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1.
J Psychiatr Res ; 175: 418-424, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38781676

RESUMO

AIM: Tourette syndrome (TS) is a neurodevelopmental disorder that cause sudden uncontrolled rapid and repeated vocal sounds or movements called tics. Herein, diffusion magnetic resonance imaging (dMRI) connectometry was implemented to evaluate the white matter connectivity differences among TS patients. METHODS: A total of 63 TS and 77 typically developed (TD) individuals were enrolled in the present study. dMRI connectometry was utilized to identify differences in connectivity patterns of white matter tracts in TS patients based on quantitative anisotropy (QA). QA was compared between TS and TD patients and correlated with severity scores such as Yale Global Tic Severity Scale (YGTSS) and Premonitory Urge for Tics Scale (PUTS). RESULTS: Higher white matter connectivity of corpus callosum and bilateral cingulum as well as lower connectivity of corticothalamic and corticostriatal pathways were evident in TS relative to TD. The baseline YGTSS motor, YGTSS total, and PUTS were negatively correlated with corticostriatal pathway, corticothalamic pathway, and bilateral cingulum integrity, respectively. The changes in tic severity scores were also positively correlated with alterations in the white matter integrity of these brain regions following behavioral therapy. CONCLUSION: Patients with TS have several abnormalities in their white matter microstructure particularly in the cortico-striato-thalamo-cortical (CSTC) circuit, correlated with the severity of the disease. Besides, the post-behavioral therapy changes in the white matter integrity of these regions are demonstrated as response predictors.

2.
Front Pharmacol ; 15: 1377836, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818379

RESUMO

Testicular torsion is a critical urologic condition for which testicular detorsion surgery is considered irreplaceable as well as the golden method of reversal. However, the surgical treatment is equivalent to a blood reperfusion process, and no specific drugs are available to treat blood reperfusion injuries. Salidroside (SAL) is one of the main effective substances in rhodiola, which has been shown to have antioxidant and antiapoptosis activities. This study was designed to determine whether SAL exerted a protective effect on testicular ischemia-reperfusion (I/R) injury. In this study, the I/R injury model of the testes and reoxygenation (OGD/R) model were used for verification, and SAL was administered at doses of 100 mg/kg and 0.05 mmol/L, respectively. After the experiments, the testicular tissue and TM4 Sertoli cells were collected for histopathologic and biochemical analyses. The results revealed that SAL improves the structure of testicular tissue and regulates the oxidation-antioxidation system. To further understand the molecular mechanisms of SAL in treating testicular I/R injuries, transcriptomics and metabonomics analyses were integrated. The results show that the Nfr2/HO-1/GPX4/ferroptosis signaling pathway is enriched significantly, indicating that it may be the main regulatory pathway for SAL in the treatment of testicular I/R injuries. Thereafter, transfection with Nrf2 plasmid-liposome was used to reverse verify that the Nfr2/HO-1/GPX4/ferroptosis signaling pathway was the main pathway for SAL anti-testicular I/R injury treatment. Thus, it is suggested that SAL can protect against testicular I/R injuries by regulating the Nfr2/HO-1/GPX4 signaling pathway to inhibit ferroptosis and that SAL may be a potential drug for the treatment of testicular I/R injuries.

3.
Int J Rheum Dis ; 27(3): e15102, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38450839

RESUMO

BACKGROUND: The cancer risk in rheumatoid arthritis (RA) patients has been discussed. Hydroxychloroquine (HCQ) may exert protective effects against malignancy. The study investigated the association between HCQ use and the risk of subsequent malignancy in RA patients. METHODS: Catastrophic illness certificated RA patients were extracted from the National Health Insurance Research Database. The index date was set 180 days after the RA diagnosis date to avoid immortal time bias. Two groups were matched in a 1-to-1 ratio by propensity score regarding age, gender, index date, relevant comorbidities, and comedication. HCQ users prior to the diagnosis of RA were exempted to ensure compliance with the new-user design. Cancers diagnosed before or less than 180 days after the index date were excluded to mitigate protopathic bias. The study adopted the Kaplan-Meier curve and Cox proportional hazards model to examine the association between HCQ use and cancer risk. The assumption of proportional hazard was also tested. RESULTS: Based on strict criteria, we included 492 eligible RA patients and divided them into study and control groups (N = 246 in each group). HCQ users exhibited a neutral risk of cancer relative to the controls (adjusted hazard ratio, 0.99; 95% CI, 0.44-2.21, p > .05). The assumption of proportional hazard was not violated. CONCLUSION: This study does not observe the effect of using HCQ as a primary regimen to prevent cancer in RA patients. We are assured that HCQ is not associated with an increased risk of subsequent malignancy in RA patients. Further mechanistic research is needed.


