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1.
J Ethnopharmacol ; 331: 118303, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38734390

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar, a traditional mineral Chinese medicine, has been used in China for more than 2000 years. It has been recorded in many ancient and modern works that it has anti-cancer and anti-tumor effects. Of course, colon cancer is also within the scope of its treatment. Realgar needs to be processed into realgar decoction pieces by water grinding before being used for medicine. To ensure the consistency of efficacy and quality of realgar decoction pieces, modern methods need to be used for further quality control. AIM OF THE STUDY: The research of traditional mineral Chinese medicine is relatively difficult, and the related research is less. The purpose of this study is to control the quality of realgar decoction pieces by modern analytical technology and analyze its components. On this basis, its anti-colon cancer activity was discussed. MATERIALS AND METHODS: Several batches of realgar decoction pieces were analyzed by XRD, and the components of realgar decoction pieces were obtained. The quality control fingerprints of realgar decoction pieces were established by processing XRD spectra and similarity evaluation. Then, the effects of realgar decoction pieces on apoptosis of CT26 and HTC-116 cells were observed in vitro by Hoechst 33258 staining, flow cytometry, measurement of mitochondrial membrane potential and Western blot; In vivo, the mouse model of tumor-in-situ transplantation of colon cancer was established, and the related indexes were observed. RESULT: The explorations showed that the XRD Fourier fingerprints of realgar decoction pieces samples that had the same phase revealed 10 common peaks, respectively. The similarity evaluation of the established XRD Fourier fingerprint was greater than 0.900. We also demonstrated that realgar decoction pieces can promote apoptosis and inhibit tumor growth in colon cancer cells, its activating effect on p53 protein, and its safety when used within reasonable limits. CONCLUSION: The quality control of realgar decoction pieces by XRD is scientific and has the inhibitory effect on colon cancer, which has the development potential.


Assuntos
Apoptose , Neoplasias do Colo , Animais , Apoptose/efeitos dos fármacos , Camundongos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Humanos , Sulfetos/farmacologia , Sulfetos/uso terapêutico , Arsenicais/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Masculino , Controle de Qualidade , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico
2.
Talanta ; 276: 126251, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38761657

RESUMO

Monitoring of glutathione has attracted considerable attention owing to its biological and clinical significance. An eco-friendly, economic, simple, biocompatible probe with excellent sensitivity and selectivity is very important. Herein, FeOOH QD@ATP-BODIPY nanocomposite was fabricated from one-step synthesized FeOOH quantum dots (FeOOH QD) and commercial boron-dipyrromethene-conjugated adenosine 5'-triphosphate (ATP-BODIPY) for glutathione (GSH) sensing in solutions and living cells. Three fascinate merits of FeOOH QD were confirmed: (a) as fluorescence quencher for ATP-BODIPY, (b) as selective recognizer of GSH and (c) with carrier effects and membrane permeability. The construction and response mechanism of the nanocomposite was based on the competitive coordination chemistry and redox reaction of FeOOH QD between GSH and phosphate group of ATP-BODIPY. Under the optimal conditions, the detection limit for GSH was as low as 68.8 nM. Excellent linear range of 0.2-400 µM was obtained. Furthermore, the chemical response of the nanocomposite exhibits high selectivity toward GSH over other electrolytes and biomolecules. It was successfully applied for GSH determination in human serum samples. The MTT assay exhibited FeOOH QD@ATP-BODIPY nanocomposite own good biocompatibility. FeOOH QD@ATP-BODIPY respond to GSH in living cells in situ was also proved via fluorescence imaging. These suggested that the FeOOH QD@ATP-BODIPY nanocomposite had potential application in biological and clinical applications.

