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1.
Sci Rep ; 14(1): 15171, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956417

RESUMO

We present the first machine learning-based autonomous hyperspectral neutron computed tomography experiment performed at the Spallation Neutron Source. Hyperspectral neutron computed tomography allows the characterization of samples by enabling the reconstruction of crystallographic information and elemental/isotopic composition of objects relevant to materials science. High quality reconstructions using traditional algorithms such as the filtered back projection require a high signal-to-noise ratio across a wide wavelength range combined with a large number of projections. This results in scan times of several days to acquire hundreds of hyperspectral projections, during which end users have minimal feedback. To address these challenges, a golden ratio scanning protocol combined with model-based image reconstruction algorithms have been proposed. This novel approach enables high quality real-time reconstructions from streaming experimental data, thus providing feedback to users, while requiring fewer yet a fixed number of projections compared to the filtered back projection method. In this paper, we propose a novel machine learning criterion that can terminate a streaming neutron tomography scan once sufficient information is obtained based on the current set of measurements. Our decision criterion uses a quality score which combines a reference-free image quality metric computed using a pre-trained deep neural network with a metric that measures differences between consecutive reconstructions. The results show that our method can reduce the measurement time by approximately a factor of five compared to a baseline method based on filtered back projection for the samples we studied while automatically terminating the scans.

2.
J Med Chem ; 67(6): 5011-5031, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38450627

RESUMO

Effective vascular and hepatic enhancement and better safety are the key drivers for exploring gadolinium-free hepatobiliary contrast agents. Herein, a facile strategy proposes that the high lipophilicity may be favorable to enhancing sequentially vascular and hepatobiliary signal intensity based on the structure-activity relationship that both hepatic uptake and interaction with serum albumins partly depend on lipophilicity. Therefore, 11 newly synthesized derivatives of manganese o-phenylenediamine-N,N,N',N'-tetraacetic acid (MnLs) were evaluated as vascular and hepatobiliary agents. The maximum signal intensities of the heart, liver, and kidneys were strongly correlated with log P, a key indicator of lipophilicity. The most lipophilic agent, MnL6, showed favorable relaxivity when binding with serum albumin, good vascular enhancement, rapid excretion, and reliable hepatobiliary phases comparable to a classic hepatobiliary agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for in vivo liver tumor imaging. Inhibition experiments confirmed the hepatic targeting of MnL6 is mediated by organic anion-transporting polypeptides.


Assuntos
Meios de Contraste , Neoplasias Hepáticas , Humanos , Meios de Contraste/metabolismo , Manganês , Gadolínio DTPA/metabolismo , Fígado/metabolismo , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos
3.
Postgrad Med J ; 98(1162): 577-583, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33879548

RESUMO

INTRODUCTION: Prostate cancer is a common malignancy in men that is difficult to treat and carries a high risk of death. miR-219-5p is expressed in reduced amounts in many malignancies. However, the prognostic value of miR-219-5p for patients with prostate cancer remains unclear. METHODS: We retrospectively analysed data from 213 prostate cancer patients from 10 June 2012 to 9 May 2015. Overall survival was assessed by Kaplan-Meier analysis and Cox regression models. Besides, a prediction model was constructed, and calibration curves evaluated the model's accuracy. RESULTS: Of the 213 patients, a total of 72 (33.8%) died and the median survival time was 60.0 months. We found by multifactorial analysis that miR-219-5p deficiency increased the risk of death by nearly fourfold (HR: 3.86, 95% CI): 2.01 to 7.44, p<0.001) and the risk of progression by twofold (HR: 2.79, 95% CI: 1.68 to 4.64, p<0.001). To quantify each covariate's weight on prognosis, we screened variables by cox model to construct a predictive model. The Nomogram showed excellent accuracy in estimating death's risk, with a corrected C-index of 0.778. CONCLUSIONS: miR-219-5p can be used as a biomarker to predict death risk in prostate cancer patients. The mortality risk prediction model constructed based on miR-219-5p has good consistency and validity in assessing patient prognosis.