Assuntos
Artrite Reumatoide , Neoplasias , Humanos , Hidroxicloroquina/efeitos adversos , Estudos Retrospectivos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Bases de Dados Factuais
4.
Opt Lett ; 48(7): 1686-1689, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37221741

RESUMO

Optical metasurfaces provide a significant approach for the production of structural colors due to their excellent optical control abilities. Herein, we propose trapezoidal structural metasurfaces for achieving multiplex grating-type structural colors with high comprehensive performance originating from the anomalous reflection dispersion in the visible band. Single trapezoidal metasurfaces with different x-direction periods can tune the angular dispersion regularly from 0.036 rad/nm to 0.224 rad/nm to generate various structural colors, and composite trapezoidal metasurfaces with three kinds of combinations can achieve multiplex sets of structural colors. The brightness can be controlled by adjusting the distance between the trapezoids in a pair accurately. The designed structural colors have higher saturation than traditional pigmentary colors, whose excitation purity can reach 1.00. The gamut is about 158.1% of the Adobe RGB standard. This research has application potential in ultrafine displays, information encryption, optical storage, and anti-counterfeit tagging.

5.
J Am Med Inform Assoc ; 30(6): 1022-1031, 2023 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-36921288

RESUMO

OBJECTIVE: To develop a computable representation for medical evidence and to contribute a gold standard dataset of annotated randomized controlled trial (RCT) abstracts, along with a natural language processing (NLP) pipeline for transforming free-text RCT evidence in PubMed into the structured representation. MATERIALS AND METHODS: Our representation, EvidenceMap, consists of 3 levels of abstraction: Medical Evidence Entity, Proposition and Map, to represent the hierarchical structure of medical evidence composition. Randomly selected RCT abstracts were annotated following EvidenceMap based on the consensus of 2 independent annotators to train an NLP pipeline. Via a user study, we measured how the EvidenceMap improved evidence comprehension and analyzed its representative capacity by comparing the evidence annotation with EvidenceMap representation and without following any specific guidelines. RESULTS: Two corpora including 229 disease-agnostic and 80 COVID-19 RCT abstracts were annotated, yielding 12 725 entities and 1602 propositions. EvidenceMap saves users 51.9% of the time compared to reading raw-text abstracts. Most evidence elements identified during the freeform annotation were successfully represented by EvidenceMap, and users gave the enrollment, study design, and study Results sections mean 5-scale Likert ratings of 4.85, 4.70, and 4.20, respectively. The end-to-end evaluations of the pipeline show that the evidence proposition formulation achieves F1 scores of 0.84 and 0.86 in the adjusted random index score. CONCLUSIONS: EvidenceMap extends the participant, intervention, comparator, and outcome framework into 3 levels of abstraction for transforming free-text evidence from the clinical literature into a computable structure. It can be used as an interoperable format for better evidence retrieval and synthesis and an interpretable representation to efficiently comprehend RCT findings.


Assuntos
COVID-19 , Compreensão , Humanos , Processamento de Linguagem Natural , PubMed
6.
JCI Insight ; 8(6)2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36809299

