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2.
Phytomedicine ; 135: 156069, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39341123

RESUMO

BACKGROUND: Neuroinflammation with associated oxidative stress aggravates the pathogenesis and progression of migraine. Ligustrazine (LGZ) is a key component from traditional edible-medicinal herb Ligusticum chuanxiong Hort., and has the effects of anti-platelet aggregation, expanding small arteries, improving microcirculation and promoting blood circulation and removing blood stasis in clinic. HYPOTHESIS/PURPOSE: This study aims to investigate the pharmacological effect and mechanism of LGZ in migraine. STUDY DESIGN/METHODS: A mouse model of migraine was induced by nitroglycerin (NTG), and LPS/IFN-γ stimulated microglial cell model was conducted to investigate neuroinflammation, the paracrine interactions between microglia and neurons were determined by the co-culture system, and the effect of LGZ on stability of SIRT1 protein was measured by cellular thermal shift assay (CETSA). Whilst, the SIRT1 inhibitor EX527 was used alone or co-treatment with LGZ in vitro or in vivo. RESULTS: LGZ significantly attenuated migraine-like behaviors in NTG-induced mice, and ameliorated neuroinflammation and related oxidative damage in brain tissue, but co-treatment with SIRT1 inhibitor EX527 abolished the protective effects of LGZ. Mechanistically, LGZ mitigated neuroinflammation by upregulating SIRT1 expression and subsequently inhibiting the activation of NF-κB pathway in microglia. CETSA indicated that LGZ significantly maintained the stability of SIRT1 protein in microglia. While, in the co-culture system, culture medium from LPS/IFN-γ-treated microglia exacerbated neuronal damage and oxidative stress, which was suppressed by treating LPS/IFN-γ-induced microglia with LGZ, this effect might be related to the activation of Nrf2 signals in neurons. Notably, SIRT1 inhibitor EX527 abrogated the effects of LGZ both in vitro and in vivo. CONCLUSION: Consequently, SIRT1 might be an important pharmacological target of LGZ, which attenuates migraine associated neuroinflammation and oxidative stress by interfering the crosstalk between microglia and neurons, thereby relieving migraine.

3.
Nanoscale ; 16(37): 17537-17548, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39225229

RESUMO

Theoretically determining the lowest-energy structure of a cluster has been a persistent challenge due to the inherent difficulty in accurate description of its potential energy surface (PES) and the exponentially increasing number of local minima on the PES with the cluster size. In this work, density-functional theory (DFT) calculations of Co clusters were performed to construct a dataset for training deep neural networks to deduce a deep potential (DP) model with near-DFT accuracy while significantly reducing computational consumption comparable to classic empirical potentials. Leveraging the DP model, a high-efficiency hybrid differential evolution (HDE) algorithm was employed to search for the lowest-energy structures of CoN (N = 11-50) clusters. Our results revealed 38 of these clusters superior to those recorded in the Cambridge Cluster Database and identified diverse architectures of the clusters, evolving from layered structures for N = 11-27 to Marks decahedron-like structures for N = 28-42 and to icosahedron-like structures for N = 43-50. Subsequent analyses of the atomic arrangement, structural similarity, and growth pattern further verified their hierarchical structures. Meanwhile, several highly stable clusters, i.e., Co13, Co19, Co22, Co39, and Co43, were discovered by the energetic analyses. Furthermore, the magnetic stability of the clusters was verified, and a competition between the coordination number and bond length in affecting the magnetic moment was observed. Our study provides high-accuracy and high-efficiency prediction of the optimal structures of clusters and sheds light on the growth trend of Co clusters containing tens of atoms, contributing to advancing the global optimization algorithms for effective determination of cluster structures.

5.
Food Chem ; 460(Pt 2): 140614, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39089013

RESUMO

Migraine as a common neurological disorder still lacks effective therapies. Tetramethylpyrazine (TMP) is the main bioactive component from Ligusticum chuanxiong hort., a traditional edible-medicinal herb. This study aimed to investigate the action of TMP on migraine by metabolomics with mass spectrometry imaging (MSI) analysis and molecular exploring, including random forest model analysis, KEGG enrichment analysis and metabolite-metabolite interaction network analysis. The results indicated that 26 key representative metabolic biomarkers were identified, especially γ-glu-cys, which were highly related to glutathione (GSH) metabolism. MSI found the abundance of eleven endogenous metabolites were modulated by TMP, particularly glucose, the most important energy metabolism molecule, and GSH were increased that maintains intracellular redox balance, which was consistent with activation of Nrf2 signals by TMP. These findings provide insights into the effectiveness of metabolomics integrated with MSI in explaining the metabolic mechanisms of TMP, and afford valuable information for healthy development of TMP in migraine.


