publications included in the study originated from 90 nations. The United States had the largest number of published papers, accounting for more than 31.01% of the total. The leading institution in this field is the Chinese Academy of Sciences, with a publishing output of 2.35%. Farokhzad, Omid C., is the most prolific author, with 21 articles, and has garnered the most citations, totaling 6271. The latest phrase to enter the top ten most common lists was "gold nanoparticles." We searched for papers in the Web of Science Core Collection from January 1, 2000, to November 28, 2023. Only reviews and original articles written in English were considered. This is the first bibliometric study of nanomedicine in urologic cancer. This article provides a comprehensive analysis of the current state of research on nanomedicine in urologic cancer over the last 23 years. On the basis of this study, future researchers can identify noteworthy publications, journals, and potential collaborators and explore cutting-edge research directions.
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Objective: To explore the perspectives and needs related to fertility preservation decision-making in patients of childbearing age with breast cancer. Methods: Semistructured face-to-face interviews were conducted in a tertiary hospital in Baoding, China from July to October 2023. Purposive sampling was used to ensure the diversity of samples. The interview guide is based on the literature review and the discussions within the research team. A traditional content analysis approach was used for data analysis. Results: A total of 18 participants were interviewed. Three themes emerged from the data: conflicts between subjective desires and concerns, coexistence of objective benefits and challenges, and decision-making support needs. The conflicts between subjective desires and concerns included five sub-themes, the coexistence of objective benefits and challenges also included five sub-themes, and the decision-making support needs included two sub-themes. Conclusions: Patients faced a difficult trade-off between desires and concerns, benefits, and challenges regarding fertility preservation decisions, with numerous unmet needs. Healthcare professionals should prioritize patients' fertility desires, providing timely fertility preservation information and adequate counseling after a cancer diagnosis. This approach can help alleviate unnecessary concerns, facilitate satisfactory decision-making, and improve patients' quality of life.
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Phenolic compounds have long captivated the interest of organic synthesis, particularly in their quest for selective hydroxylation of arenes using H2O as a hydroxyl source. However, the inherent high reactivity and low redox potential of phenols often lead to undesirable overoxidation byproducts. To address this challenge, herein, we develop an electrophotochemical approach, finetuning substrate oxidative potential and enabling para-selective hydroxylation of anilides. This method showcases versatility, accommodating a wide array of substrates, while revealing high regional selectivity and compatibility with diverse functional groups. Moreover, the protocol allows facile late-stage functionalization of biologically active molecules. Mechanistic investigations demonstrate the activation of anilides by the excited state photocatalyst, effectively decreasing their oxidative potential and enhancing regional selectivity during hydroxylation. By using this protocol, important drug molecules such as Paracetamol, Fenretinide, Practolol, and AM404 could be synthesized, demonstrating the applicability of this approach in drug synthesis and late-stage functionalization.
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The term type 3 diabetes mellitus (T3DM) has been considered for Alzheimer's disease (AD) due to the common molecular and cellular characteristics found between type 2 diabetes mellitus (T2DM) and cognitive deficits. However, the specific mechanism of T3DM remains elusive, especially the neuroprotective effects of dietary components in hyperglycemic individuals. In this study, a peptide, Leu-Val-Arg-Leu (LVRL), found in walnuts significantly improved memory decline in streptozotocin (STZ)- and high-fat-diet (HFD)-stimulated T2DM mouse models (p < 0.05). The LVRL peptide also mitigated hyperglycemia, enhanced synaptic plasticity, and ameliorated mitochondrial dysfunction, as demonstrated by Morris water maze tests, immunoblotting, immunofluorescence, immunohistochemistry, transmission electron microscopy, and cellular staining. A Wnt3a inhibitor, DKK1, was subsequently used to verify the possible role of the Wnt3a/ß-Catenin/GSK-3ß pathway in glucose-induced insulin resistance in PC12 cells. In vitro LVRL treatment dramatically modulated the protein expression of p-Tau (Ser404), Synapsin-1, and PSD95, elevated the insulin level, increased glucose consumption, and relieved the mitochondrial membrane potential, and MitoSOX (p < 0.05). These data suggested that peptides like LVRL could modulate the relationship between brain insulin and altered cognition status via the Wnt3a/ß-Catenin/GSK-3ß pathway.