RESUMO

Anti-CD36 Abs have been suggested to induce transfusion-related acute lung injury (TRALI) upon blood transfusion, particularly in Asian populations. However, little is known about the pathological mechanism of anti-CD36 Ab-mediated TRALI, and potential therapies have not yet been identified. Here, we developed a murine model of anti-CD36 Ab-mediated TRALI to address these questions. Administration of mouse mAb against CD36 (mAb GZ1) or human anti-CD36 IgG, but not GZ1 F(ab')2 fragments, induced severe TRALI in Cd36+/+ male mice. Predepletion of recipient monocytes or complement, but not neutrophils or platelets, prevented the development of murine TRALI. Moreover, plasma C5a levels after TRALI induction by anti-CD36 Abs increased more than 3-fold, implying a critical role of complement C5 activation in the mechanism of Fc-dependent anti-CD36-mediated TRALI. Administration of GZ1 F(ab')2, antioxidant (N-acetyl cysteine, NAC), or C5 blocker (mAb BB5.1) before TRALI induction completely protected mice from anti-CD36-mediated TRALI. Although no significant amelioration in TRALI was observed when mice were injected with GZ1 F(ab')2 after TRALI induction, significant improvement was achieved when mice were treated postinduction with NAC or anti-C5. Importantly, anti-C5 treatment completely rescued mice from TRALI, suggesting the potential role of existing anti-C5 drugs in the treatment of patients with TRALI caused by anti-CD36.


Assuntos
Lesão Pulmonar Aguda Relacionada à Transfusão , Camundongos , Humanos , Masculino , Animais , Lesão Pulmonar Aguda Relacionada à Transfusão/patologia , Plaquetas/patologia , Monócitos/patologia , Proteínas do Sistema Complemento , Ativação do Complemento
7.
Stud Health Technol Inform ; 290: 268-272, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35673015

RESUMO

While the PICO framework is widely used by clinicians for clinical question formulation when querying the medical literature, it does not have the expressiveness to explicitly capture medical findings based on any standard. In addition, findings extracted from the literature are represented as free-text, which is not amenable to computation. This research extends the PICO framework with Observation elements, which capture the observed effect that an Intervention has on an Outcome, forming Intervention-Observation-Outcome triplets. In addition, we present a framework to normalize Observation elements with respect to their significance and the direction of the effect, as well as a rule-based approach to perform the normalization of these attributes. Our method achieves macro-averaged F1 scores of 0.82 and 0.73 for identifying the significance and direction attributes, respectively.

8.
Stud Health Technol Inform ; 290: 592-596, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35673085

RESUMO

Complex interventions are ubiquitous in healthcare. A lack of computational representations and information extraction solutions for complex interventions hinders accurate and efficient evidence synthesis. In this study, we manually annotated and analyzed 3,447 intervention snippets from 261 randomized clinical trial (RCT) abstracts and developed a compositional representation for complex interventions, which captures the spatial, temporal and Boolean relations between intervention components, along with an intervention normalization pipeline that automates three tasks: (i) treatment entity extraction; (ii) intervention component relation extraction; and (iii) attribute extraction and association. 361 intervention snippets from 29 unseen abstracts were included to report on the performance of the evaluation. The average F-measure was 0.74 for treatment entity extraction on an exact match and 0.82 for attribute extraction. The F-measure for relation extraction of multi-component complex interventions was 0.90. 93% of extracted attributes were correctly attributed to corresponding treatment entities.


Assuntos
Armazenamento e Recuperação da Informação , Processamento de Linguagem Natural , Humanos
9.
Mitochondrial DNA B Resour ; 7(3): 503-504, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35342795

RESUMO

Sophora davidii (Franch.) Pavol. is a deciduous or evergreen shrubs belonging to the genus Sophora, Fabaceae. The roots of S. davidii have been traditionally used as a medicinal herb in China to clear internal heat, relieve sore throat, and reduce swelling. Here we sequenced the whole genome of the chloroplast of S. davidii. The complete length of the chloroplast genome in S. davidii is 153,584 bp, containing a large single-copy region of 83,930 bp, a small single-copy region of 15,008 bp, and a pair of inverted repeats regions of 25,823 bp. The total guanine-cytosine (GC) percentage of the chloroplast genome was 36.7%. A total of 131 genes were annotated from the chloroplast genome of S. davidii, including 85 protein-coding genes, 8 rRNA genes and 38 tRNA genes. The phylogenetic analysis showed that S. davidii is closely related to the other three species of genus Sophora.