Assuntos
MicroRNAs , Neoplasias da Próstata , Biomarcadores Tumorais/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , MicroRNAs/genética , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade , Estudos Retrospectivos
4.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(6): 637-641, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33719273

RESUMO

Objective: To investigate the effects of miRNA-191 on the proliferation, migration and invasion of prostate cancer, and to explore its mechanism. Methods: The expression levels of miRNA-191 in four human prostate cancer cell lines (PC-3, DU-145, LNCa P, 22RU1) and human normal prostate cell line RWPE-2 were detected, and prostate cancer cell line PC-3 was selected as the experimental object. PC-3 cells were divided into three groups: blank control group (no transfection), miRNA-191 NC group (PC-3 cells transfected with Inhibitor NC) and miRNA-191 Inhibitor group (PC-3 cells transfected with miRNA-191 Inhibitor), and each group was provided with three multiple pores. The expression levels of miRNA-191 and PLCD1 were detected by RT-PCR. The cell proliferation was detected by CCK8 assay. Scratch test and invasive test were used to detect cell migration and invasive ability. Through Targetscan target gene prediction website, PLCD1 was screened as the target protein of miRNA-191, and verified by double luciferase target experiment.Western blot assay was used to detect the expression of PLCD1 in cells of each group. Results: Compared with RWPE-2 cells, the expression level of miRNA-191 in human prostate cancer cells was significantly higher (P <0.05), and the expression level of miRNA191 in PC-3 was significantly higher than that in other three cell lines (P<0.05). After inhibiting the expression of miRNA-191, the expression levels of PLCD1 was significantly higher while PC-3 cells' proliferation ability was inhibited, and their migration and invasion ability were significantly lower than those of blank control group and miRNA-191 NC group (P< 0.05). The results of double luciferase reporter gene assay showed that PLCD1 gene was a target gene of miRNA-191. Conclusion: miRNA-191 promote the proliferation, migration and invasion of prostate cancer PC-3 cells by targeting PLCD1.


Assuntos
MicroRNAs , Neoplasias da Próstata , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Fosfolipase C delta , Neoplasias da Próstata/genética
5.
RSC Adv ; 8(25): 13871-13878, 2018 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35539324

RESUMO

Notoginsenoside R1 (NGR1) is separate from Panax notoginsenosides (PNS), and plays a role similar to phytoestrogen in preventing and treating cardiovascular diseases. However, the protective mechanism of NGR1 in the myocardial ischemia/reperfusion injury via the estrogen receptor (ER) pathway remains unclear, which hinder its application. This study aimed to study the preventive mechanisms of NGR1 in the apoptosis of H9c2 cardiomyocytes after hypoxia/reoxygenation (H/R). NGR1 did not affect the expression of ERα and ERß proteins in normal H9c2 cardiomyocytes. However, NGR1 could upregulate the ERα and G protein-coupled receptor 30 (GPR30) proteins in H9c2 cardiomyocytes after H/R without affecting ERß levels. Moreover, it significantly affected the expression levels of PI3K and its downstream apoptosis proteins such as Bcl-2 Associated X Protein (Bax), B cell lymphoma/lewkmia-2 (Bcl-2), caspase-3, and so forth. Whereas, after adding the PI3K protein antagonist, the modulatory expression levels of PI3K and its downstream apoptosis proteins were remarkably abolished. After adding ERα and GPR30 antagonists, NGR1 had no significant effect on the expression of PI3K and its downstream Akt protein in the model group. The data of flow cytometry showed that after adding the ERα, GPR30 and PI3K antagonists, the apoptotic rate of cardiomyocytes had no significant changes compared with the model group. This study demonstrated that NGR1 protected H9c2 cardiomyocytes from the injury after H/R by affecting ERα and GPR30 to regulate the expression levels of PI3K and its downstream apoptosis proteins.

