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1.
Acta Radiol ; 65(3): 284-293, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38115811

RESUMO

BACKGROUND: An applicable magnetic resonance imaging (MRI) biomarker for diffuse midline glioma (DMG), H3 K27-altered of the spinal cord is important for non-invasive diagnosis. PURPOSE: To evaluate the efficacy of conventional MRI (cMRI) in distinguishing between DMGs, H3 K27-altered, gliomas without H3 K27-alteration, and demyelinating lesions in the spinal cord. MATERIAL AND METHODS: Between January 2017 and February 2023, patients with pathology-confirmed spinal cord gliomas (including ependymomas) with definite H3 K27 status and demyelinating diseases diagnosed by recognized criteria were recruited as the training set for this retrospective study. Morphologic parameter assessment was performed by two neuroradiologists on T1-weighted, T2-weighted, and contrast-enhanced T1-weighted imaging. Variables with high inter- and intra-observer agreement were included in univariable correlation analysis and multivariable logistic regression. The performance of the final model was verified by internal and external testing sets. RESULTS: The training cohort included 21 patients with DMGs (13 men; mean age = 34.57 ± 13.489 years), 21 with wild-type gliomas (10 men; mean age = 46.76 ± 17.017 years), and 20 with demyelinating diseases (5 men; mean age = 49.50 ± 18.872 years). A significant difference was observed in MRI features, including cyst(s), hemorrhage, pial thickening with enhancement, and the maximum anteroposterior diameter of the spinal cord. The prediction model, integrating age, age2, and morphological characteristics, demonstrated good performance in the internal and external testing cohort (accuracy: 0.810 and 0.800, specificity: 0.810 and 0.720, sensitivity: 0.872 and 0.849, respectively). CONCLUSION: Based on cMRI, we developed a model with good performance for differentiating among DMGs, H3 K27-altered, wild-type glioma, and demyelinating lesions in the spinal cord.


Assuntos
Neoplasias Encefálicas , Doenças Desmielinizantes , Glioma , Masculino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Glioma/diagnóstico por imagem , Glioma/patologia , Imageamento por Ressonância Magnética/métodos , Medula Espinal/diagnóstico por imagem , Doenças Desmielinizantes/diagnóstico por imagem , Neoplasias Encefálicas/patologia
2.
Ren Fail ; 46(1): 2337287, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38627212

RESUMO

OBJECTIVE: This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats. METHODS: CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 µg/kg, and CP + Dex 25 µg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting. RESULTS: Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1. CONCLUSION: Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.


Assuntos
Injúria Renal Aguda , Dexmedetomidina , Ratos , Animais , Dexmedetomidina/efeitos adversos , Cisplatino/toxicidade , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/patologia , Rim/patologia , Interleucina-1beta , Caspases/efeitos adversos
3.
Bioorg Chem ; 133: 106425, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36801788

RESUMO

Vascular epidermal growth factor receptor-2 (VEGFR-2), as an important tyrosine transmembrane protein, plays an important role in regulating endothelial cell proliferation and migration, regulating angiogenesis and other biological functions. VEGFR-2 is aberrantly expressed in many malignant tumors, and it is also related to the occurrence, development, and growth of tumors and drug resistance. Currently, there are nine VEGFR-2 targeted inhibitors approved by US.FDA for clinical use as anticancer drugs. Due to the limited clinical efficacy and potential toxicity of VEGFR inhibitors, it is necessary to develop new strategies to improve the clinical efficacy of VEGFR inhibitors. The development of multitarget therapy, especially dual-target therapy, has become a hot research field of cancer therapy, which may provide an effective strategy with higher therapeutic efficacy, pharmacokinetic advantages and low toxicity. Many groups have reported that the therapeutic effects could be improved by simultaneously inhibiting VEGFR-2 and other targets, such as EGFR, c-Met, BRAF, HDAC, etc. Therefore, VEGFR-2 inhibitors with multi-targeting capabilities have been considered to be promising and effective anticancer agents for cancer therapy. In this work, we reviewed the structure and biological functions of VEGFR-2, and summarized the drug discovery strategies, and inhibitory activities of VEGFR-2 inhibitors with multi-targeting capabilities reported in recent years. This work might provide the reference for the development of VEGFR-2 inhibitors with multi-targeting capabilities as novel anticancer agents.


Assuntos
Antineoplásicos , Neoplasias , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Humanos , Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Proliferação de Células , Descoberta de Drogas , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/química , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
4.
J Comput Assist Tomogr ; 47(4): 650-658, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37380154