10.
Neuropharmacology ; 208: 108979, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35131297

RESUMO

Defensive behavior, a group of responses that evolved due to threatening stimuli, is crucial for animal survival in the natural environment. For defensive measures to be timely and successful, a high arousal state and immediate sleep-to-wakefulness transition are required. Recently, the glutamatergic basal forebrain (BF) has been implicated in sleep-wake regulation; however, the associated physiological functions and underlying neural circuits remain unknown. Here, using in vivo fiber photometry, we found that BF glutamatergic neuron is activated by various threatening stimuli, including predator odor, looming threat, sound, and tail suspension. Optogenetic activation of BF glutamatergic neurons induced a series of context-dependent defensive behaviors in mice, including escape, fleeing, avoidance, and hiding. Similar to the effects of activated BF glutamatergic cell body, photoactivation of BF glutamatergic terminals in the ventral tegmental area (VTA) strongly drove defensive behaviors in mice. Using synchronous electroencephalogram (EEG)/electromyogram (EMG) recording, we showed that photoactivation of the glutamatergic BF-VTA pathway produced an immediate transition from sleep to wakefulness and significantly increased wakefulness. Collectively, our results clearly demonstrated that the glutamatergic BF is a key neural substrate involved in wakefulness and defensive behaviors, and encodes these behaviors through glutamatergic BF-VTA pathway. Overexcitation of the glutamatergic BF-VTA pathway may be implicated in clinical psychiatric diseases characterized by exaggerated defensive responses, such as autism spectrum disorders.


Assuntos
Prosencéfalo Basal , Vigília , Animais , Prosencéfalo Basal/fisiologia , Eletroencefalografia/métodos , Mesencéfalo , Camundongos , Sono/fisiologia , Vigília/fisiologia
11.
Redox Biol ; 48: 102129, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34526248

RESUMO

Hepatotoxicity caused by an overdose of acetaminophen (APAP) is the leading reason for acute drug-related liver failure. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a protein that helps to regulate redox homeostasis and coordinate stress responses via binding to the Kelch-like ECH-associated protein 1 (Keap1). Targeting the Keap1-Nrf2 interaction has recently emerged as a potential strategy to alleviate liver injury caused by APAP. Here, we designed and synthesized a number of iridium (III) and rhodium (III) complexes bearing ligands with reported activity against oxidative stress, which is associated with Nrf2 transcriptional activation. The iridium (III) complex 1 bearing a bioactive ligand 2,9-dimethyl-1,10-phenanthroline and 4-chloro-2-phenylquinoline, a derivative of the bioactive ligand 2-phenylquinoline, was identified as a direct small-molecule inhibitor of the Keap1-Nrf2 protein-protein interaction. 1 could stabilize Keap1 protein, upregulate HO-1 and NQO1, and promote Nrf2 nuclear translocation in normal liver cells. Moreover, 1 reversed APAP-induced liver damage by disrupting Keap1-Nrf2 interaction and without inducing organ damage and immunotoxicity in mice. Our study demonstrates the identification of a selective and efficacious antagonist of Keap1-Nrf2 interaction possessed good cellular permeability in cellulo and ideal pharmacokinetic parameters in vivo, and, more importantly, validates the feasibility of conjugating metal complexes with bioactive ligands to generate metal-based drug leads as non-toxic Keap1-Nrf2 interaction inhibitors for treating APAP-induced acute liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Complexos de Coordenação , Acetaminofen/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Complexos de Coordenação/metabolismo , Complexos de Coordenação/farmacologia , Irídio/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Ligantes , Fígado/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo
12.
J Am Med Inform Assoc ; 28(8): 1703-1711, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-33956981

RESUMO

OBJECTIVE: We introduce Medical evidence Dependency (MD)-informed attention, a novel neuro-symbolic model for understanding free-text clinical trial publications with generalizability and interpretability. MATERIALS AND METHODS: We trained one head in the multi-head self-attention model to attend to the Medical evidence Ddependency (MD) and to pass linguistic and domain knowledge on to later layers (MD informed). This MD-informed attention model was integrated into BioBERT and tested on 2 public machine reading comprehension benchmarks for clinical trial publications: Evidence Inference 2.0 and PubMedQA. We also curated a small set of recently published articles reporting randomized controlled trials on COVID-19 (coronavirus disease 2019) following the Evidence Inference 2.0 guidelines to evaluate the model's robustness to unseen data. RESULTS: The integration of MD-informed attention head improves BioBERT substantially in both benchmark tasks-as large as an increase of +30% in the F1 score-and achieves the new state-of-the-art performance on the Evidence Inference 2.0. It achieves 84% and 82% in overall accuracy and F1 score, respectively, on the unseen COVID-19 data. CONCLUSIONS: MD-informed attention empowers neural reading comprehension models with interpretability and generalizability via reusable domain knowledge. Its compositionality can benefit any transformer-based architecture for machine reading comprehension of free-text medical evidence.


