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1.
Colloids Surf B Biointerfaces ; 245: 114238, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39270401

RESUMO

Fungal infections associated with oral, gynecological, and skin ailments pose significant clinical challenges. The presence of biofilms often hampers the efficacy of conventional antifungal drugs owing to the complex microenvironment they create. In this study, the widely used antifungal medication fluconazole is utilized as a foundational component to be incorporated into zinc 2-methylimidazolate frameworks, resulting in the synthesis of nanoscale fluconazole-constructed metal-organic frameworks (F-ZIF). The F-ZIF is constructed through coordination interactions between zinc and fluconazole, retaining the structure and pH-responsiveness of the zinc 2-methylimidazolate framework. The pH-responsiveness F-ZIF makes sure the fluconazole can be released in acidic biofilm, which prevents the undesired release in healthy tissue, resulting in good biocompatibility both in vitro and in vivo. The in vitro studies demonstrated that F-ZIF exhibits enhanced efficacy in eradicating fungal pathogens in their biofilm growth state compared with the free fluconazole. Furthermore, in vivo experiments reveal the better effectiveness of F-ZIF in treating Candida albicans-induced vulvovaginal candidiasis, and less infection-related inflammation was observed. Hence, the one-port synthetic F-ZIF presents a promising solution for addressing fungal biofilm-related infections.

2.
Front Pharmacol ; 15: 1445349, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39239656

RESUMO

Coronary heart disease is a prevalent cardiovascular ailment globally, with myocardial infarction (MI) being one of its most severe manifestations. The morbidity and mortality of MI are escalating, showing an increasing trend among younger, highly educated individuals, thereby posing a serious threat to public health. Currently, thrombolysis, percutaneous coronary intervention, and coronary artery bypass grafting are the primary clinical treatments for MI. Although these methods significantly reduce patient mortality, complications often result in poor prognoses. Due to limitations in chemical synthetic drug research, the focus has shifted towards developing herbs based on natural substances. Natural medicines represent a novel approach for safer and more effective MI management and treatment. They can control multiple pathogenic variables by targeting various pathways and systems. This paper investigates the molecular mechanisms of MI and evaluates the application of natural products and medicinal plants in MI treatment over the past 5 years, demonstrating their specific good therapeutic potential and superior tolerance. These natural therapies have been shown to mitigate myocardial cell damage caused by MI through mechanisms such as oxidative stress, inflammation, apoptosis, angiogenesis, myocardial fibrosis, autophagy, endoplasmic reticulum stress, mitophagy, and pyroptosis. This review offers the latest insights into the application of natural products and medicinal plants in MI treatment, elucidating their mechanisms of action and serving as an important reference for MI prevention.

3.
Angew Chem Int Ed Engl ; : e202415949, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289891

RESUMO

Ion migration is a major issue hindering the long-term stability of perovskite solar cells (PSCs). As an intrinsic characteristic of metal halide perovskite materials, ion migration is closely related to the atomic arrangement and coordination, which are the basic characteristic differences among various facets. Herein, we report the facet-related ion migration, and then achieve the inhibition of ion migration in perovskite through finely modulating the facet orientation. We show that the (100) facet is substantially more vulnerable to cationic migration than the (111) facet. The main reason for this difference in migration is that the cationic migration route in the (111) facet deviates from that in the (100) facet, which increases the active migration energy and weakens the contribution from the electric field during operation. We prepare a (111)-dominated perovskite film by incorporating a facile and green addition of water (H2O) into the antisolvent, further achieving a power conversion efficiency (PCE) of 26.0% (25.4% certification) on regular planar PSCs and 25.8% on inverted PSCs. Moreover, the unencapsulated PSCs can maintain 95% of their initial PCE after 3500-hours operation under simulated AM1.5 illumination at the maximum power point.