3.
Biosens Bioelectron ; 259: 116422, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38797034

RESUMO

The biology-material hybrid method for chemical-electricity conversion via microbial fuel cells (MFCs) has garnered significant attention in addressing global energy and environmental challenges. However, the efficiency of these systems remains unsatisfactory due to the complex manufacturing process and limited biocompatibility. To overcome these challenges, here, we developed a simple bio-inorganic hybrid system for bioelectricity generation in Shewanella oneidensis (S. oneidensis) MR-1. A biocompatible surface display approach was designed, and silver-binding peptide AgBP2 was expressed on the cell surface. Notably, the engineered Shewanella showed a higher electrochemical sensitivity to Ag+, and a 60 % increase in power density was achieved even at a low concentration of 10 µM Ag+. Further analysis revealed significant upregulations of cell surface negative charge intensity, ATP metabolism, and reducing equivalent (NADH/NAD+) ratio in the engineered S. oneidensis-Ag nanoparticles biohybrid. This work not only provides a novel insight for electrochemical biosensors to detect metal ions, but also offers an alternative biocompatible surface display approach by combining compatible biomaterials with electricity-converting bacteria for advancements in biohybrid MFCs.

4.
Front Microbiol ; 15: 1291876, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38765679

RESUMO

Introduction: Antibiotic misuse and overuse have led to the emergence of carbapenem-resistant bacteria. The global spread of resistance to the novel antibiotic combination ceftazidime-avibactam (CZA) is becoming a severe problem. Antimicrobial peptide PAM-1 offers a novel approach for treating infections caused by antibiotic-resistant bacteria. This study explores its antibacterial and anti-biofilm activities and mechanisms against CZA-resistant Escherichia. Coli (E. coli), evaluating its stability and biosafety as well. Methods: The broth microdilution method, growth curve analysis, crystal violet staining, scanning electron microscopy, and propidium iodide staining/N-phenyl-1-naphthylamine uptake experiments were performed to explore the antibacterial action and potential mechanism of PAM-1 against CZA-resistant E. coli. The biosafety in diverse environments of PAM-1 was evaluated by red blood cell hemolysis, and cytotoxicity tests. Its stability was further assessed under different temperatures, serum concentrations, and ionic conditions using the broth microdilution method to determine its minimum inhibitory concentration (MIC). Galleria mellonella infection model and RT-qPCR were used to investigate the in vivo antibacterial and anti-inflammatory effects. Results and discussion: In vitro antibacterial experiments demonstrated that the MICs of PAM-1 ranged from 2 to 8 µg/mL, with its effectiveness sustained for a duration of 24 h. PAM-1 exhibited significant antibiofilm activities against CZA-resistant E. coli (p < 0.05). Furthermore, Membrane permeability test revealed that PAM-1 may exert its antibacterial effect by disrupting membrane integrity by forming transmembrane pores (p < 0.05). Red blood cell hemolysis and cytotoxicity tests revealed that PAM-1 exerts no adverse effects at experimental concentrations (p < 0.05). Moreover, stability tests revealed its effectiveness in serum and at room temperature. The Galleria mellonella infection model revealed that PAM-1 can significantly improve the survival rate of Galleria mellonella (>50%)for in vivo treatment. Lastly, RT-qPCR revealed that PAM-1 downregulates the expression of inflammatory cytokines (p < 0.05). Overall, our study findings highlight the potential of PAM-1 as a therapeutic agent for CZA-resistant E. coli infections, offering new avenues for research and alternative antimicrobial therapy strategies.

5.
Soft Matter ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747973

RESUMO

The self-oscillation of objects that perform continuous and periodic motions upon unchanging and constant stimuli is highly important for intelligent actuators, advanced robotics, and biomedical machines. Liquid crystalline elastomer (LCE) materials are superior to traditional stimuli-responsive polymeric materials in the development of self-oscillators because of their reversible, large and anisotropic shape-changing ability, fast response ability and versatile structural design. In addition, fiber-shaped oscillators have attracted much interest due to their agility, flexibility and diverse oscillation modes. Herein, we present a strategy for fabricating fiber-shaped LCE self-oscillators using soft tubes as molds. Through the settlement of different configuration states of the soft tubes, the prepared fiber-shaped LCE oscillators can perform continuous rotational self-oscillation or up-and-down shifting self-oscillation under constant light stimuli, which are realized by photoinduced repetitive self-winding motion and self-waving motion, respectively. The mechanism of self-oscillating movements is attributed to the local temperature oscillation of LCE fibers caused by repetitive self-shadowing effects. LCE self-oscillators can operate stably over many oscillating cycles without obvious performance attenuation, revealing good robustness. Our work offers a versatile way by which LCE self-oscillators can be conveniently designed and fabricated in bulk and at low cost, and broadens the road for developing self-oscillating materials for biological robotics and health care machines.

