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1.
Biol Cybern ; 118(1-2): 21-37, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38472417

RESUMEN

Motor imagery electroencephalogram (EEG) is widely employed in brain-computer interface (BCI) systems. As a time-frequency analysis method for nonlinear and non-stationary signals, multivariate empirical mode decomposition (MEMD) and its noise-assisted version (NA-MEMD) has been widely used in the preprocessing step of BCI systems for separating EEG rhythms corresponding to specific brain activities. However, when applied to multichannel EEG signals, MEMD or NA-MEMD often demonstrate low robustness to noise and high computational complexity. To address these issues, we have explored the advantages of our recently proposed fast multivariate empirical mode decomposition (FMEMD) and its noise-assisted version (NA-FMEMD) for analyzing motor imagery data. We emphasize that FMEMD enables a more accurate estimation of EEG frequency information and exhibits a more noise-robust decomposition performance with improved computational efficiency. Comparative analysis with MEMD on simulation data and real-world EEG validates the above assertions. The joint average frequency measure is employed to automatically select intrinsic mode functions that correspond to specific frequency bands. Thus, FMEMD-based classification architecture is proposed. Using FMEMD as a preprocessing algorithm instead of MEMD can improve the classification accuracy by 2.3% on the BCI Competition IV dataset. On the Physiobank Motor/Mental Imagery dataset and BCI Competition IV Dataset 2a, FMEMD-based architecture also attained a comparable performance to complex algorithms. The results indicate that FMEMD proficiently extracts feature information from small benchmark datasets while mitigating dimensionality constraints resulting from computational complexity. Hence, FMEMD or NA-FMEMD can be a powerful time-frequency preprocessing method for BCI.


Asunto(s)
Interfaces Cerebro-Computador , Electroencefalografía , Imaginación , Humanos , Electroencefalografía/métodos , Imaginación/fisiología , Algoritmos , Procesamiento de Señales Asistido por Computador , Análisis Multivariante , Encéfalo/fisiología , Simulación por Computador
4.
Eur J Cancer ; 195: 113286, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37968194

RESUMEN

To the editor: Hand-foot skin reaction (HFSR), characterized by skin abnormalities on palmoplantar surfaces, has an overall incidence of about 35% upon vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) treatment.1 Zinc, which plays a role in maintaining skin health, may be implicated in the pathogenesis of HFSR.2 Zinc deficiency has been shown to associate with dermatological toxicities of epidermal growth factor receptor (EGFR)-TKI.3, 4 Regorafenib, an oral multi-kinase inhibitor targeting VEGFR 1-3, PDGFR, cKIT, BRAF, and RET1, is approved for the treatment of metastatic colorectal cancer (mCRC) but commonly causes HFSR.5 This phase II randomized trial aimed to investigate whether zinc supplementation can reduce the severity of HFSR induced by regorafenib within the first 8 weeks of treatment (NCT03898102).


Asunto(s)
Factor A de Crecimiento Endotelial Vascular , Zinc , Humanos , Incidencia , Compuestos de Fenilurea/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Suplementos Dietéticos
5.
Medicine (Baltimore) ; 102(41): e35405, 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37832041

RESUMEN

BACKGROUND: This study aimed to assess the efficacy and safety of Tongxinluo capsule (TXLC) in combination with conventional therapies for treating stable angina pectoris (SAP) through a comprehensive meta-analysis and systematic review. METHODS: We conducted a systematic search of the China National Knowledge Infrastructure, Wanfang, VIP, PubMed, Embase, and CENTRAL databases for randomized controlled trials investigating the use of TXLC as adjuvant therapy for SAP published up to June 2023. The Cochrane Handbook was used to evaluate the risk of bias. Meta-analysis was performed using Review Manager 5.4.1, and publication bias was assessed using Begg test and Egger test in the Stata SE 12.0 software. GRADEpro was used to assess the quality of the evidence. RESULTS: This meta-analysis included 26 randomized controlled trials with a total of 2352 patients. TXLC co-administration demonstrated significant reduction in angina attack frequency (mean difference (MD) -0.91, 95% confidence interval (CI) -0.97 to -0.84, P < .00001) and duration (MD -1.71, 95% CI -2.24 to -1.19, P < .00001), decreased use of nitroglycerin tablets (MD -6.28, 95% CI -7.16 to -5.41, P < .00001), lowered C-reactive protein (MD -1.19, 95% CI -1.35 to -1.03, P < .00001) and low-density lipoprotein cholesterol levels (MD -0.68, 95% CI -0.86 to -0.51, P < .00001). TXLC co-administration did not increase gastrointestinal reactions (RR 1.17, 95% CI 0.38 to 3.57, P = .78). The Begg test and Egger test results indicated no publication bias. The evidence quality was rated as very low for frequency of angina attack, duration of angina attack, and nitroglycerin usage, and low for C-reactive protein, low-density lipoprotein cholesterol levels, and gastrointestinal reaction events. CONCLUSION: This meta-analysis supports TXLC as a beneficial adjunct treatment for SAP.