4.
Small Methods ; : e2401221, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39291906

RESUMO

Regulating the distribution of surface elements in lithium-rich cathode materials can effectively change the electrochemical performance of cathode materials. Considering that the enrichment of Mn element on the surface is the main reason for the irreversible phase transition and dissolution of its surface structure, which in turn is the main reason for performance degradation. Based on the molten salt-assisted sintering method, a lithium rich cathode material with surface rich Ni and Co is designed and prepared. The surface enrichment of Ni and Co effectively reduces the dissolution of Mn, promotes the occurrence of irreversible collapse of surface structure from layered phase to rock salt phase on the material surface, improves the stability of surface crystal phase structure, and improves the cycling stability of positive electrode materials. Notably, after 500 cycles at 1 C current density, the discharge-specific capacity attained 189.8 mAh g -1, with a capacity retention rate of 88.9%, indicating a 42.1% improvement in capacity retention. Molten salt treatment is widely used in the modification of positive electrode materials. The research work will provide new ideas for improving the stability of lithium rich materials and promoting their commercial applications.

5.
J Adv Pharm Technol Res ; 15(3): 185-193, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39290539

RESUMO

BaiYangJie (BYJ) is a terrestrial perennial plant commonly used as a Dai medicine and has therapeutic effects on liver and kidney diseases. Cisplatin (CP), a chemotherapy drug, has good therapeutic effects but causes many side effects, including nephrotoxicity. This article investigated the toxicology of the methanol extract of BYJ (ME-BYJ) and its protective effect on CP-induced acute kidney injury (AKI) through pharmacological experiments. The results showed that the treated mice had no toxicological symptoms and no anatomical, physiological, or histological abnormalities. The BYJ-high-dose group showed significantly attenuated CP-induced AKI. It is concluded that ME-BYJ has the most significant protective effect on AKI at a dose of 8 g/kg and BYJ was not toxic.

6.
Biophys Rep ; 10(4): 213-229, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39281195

RESUMO

Alzheimer's disease (AD) has been conceptualized as a syndrome of brain network dysfunction. Recent imaging connectomics studies have provided unprecedented opportunities to map structural and functional brain networks in AD. By reviewing molecular, imaging, and computational modeling studies, we have shown that highly connected brain hubs are primarily distributed in the medial and lateral prefrontal, parietal, and temporal regions in healthy individuals and that the hubs are selectively and severely affected in AD as manifested by increased amyloid-beta deposition and regional atrophy, hypo-metabolism, and connectivity dysfunction. Furthermore, AD-related hub degeneration depends on the imaging modality with the most notable degeneration in the medial temporal hubs for morphological covariance networks, the prefrontal hubs for structural white matter networks, and in the medial parietal hubs for functional networks. Finally, the AD-related hub degeneration shows metabolic, molecular, and genetic correlates. Collectively, we conclude that the brain-network-hub-degeneration framework is promising to elucidate the biological mechanisms of network dysfunction in AD, which provides valuable information on potential diagnostic biomarkers and promising therapeutic targets for the disease.

7.
RSC Adv ; 14(40): 29588-29594, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39297043

RESUMO

The Ritter reaction is the most attractive method for synthesizing amides, and various acids have been used to promote this reaction. Compared to these acids, Fe(NO3)3·9H2O is less toxic and costly, and it shows relatively high Lewis acidity and great catalytic activity. In this study, a simple and efficient protocol involving Fe(NO3)3·9H2O as an additive for the synthesis of amides was developed. Various secondary alcohols could be reacted with CH3CN to obtain their corresponding products, with CH3CN being used as a reactant and solvent. This protocol was found to be applicable to a wide range of alcohols and nitrile substrates. In general, it was found that substrates containing electron-donating-groups offered the corresponding amides in good to excellent yields, while those with electron-withdrawing groups offered low to moderate yields. Meanwhile, this approach was scalable to the gram level, offering an attractive opportunity for further application in organic synthesis.