Assuntos
Inteligência Artificial , Ensaios Clínicos como Assunto , Armazenamento e Recuperação da Informação/métodos , Modelos Neurológicos , Processamento de Linguagem Natural , COVID-19 , Simulação por Computador , Mineração de Dados , Humanos , Software
13.
J Am Med Inform Assoc ; 28(4): 812-823, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33367705

RESUMO

OBJECTIVE: The study sought to develop and evaluate a knowledge-based data augmentation method to improve the performance of deep learning models for biomedical natural language processing by overcoming training data scarcity. MATERIALS AND METHODS: We extended the easy data augmentation (EDA) method for biomedical named entity recognition (NER) by incorporating the Unified Medical Language System (UMLS) knowledge and called this method UMLS-EDA. We designed experiments to systematically evaluate the effect of UMLS-EDA on popular deep learning architectures for both NER and classification. We also compared UMLS-EDA to BERT. RESULTS: UMLS-EDA enables substantial improvement for NER tasks from the original long short-term memory conditional random fields (LSTM-CRF) model (micro-F1 score: +5%, + 17%, and +15%), helps the LSTM-CRF model (micro-F1 score: 0.66) outperform LSTM-CRF with transfer learning by BERT (0.63), and improves the performance of the state-of-the-art sentence classification model. The largest gain on micro-F1 score is 9%, from 0.75 to 0.84, better than classifiers with BERT pretraining (0.82). CONCLUSIONS: This study presents a UMLS-based data augmentation method, UMLS-EDA. It is effective at improving deep learning models for both NER and sentence classification, and contributes original insights for designing new, superior deep learning approaches for low-resource biomedical domains.


Assuntos
Pesquisa Biomédica , Armazenamento e Recuperação da Informação/métodos , Processamento de Linguagem Natural , Unified Medical Language System , Gerenciamento de Dados
14.
J Int Med Res ; 48(7): 300060520943792, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32721183

RESUMO

OBJECTIVE: To investigate the anti-proliferative and pro-apoptotic effects of curcumin on diffuse large B-cell lymphoma (DLBCL) cells and explore the mechanism. METHODS: OCI-LY7 cells were treated with curcumin (2.5, 5, 10, 20, and 40 µM) for 24, 48, or 72 hours. Cell viability and apoptosis were determined using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyl tetrazolium bromide assay and TdT-mediated dUTP nick-end labeling staining, respectively. MiR-28-5p expression was detected via qRT-PCR. The binding site of miR-28-5p was predicted using online databases and verified using the dual-luciferase reporter assay. MiR-28-5p overexpression and inhibition were achieved via transfection with an miR-28-5p mimic and inhibitor, respectively. RESULTS: Curcumin decreased the viability of OCI-LY7 cells in a concentration- and time-dependent manner, and these effects were attenuated by miR-28-5p inhibition. MiR-28-5p expression was upregulated by curcumin. Curcumin increased the numbers of apoptotic cells and upregulated cleaved caspase-3 expression, and these effects were attenuated by miR-28-5p inhibition. The dual-luciferase reporter assay confirmed that miR-28-5p directly targets the 3'-untranslated region of BECN1. Curcumin downregulated BECN1 and microtubule-associated protein 1 light chain 3 beta-II/I expression and upregulated p62 expression. CONCLUSIONS: Our results described the curcumin exerted anti-proliferative and pro-apoptotic effects on OCI-LY7 cells through a mechanism potentially involving miR-28-5p.