Asunto(s)
Angina Estable , Medicamentos Herbarios Chinos , Humanos , Angina Estable/tratamiento farmacológico , Nitroglicerina , Proteína C-Reactiva , Medicamentos Herbarios Chinos/uso terapéutico , Lipoproteínas LDL , Colesterol
6.
Medicine (Baltimore) ; 102(39): e35106, 2023 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-37773840

RESUMEN

BACKGROUND: Guanxinning tablet (GXNT), a Chinese patent medicine, is composed of salvia miltiorrhiza bunge and ligusticum striatum DC, which may play the role of endothelial protection through many pathways. We aimed to explore the molecular mechanisms of GXNT against atherosclerosis (AS) through network pharmacology and molecular docking verification. METHODS: The active ingredients and their potential targets of GXNT were obtained in traditional Chinese medicine systems pharmacology database and analysis platform and bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine databases. DrugBank, TTD, DisGeNET, OMIM, and GeneCards databases were used to screen the targets of AS. The intersection targets gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis were performed in DAVID database. GXNT-AS protein-protein interaction network, ingredient-target network and herb-target-pathway network were constructed by Cytoscape. Finally, we used AutoDock for molecular docking. RESULTS: We screened 65 active ingredients of GXNT and 70 GXNT-AS intersection targets. The key targets of protein-protein interaction network were AKT1, JUN, STAT3, TNF, TP53, IL6, EGFR, MAPK14, RELA, and CASP3. The Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that pathways in cancer, lipid and atherosclerosis, and PI3K-Akt signaling pathway were the main pathways. The ingredient-target network showed that the key ingredients were luteolin, tanshinone IIA, myricanone, dihydrotanshinlactone, dan-shexinkum d, 2-isopropyl-8-methylphenanthrene-3,4-dione, miltionone I, deoxyneocryptotanshinone, Isotanshinone II and 4-methylenemiltirone. The results of molecular docking showed that tanshinone IIA, dihydrotanshinlactone, dan-shexinkum d, 2-isopropyl-8-methylphenanthrene-3,4-dione, miltionone I, deoxyneocryptotanshinone, Isotanshinone II and 4-methylenemiltirone all had good binding interactions with AKT1, EGFR and MAPK14. CONCLUSION: The results of network pharmacology and molecular docking showed that the multiple ingredients within GXNT may confer protective effects on the vascular endothelium against AS through multitarget and multichannel mechanisms. AKT1, EGFR and MAPK14 were the core potential targets of GXNT against AS.


Asunto(s)
Aterosclerosis , Medicamentos Herbarios Chinos , Proteína Quinasa 14 Activada por Mitógenos , Humanos , Simulación del Acoplamiento Molecular , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Aterosclerosis/tratamiento farmacológico , Receptores ErbB , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico
8.
Adv Healthc Mater ; 12(27): e2301116, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37541296

RESUMEN

Currently, clinical photothermal therapy (PTT) is greatly limited by the poor tissue penetration of the excitation light sources in visible (390-780 nm) and first near-infrared (NIR-I, 780-900 nm) window. Herein, based on space and bond synergistic conjugation, a multiple-aniline organic small molecule (TPD), is synthesized for high-efficiency second near-infrared (NIR-II, 900-1700 nm) photoacoustic imaging guided PTT. With the heterogeneity of six nitrogen atoms in TPD, the lone electrons on the nitrogen atom and the π bond orbital on the benzene ring form multielectron conjugations with highly delocalized state, which endowed TPD with strong NIR-II absorption (maximum peak at 925 nm). Besides, according to the single molecular reorganization, the alkyl side chains on TPD make more free space for intramolecular motion to enhance the photothermal conversion ability. Forming TPD nanoparticles (NPs) in J-aggregation, they show a further bathochromic-shifted absorbance (maximum peak at 976 nm) as well as a high photothermal conversion efficiency (66.7%) under NIR-II laser irradiation. In vitro and in vivo experiments demonstrate that TPD NPs can effectively inhibit the growth of tumors without palpable side effects. The study provides a novel NIR-II multiple-aniline structure based on multielectron hyperconjugation, and opens a new design thought for photothermal agents.