8.
Plant Cell Environ ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39301882

RESUMO

Soybean mosaic virus (SMV) stands as a prominent and widespread threat to soybean (Glycine max L. Merr.), the foremost legume crop globally. Attaining a thorough comprehension of the alterations in the transcriptional network of soybeans in response to SMV infection is imperative for a profound insight into the mechanisms of viral pathogenicity and host resistance. In this investigation, we isolated 50 294 protoplasts from the newly developed leaves of soybean plants subjected to both SMV infection and mock inoculation. Subsequently, we utilized single-cell RNA sequencing (scRNA-seq) to construct the transcriptional landscape at a single-cell resolution. Nineteen distinct cell clusters were identified based on the transcriptomic profiles of scRNA-seq. The annotation of three cell types-epidermal cells, mesophyll cells, and vascular cells-was established based on the expression of orthologs to reported marker genes in Arabidopsis thaliana. The differentially expressed genes between the SMV- and mock-inoculated samples were analyzed for different cell types. Our investigation delved deeper into the tau class of glutathione S-transferases (GSTUs), known for their significant contributions to plant responses against abiotic and biotic stress. A total of 57 GSTU genes were identified by a thorough genome-wide investigation in the soybean genome G. max Wm82.a4.v1. Two specific candidates, GmGSTU23 and GmGSTU24, exhibited distinct upregulation in all three cell types in response to SMV infection, prompting their selection for further research. The transient overexpression of GmGSTU23 or GmGSTU24 in Nicotiana benthamiana resulted in the inhibition of SMV infection, indicating the antiviral function of soybean GSTU proteins.

9.
Artigo em Inglês | MEDLINE | ID: mdl-39244722

RESUMO

OBJECTIVE: To explore the effectiveness of HPV 16/18 E7 oncoprotein in detecting high-grade cervical intraepithelial neoplasia (CIN) and predicting disease outcomes in HPV 16/18-positive patients. METHODS: The present study was a cross-sectional study with a 2-year follow up. We collected 915 cervical exfoliated cell samples from patients who tested positive for HPV 16/18 in gynecologic clinics of three tertiary hospitals in Beijing from March 2021 to October 2022 for HPV 16/18 E7 oncoprotein testing. Subsequently, 2-year follow up of 408 patients with baseline histologic CIN1 or below were used to investigate the predictive role of HPV 16/18 E7 oncoprotein in determining HPV persistent infection and disease progression. RESULTS: The positivity rate of the HPV 16/18 E7 oncoprotein assay was 42.06% (249/592) in the inflammation/CIN 1 group and 85.45% (277/324) in the CIN2+ group. For CIN2+ detection, using the HPV 16/18 E7 oncoprotein assay combined with HPV 16/18 testing, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 85.45%, 57.94%, 52.57%, and 87.95%, respectively. During the 2-year follow up, the sensitivity, specificity, PPV, and NPV for predicting persistent HPV infection were 48.44%, 58.21%, 34.64%, and 71.18% in the baseline inflammation and CIN1 group. CONCLUSIONS: As a triage method for high-grade CIN screening in HPV 16/18-positive patients, HPV 16/18 E7 oncoprotein demonstrated a relatively high NPV, making it suitable for clinical use in triaging HPV 16/18-positive cases and potentially reducing the colposcopic referral rate. HPV 16/18 E7 oncoprotein exhibited a preferably predictive value in determining HPV infection outcomes and disease progression.

10.
Front Microbiol ; 15: 1451563, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39234535

RESUMO

The resistance of Helicobacter pylori (H. pylori) has increased in recent years, prompting a trend in the research and development of new drugs. In our study, three derivatives (JF-1, JF-2, and JF-3) were synthesized using 6-gingerol as the main component, while JF-4, containing both 6-gingerol and 6-shogaol as the main components, was extracted from dried ginger. The minimum inhibitory concentrations (MICs), determined using the ratio dilution method, were 80 µg/mL for JF-1, 40 µg/mL for JF-2, 30 µg/mL for JF-3, 40 µg/mL for JF-4, 60 µg/mL for 6-gingerol standard (SS), and 0.03 µg/mL for amoxicillin (AMX). After treating H. pylori-infected mice, the inflammation of the gastric mucosa was suppressed. The eradication rate of H. pylori was 16.7% of JF-3 low-dose treatment (LDT), 25.0% of JF-3 high-dose treatment (HDT), 16.7% of JF-4 LDT, 16.7% of JF-4 HDT, 30% of SS LDT, 50% of SS HDT, and 36.4% of the positive control group (PCG). The levels of gastrin, somatostatin (SST), IFN-γ, IL-4, and IL-8 were significantly recovered in the JF-3 and JF-4 administration groups, but the effect was stronger in the high-dose group. These results demonstrate that 6-gingerol and its derivatives have significant anti-Helicobacter pylori effects and are promising potential treatments for H. pylori infection.