Assuntos
Curcumina , Linfoma Difuso de Grandes Células B , MicroRNAs , Apoptose , Linhagem Celular Tumoral , Curcumina/farmacologia , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , MicroRNAs/genética
15.
Biosens Bioelectron ; 155: 112102, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32090874

RESUMO

A molecularly imprinted magnetic sensor with electroluminescent tags (MIP-ECL sensor) was developed for ultrasensing diethylstilbestrol (DES). A strategy is exploited to enhance ECL emission of the [Ru(bpy)3]2 +-tripropyl amine (TPrA) system by CdTe@ZnS quantum-dots (QDs) through energy transfer. Magnetically molecularly imprinted nanoparticles (MMIPs NPs) based on Fe3O4@SiO2 carriers are artificial, easily reproducible, and could replace easily inactivated first antibodies for capturing more DES molecules. Functionalized bio-conjugates of single antibody-CdTe@ZnS (Ab-CdTe@ZnS) are for the first time loaded on signal labels of Ru(bpy)32 +-doped silica nanocomposites (Ru@SiO2) for signal amplification. The final bio-conjugated signal probes are denoted as Ab-DES/CdTe@ZnS-Ru@SiO2. MMIPs beads that have captured antigens are bio-conjugated with antibody-labeled luminescent probes by specific immunoreactive reaction, and then the luminescent immunocomplex generates ECL signal on the magnetic electrode. The logarithm of ECL intensities depend linearly on the logarithm of DES concentrations in the range from 4.8 × 10- 4 to 36.0 nM with a detection limit of 0.025 pM. This novel assay is much more sensitive than other MIP sensors, and achieves lower cost and more enhanced stability than other immunosensors. The sensor is significantly potential and has been applied to DES detection in actual environment.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Medições Luminescentes , Nanopartículas Metálicas , Polímeros , Pontos Quânticos , Compostos de Cádmio , Dietilestilbestrol , Medições Luminescentes/métodos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Dióxido de Silício , Sulfetos , Telúrio , Compostos de Zinco
16.
Chem Sci ; 11(7): 1750-1760, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34123270

RESUMO

Many cancers have developed resistance to 5-FU, due to removal by the enzyme uracil-DNA glycosylase (UDG), a type of base excision repair enzyme (BER) that can excise uracil and 5-fluorouracil (5-FU) from DNA. However, the development of UDG inhibitor screening methods, especially for the rapid and efficient screening of natural product/natural product-like compounds, is still limited so far. We developed herein a robust time-resolved photoluminescence method for screening UDG inhibitors, which could significantly improve sensitivity over the screening method based on the conventional steady-state spectroscopy, reducing the substantial fluorescence background interference. As a proof-of-concept, two potential UDG inhibitors were identified from a database of natural products and approved drugs. Co-treatment of these two compounds with 5-FU showed synergistic cytotoxicity, providing the basis for treating drug-resistant cancers. Overall, this method provides an avenue for the rapid screening of small molecule regulators of other BER enzyme activities that can avoid false negatives arising from the background fluorescence.

17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-828407

RESUMO

Osteoporosis fracture with high disability and mortality is a difficult problem that seriously affects the life quality of individuals. At present, there is still a lack of anti-osteoporosis drugs with clear target and significant efficacy in the clinical practice. Rehmanniae Radix and its prescriptions have significant clinical effects. In this regard, more and more studies have reported the effects and mechanisms of Rehmanniae Radix and its active components, and the certain research outputs have been achieved. In this article, the PubMed, Web of science, China National Knowledge Infrastructure, and Wanfang database were searched to collect and organize the latest research progress of Rehmanniae Radix treatment of osteoporosis in the recent 10 years. We summarized the research dynamics as well as the function indexes and mechanisms of the raw and processed Rehmanniae Radix, active ingredients such as catalpol, aucubin, acteoside and Rehmanniae Radix polysaccharide, and their formulating prescriptions, and then excavated the potential active ingredients, targets and signaling pathways, including the effect on bone marrow mesenchymal stem cells, promoting the osteoblast proliferation and promoting osteogenesis differentiation(increasing alkaline phosphatase, typeⅠ collagen, osteoprotegerin, and osteocalcin and promoting calcium deposits), increasing the bone density, inhibiting the osteoclast quantity and differentiation, promoting the osteoclast apoptosis, and reducing tartrate resistant acid phosphatase and bone resorption pit area to provide the reference and develop new ideas for developing Rehmanniae Radix prescriptions for treatment of osteoporosis and exploring its mechanism.