Asunto(s)
Nanopartículas , Técnicas Fotoacústicas , Fototerapia/métodos , Terapia Fototérmica , Técnicas Fotoacústicas/métodos , Nanopartículas/uso terapéutico , Nanopartículas/química , Compuestos de Anilina/farmacología , Nitrógeno
9.
Phytomedicine ; 117: 154916, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37327643

RESUMEN

BACKGROUND: With population aging, the incidence of aging-related Alzheimer's disease (AD) is increasing, accompanied by decreased autophagy activity. At present, Caenorhabditis elegans (C. elegans) is widely employed to evaluate autophagy and in research on aging and aging-related diseases in vivo. To discover autophagy activators from natural medicines and investigate their therapeutic potential in antiaging and anti-AD effects, multiple C. elegans models related to autophagy, aging, and AD were used. METHOD: In this study, we employed the DA2123 and BC12921 strains to discover potential autophagy inducers using a self-established natural medicine library. The antiaging effect was evaluated by determining the lifespan, motor ability, pumping rate, lipofuscin accumulation of worms, and resistance ability of worms under various stresses. In addition, the anti-AD effect was examined by detecting the paralysis rate, food-sensing behavior, and amyloid-ß and Tau pathology in C. elegans. Moreover, RNAi technology was used to knock down the genes related to autophagy induction. RESULTS: We discovered that Piper wallichii extract (PE) and the petroleum ether fraction (PPF) activated autophagy in C. elegans, as evidenced by increased GFP-tagged LGG-1 foci and decreased GFP-p62 expression. In addition, PPF extended the lifespan and enhanced the healthspan of worms by increasing body bends and pumping rates, decreasing lipofuscin accumulation, and increasing resistance to oxidative, heat, and pathogenic stress. Moreover, PPF exhibited an anti-AD effect by decreasing the paralysis rate, improving the pumping rate and slowing rate, and alleviating Aß and Tau pathology in AD worms. However, the feeding of RNAi bacteria targeting unc-51, bec-1, lgg-1, and vps-34 abolished the antiaging and anti-AD effects of PPF. CONCLUSION: Piper wallichii may be a promising drug for antiaging and anti-AD. More future studies are also needed to identify autophagy inducers in Piper wallichii and clarify their molecular mechanisms.


Asunto(s)
Enfermedad de Alzheimer , Proteínas de Caenorhabditis elegans , Animales , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Lipofuscina/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Longevidad , Péptidos beta-Amiloides/metabolismo , Parálisis , Autofagia , Estrés Oxidativo
10.
Compr Rev Food Sci Food Saf ; 22(4): 2945-2976, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37166996

RESUMEN

Due to its rich health benefits and unique cultural charm, tea drinking is increasingly popular with the public in modern society. The safety of tea is the top priority that affects the development of tea industry and the health of consumers. During the process of tea growth, pesticides are used to prevent the invasion of pests and diseases with maintaining high quality and stable yield. Because hot water brewing is the traditional way of tea consumption, water is the main carrier for pesticide residues in tea into human body accompanied by potential risks. In this review, pesticides used in tea gardens are divided into two categories according to their solubility, among which water-soluble pesticides pose a greater risk. We summarized the methods of the sample pretreatment and detection of pesticide residues and expounded the migration patterns and influencing factors of tea throughout the process of growth, processing, storage, and consumption. Moreover, the toxicity and safety of pesticide residues and diseases caused by human intake were analyzed. The risk assessment and traceability of pesticide residues in tea were carried out, and potential eco-friendly improvement strategies were proposed. The review is expected to provide a valuable reference for reducing risks of pesticide residues in tea and ensuring the safety of tea consumption.