11.
Int J Biol Macromol ; 278(Pt 1): 134566, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39116988

RESUMO

Dictyophora species is an edible and medicinal fungus belonging to the Basidiomycotina, Gasteromycetes, Phallales, family Phallaceae, and genus Dictyophora, which is popular with consumers in China and across various Asian regions. Polysaccharides from Dictyophora species (DPs) are important bioactive macromolecules with multiple health benefits, according to published studies, including anti-tumor, antioxidative, anti-obesity, anti-hyperlipidemic, hepatoprotective, immunomodulatory, anti-inflammatory, regulation of gut microbiota, antibacterial, renoprotective, and other pharmacological effects. Based on their rich pharmacological activities, the preparation techniques, structural characteristics and pharmacological activities of DPs have been extensively studied. However, to the best of our knowledge, there is no dedicated review to shed light on recent advances in DPs. Therefore, in order to fill this gap, this review provides a comprehensive overview of the research on DPs, including the latest advances in extraction, isolation and purification, structural characteristics, pharmacological properties, safety assessment and potential utilizations, which will provide a theoretical basis for the research and development of subsequent DPs-related products.


Assuntos
Polissacarídeos Fúngicos , Humanos , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/isolamento & purificação , Basidiomycota/química , Animais , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação
12.
Mol Biol Rep ; 51(1): 941, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39196412

RESUMO

BACKGROUND: Traumatic brain injury (TBI) is a major cause of neurological disability, and current treatments have limited effectiveness. Recent studies have emphasized the potential of exosomes derived from umbilical cord mesenchymal stem cells (UC-MSCs-Exo) in TBI treatment, but the molecular mechanisms underlying their therapeutic effects are not fully understood. METHODS AND RESULTS: In this study, UC-MSCs-Exo was isolated using ultracentrifugation and intraventricularly injected to TBI rat model. The neurofunctional motor function of the rats was evaluated using the modified neurological severity score (mNSS), and the activation of microglia was assessed through immunofluorescence detection of IBA1 expression levels. Additionally, we established an in vitro neuroinflammatory model using BV2 microglia to investigate the effects of UC-MSCs-Exo and miRNA-21. Our findings indicate that UC-MSCs-Exo promote neurological recovery in TBI rats and inhibit excessive microglia activation. Furthermore, UC-MSCs-Exo highly expresses miRNA-21 and inhibited the proliferation, migration, and release of inflammatory mediators of BV2 microglia by transporting miRNA-21. CONCLUSIONS: The present study suggests that the promotion of neurological recovery in TBI rats by UC-MSCs-Exo may be attributed to the inhibition of excessive microglia activation through miRNA-21.


Assuntos
Lesões Encefálicas Traumáticas , Modelos Animais de Doenças , Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Microglia , Cordão Umbilical , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Microglia/metabolismo , Células-Tronco Mesenquimais/metabolismo , Exossomos/metabolismo , Ratos , Cordão Umbilical/citologia , Lesões Encefálicas Traumáticas/terapia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/genética , Lesões Encefálicas Traumáticas/patologia , Ratos Sprague-Dawley , Transplante de Células-Tronco Mesenquimais/métodos , Masculino , Humanos , Proliferação de Células , Movimento Celular
13.
Neuroimage ; 297: 120762, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39089603

RESUMO

Chronic insomnia (CI) is a complex disease involving multiple factors including genetics, gut microbiota, and brain structure and function. However, there lacks a unified framework to elucidate how these factors interact in CI. By combining data of clinical assessment, sleep behavior recording, cognitive test, multimodal MRI (structural, functional, and perfusion), gene, and gut microbiota, this study demonstrated that enhanced cerebral blood flow (CBF) similarities of the somatomotor network (SMN) acted as a key mediator to link multiple factors in CI. Specifically, we first demonstrated that only CBF but not morphological or functional networks exhibited alterations in patients with CI, characterized by increases within the SMN and between the SMN and higher-order associative networks. Moreover, these findings were highly reproducible and the CBF similarity method was test-retest reliable. Further, we showed that transcriptional profiles explained 60.4 % variance of the pattern of the increased CBF similarities with the most correlated genes enriched in regulation of cellular and protein localization and material transport, and gut microbiota explained 69.7 % inter-individual variance in the increased CBF similarities with the most contributions from Negativicutes and Lactobacillales. Finally, we found that the increased CBF similarities were correlated with clinical variables, accounted for sleep behaviors and cognitive deficits, and contributed the most to the patient-control classification (accuracy = 84.4 %). Altogether, our findings have important implications for understanding the neuropathology of CI and may inform ways of developing new therapeutic strategies for the disease.