6.
PLoS One ; 19(5): e0303199, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38723048

RESUMO

This paper presents an optimized preparation process for external ointment using the Definitive Screening Design (DSD) method. The ointment is a Traditional Chinese Medicine (TCM) formula developed by Professor WYH, a renowned TCM practitioner in Jiangsu Province, China, known for its proven clinical efficacy. In this study, a stepwise regression model was employed to analyze the relationship between key process factors (such as mixing speed and time) and rheological parameters. Machine learning techniques, including Monte Carlo simulation, decision tree analysis, and Gaussian process, were used for parameter optimization. Through rigorous experimentation and verification, we have successfully identified the optimal preparation process for WYH ointment. The optimized parameters included drug ratio of 24.5%, mixing time of 8 min, mixing speed of 1175 rpm, petroleum dosage of 79 g, liquid paraffin dosage of 6.7 g. The final ointment formulation was prepared using method B. This research not only contributes to the optimization of the WYH ointment preparation process but also provides valuable insights and practical guidance for designing the preparation processes of other TCM ointments. This advanced DSD method enhances the screening approach for identifying the best preparation process, thereby improving the scientific rigor and quality of TCM ointment preparation processes.


Assuntos
Aprendizado de Máquina , Pomadas , Reologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/administração & dosagem , Medicina Tradicional Chinesa , Composição de Medicamentos/métodos , Dodecilsulfato de Sódio/química , Método de Monte Carlo
7.
Nat Commun ; 15(1): 3534, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38670989

RESUMO

Glutamine synthetase (GS) is vital in maintaining ammonia and glutamate (Glu) homeostasis in living organisms. However, the natural enzyme relies on adenosine triphosphate (ATP) to activate Glu, resulting in impaired GS function during ATP-deficient neurotoxic events. To date, no reports demonstrate using artificial nanostructures to mimic GS function. In this study, we synthesize aggregation-induced emission active polyP-Mn nanosheets (STPE-PMNSs) based on end-labeled polyphosphate (polyP), exhibiting remarkable GS-like activity independent of ATP presence. Further investigation reveals polyP in STPE-PMNSs serves as phosphate source to activate Glu at low ATP levels. This self-feeding mechanism offers a significant advantage in regulating Glu homeostasis at reduced ATP levels in nerve cells during excitotoxic conditions. STPE-PMNSs can effectively promote the conversion of Glu to glutamine (Gln) in excitatory neurotoxic human neuroblastoma cells (SH-SY5Y) and alleviate Glu-induced neurotoxicity. Additionally, the fluorescence signal of nanosheets enables precise monitoring of the subcellular distribution of STPE-PMNSs. More importantly, the intracellular fluorescence signal is enhanced in a conversion-responsive manner, allowing real-time tracking of reaction progression. This study presents a self-sustaining strategy to address GS functional impairment caused by ATP deficiency in nerve cells during neurotoxic events. Furthermore, it offers a fresh perspective on the potential biological applications of polyP-based nanostructures.