Asunto(s)
Residuos de Plaguicidas , Plaguicidas , Humanos , Residuos de Plaguicidas/análisis , Residuos de Plaguicidas/química , Té/química , Plaguicidas/análisis , Medición de Riesgo/métodos , Agua
11.
Biomater Adv ; 149: 213418, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37062124

RESUMEN

With excellent biocompatibility, stable chemical and optical properties, small organic molecules-based agents have always been a research hotspot in cancer photothermal therapy (PTT). In this work, a novel croconic acid-based molecule (CR) was designed and synthesized as an ideal photothermal agent (PTA), which showed abundant near-infrared (NIR) light absorption, high photothermal conversion ability, and excellent photothermal stability. By loading CR and quercetin (Qu) in CaO2, and coated with DSPE-PEG2000, a multifunctional theranostic nanoparticle (CCQ) was successfully prepared for calcium overloading mitochondrial metabolism inhibition synergetic mild PTT. Upon entering tumor microenvironment, CCQ can produce abundant H2O2 and a large amount of calcium ions, which lead to the imbalance of calcium concentration in the internal environment of tumor cells and induced mitochondrial apoptosis. With the existence of Qu, CCQ can effectively inhibit the expression of heat shock proteins (Hsp) during the PTT process, which weaken the heat resistance of tumors, ablate tumors at lower temperature (~45 °C), and reduce the damage to normal tissues. Guided by photoacoustic imaging (PAI), CCQ showed excellent multimodal therapeutic effect of tumors. This study provided a novel CR organic molecule-based theranostic nanoplatform that can be used to treat tumors via calcium overload therapy synergetic PTT at safe temperatures, which has promising potential for the future clinical cancer treatment.


Asunto(s)
Neoplasias , Fototerapia , Humanos , Fototerapia/métodos , Quercetina/farmacología , Quercetina/uso terapéutico , Terapia Fototérmica , Peróxido de Hidrógeno , Neoplasias/terapia , Neoplasias/patología , Microambiente Tumoral
12.
Cell ; 186(7): 1352-1368.e18, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-37001500

RESUMEN

Resilience enables mental elasticity in individuals when rebounding from adversity. In this study, we identified a microcircuit and relevant molecular adaptations that play a role in natural resilience. We found that activation of parvalbumin (PV) interneurons in the primary auditory cortex (A1) by thalamic inputs from the ipsilateral medial geniculate body (MG) is essential for resilience in mice exposed to chronic social defeat stress. Early attacks during chronic social defeat stress induced short-term hyperpolarizations of MG neurons projecting to the A1 (MGA1 neurons) in resilient mice. In addition, this temporal neural plasticity of MGA1 neurons initiated synaptogenesis onto thalamic PV neurons via presynaptic BDNF-TrkB signaling in subsequent stress responses. Moreover, optogenetic mimicking of the short-term hyperpolarization of MGA1 neurons, rather than merely activating MGA1 neurons, elicited innate resilience mechanisms in response to stress and achieved sustained antidepressant-like effects in multiple animal models, representing a new strategy for targeted neuromodulation.


Asunto(s)
Corteza Auditiva , Ratones , Animales , Corteza Auditiva/metabolismo , Tálamo/fisiología , Neuronas/metabolismo , Cuerpos Geniculados , Interneuronas/fisiología , Parvalbúminas/metabolismo
13.
Biol Trace Elem Res ; 201(12): 5540-5545, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36892689

RESUMEN

Hand-foot skin reaction (HFSR) is a common skin-related adverse event induced by multikinase inhibitors targeting both platelet-derived growth factor receptor and vascular endothelial growth factor receptor, possibly due to inadequate repair following frictional trauma. Zinc is a trace element and essential nutrient in humans that plays critical roles in the development and differentiation of skin cells. Zinc transporters (Zrt- and Irt-like proteins and Zn transporters) and metallothioneins are involved in zinc efflux, uptake, and homeostasis and have been reported to be involved in skin differentiation. The underlying mechanism of HFSR remains unclear, and the association between HFSR and zinc has not been previously studied. However, some case reports and case series provide potential evidence to suggest that zinc deficiency may be involved in HFSR development and zinc supplementation may relieve HFSR symptoms. However, no large-scale clinical studies have been conducted to examine this role. Therefore, this review summarizes the evidence supporting a possible link between HFSR development and zinc and proposes potential mechanisms underlying this association based on current evidence.