6.
Regul Toxicol Pharmacol ; 83: 81-88, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27916537

RESUMO

Zishen Yutai pill (ZYP) is an oriental herbal formula, while hepatotoxicity assessment of ZYP was rarely evaluated. Therefore, our aim is to re-evaluate its hepatotoxicity in both normal and carbon tetrachloride (CCl4) induced chronic liver injury rats. In the normal model, two doses of ZYP (1.575 and 9.450 g kg-1 d-1; i.e. 1 × , 6 × clinical doses) were given orally to rats for 24 weeks. In the chronic liver injury model, 10% CCl4 was administered to rats abdominally twice a week at a dose of 5 mL kg-1 for 12 consecutive weeks. Administration time started from 4 weeks after the beginning of CCl4 treatment. Toxicological parameters included mortality, body weight, food consumption, clinical signs, biochemical parameters, gross observation, organ weight, necropsy findings and histopathology were monitored. In the normal model, we found no any mortality or abnormality in clinical signs, relative liver weight, biochemical parameters and histopathology in ZYP treatment groups. In the chronic liver injury model, liver damage related parameter such as ALT was elevated at the high dose of ZYP treatment in contrast to the CCl4-treated group (P < 0.01). In histopathological assessment, there were no significant difference between ZYP treatment groups and CCl4-treated group. No observed adverse effect on livers were established for 9.450 g kg-1 d-1 ZYP in the normal rats and 9.450 g kg-1 d-1 ZYP in the injury rats.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Medicamentos de Ervas Chinesas/toxicidade , Fígado/efeitos dos fármacos , Testes de Toxicidade Crônica , Administração Oral , Alanina Transaminase/sangue , Animais , Biomarcadores/sangue , Peso Corporal/efeitos dos fármacos , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Fígado/metabolismo , Fígado/patologia , Necrose , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Medição de Risco , Fatores de Tempo
7.
Zhongguo Zhong Yao Za Zhi ; 41(20): 3721-3726, 2016 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-28929647

RESUMO

Coronary artery heart disease (CHD) is one of the common cardiovascular diseases in clinical. The morbidity and mortality of CHD recently continue increasing in our country, which has aroused wide attention. Many studies confirm that traditional Chinese medicine has better therapeutic effect on CHD. Guanxin Danshen formula, widely used in the treatment of CHD, consists of Salviae Miltiorrhizae Radix et Rhizoma, Notoginseng Radix et Rhizoma and volatile oil from Dalbergiae Odoriferae Lignum, and has the efficacy in promoting blood circulation to resolve stasis, regulating the circulation of Qi and alleviating pain. This review summarized the pharmacologic effects and mechanism of Guanxin Danshen formula and its effective components in the treatment of CHD to provide reference for its fundamental research and clinical application.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Cardiopatias/tratamento farmacológico , Vasos Coronários/fisiopatologia , Humanos , Medicina Tradicional Chinesa , Rizoma , Salvia miltiorrhiza
8.
Yao Xue Xue Bao ; 51(7): 1047-53, 2016 07.
Artigo em Chinês | MEDLINE | ID: mdl-29897172

RESUMO

Epigenetic is a hotspot of post-genomic era research, and epigenetic modification is a mechanism in the study of cardiovascular disease. Myocardial ischemia-reperfusion injury (MIRI) is one of the problems in the cardiovascular disease, and many experimental interventions are reported in the protection of the ischemic myocardium in experimental animals. However, with the exception of early reperfusion, none has been translated into clinical practice. There is an advantage of traditional Chinese medicine (TCM) in the regulation of epigenetic modification, and pathogenesis of myocardial ischemia-reperfusion injury. This review article is prepared to cover the research progress in the treatment of myocardial ischemia-reperfusion injury by TCM with a focus on epigenetic regulation. The epigenetic regulation is documented in TCM theory through a systematic review of the protecting drugs in the MIRI development guidelines.


Assuntos
Epigênese Genética , Medicina Tradicional Chinesa , Traumatismo por Reperfusão Miocárdica/terapia , Animais , Substâncias Protetoras/farmacologia
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