Assuntos
Trifosfato de Adenosina , Glutamato-Amônia Ligase , Ácido Glutâmico , Glutamina , Manganês , Nanoestruturas , Neurônios , Polifosfatos , Glutamato-Amônia Ligase/metabolismo , Humanos , Polifosfatos/química , Polifosfatos/metabolismo , Polifosfatos/farmacologia , Nanoestruturas/química , Trifosfato de Adenosina/metabolismo , Linhagem Celular Tumoral , Ácido Glutâmico/metabolismo , Ácido Glutâmico/toxicidade , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Glutamina/metabolismo , Manganês/metabolismo , Manganês/química , Materiais Biocompatíveis/química
8.
Int J Biol Macromol ; 266(Pt 2): 131345, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574935

RESUMO

Cotton fiber holds immense importance as the primary raw material for the textile industry. Consequently, comprehending the regulatory mechanisms governing fiber development is pivotal for enhancing fiber quality. Our study aimed to construct a regulatory network of competing endogenous RNAs (ceRNAs) and assess the impact of non-coding RNAs on gene expression throughout fiber development. Through whole transcriptome data analysis, we identified differentially expressed genes (DEGs) regulated by non-coding RNA (ncRNA) that were predominantly enriched in phenylpropanoid biosynthesis and the fatty acid elongation pathway. This analysis involved two contrasting phenotypic materials (J02-508 and ZRI015) at five stages of fiber development. Additionally, we conducted a detailed analysis of genes involved in fatty acid elongation, including KCS, KCR, HACD, ECR, and ACOT, to unveil the factors contributing to the variation in fatty acid elongation between J02-508 and ZRI015. Through the integration of histochemical GUS staining, dual luciferase assay experiments, and correlation analysis of expression levels during fiber development stages for lncRNA MSTRG.44818.23 (MST23) and GhKCR2, we elucidated that MST23 positively regulates GhKCR2 expression in the fatty acid elongation pathway. This identification provides valuable insights into the molecular mechanisms underlying fiber development, emphasizing the intricate interplay between non-coding RNAs and protein-coding genes.


Assuntos
Ácidos Graxos , Regulação da Expressão Gênica de Plantas , Gossypium , RNA não Traduzido , Fibra de Algodão , Ácidos Graxos/metabolismo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Gossypium/genética , Gossypium/metabolismo , Redes e Vias Metabólicas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Transcriptoma
9.
Talanta ; 273: 125904, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38508131

RESUMO

Specific staining of cancer cells is momentous for cancer research. Nanoprobe with multivalent recognition is emerging as powerful tools for bioimaging, but the nonspecific cell uptake and complex functional modification procedures are still obstacles for specific detection and convenient synthesis. Carbon dots (CDs) with an intrinsic targeting ability, excellent optical properties and biocompatibility acquired from an efficient one-step fabrication procedure were urgently desired in specific cancer cells visualization. Herein, inspired by the interrelationships between interface and biomolecular mechanisms, we suggested that it was possible to construct CDs with the desired characteristics for folate receptor (FR) positive-expressed cancer cell imaging via rich hydroxyl groups Tris-assisted one-step hydrothermal treatment of folate acid (FA) and l-Arginine (L-Arg) precursors. The prepared small-sized F-CDs were equipped with abundant hydroxyl, pterin and negative charge surface, and possessed environmental friendliness, outstanding photostability and biocompatibility. Moreover, F-CDs had an intrinsic FR positive-expressed cancer cell targeting ability without any post-modification of the ligands. Rich hydroxyl groups play a vital role in endowing the optical properties and biological effects of F-CDs. F-CDs could be used as a promising candidate for FR-expressed cancer cell labeling and tracking. In addition, the caveolae-mediated endocytosis pathway of F-CDs was ascertained. More importantly, experimental results confirmed that the combination of physicochemical properties may provide an efficient strategy to overcome non-specific cell uptake interactions for cell labeling. Our strategy put forward a promising alternative to design fluorescent CDs for extensive chemical and biomedical applications.