Asunto(s)
Desnutrición , Enfermedades de la Piel , Zinc , Humanos , Inhibidores de Proteínas Quinasas/efectos adversos , Piel/patología , Factor A de Crecimiento Endotelial Vascular , Zinc/deficiencia , Enfermedades de la Piel/inducido químicamente
14.
Kaohsiung J Med Sci ; 39(5): 501-510, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36757049

RESUMEN

Atopic dermatitis (AD) is a common inflammatory skin disease. Matrine is the main component of the traditional Chinese medicine Sophora flavescens, and it poses good therapeutic effects on inflammatory diseases. This study aimed to explore the pharmacological effects of matrine on AD and its underlying mechanism. An AD mouse model and inflamed human epidermal keratinocyte cells (HaCaT) cells were established. Histopathological aspects were examined using hematoxylin and eosin staining, toluidine blue staining, and immunohistochemistry. The mRNA and protein expressions were assessed using quantitative real-time polymerase chain reaction and Western blot, respectively. The secretions of cytokines and chemokines were examined by enzyme-linked immunosorbent assay. Flow cytometry was carried out to analyze the proportions of T-helper (Th) 1 and Th2 cells. Herein, our results displayed that matrine diminished AD symptoms and decreased heat shock protein 90 (Hsp90) expression. Matrine decreased the Th2 cytokine levels in the ear tissues and serum, and it also significantly repressed inflammatory cytokines (thymus activation regulated chemokine and interleukin-6) secretions by repressing the Hsp90/NF-κB signaling axis in inflamed HaCaT cells. Furthermore, matrine inhibited Th2 differentiation of CD4+ T cells when co-cultured with inflamed HaCaT cells. Matrine can regulate the Th1/Th2 inflammatory response by inhibiting the Hsp90/NF-κB signaling axis to alleviate AD. Therefore, it may be a candidate for AD treatment.


Asunto(s)
Dermatitis Atópica , Ratones , Animales , Humanos , Dermatitis Atópica/tratamiento farmacológico , FN-kappa B/genética , FN-kappa B/metabolismo , Matrinas , Factor de Necrosis Tumoral alfa/metabolismo , Queratinocitos/metabolismo , Citocinas/metabolismo , Quimiocinas/metabolismo
15.
Oxid Med Cell Longev ; 2022: 6256450, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36583098

RESUMEN

This study is an attempt to evaluate the therapeutic effect of the ethanolic extract of Lindera aggregata on the liver and intestinal microbiota in rats with alcohol-induced liver injury (ALI). Rats were treated with 70 mg probiotics, 1 g/kg, 2 g/kg, and 3 g/kg ethanolic extract of Lindera aggregata, respectively, for 10 days. We found that Lindera aggregata could significantly reduce the biochemical parameters in the serum of ALD rats. Lindera aggregata alleviates oxidative stress and inflammation by upregulating SIRT1 and Nrf2 and downregulating COX2 and NF-κB. The results of 16S rRNA gene sequencing showed that the medium dose of Lindera aggregata had the best effect on the growth of beneficial bacteria. Diversity analysis and LEfSe analysis showed that beneficial bacteria gradually occupied the dominant niche. The relative abundance of potential pathogens in the gut decreased significantly. We demonstrated that the ethanolic extract of Lindera aggregata can alleviate the oxidative stress and inflammation induced by alcohol through the SIRT1/Nrf2/NF-κB pathway and can modulate the disturbance of gut microbiota induced by alcohol intake.


Asunto(s)
Microbioma Gastrointestinal , Lindera , Extractos Vegetales , Animales , Ratas , Disbiosis/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Lindera/química , Hígado/metabolismo , Hígado/fisiopatología , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , ARN Ribosómico 16S/metabolismo , Sirtuina 1/metabolismo
16.
BMJ Open ; 12(12): e064212, 2022 12 23.
Artículo en Inglés | MEDLINE | ID: mdl-36564122