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Diabetes Mellitus Tipo 2 , Glucógeno Sintasa Quinasa 3 beta , Juglans , Fármacos Neuroprotectores , Proteína Wnt3A , beta Catenina , Animales , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Masculino , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , Ratones , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/química , beta Catenina/metabolismo , beta Catenina/genética , Humanos , Ratas , Juglans/química , Proteína Wnt3A/metabolismo , Proteína Wnt3A/genética , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/metabolismo , Ratones Endogámicos C57BL , Péptidos/química , Péptidos/farmacología , Péptidos/administración & dosificación , Células PC12 , Transducción de Señal/efectos de los fármacosRESUMEN
Diabetic retinopathy (DR), a significant and vision-endangering complication associated with diabetes mellitus, constitutes a substantial portion of acquired instances of preventable blindness. The progression of DR appears to prominently feature the loss of retinal cells, encompassing neural retinal cells, pericytes, and endothelial cells. Therefore, mitigating the apoptosis of retinal cells in DR could potentially enhance the therapeutic approach for managing the condition by suppressing retinal vascular leakage. Recent advancements have highlighted the crucial regulatory roles played by non-coding RNAs (ncRNAs) in diverse biological processes. Recent advancements have highlighted that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), act as central regulators in a wide array of biogenesis and biological functions, exerting control over gene expression associated with histogenesis and cellular differentiation within ocular tissues. Abnormal expression and activity of ncRNAs has been linked to the regulation of diverse cellular functions such as apoptosis, and proliferation. This implies a potential involvement of ncRNAs in the development of DR. Notably, ncRNAs and apoptosis exhibit reciprocal regulatory interactions, jointly influencing the destiny of retinal cells. Consequently, a thorough investigation into the complex relationship between apoptosis and ncRNAs is crucial for developing effective therapeutic and preventative strategies for DR. This review provides a fundamental comprehension of the apoptotic signaling pathways associated with DR. It then delves into the mutual relationship between apoptosis and ncRNAs in the context of DR pathogenesis. This study advances our understanding of the pathophysiology of DR and paves the way for the development of novel therapeutic strategies.
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Apoptosis , Retinopatía Diabética , ARN no Traducido , Transducción de Señal , Retinopatía Diabética/genética , Retinopatía Diabética/metabolismo , Retinopatía Diabética/terapia , Humanos , Apoptosis/genética , Transducción de Señal/genética , Animales , ARN no Traducido/genética , ARN no Traducido/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Retina/metabolismo , Retina/patologíaRESUMEN
PURPOSE: To develop multiphoton excitation techniques for simultaneous multislice (SMS) imaging and evaluate their performance and specific absorption rate (SAR) benefit. To improve multiphoton SMS reconstruction quality with a novel CAIPIRINHA (controlled aliasing in parallel imaging results in higher acceleration) design. THEORY AND METHODS: When a conventional single-slice RF field is applied together with an oscillating gradient field, the two can combine to generate multiphoton excitation at multiple discrete spatial locations. Because the conventional RF is reused at multiple spatial locations, multiphoton excitation offers reduced SAR for SMS applications. CAIPIRINHA shifts are often used to improve parallel-imaging acceleration. Interestingly, CAIPIRINHA-type shifts can be obtained for multiphoton SMS by updating the oscillating gradient phase at every phase encode. In this work, both a gradient-echo and a spin-echo sequence with multiphoton CAIPIRINHA-SMS excitation pulses are implemented for in vivo human imaging at 3 T. RESULTS: For three slices, multiphoton SMS provides a 51% reduction in SAR compared with conventional superposition SMS, whereas for five slices, SAR is reduced by 66%. Multiphoton SMS outperforms PINS (power independent of number of slices) and MultiPINS in terms of SAR reduction especially when the pulse duration is short, slices are thin, and/or the slice spacing is large. A custom CAIPIRINHA phase-encoding design for multiphoton SMS significantly improves reconstruction quality. CONCLUSION: Multiphoton SMS excitation can be obtained by combining conventional single-slice RF pulses with an oscillating gradient and offers significant SAR benefits compared with conventional superposition SMS. A novel CAIPIRINHA design allows higher multiband factors for multiphoton SMS imaging.
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Algoritmos , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Encéfalo/diagnóstico por imagen , Fantasmas de ImagenRESUMEN
MOTIVATION: Single-cell omics technologies have enabled the quantification of molecular profiles in individual cells at an unparalleled resolution. Deep learning, a rapidly evolving sub-field of machine learning, has instilled a significant interest in single-cell omics research due to its remarkable success in analysing heterogeneous high-dimensional single-cell omics data. Nevertheless, the inherent multi-layer nonlinear architecture of deep learning models often makes them 'black boxes' as the reasoning behind predictions is often unknown and not transparent to the user. This has stimulated an increasing body of research for addressing the lack of interpretability in deep learning models, especially in single-cell omics data analyses, where the identification and understanding of molecular regulators are crucial for interpreting model predictions and directing downstream experimental validations. RESULTS: In this work, we introduce the basics of single-cell omics technologies and the concept of interpretable deep learning. This is followed by a review of the recent interpretable deep learning models applied to various single-cell omics research. Lastly, we highlight the current limitations and discuss potential future directions.