Assuntos
Circulação Cerebrovascular , Microbioma Gastrointestinal , Imageamento por Ressonância Magnética , Distúrbios do Início e da Manutenção do Sono , Transcriptoma , Humanos , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Microbioma Gastrointestinal/fisiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Circulação Cerebrovascular/fisiologia , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Fenótipo
14.
Front Robot AI ; 11: 1387491, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39184863

RESUMO

Colonoscopy is a reliable diagnostic method to detect colorectal polyps early on and prevent colorectal cancer. The current examination techniques face a significant challenge of high missed rates, resulting in numerous undetected polyps and irregularities. Automated and real-time segmentation methods can help endoscopists to segment the shape and location of polyps from colonoscopy images in order to facilitate clinician's timely diagnosis and interventions. Different parameters like shapes, small sizes of polyps, and their close resemblance to surrounding tissues make this task challenging. Furthermore, high-definition image quality and reliance on the operator make real-time and accurate endoscopic image segmentation more challenging. Deep learning models utilized for segmenting polyps, designed to capture diverse patterns, are becoming progressively complex. This complexity poses challenges for real-time medical operations. In clinical settings, utilizing automated methods requires the development of accurate, lightweight models with minimal latency, ensuring seamless integration with endoscopic hardware devices. To address these challenges, in this study a novel lightweight and more generalized Enhanced Nanonet model, an improved version of Nanonet using NanonetB for real-time and precise colonoscopy image segmentation, is proposed. The proposed model enhances the performance of Nanonet using Nanonet B on the overall prediction scheme by applying data augmentation, Conditional Random Field (CRF), and Test-Time Augmentation (TTA). Six publicly available datasets are utilized to perform thorough evaluations, assess generalizability, and validate the improvements: Kvasir-SEG, Endotect Challenge 2020, Kvasir-instrument, CVC-ClinicDB, CVC-ColonDB, and CVC-300. Through extensive experimentation, using the Kvasir-SEG dataset, our model achieves a mIoU score of 0.8188 and a Dice coefficient of 0.8060 with only 132,049 parameters and employing minimal computational resources. A thorough cross-dataset evaluation was performed to assess the generalization capability of the proposed Enhanced Nanonet model across various publicly available polyp datasets for potential real-world applications. The result of this study shows that using CRF (Conditional Random Fields) and TTA (Test-Time Augmentation) enhances performance within the same dataset and also across diverse datasets with a model size of just 132,049 parameters. Also, the proposed method indicates improved results in detecting smaller and sessile polyps (flats) that are significant contributors to the high miss rates.

15.
Animals (Basel) ; 14(16)2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39199938

RESUMO

Understanding migratory routes is crucial for the conservation of birds and their habitats. Zhejiang is a crucial stopover and wintering area for birds in the East Asian-Australasian Flyway; however, detailed information on this area, and particularly on connections between coastal areas, is limited. By synthesizing ringed and recapture records from local bird-ringing projects and re-sighting community science data (208 records of 35 species), we established migratory connectivity between the Zhejiang coast and nine countries (i.e., Russia, Mongolia, the United States, Korea, Japan, Malaysia, Singapore, Thailand, and Australia), as well as eleven sites within China, and established its crucial role in this flyway. Stopover fidelity was verified by some species with high recapture frequency (seven species exceeded 1%) and species with duplicated re-sighted records (seven Black-faced Spoonbill, one Dalmatian Pelican, and two Spoon-billed Sandpiper individuals). We identified six areas-Hangzhou Bay, Aiwan Bay, Xuanmen National Park, Wenzhou Bay, the reclaimed area between the Ou and Feiyun Rivers, and the Wenzhou Jiangnan Reclamation Area-as crucial stopovers and wintering refuges for waterbirds. Notably, in Xuanmen National Park and the coastal regions along Wenzhou, there were many recovery records for flagship species, such as the Black-faced Spoonbill and Spoon-billed Sandpiper. There were several cases of the recovery of the same individual studied across the years. These findings indicate that these unprotected wetlands require particular attention. Broadly, our findings highlight the feasibility of integrating comprehensive ringing projects with citizen science data to formulate effective conservation strategies and underscore the critical importance of the Zhejiang Coast for migratory waterbirds, particularly those with high conservation concerns, emphasizing the need to mitigate the threats faced by these vulnerable populations.