Assuntos
Neoplasias , Pontos Quânticos , Pontos Quânticos/química , Carbono/química , Diagnóstico por Imagem , Ácido Fólico/química , Corantes Fluorescentes/química , Neoplasias/diagnóstico por imagem
10.
Nat Commun ; 15(1): 2137, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459019

RESUMO

Translational control is crucial for protein production in various biological contexts. Here, we use Ribo-seq and RNA-seq to show that genes related to oxidative phosphorylation are translationally downregulated during heart regeneration. We find that Nat10 regulates the expression of Uqcr11 and Uqcrb mRNAs in mouse and human cardiomyocytes. In mice, overexpression of Nat10 in cardiomyocytes promotes cardiac regeneration and improves cardiac function after injury. Conversely, treating neonatal mice with Remodelin-a Nat10 pharmacological inhibitor-or genetically removing Nat10 from their cardiomyocytes both inhibit heart regeneration. Mechanistically, Nat10 suppresses the expression of Uqcr11 and Uqcrb independently of its ac4C enzyme activity. This suppression weakens mitochondrial respiration and enhances the glycolytic capacity of the cardiomyocytes, leading to metabolic reprogramming. We also observe that the expression of Nat10 is downregulated in the cardiomyocytes of P7 male pig hearts compared to P1 controls. The levels of Nat10 are also lower in female human failing hearts than non-failing hearts. We further identify the specific binding regions of Nat10, and validate the pro-proliferative effects of Nat10 in cardiomyocytes derived from human embryonic stem cells. Our findings indicate that Nat10 is an epigenetic regulator during heart regeneration and could potentially become a clinical target.


Assuntos
Miócitos Cardíacos , Processamento de Proteína Pós-Traducional , Animais , Feminino , Humanos , Masculino , Camundongos , Acetiltransferases/metabolismo , Miócitos Cardíacos/metabolismo , Acetiltransferases N-Terminal/metabolismo , RNA Mensageiro/metabolismo , Suínos
11.
Angew Chem Int Ed Engl ; 63(15): e202400829, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38349715

RESUMO

Due to multidrug resistance and the high risk of recurrence, effective and less toxic alternative pancreatic cancer treatments are urgently needed. Pancreatic cancer cells are highly resistant to apoptosis but sensitive to ferroptosis. In this study, an innovative nanoplatform (AsIr@PDA) was developed by electrostatic adsorption of a cationic iridium complex (IrFN) onto two-dimensional (2D) arsenene nanosheets. This nanoplatform exhibits superior ferroptosis-inducing effects with high drug loading capacity and, importantly, excellent anti-cancer immune activation function, leading to efficient elimination of pancreatic tumors with no observable side effects. Interestingly, AsIr@PDA significantly prevents the recurrence of pancreatic cancer in vivo when compared with a cisplatin-loaded nanoplatform. This designed nanoplatform demonstrated superior therapeutic efficacy by synergistic ferroptosis-induced chemotherapy with immunotherapy via an all-in-one strategy, providing new insights for future pancreatic cancer therapy.


Assuntos
Ferroptose , Neoplasias Pancreáticas , Humanos , Irídio , Neoplasias Pancreáticas/tratamento farmacológico , Imunoterapia , Adsorção , Linhagem Celular Tumoral
12.
Plant J ; 118(4): 1119-1135, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38308390

RESUMO

Salicylic acid (SA) is known to enhance salt tolerance in plants. However, the mechanism of SA-mediated response to high salinity in halophyte remains unclear. Using electrophysiological and molecular biological methods, we investigated the role of SA in response to high salinity in mangrove species, Kandelia obovata, a typical halophyte. Exposure of K. obovata roots to high salinity resulted in a rapid increase in endogenous SA produced by phenylalanine ammonia lyase pathway. The application of exogenous SA improved the salt tolerance of K. obovata, which depended on the NADPH oxidase-mediated H2O2. Exogenous SA and H2O2 increased Na+ efflux and reduced K+ loss by regulating the transcription levels of Na+ and K+ transport-related genes, thus reducing the Na+/K+ ratio in the salt-treated K. obovata roots. In addition, exogenous SA-enhanced antioxidant enzyme activity and its transcripts, and the expressions of four genes related to AsA-GSH cycle as well, then alleviated oxidative damages in the salt-treated K. obovata roots. However, the above effects of SA could be reversed by diphenyleneiodonium chloride (the NADPH oxidase inhibitor) and paclobutrazol (a SA biosynthesis inhibitor). Collectively, our results demonstrated that SA-induced salt tolerance of K. obovata depends on NADPH oxidase-generated H2O2 that affects Na+/K+ and redox homeostasis in response to high salinity.