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Aprendizaje Profundo , Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Humanos , Biología Computacional/métodos , Genómica/métodosRESUMEN
Quantitative susceptibility mapping (QSM) is an MRI modality used to non-invasively measure iron content in the brain. Iron exhibits a specific anatomically varying pattern of accumulation in the brain across individuals. The highest regions of accumulation are the deep grey nuclei, where iron is stored in paramagnetic molecule ferritin. This form of iron is considered to be what largely contributes to the signal measured by QSM in the deep grey nuclei. It is also known that QSM is affected by diamagnetic myelin contents. Here, we investigate spatial gene expression of iron and myelin related genes, as measured by the Allen Human Brain Atlas, in relation to QSM images of age-matched subjects. We performed multiple linear regressions between gene expression and the average QSM signal within 34 distinct deep grey nuclei regions. Our results show a positive correlation (p < .05, corrected) between expression of ferritin and the QSM signal in deep grey nuclei regions. We repeated the analysis for other genes that encode proteins thought to be involved in the transport and storage of iron in the brain, as well as myelination. In addition to ferritin, our findings demonstrate a positive correlation (p < .05, corrected) between the expression of ferroportin, transferrin, divalent metal transporter 1, several gene markers of myelinating oligodendrocytes, and the QSM signal in deep grey nuclei regions. Our results suggest that the QSM signal reflects both the storage and active transport of iron in the deep grey nuclei regions of the brain.
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Ferritinas , Homeostasis , Hierro , Imagen por Resonancia Magnética , Vaina de Mielina , Humanos , Hierro/metabolismo , Masculino , Femenino , Vaina de Mielina/metabolismo , Vaina de Mielina/genética , Adulto , Homeostasis/fisiología , Ferritinas/metabolismo , Ferritinas/genética , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Expresión Génica , Persona de Mediana Edad , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Adulto Joven , Mapeo Encefálico/métodosRESUMEN
Microglia phagocytose synapses have an important effect on the pathogenesis of neurological disorders. Here, we investigated the neuroprotective effects of the walnut-derived peptide, TWLPLPR(TW-7), against LPS-induced cognitive deficits in mice and explored the underlying C1q-mediated microglia phagocytose synapses mechanisms in LPS-treated HT22 cells. The MWM showed that TW-7 improved the learning and memory capacity of the LPS-injured mice. Both transmission electron microscopy and immunofluorescence analysis illustrated that synaptic density and morphology were increased while associated with the decreased colocalized synapses with C1q. Immunohistochemistry and immunofluorescence demonstrated that TW-7 effectively reduced the microglia phagocytosis of synapses. Subsequently, overexpression of C1q gene plasmid was used to verify the contribution of the TW-7 via the classical complement pathway-regulated mitochondrial function-mediated microglia phagocytose synapses in LPS-treated HT22 cells. These data suggested that TW-7 improved the learning and memory capability of LPS-induced cognitively impaired mice through a mechanism associated with the classical complement pathway-mediated microglia phagocytose synapse.
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Objectives: Medical research continues to be extensively devoted to investigating the pathogenesis and treatment approaches of hereditary renal cancer. By aspect including researchers, institutions, countries, journals, and keywords, we conduct a bibliometric analysis of the literature pertaining to hereditary renal cancer over the last 23 years. Methods: From the Web of Science Core Collection, we conducted a search for publications published between January 1, 2000 and November 28, 2023. Reviews and original articles were included. Results: A cumulative count of 2,194 publications met the specified criteria for inclusion. The studies of the included articles involved a collective of 2,402 institutions representing 80 countries. Notably, the United States exhibited the highest number of published documents, constituting approximately 45.49% of the total. The preeminent institution in this discipline is the National Cancer Institute (NCI), which maintains a publication volume of 8.98%. In addition to being the most prolific author (125 publications), Linehan WM's works received the highest number of citations (11,985). In a comprehensive count, 803 journals have published related articles. In the top 10 most recent occurrences were the terms "hereditary leiomyomatosis" and "fumarate hydratase." Conclusion: This is the first bibliometric analysis of the literature on hereditary renal cancer. This article offers a thorough examination of the present status of investigations concerning hereditary renal cancer during the previous 23 years.