16.
Adv Sci (Weinh) ; 11(35): e2400061, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39005232

RESUMO

Although white matter (WM) accounts for nearly half of adult brain, its wiring diagram is largely unknown. Here, an approach is developed to construct WM networks by estimating interregional morphological similarity based on structural magnetic resonance imaging. It is found that morphological WM networks showed nontrivial topology, presented good-to-excellent test-retest reliability, accounted for phenotypic interindividual differences in cognition, and are under genetic control. Through integration with multimodal and multiscale data, it is further showed that morphological WM networks are able to predict the patterns of hamodynamic coherence, metabolic synchronization, gene co-expression, and chemoarchitectonic covariance, and associated with structural connectivity. Moreover, the prediction followed WM functional connectomic hierarchy for the hamodynamic coherence, is related to genes enriched in the forebrain neuron development and differentiation for the gene co-expression, and is associated with serotonergic system-related receptors and transporters for the chemoarchitectonic covariance. Finally, applying this approach to multiple sclerosis and neuromyelitis optica spectrum disorders, it is found that both diseases exhibited morphological dysconnectivity, which are correlated with clinical variables of patients and are able to diagnose and differentiate the diseases. Altogether, these findings indicate that morphological WM networks provide a reliable and biologically meaningful means to explore WM architecture in health and disease.


Assuntos
Imageamento por Ressonância Magnética , Substância Branca , Substância Branca/diagnóstico por imagem , Substância Branca/metabolismo , Humanos , Masculino , Feminino , Adulto , Imageamento por Ressonância Magnética/métodos , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/metabolismo , Esclerose Múltipla/patologia , Esclerose Múltipla/genética , Esclerose Múltipla/metabolismo , Esclerose Múltipla/diagnóstico por imagem , Reprodutibilidade dos Testes , Conectoma/métodos
17.
Eur J Med Chem ; 276: 116689, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39053191

RESUMO

Acute myeloid leukemia (AML) represents a highly malignant subtype of leukemia with limited therapeutic options. In this study, we propose a novel therapeutic strategy for treating AML by inhibiting SIRT3 to regulate mitochondrial metabolism network involved in energy metabolism and epigenetic modifications essential for AML survival. A series of thieno [3,2-d]pyrimidine-6-carboxamide derivatives were designed and synthesized by structure-based strategy, 17f was documented to be a potent and acceptable selective SIRT3 inhibitor with IC50 value of 0.043 µM and exhibited profound anti-proliferative activity in MOLM13, MV4-11, and HL-60 cells. Through CETSA assay and the degree of deacetylation of intracellular SIRT3 substrates, we confirmed that 17f could effectively bind and inhibit SIRT3 activity in AML cells. Mechanistically, 17f suppressed mitochondrial function, triggered the accumulation of ROS, and significantly inhibited the production of ATP in AML cells. With the breakdown of mitochondrial function, 17f eventually induced apoptosis of AML cells. In addition, 17f also showed excellent anti-AML potential in nude mouse tumor models of HL-60-Luc. Collectively, these results demonstrate that 17f is a potent and acceptable selective SIRT3 inhibitor with promising potential to treat AML.