Assuntos
Homeostase , Peróxido de Hidrogênio , NADPH Oxidases , Oxirredução , Raízes de Plantas , Potássio , Ácido Salicílico , Tolerância ao Sal , Sódio , Peróxido de Hidrogênio/metabolismo , NADPH Oxidases/metabolismo , NADPH Oxidases/genética , Ácido Salicílico/metabolismo , Ácido Salicílico/farmacologia , Potássio/metabolismo , Tolerância ao Sal/genética , Sódio/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Raízes de Plantas/metabolismo , Plantas Tolerantes a Sal/genética , Plantas Tolerantes a Sal/metabolismo , Plantas Tolerantes a Sal/fisiologia , Regulação da Expressão Gênica de Plantas , Rhizophoraceae/fisiologia , Rhizophoraceae/genética , Rhizophoraceae/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
13.
ACS Nano ; 18(5): 4398-4413, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38275273

RESUMO

Arsenic trioxide (As2O3) has achieved groundbreaking success in the treatment of acute promyelocytic leukemia (APL). However, its toxic side effects seriously limit its therapeutic application in the treatment of solid tumors. To detoxify the severe side effects of arsenic, herein we synthesized innovative 2D ultrathin As2Se3 nanosheets (As2Se3 NSs) with synergistic photothermal-triggered immunotherapy effects. As2Se3 NSs are biocompatible and biodegradable under physiological conditions and can release As(III) and Se(0). Furthermore, selenium increases the immunomodulatory efficacy of arsenic treatments, facilitating reprogramming of the tumor microenvironment by As2Se3 NSs by enhancing the infiltration of natural killer cells and effector tumor-specific CD8+ T cells. The synergistic combination of photothermal therapy and immunotherapy driven by As2Se3 NSs via a simple but effective all-in-one strategy achieved efficient anticancer effects, addressing the key limitations of As2O3 for solid tumor treatment. This work demonstrates not only the great potential of selenium for detoxifying arsenic but also the application of 2D As2Se3 nanosheets for cancer therapy.


Assuntos
Antineoplásicos , Arsênio , Arsenicais , Neoplasias , Selênio , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linfócitos T CD8-Positivos , Imunoterapia , Neoplasias/tratamento farmacológico , Óxidos/farmacologia , Selênio/farmacologia , Selênio/uso terapêutico , Microambiente Tumoral , Trióxido de Arsênio
14.
Asian J Psychiatr ; 93: 103921, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38237533

RESUMO

Mild cognitive impairment (MCI) is a significant precursor to dementia, highlighting the critical need for early identification of individuals at high risk of MCI to prevent cognitive decline. The study aimed to investigate the changes in brain structure and function before the onset of MCI. This study enrolled 19 older adults with progressive normal cognition (pNC) to MCI and 19 older adults with stable normal cognition (sNC). The gray matter (GM) volume and functional connectivity (FC) were estimated via magnetic resonance imaging during their normal cognition state 3 years prior. Additionally, spatial associations between FC maps and neurochemical profiles were examined using JuSpace. Compared to the sNC group, the pNC group showed decreased volume in the left hippocampus and left amygdala. The significantly positive correlation was observed between the GM volume of the left hippocampus and the MMSE scores after 3 years in pNC group. Besides, it showed that the pNC group had increased FC between the left hippocampus and the anterior-posterior cingulate gyrus, which was significantly correlated with the spatial distribution of dopamine D2 and noradrenaline transporter. Taken together, the study identified the abnormal brain characteristics before the onset of MCI, which might provide insight into clinical research.