RESUMEN

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterised by progressive and irreversible fibrosis of the lung parenchyma, resulting in reduced lung function. Since conventional medicines can be associated with low effective rates and adverse events, pulmonary rehabilitation may be a promising non-pharmacological therapy for IPF. Thus, we aimed to evaluate the effects of full-body exercise-based pulmonary rehabilitation on patients with IPF by conducting a systematic review and meta-analysis of randomised controlled trials (RCTs). METHODS AND ANALYSIS: This systematic review and meta-analysis has been registered in the International Prospective Register of Systematic Reviews (PROSPERO). From inception to 31 August 2022, electronic databases in English and Chinese were searched, including PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials among the English databases. China National Knowledge Infrastructure, Chinese Biomedical Literature, VIP Chinese Science and Technology Periodical, and Wan Fang Data were among the Chinese databases. Two independent reviewers then screened the potential RCT studies, which were analysed according to the Cochrane Handbook criteria. The efficacy and safety of full-body exercise pulmonary rehabilitation for IPF were evaluated based on outcomes, including exercise capacity measured by 6 min walking distance and quality of life measured by St. George's Respiratory Questionnaire. Lung function was measured based on the forced vital capacity, total lung capacity, diffusing capacity of the lungs for carbon monoxide and dyspnoea assessed by the modified Medical Research Council scale. ETHICS AND DISSEMINATION: Ethical approval was not required for this systematic review and meta-analysis. Results will be published in a peer-reviewed journal and presented at conferences. PROSPERO REGISTRATION NUMBER: CRD42021284293.


Asunto(s)
Fibrosis Pulmonar Idiopática , Pulmón , Humanos , Terapia por Ejercicio , Ejercicio Físico , Medicina Tradicional China/métodos , Calidad de Vida , Metaanálisis como Asunto , Revisiones Sistemáticas como Asunto
17.
Artículo en Inglés | MEDLINE | ID: mdl-36411840

RESUMEN

Fuzheng Huayu's (FZHY) formula ameliorated liver fibrosis in clinical and experimental practice. Based on the close link between fibrosis and inflammation, its anti-inflammatory effect and related mechanisms were explored in this present study. With the aid of the inflammatory macrophage model, FZHY significantly blocked nitrite accumulation without observable cytotoxicity due to its suppression of inducible nitric oxide synthase (iNOS) gene and protein expressions in a concentration-depended manner. Proinflammatory mediators including IL-6, CD86, and CD40 were also restrained by FZHY. Interestingly, FZHY induced anti-inflammatory mediators heme oxygenase 1 (HO-1) and peroxisome proliferator-activated receptor γ (PPAR-γ) expressions simultaneously. Downregulation of iNOS and miR-155 and upregulation of PPAR-γ were also observed in CCl4-induced liver fibrosis mice upon FZHY administration. Mechanically, FZHY strikingly eliminated the phosphorylation of STAT1 and MAPK. Taken together, FZYH regulated the balance of proinflammatory and anti-inflammatory mediators partially via modulating STAT1/MAPK pathways and the miR-155/PPAR-γ axis.

18.
Acta Biomater ; 152: 546-561, 2022 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-36031034

RESUMEN

The development of new diagnostic imaging and precise treatment methods for glioblastoma multiforme (GBM) is significant to improve patients' quality of life and prolong their survival time. Herein, we proposed a photoacoustic imaging (PAI)-guided GBM high-efficient photothermal therapy (PTT) based on a second near-infrared (NIR-II) absorptive polymer (PDTP-TBZ) conjugated with intense electron donor dithienopyrrole (DTP) and strong electron acceptor thiadiazolobenzotriazole (TBZ). By nanoprecipitation, PDTP-TBZ can form into nanoparticles (PT NPs), and c(RGDfK) cyclic peptide with integrin-specific targeting was then modified on the surface of PT NPs to obtain the ability of active targeting GBM multifunctional nano-reagent (cRGD@PT NPs). Both in vitro and in vivo experiments demonstrated that cRGD@PT NPs as NIR-II GBM phototheranostic reagents can greatly improve the enrichment rate at tumor sites under PAI monitoring, and carry out precise NIR-II PTT with high effective tumor cell phototoxicity and high biological safety. Thus, cRGD@PT NPs have great potential for the future GBM phototheranostic application in clinic. STATEMENT OF SIGNIFICANCE: In this work, we successfully constructed an intense electron donor dithienopyrrole (DTP) with a strong electron acceptor thiadiazolobenzotriazole (TBZ) into a novel NIR-II optical absorptive conjugated polymer (PDTP-TBZ). Then, the c(RGDfK) cyclic peptide was modified on the surface of PT NPs to obtain multifunctional nanodiagnostic reagents (cRGD@PT NPs) that can effectively target GBM neovascularization and tumor cells. Both in vitro and in vivo experiments demonstrate that cRGD@PT NPs possess high photothermal conversion efficiency and practical photoacoustic imaging capability under 1064 nm laser irradiation. The results of this work suggested that cRGD@PT NPs have great potential in efficient NIR-II PTT guided by accurate PAI, which provide a good perspective for the treatment and diagnosis of GBM.