Assuntos
Antineoplásicos , Proliferação de Células , Desenho de Fármacos , Leucemia Mieloide Aguda , Sirtuína 3 , Animais , Humanos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Sítios de Ligação/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Camundongos Nus , Estrutura Molecular , NAD/metabolismo , Sirtuína 3/antagonistas & inibidores , Sirtuína 3/metabolismo , Relação Estrutura-Atividade
18.
Clin Neurophysiol ; 165: 90-96, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38991378

RESUMO

OBJECTIVE: To investigate the local cortical morphology and individual-based morphological brain networks (MBNs) changes in children with Rolandic epilepsy (RE). METHODS: Based on the structural MRI data of 56 children with RE and 56 healthy controls (HC), we constructed four types of individual-based MBNs using morphological indices (cortical thickness [CT], fractal dimension [FD], gyrification index [GI], and sulcal depth [SD]). The global and nodal properties of the brain networks were analyzed using graph theory. The between-group difference in local morphology and network topology was estimated, and partial correlation analysis was further analyzed. RESULTS: Compared with the HC, children with RE showed regional GI increases in the right posterior cingulate gyrus and SD increases in the right anterior cingulate gyrus and medial prefrontal cortex. Regarding the network level, RE exhibited increased characteristic path length in CT-based and FD-based networks, while decreased FD-based network node efficiency in the right inferior frontal gyrus. No significant correlation between altered morphological features and clinical variables was found in RE. CONCLUSIONS: These findings indicated that children with RE have disrupted morphological brain network organization beyond local morphology changes. SIGNIFICANCE: The present study could provide more theoretical basis for exploring the neuropathological mechanisms in RE.


Assuntos
Epilepsia Rolândica , Imageamento por Ressonância Magnética , Rede Nervosa , Humanos , Epilepsia Rolândica/fisiopatologia , Epilepsia Rolândica/diagnóstico por imagem , Criança , Masculino , Feminino , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Adolescente
19.
Nat Commun ; 15(1): 5852, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38992018

RESUMO

The establishment of symbiotic interactions between leguminous plants and rhizobia requires complex cellular programming activated by Rhizobium Nod factors (NFs) as well as type III effector (T3E)-mediated symbiotic signaling. However, the mechanisms by which different signals jointly affect symbiosis are still unclear. Here we describe the mechanisms mediating the cross-talk between the broad host range rhizobia Sinorhizobium fredii HH103 T3E Nodulation Outer Protein L (NopL) effector and NF signaling in soybean. NopL physically interacts with the Glycine max Remorin 1a (GmREM1a) and the NFs receptor NFR5 (GmNFR5) and promotes GmNFR5 recruitment by GmREM1a. Furthermore, NopL and NF influence the expression of GmRINRK1, a receptor-like kinase (LRR-RLK) ortholog of the Lotus RINRK1, that mediates NF signaling. Taken together, our work indicates that S. fredii NopL can interact with the NF signaling cascade components to promote the symbiotic interaction in soybean.


Assuntos
Proteínas de Bactérias , Regulação da Expressão Gênica de Plantas , Glycine max , Proteínas de Plantas , Sinorhizobium fredii , Simbiose , Glycine max/microbiologia , Glycine max/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Sinorhizobium fredii/metabolismo , Sinorhizobium fredii/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Transdução de Sinais , Nodulação/genética , Plantas Geneticamente Modificadas
20.
Int J Mol Sci ; 25(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-39000226

RESUMO

E3 ubiquitin ligases (UBLs), as enzymes capable of specifically recognizing target proteins in the process of protein ubiquitination, play crucial roles in regulating responses to abiotic stresses such as drought, salt, and temperature. Abscisic acid (ABA), a plant endogenous hormone, is essential to regulating plant growth, development, disease resistance, and defense against abiotic stresses, and acts through a complex ABA signaling pathway. Hormone signaling transduction relies on protein regulation, and E3 ubiquitin ligases play important parts in regulating the ABA pathway. Therefore, this paper reviews the ubiquitin-proteasome-mediated protein degradation pathway, ABA-related signaling pathways, and the regulation of ABA-signaling-pathway-related genes by E3 ubiquitin ligases, aiming to provide references for further exploration of the relevant research on how plant E3 ubiquitin ligases regulate the ABA pathway.


Assuntos
Ácido Abscísico , Transdução de Sinais , Ubiquitina-Proteína Ligases , Ubiquitina-Proteína Ligases/metabolismo , Ácido Abscísico/metabolismo , Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico , Ubiquitinação , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Reguladores de Crescimento de Plantas/metabolismo
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