Assuntos
Disfunção Cognitiva , Humanos , Idoso , Cognição , Encéfalo , Hipocampo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
16.
Plant Cell Environ ; 47(2): 511-526, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37869766

RESUMO

Brassinosteroid (BR) has been shown to modulate plant tolerance to various stresses. S-nitrosoglutathione reductase (GSNOR) is involved in the plant response to environment stress by fine-turning the level of nitric oxide (NO). However, whether GSNOR is involved in BR-regulated Na+ /K+ homeostasis to improve the salt tolerance in halophyte is unknown. Here, we firstly reported that high salinity increases the expression of BR-biosynthesis genes and the endogenous levels of BR in mangrove Kandelia obovata. Then, salt-induced BR triggers the activities and gene expressions of GSNOR and antioxidant enzymes, thereafter decrease the levels of malondialdehyde, hydrogen peroxide. Subsequently, BR-mediated GSNOR negatively regulates NO contributions to the reduction of reactive oxygen species generation and induction of the gene expression related to Na+ and K+ transport, leading to the decrease of Na+ /K+ ratio in the roots of K. obovata. Finally, the applications of exogenous BR, NO scavenger, BR biosynthetic inhibitor and GSNOR inhibitor further confirm the function of BR. Taken together, our result provides insight into the mechanism of BR in the response of mangrove K. obovata to high salinity via GSNOR and NO signaling pathway by reducing oxidative damage and modulating Na+ /K+ homeostasis.


Assuntos
Óxido Nítrico , Rhizophoraceae , Óxido Nítrico/metabolismo , Oxirredutases/metabolismo , Brassinosteroides/farmacologia , Brassinosteroides/metabolismo , Rhizophoraceae/genética , Rhizophoraceae/metabolismo , Tolerância ao Sal , Transdução de Sinais
17.
Adv Sci (Weinh) ; 11(2): e2307598, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38032131

RESUMO

Sphingosine (Sph) plays important roles in various complex biological processes. Abnormalities in Sph metabolism can result in various diseases, including neurodegenerative disorders. However, due to the lack of rapid and accurate detection methods, understanding sph metabolic in related diseases is limited. Herein, a series of near-infrared fluorogenic probes DMS-X (X = 2F, F, Cl, Br, and I) are designed and synthesized. The fast oxazolidinone ring formation enables the DMS-2F to detect Sph selectively and ultrasensitively, and the detection limit reaches 9.33 ± 0.41 nm. Moreover, it is demonstrated that DMS-2F exhibited a dose- and time-dependent response to Sph and can detect sph in living cells. Importantly, for the first time, the changes in Sph levels induced by Aß42 oligomers and H2 O2 are assessed through a fluorescent imaging approach, and further validated the physiological processes by which Aß42 oligomers and reactive oxygen species (ROS)-induce changes in intracellular Sph levels. Additionally, the distribution of Sph in living zebrafish is successfully mapped by in vivo imaging of a zebrafish model. This work provides a simple and efficient method for probing Sph in living cells and in vivo, which will facilitate investigation into the metabolic process of Sph and the connection between Sph and disease pathologies.


Assuntos
Esfingosina , Peixe-Zebra , Animais , Esfingosina/metabolismo , Esfingosina/farmacologia , Peixe-Zebra/metabolismo , Células Cultivadas , Plaquetas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
18.
Eur J Pharmacol ; 963: 176245, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38052413