Assuntos
Humanos , China , Medicamentos de Ervas Chinesas , Osteogênese , Osteoporose , Rehmannia
18.
J Vet Pharmacol Ther ; 42(6): 602-608, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31529627

RESUMO

Ceftiofur, a third-generation cephalosporin antibiotic, is being extensively used by pet doctors in China. In the current study, the detection method was developed for ceftiofur and its metabolites, desfuroylceftiofur (DCE) and desfuroylceftiofur conjugates (DCEC), in feline plasma. Then, the pharmacokinetics studies were performed following one single intravenous and subcutaneous injection of ceftiofur sodium in cats both at 5 mg/kg body weight (BW) (calculated as pure ceftiofur). Ceftiofur, DCE, and DCEC were extracted from plasma samples, then derivatized and further quantified by high-performance liquid chromatography. The concentrations versus time data were subjected to noncompartmental analysis to obtain the pharmacokinetics parameters. The terminal half-life (t1/2λz ) was calculated as 11.29 ± 1.09 and 10.69 ± 1.31 hr following intravenous and subcutaneous injections, respectively. After intravenous treatment, the total body clearance (Cl) and volume of distribution at steady-state (VSS ) were determined as 14.14 ± 1.09 ml hr-1  kg-1 and 241.71 ± 22.40 ml/kg, respectively. After subcutaneous injection, the peak concentration (Cmax ; 14.99 ± 2.29 µg/ml) was observed at 4.17 ± 0.41 hr, and the absorption half-life (t1/2ka ) and absolute bioavailability (F) were calculated as 2.83 ± 0.46 hr and 82.95%±9.59%, respectively. The pharmacokinetic profiles of ceftiofur sodium and its related metabolites demonstrated their relatively slow, however, good absorption after subcutaneous administration, poor distribution, and slow elimination in cats. Based on the time of drug concentration above the minimum inhibitory concentration (MIC) (T>MIC) calculated in the current study, an intravenous or subcutaneous dose at 5 mg/kg BW of ceftiofur sodium once daily is predicted to be effective for treating feline bacteria with a MIC value of ≤4.0 µg/ml.


Assuntos
Antibacterianos/farmacocinética , Gatos , Cefalosporinas/farmacocinética , Animais , Área Sob a Curva , Feminino , Meia-Vida , Injeções Intravenosas , Injeções Subcutâneas , Masculino , Testes de Sensibilidade Microbiana
19.
Stud Health Technol Inform ; 264: 188-192, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31437911

RESUMO

PICO (Population/problem, Intervention, Comparison, and Outcome) is widely adopted for formulating clinical questions to retrieve evidence from the literature. It plays a crucial role in Evidence-Based Medicine (EBM). This paper contributes a scalable deep learning method to extract PICO statements from RCT articles. It was trained on a small set of richly annotated PubMed abstracts using an LSTM-CRF model. By initializing our model with pretrained parameters from a large related corpus, we improved the model performance significantly with a minimal feature set. Our method has advantages in minimizing the need for laborious feature handcrafting and in avoiding the need for large shared annotated data by reusing related corpora in pretraining with a deep neural network.


Assuntos
Medicina Baseada em Evidências , Redes Neurais de Computação , PubMed , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Stud Health Technol Inform ; 264: 442-446, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31437962

RESUMO

Discovering disease similarities are beneficial for the diagnosis and treatment of mental diseases. In this research, we proposed a data driven method, that is, integrating a variety of publicly available data resources including Unified Medical Language System (UMLS) Metathesaurus, Systematized Nomenclature of Medicine - Clinical Terms (SNOMED CT) and cui2vec concept embedding to construct a mental disease similarity network. The resulting mental disease similarity network offered a new view for navigating and investigating disease relations; it also revealed popular mental disease in the literature in terms of the number of connections and similarities with other diseases. It shows that depressive disorder is directly connected with nine other popular diseases and connects 52 other diseases in the network. The top three popular mental diseases are depressive disorder, dysthymia (now known as persistent depressive disorder), and neurosis. Future research will focus on studying the clusters generated from the similarity network.


Assuntos
Systematized Nomenclature of Medicine , Unified Medical Language System , Ontologias Biológicas
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