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Methane, the most significant reduced form of carbon on Earth, acts as a crucial fuel and greenhouse gas. Globally, microbial methane sinks encompass both aerobic oxidation of methane (AeOM), conducted by oxygen-utilizing methanotrophs, and anaerobic oxidation of methane (AOM), performed by anaerobic methanotrophs employing various alternative electron acceptors. These electron acceptors involved in AOM include sulfate, nitrate/nitrite, humic substances, and diverse metal oxides. The known anaerobic methanotrophic pathways comprise the internal aerobic oxidation pathway found in NC10 bacteria and the reverse methanogenesis pathway utilized by anaerobic methanotrophic archaea (ANME). Diverse anaerobic methanotrophs can perform AOM independently or in cooperation with symbiotic partners through several extracellular electron transfer (EET) pathways. AOM has been documented in various environments, including seafloor methane seepages, coastal wetlands, freshwater lakes, soils, and even extreme environments like hydrothermal vents. The environmental activities of AOM processes, driven by different electron acceptors, primarily depend on the energy yields, availability of electron acceptors, and environmental adaptability of methanotrophs. It has been suggested that different electron acceptors driving AOM may occur across a wider range of habitats than previously recognized. Additionally, it is proposed that methanotrophs have evolved flexible metabolic strategies to adapt to complex environmental conditions. This review primarily focuses on AOM, driven by different electron acceptors, discussing the associated reaction mechanisms and the habitats where these processes are active. Furthermore, it emphasizes the pivotal role of AOM in mitigating methane emissions.
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Metano , Oxidación-Reducción , Metano/metabolismo , Anaerobiosis , Archaea/metabolismo , Electrones , Bacterias/metabolismo , Transporte de ElectrónRESUMEN
Magnetogenetics was developed to remotely control genetically targeted neurons. A variant of magnetogenetics uses magnetic fields to activate transient receptor potential vanilloid (TRPV) channels when coupled with ferritin. Stimulation with static or RF magnetic fields of neurons expressing these channels induces Ca2+ transients and modulates behavior. However, the validity of ferritin-based magnetogenetics has been questioned due to controversies surrounding the underlying mechanisms and deficits in reproducibility. Here, we validated the magnetogenetic approach Ferritin-iron Redistribution to Ion Channels (FeRIC) using electrophysiological (Ephys) and imaging techniques. Previously, interference from RF stimulation rendered patch-clamp recordings inaccessible for magnetogenetics. We solved this limitation for FeRIC, and we studied the bioelectrical properties of neurons expressing TRPV4 (nonselective cation channel) and transmembrane member 16A (TMEM16A; chloride-permeable channel) coupled to ferritin (FeRIC channels) under RF stimulation. We used cultured neurons obtained from the rat hippocampus of either sex. We show that RF decreases the membrane resistance (Rm) and depolarizes the membrane potential in neurons expressing TRPV4FeRIC RF does not directly trigger action potential firing but increases the neuronal basal spiking frequency. In neurons expressing TMEM16AFeRIC, RF decreases the Rm, hyperpolarizes the membrane potential, and decreases the spiking frequency. Additionally, we corroborated the previously described biochemical mechanism responsible for RF-induced activation of ferritin-coupled ion channels. We solved an enduring problem for ferritin-based magnetogenetics, obtaining direct Ephys evidence of RF-induced activation of ferritin-coupled ion channels. We found that RF does not yield instantaneous changes in neuronal membrane potentials. Instead, RF produces responses that are long-lasting and moderate, but effective in controlling the bioelectrical properties of neurons.