RESUMO

Mammalian heart is capable to regenerate almost completely early after birth through endogenous cardiomyocyte proliferation. However, this regenerative capacity diminishes gradually with growth and is nearly lost in adulthood. Cannabidiol (CBD) is a major component of cannabis and has various biological activities to regulate oxidative stress, fibrosis, inflammation, and cell death. The present study was conducted to investigate the pharmacological effects of CBD on heart regeneration in post-MI mice. MI models in adult mice were constructed via coronary artery ligation, which were administrated with or without CBD. Our results demonstrate that systemic administration (10 mg/kg) of CBD markedly increased cardiac regenerative ability, reduced infarct size, and restored cardiac function in MI mice. Consistently, in vitro study also showed that CBD was able to promote the proliferation of neonatal cardiomyocytes. Mechanistically, the expression of miR-143-3p related to cardiomyocyte proliferation was significantly down-regulated in CBD-treated cardiomyocytes, while the overexpression of miR-143-3p inhibited cardiomyocyte mitosis and eliminated CBD-induced cardiomyocyte proliferation. Moreover, CBD enhanced the expression of Yap and Ctnnd1, which were demonstrated as the target genes of miR-143-3p. Silencing of Yap and Ctnnd1 hindered the proliferative effects of CBD. We further revealed that inhibition of the cannabinoid receptor 2 impeded the regulatory effect of CBD on miR-143-3p and its downstream target Yap/Ctnnd1, which ultimately eliminated the pro-proliferative effect of CBD on neonatal and adult cardiomyocytes. Taken together, CBD promotes cardiomyocyte proliferation and heart regeneration after MI via miR-143-3p/Yap/Ctnnd1 signaling pathway, which provides a new strategy for cardiac repair in adult myocardium.


Assuntos
Canabidiol , MicroRNAs , Infarto do Miocárdio , Animais , Camundongos , Miócitos Cardíacos , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Infarto do Miocárdio/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células , Regeneração/fisiologia , Mamíferos/genética
19.
Neurol Sci ; 45(5): 2261-2270, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37996775

RESUMO

BACKGROUND: Developmental dyslexia (DD) is a neurodevelopmental disorder that is characterized by difficulties with all aspects of information acquisition in the written word, including slow and inaccurate word recognition. The neural basis behind DD has not been fully elucidated. METHOD: The study included 22 typically developing (TD) children, 16 children with isolated spelling disorder (SpD), and 20 children with DD. The cortical thickness, folding index, and mean curvature of Broca's area, including the triangular part of the left inferior frontal gyrus (IFGtriang) and the opercular part of the left inferior frontal gyrus, were assessed to explore the differences of surface morphology among the TD, SpD, and DD groups. Furthermore, the structural covariance network (SCN) of the triangular part of the left inferior frontal gyrus was analyzed to explore the changes of structural connectivity in the SpD and DD groups. RESULTS: The DD group showed higher curvature and cortical folding of the left IFGtriang than the TD group and SpD group. In addition, compared with the TD group and the SpD group, the structural connectivity between the left IFGtriang and the left middle-frontal gyrus and the right mid-orbital frontal gyrus was increased in the DD group, and the structural connectivity between the left IFGtriang and the right precuneus and anterior cingulate was decreased in the DD group. CONCLUSION: DD had atypical structural connectivity in brain regions related to visual attention, memory and which might impact the information input and integration needed for reading and spelling.


Assuntos
Dislexia , Criança , Humanos , Dislexia/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Leitura , Mapeamento Encefálico , Lobo Frontal , Imageamento por Ressonância Magnética
20.
ACS Macro Lett ; 12(10): 1403-1408, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37793171

RESUMO

Synthesis of high molecular weight polyesters prepared by acyclic diene metathesis (ADMET) polymerization of bis(undec-10-enoate) with isosorbide (M1), isomannide (M2), and 1,3-propanediol (M3) and the subsequent hydrogenation have been achieved by using a molybdenum-alkylidene catalyst. The resultant polymers (P1) prepared by the ADMET polymerization of M1 (in toluene at 25 °C) possessed high Mn values (Mn = 44400-49400 g/mol), and no significant differences in the Mn values and the PDI (Mw/Mn) values were observed in the samples after the hydrogenation. Both the tensile strength and the elongation at break in the hydrogenated polymers from M1 (HP1) increased upon increasing the molar mass, and the sample with an Mn value of 48200 exhibited better tensile properties (tensile strength of 39.7 MPa, elongation at break of 436%) than conventional polyethylene, polypropylene, as well as polyester containing C18 alkyl chains. The tensile properties were affected by the diol segment employed, whereas HP2 showed a similar property to HP1.

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