Asunto(s)
Glioblastoma , Técnicas Fotoacústicas , Diagnóstico por Imagen , Glioblastoma/diagnóstico por imagen , Glioblastoma/terapia , Humanos , Integrinas , Péptidos Cíclicos/farmacología , Técnicas Fotoacústicas/métodos , Fototerapia , Terapia Fototérmica , Polímeros/farmacología , Calidad de Vida
19.
Adv Healthc Mater ; 11(17): e2200962, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35735086

RESUMEN

Triple-negative breast cancer (TNBC) presents special biological behavior and clinicopathological characteristics and leads to a worse prognosis than other types of breast cancer. The development of an effective therapeutic method is significant to improve the survival rate of TNBC cancer patients. In this work, an engineered red blood cell membrane (RBCm)-coating salidroside/indocyanine green nanovesicle (ARISP) is successfully prepared for hypoxic targeting phototherapy of TNBC. Salidroside in ARISP effectively ameliorates hypoxia-induced tumorigenesis by downregulating the expression of hypoxia-inducible factor 1α (HIF-1α), which increases the killing effect of reactive oxygen species on tumor cells during photodynamic therapy (PDT) using the photosensitizer indocyanine green. Besides, ARISP has an anti-LDLR modified RBCm-coating that extends its circulation time in the blood and escapes from immune surveillance and enhances hypoxia-targeted cellular uptake via the overexpressed LDLR receptor in hypoxic tumor sites. Moreover, guided by near-infrared fluorescence imaging and photoacoustic imaging, ARISP can eliminate tumors via high-efficiency phototherapy and inhibit lung and liver metastasis in TNBC models. Cytotoxicity assay of ARISP indicates the excellent biocompatibility with normal cells and tissues. This study provides fulfilling insights into the anticancer mechanism of reducing HIF-1α for enhanced PDT and has a promising therapeutic potential for TNBC treatment.


Asunto(s)
Nanopartículas , Fotoquimioterapia , Neoplasias de la Mama Triple Negativas , Línea Celular Tumoral , Membrana Eritrocítica , Glucósidos , Humanos , Hipoxia , Verde de Indocianina/uso terapéutico , Nanopartículas/uso terapéutico , Fenoles , Fotoquimioterapia/métodos , Fototerapia/métodos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología
20.
Plant Biotechnol J ; 20(9): 1807-1818, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35642379

RESUMEN

Seed size is one of the most important agronomic traits determining the yield of crops. Cloning the key genes controlling seed size and pyramiding their elite alleles will facilitate yield improvement. To date, few genes controlling seed size have been identified in soybean, a major crop that provides half of the plant oil and one quarter of the plant protein globally. Here, through a genome-wide association study of over 1800 soybean accessions, we determined that natural allelic variation at GmST05 (Seed Thickness 05) predominantly controlled seed thickness and size in soybean germplasm. Further analyses suggested that the two major haplotypes of GmST05 differed significantly at the transcriptional level. Transgenic experiments demonstrated that GmST05 positively regulated seed size and influenced oil and protein contents, possibly by regulating the transcription of GmSWEET10a. Population genetic diversity analysis suggested that allelic variations of GmST05 were selected during geographical differentiation but have not been fixed. In summary, natural variation in GmST05 determines transcription levels and influences seed size and quality in soybean, making it an important gene resource for soybean molecular breeding.


Asunto(s)
Alelos , Estudio de Asociación del Genoma Completo , Glycine max/genética , Semillas/anatomía & histología , Semillas/genética , Clonación Molecular , Variación Genética , Haplotipos , Polimorfismo de Nucleótido Simple , Glycine max/crecimiento & desarrollo
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