Assuntos
Espectrometria de Massas , Metabolômica , Transtornos de Enxaqueca , Pirazinas , Pirazinas/metabolismo , Pirazinas/análise , Transtornos de Enxaqueca/metabolismo , Transtornos de Enxaqueca/tratamento farmacológico , Humanos , Animais , Ratos , Ligusticum/química , Ligusticum/metabolismo , Biomarcadores/metabolismo , Biomarcadores/análise , Ratos Sprague-Dawley , Masculino , Glutationa/metabolismo , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/química
6.
Blood Rev ; : 101226, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39164126

RESUMO

Measurable residual disease (MRD)-testing is used in many haematological cancers to estimate relapse risk and to direct therapy. Sometimes MRD-test results are used for regulatory approval. However, some people including regulators wrongfully believe results of MRD-testing are highly accurate and of proven efficacy in directing therapy. We review MRD-testing technologies and evaluate the accuracy of MRD-testing for predicting relapse and the strength of evidence supporting efficacy of MRD-guided therapy. We show that at the individual level MRD-test results are often an inaccurate relapse predictor. Also, no convincing data indicate that increasing therapy-intensity based on a positive MRD-test reduces relapse risk or improves survival. We caution against adjusting therapy-intensity based solely on results of MRD-testing.

7.
Int Urol Nephrol ; 56(10): 3361-3380, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38814370

RESUMO

BACKGROUND AND OBJECTIVE: Rapid advances in computer vision (CV) have the potential to facilitate the examination, diagnosis, and treatment of diseases of the kidney. The bibliometric study aims to explore the research landscape and evolving research focus of the application of CV in kidney medicine research. METHODS: The Web of Science Core Collection was utilized to identify publications related to the research or applications of CV technology in the field of kidney medicine from January 1, 1900, to December 31, 2022. We analyzed emerging research trends, highly influential publications and journals, prolific researchers, countries/regions, research institutions, co-authorship networks, and co-occurrence networks. Bibliographic information was analyzed and visualized using Python, Matplotlib, Seaborn, HistCite, and Vosviewer. RESULTS: There was an increasing trend in the number of publications on CV-based kidney medicine research. These publications mainly focused on medical image processing, surgical procedures, medical image analysis/diagnosis, as well as the application and innovation of CV technology in medical imaging. The United States is currently the leading country in terms of the quantities of published articles and international collaborations, followed by China. Deep learning-based segmentation and machine learning-based texture analysis are the most commonly used techniques in this field. Regarding research hotspot trends, CV algorithms are shifting toward artificial intelligence, and research objects are expanding to encompass a wider range of kidney-related objects, with data dimensions used in research transitioning from 2D to 3D while simultaneously incorporating more diverse data modalities. CONCLUSION: The present study provides a scientometric overview of the current progress in the research and application of CV technology in kidney medicine research. Through the use of bibliometric analysis and network visualization, we elucidate emerging trends, key sources, leading institutions, and popular topics. Our findings and analysis are expected to provide valuable insights for future research on the use of CV in kidney medicine research.


Assuntos
Bibliometria , Humanos , Nefrologia , Nefropatias , Pesquisa Biomédica/tendências , Inteligência Artificial
9.
EJHaem ; 5(2): 333-345, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38633121

RESUMO

ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low-risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low-risk ETV6::RUNX1-positive B-cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome-wide transcriptome and single-nucleotide variants. We found high TIMD4 expression (> 85th-percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR] = 5.07 [1.76, 14.62]; p = 0.03). In an independent validation cohort of low-risk ETV6::RUNX1-positive B-cell ALL (N = 68) high TIMD4 expression at diagnosis had an HR = 4.78 [1.07, 21.36] (p = 0.04) for early relapse. In another validation cohort including 78 children with low-risk ETV6::RUNX1-negative B-cell ALL, high TIMD4 expression at diagnosis had an HR = 3.93 [1.31, 11.79] (p = 0.01). Our results suggest high TIMD4 expression at diagnosis in low-risk B-cell ALL in children might be associated with high risk for early relapse.

10.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(2): 455-460, 2024 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-38645853

RESUMO

Objective: To construct a deep learning-based target detection method to help radiologists perform rapid diagnosis of lesions in the CT images of patients with novel coronavirus pneumonia (NCP) by restoring detailed information and mining local information. Methods: We present a deep learning approach that integrates detail upsampling and attention guidance. A linear upsampling algorithm based on bicubic interpolation algorithm was adopted to improve the restoration of detailed information within feature maps during the upsampling phase. Additionally, a visual attention mechanism based on vertical and horizontal spatial dimensions embedded in the feature extraction module to enhance the capability of the object detection algorithm to represent key information related to NCP lesions. Results: Experimental results on the NCP dataset showed that the detection method based on the detail upsampling algorithm improved the recall rate by 1.07% compared with the baseline model, with the AP50 reaching 85.14%. After embedding the attention mechanism in the feature extraction module, 86.13% AP50, 73.92% recall, and 90.37% accuracy were achieved, which were better than those of the popular object detection models. Conclusion: The feature information mining of CT images based on deep learning can further improve the lesion detection ability. The proposed approach helps radiologists rapidly identify NCP lesions on CT images and provides an important clinical basis for early intervention and high-intensity monitoring of NCP patients.