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Ferritinas , Neuronas , Animales , Ferritinas/metabolismo , Ratas , Neuronas/fisiología , Masculino , Femenino , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética , Células Cultivadas , Campos Magnéticos , Ratas Sprague-Dawley , Potenciales de la Membrana/fisiología , Técnicas de Placa-Clamp , Hipocampo/fisiología , Hipocampo/citologíaRESUMEN
Although recent studies increasingly suggest the potential anti-cancer effect of quercetin, the exact underlying mechanism remains poorly demonstrated in oral squamous cell carcinoma (oSCC). Therefore, our research explored the impacts of quercetin on the ferroptosis and mTOR/S6KP70 axis in oSCC cell lines. After treating oSCC cells with quercetin or indicated compounds and transfection with SLC7A11- or S6KP70-overexpressing plasmid, cell viability was detected by CCK-8 assay. The level of ferroptosis in oSCC cells was assessed by measuring ROS and GSH levels. The activation of mTOR/S6KP70 axis was assessed by Western blotting. Quercetin promoted ferroptosis in an mTOR/S6KP70-dependent manner to inhibit tumor growth in oSCC cells. Mechanistically, we revealed that quercetin induced lipid peroxidation and reduced GSH levels by repressing SLC7A11 expression in oSCC cells. Specifically, the effects of quercetin on ferroptosis and mTOR and S6KP70 phosphorylation were partially blocked by both mTOR agonist and S6KP70 overexpression. Moreover, mTOR inhibitor promoted ferroptosis in quercetin-treated oSCC cells. Our findings showed that ferroptosis may be a new anti-tumor mechanism of quercetin. Additionally, we identified that quercetin can target mTOR/S6KP70 cascade to inhibit the growth of oSCC cells.
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Sistema de Transporte de Aminoácidos y+ , Ferroptosis , Neoplasias de la Boca , Quercetina , Serina-Treonina Quinasas TOR , Animales , Humanos , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Ratones Desnudos , Neoplasias de la Boca/patología , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/metabolismo , Quercetina/farmacología , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Transducción de Señal/efectos de los fármacos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
We investigated the protective effect of walnut peptides and YVPFPLP (YP-7) on scopolamine-induced memory impairment in mice and ß-amyloid (Aß)-induced excitotoxic injury in primary hippocampal neurons, respectively. Additionally, the protective mechanism of YP-7 on neuronal excitotoxicity was explored. Mouse behavioral and hippocampal slice morphology experiments indicate that YP-7 improves the learning and memory abilities of cognitively impaired mice and protects synaptic integrity. Immunofluorescence, western blotting, and electrophysiological experiments on primary hippocampal neurons indicate that YP-7 inhibits neuronal damage caused by excessive excitation of neurons induced by Aß. HT-22 cell treatment with peroxisome proliferator-activated receptor γ (PPARγ) activators and inhibitors showed that YP-7 activates PPARγ expression and maintains normal neuronal function by forming stable complexes with PPARγ to inhibit the extracellular regulated protein kinase pathway. Therefore, YP-7 can ameliorate glutamate-induced excitotoxicity and maintain neuronal signaling. This provides a theoretical basis for active peptides to ameliorate excitotoxicity and the development of functional foods.
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Hipocampo , Juglans , Trastornos de la Memoria , Neuronas , Péptidos , Animales , Humanos , Masculino , Ratones , Péptidos beta-Amiloides/metabolismo , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Juglans/química , Memoria/efectos de los fármacos , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Péptidos/química , Péptidos/farmacología , Proteínas de Plantas/química , Proteínas de Plantas/farmacología , PPAR gamma/metabolismo , PPAR gamma/genética , EscopolaminaRESUMEN
Correction for 'Therapeutic effects of a walnut-derived peptide on NLRP3 inflammasome activation, synaptic plasticity, and cognitive dysfunction in T2DM mice' by Yanru Li et al., Food Funct., 2024, 15, 2295-2313, https://doi.org/10.1039/D3FO05076A.
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Quantitative susceptibility mapping (QSM) is an MRI-based technique that estimates the underlying tissue magnetic susceptibility based on phase signal. Deep learning (DL)-based methods have shown promise in handling the challenging ill-posed inverse problem for QSM reconstruction. However, they require extensive paired training data that are typically unavailable and suffer from generalization problems. Recent model-incorporated DL approaches also overlook the non-local effect of the tissue phase in applying the source-to-field forward model due to patch-based training constraint, resulting in a discrepancy between the prediction and measurement and subsequently suboptimal QSM reconstruction. This study proposes an unsupervised and subject-specific DL method for QSM reconstruction based on implicit neural representation (INR), referred to as INR-QSM. INR has emerged as a powerful framework for learning a high-quality continuous representation of the signal (image) by exploiting its internal information without training labels. In INR-QSM, the desired susceptibility map is represented as a continuous function of the spatial coordinates, parameterized by a fully-connected neural network. The weights are learned by minimizing a loss function that includes a data fidelity term incorporated by the physical model and regularization terms. Additionally, a novel phase compensation strategy is proposed for the first time to account for the non-local effect of tissue phase in data consistency calculation to make the physical model more accurate. Our experiments show that INR-QSM outperforms traditional established QSM reconstruction methods and the compared unsupervised DL method both qualitatively and quantitatively, and is competitive against supervised DL methods under data perturbations.