Assuntos
Algoritmos , COVID-19 , Aprendizado Profundo , Pneumonia Viral , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Humanos , COVID-19/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Pneumonia Viral/diagnóstico por imagem , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/diagnóstico , Pandemias , Betacoronavirus
11.
Aging Dis ; 15(2): 739-754, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37548945

RESUMO

Neuroinflammation, characterized by the secretion of abundant inflammatory mediators, pro-inflammatory polarization of microglia, and the recruitment of infiltrating myeloid cells to foci of inflammation, drives or exacerbates the pathological processes of central nervous system disorders, especially in neurodegenerative diseases. Autophagy plays an essential role in neuroinflammatory processes, and the underlaying physiological mechanisms are closely correlated with neuroinflammation-related signals. Inhibition of mTOR and activation of AMPK and FOXO1 enhance autophagy and thereby suppress NLRP3 inflammasome activity and apoptosis, leading to the relief of neuroinflammatory response. And autophagy mitigates neuroinflammation mainly manifested by promoting the polarization of microglia from a pro-inflammatory to an anti-inflammatory state, reducing the production of pro-inflammatory mediators, and up-regulating the levels of anti-inflammatory factors. Notably, epigenetic modifications are intimately associated with autophagy and the onset and progression of various brain diseases. Non-coding RNAs, including microRNAs, circular RNAs and long noncoding RNAs, and histone acetylation have been reported to adjust autophagy-related gene and protein expression to alleviate inflammation in neurological diseases. The present review primarily focuses on the role and mechanisms of autophagy in neuroinflammatory responses, as well as epigenetic modifications of autophagy in neuroinflammation to reveal potential therapeutic targets in central nervous system diseases.


Assuntos
Doenças Neurodegenerativas , Doenças Neuroinflamatórias , Humanos , Epigênese Genética , Inflamação/genética , Anti-Inflamatórios/farmacologia , Autofagia/genética , Mediadores da Inflamação/farmacologia , Doenças Neurodegenerativas/genética
14.
Front Pharmacol ; 14: 1265960, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37920216

RESUMO

Naturally occurring flavonoids have long been utilized as essential templates for the development of novel drugs and as critical ingredients for functional foods. Astragalin (AG) is a natural flavonoid that can be isolated from a variety of familiar edible plants, such as the seeds of green tea, Morus alba L., and Cuscuta chinensis. It is noteworthy that AG has a wide range of pharmacological activities and possesses therapeutic effects against a variety of diseases, covering cancers, osteoarthritis, osteoporosis, ulcerative colitis, mastitis, obesity, diabetes mellitus, diabetic complications, ischemia/reperfusion injury, neuropathy, respiratory diseases, and reproductive system diseases. This article reviewed the natural source and pharmacokinetics of AG and systematically summarized the pharmacological activities and potential mechanisms of AG in treating diverse diseases in order to promote the development of AG as a functional food, in doing so providing references for its clinical application in disease therapy.

15.
Environ Pollut ; 339: 122737, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37838313

RESUMO

Alga-bacterium interaction can improve wastewater treatment efficiency. To unravel the mystery of the interaction between microalgae and bacteria in wastewater, mono-cultures and co-cultures of Chlorella vulgaris and native bacteria in pretreated biochemical wastewater from landfill leachate were investigated. The results showed that the microalgae selected dominant commensal bacteria, creating a further reduction in species richness for the co-culture, which in turn aids in the dominant commensal bacteria's survival, thereby enhancing algal and bacterial metabolic activity. Strikingly, the lipid productivity of Chlorella in co-culture - namely 41.5 mg/L·d - was 1.4 times higher than in algal monoculture. Additionally, pollutant removal was enhanced in co-cultures, attributed to the bacterial community associated with pollutants' degradation. Furthermore, this study provides an important advance towards observations on the migration and transformation pathways of nutrients and metals, and bridges the gap in algal-bacterial synergistic mechanisms in real wastewater, laying the theoretical foundation for improving wastewater treatment.


Assuntos
Chlorella vulgaris , Microalgas , Águas Residuárias , Biomassa , Microalgas/metabolismo , Bactérias , Lipídeos
16.
Phytother Res ; 37(12): 5700-5723, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37748788

RESUMO

Galangin is an important flavonoid with natural activity, that is abundant in galangal and propolis. Currently, various biological activities of galangin have been disclosed, including anti-inflammation, antibacterial effect, anti-oxidative stress and aging, anti-fibrosis, and antihypertensive effect. Based on the above bioactivities, more and more attention has been paid to the role of galangin in neurodegenerative diseases, rheumatoid arthritis, osteoarthritis, osteoporosis, skin diseases, and cancer. In this paper, the natural sources, pharmacokinetics, bioactivities, and therapeutic potential of galangin against various diseases were systematically reviewed by collecting and summarizing relevant literature. In addition, the molecular mechanism and new preparation of galangin in the treatment of related diseases are also discussed, to broaden the application prospect and provide reference for its clinical application. Furthermore, it should be noted that current toxicity and clinical studies of galangin are insufficient, and more evidence is needed to support its possibility as a functional food.


Assuntos
Flavonoides , Estresse Oxidativo , Flavonoides/farmacologia , Flavonoides/uso terapêutico
17.
Int J Mol Sci ; 24(18)2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37762063

RESUMO

Obesity is the basis of numerous metabolic diseases and has become a major public health issue due to its rapidly increasing prevalence. Nevertheless, current obesity therapeutic strategies are not sufficiently effective, so there is an urgent need to develop novel anti-obesity agents. Naturally occurring saponins with outstanding bio-activities have been considered promising drug leads and templates for human diseases. Cyclosiversioside F (CSF) is a paramount multi-functional saponin separated from the roots of the food-medicinal herb Astragali Radix, which possesses a broad spectrum of bioactivities, including lowering blood lipid and glucose, alleviating insulin resistance, relieving adipocytes inflammation, and anti-apoptosis. Recently, the therapeutic potential of CSF in obesity and relevant disorders has been gradually explored and has become a hot research topic. This review highlights the role of CSF in treating obesity and obesity-induced complications, such as diabetes mellitus, diabetic nephropathy, cardiovascular and cerebrovascular diseases, and non-alcoholic fatty liver disease. Remarkably, the underlying molecular mechanisms associated with CSF in disease therapy have been partially elucidated, especially PI3K/Akt, NF-κB, MAPK, apoptotic pathway, TGF-ß, NLRP3, Nrf-2, and AMPK, with the aim of promoting the development of CSF as a functional food and providing references for its clinical application in obesity-related disorders therapy.

18.
Front Immunol ; 14: 1287048, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37767097

RESUMO

[This corrects the article DOI: 10.3389/fimmu.2023.1089001.].

20.
Front Immunol ; 14: 1206513, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37600790

RESUMO

Background: Neuroinflammation has been reported as a potential contributing factor to brain diseases, and is characterized by activated microglia with release of multiple inflammatory mediators. 2,3,5,6-Tetramethylpyrazine (TMP) is an active alkaloid in Ligusticum chuanxiong Hort. and has various biological activities, including anti-inflammatory and neuroprotection properties. However, the anti-neuroinflammatory activity of TMP has been less studied and its potential molecular mechanisms in this field remain unclear. This study aimed to investigate the effects of TMP and its underlying mechanisms in neuroinflammation. Methods: In vitro, lipopolysaccharide (LPS)-stimulated BV2 microglia were used to assess the effects of TMP on inflammatory cytokines as well as the components of the SIRT1/NF-κB signaling pathway, which were measured by using ELISA, western blotting, qRT-qPCR and immunofluorescence. Moreover, LPS-induced acute neuroinflammation model in mice was performed to detect whether TMP could exert anti-neuroinflammatory effects in vivo, and the EX527, a SIRT1 inhibitor, were given intraperitoneally every two days prior to TMP treatment. Serums and spinal trigeminal nucleus (Sp5) tissues were collected for ELISA assay, and the Sp5 tissues were used for HE staining, Nissl staining, immunofluorescence, qRT-PCR and western blotting. Results: In vitro, TMP treatment significantly reduced the secretion of pro-inflammatory cytokines, including TNF-α and IL-6, promoted SIRT1 protein expression and inactivated NF-κB signaling pathway in LPS-induced neuroinflammation. Interestingly, pretreatment with EX527 blocked the therapeutic effects of TMP on neuroinflammation in vitro. Furthermore, TMP reduced the levels of pro-inflammatory cytokines and chemokines, and prevented microglia from polarizing towards a pro-inflammatory state through activating SIRT1 and inhibiting NF-κB activation in LPS-induced neuroinflammation in mice. And EX527 reversed the beneficial effects of TMP against LPS exposure in mice. Conclusion: In summary, this study unravels that TMP could mitigate LPS-induced neuroinflammation via SIRT1/NF-κB signaling pathway.


Assuntos
Microglia , Sirtuína 1 , Animais , Camundongos , NF-kappa B , Lipopolissacarídeos/toxicidade , Doenças Neuroinflamatórias , Citocinas
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