RESUMO

OBJECTIVE: Oligodendrocyte transcription factor 2 (OLIG2) is universally expressed in human glioblastoma (GB). Our study explores whether OLIG2 expression impacts GB patients' overall survival and establishes a machine learning model for OLIG2 level prediction in patients with GB based on clinical, semantic, and magnetic resonance imaging radiomic features. METHODS: Kaplan-Meier analysis was used to determine the optimal cutoff value of the OLIG2 in 168 GB patients. Three hundred thirteen patients enrolled in the OLIG2 prediction model were randomly divided into training and testing sets in a ratio of 7:3. The radiomic, semantic, and clinical features were collected for each patient. Recursive feature elimination (RFE) was used for feature selection. The random forest (RF) model was built and fine-tuned, and the area under the curve was calculated to evaluate the performance. Finally, a new testing set excluding IDH-mutant patients was built and tested in a predictive model using the fifth edition of the central nervous system tumor classification criteria. RESULTS: One hundred nineteen patients were included in the survival analysis. Oligodendrocyte transcription factor 2 was positively associated with GB survival, with an optimal cutoff of 10% ( P = 0.00093). One hundred thirty-four patients were eligible for the OLIG2 prediction model. An RFE-RF model based on 2 semantic and 21 radiomic signatures achieved areas under the curve of 0.854 in the training set, 0.819 in the testing set, and 0.825 in the new testing set. CONCLUSIONS: Glioblastoma patients with ≤10% OLIG2 expression tended to have worse overall survival. An RFE-RF model integrating 23 features can predict the OLIG2 level of GB patients preoperatively, irrespective of the central nervous system classification criteria, further guiding individualized treatment.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Estimativa de Kaplan-Meier , Prognóstico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Fator de Transcrição 2 de Oligodendrócitos , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Biomarcadores
5.
Int J Clin Pharmacol Ther ; 61(12): 551-560, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37877292

RESUMO

OBJECTIVE: Several studies have reported that porcine antilymphocyte globulin (pALG) has a significant effect on aplastic anemia (AA), but their conclusions are inconsistent. To objectively evaluate its efficacy and safety, a meta-analysis was conducted. MATERIALS AND METHODS: We systematically searched the relevant literature on pALG vs. rabbit antithymocyte globulin (rATG) as the first-line treatment in AA patients until August 31, 2022, in electronic databases: PubMed, Cochrane Library, Web of Science, etc. Two researchers independently extracted data and evaluated the quality of the study. Stata 14.0 was used for statistical analysis. RESULTS: 50 studies were included in the analysis. The overall responses at 3, 6, and 12 months between the pALG group and rATG group were equivalent. We analyzed early mortality, total mortality, relapse rates, and 5-year survival after the administration of pALG or rATG, and there was no significant difference between the pALG and rATG groups. In our study, the incidence of infection in the pALG group was better than that in the rATG group, OR = 0.63, 95% CI (0.44 - 0.88), p = 0.008, which showed a statistically significant difference. CONCLUSION: The efficacy of pALG in AA patients is equivalent to that of rATG. rATG was associated with a significantly higher incidence rate of infection than pALG.


Assuntos
Anemia Aplástica , Soro Antilinfocitário , Humanos , Animais , Suínos , Soro Antilinfocitário/efeitos adversos , Anemia Aplástica/diagnóstico , Anemia Aplástica/tratamento farmacológico , Estudos Retrospectivos , Terapia de Imunossupressão , Imunossupressores/efeitos adversos
6.
J Digit Imaging ; 36(4): 1910-1918, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37039950

RESUMO

It is difficult to accurately understand the angioarchitecture of cerebral arteriovenous malformations (CAVMs) before surgery using existing imaging methods. This study aimed to evaluate the ability of the stereoscopic virtual reality display system (SVRDS) to display the angioarchitecture of CAVMs by comparing its accuracy with that of the conventional computed tomography workstation (CCTW). Nineteen patients with CAVM confirmed on digital subtraction angiography (DSA) or during surgery were studied. Computed tomography angiography images in the SVRDS and CCTW were retrospectively analyzed by two experienced neuroradiologists using a double-blind method. Angioarchitectural parameters, such as the location and size of the nidus, type and number of the arterial feeders and draining veins, and draining pattern of the vessels, were recorded and compared. The diameter of the nidus ranged from 1.1 to 9 cm. Both CCTW and SVRDS correctly diagnosed the location of the nidus in 19 patients with CAVM. Among the 19 patients, 35 arterial feeders and 25 draining veins were confirmed on DSA and during surgery. With the DSA and intraoperative results as the gold standard bases, the CCTW misjudged one arterial feeder and one draining vein and missed three arterial feeders and two draining veins; meanwhile, the SVRDS missed only two arterial feeders. SVRDS had some advantages in displaying nidus, arterial branches, and draining veins of the CAVM compared with CCTW, as well as SVRDS could more intuitively display the overall angio-architectural spatial picture of CAVM.


Assuntos
Malformações Arteriovenosas Intracranianas , Realidade Virtual , Humanos , Estudos Retrospectivos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/cirurgia , Angiografia Cerebral , Tomografia Computadorizada por Raios X/métodos , Angiografia Digital
7.
J Digit Imaging ; 36(1): 114-123, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36085330

RESUMO

The accuracy of computed tomography angiography (CTA) image interpretation depends on the radiologist. This study aims to develop a new method for automatically detecting intracranial aneurysms from CTA images using deep learning, based on a convolutional neural network (CNN) implemented on the DeepMedic platform. Ninety CTA scans of patients with intracranial aneurysms are collected and divided into two datasets: training (80 subjects) and test (10 subjects) datasets. Subsequently, a deep learning architecture with a three-dimensional (3D) CNN model is implemented on the DeepMedic platform for the automatic segmentation and detection of intracranial aneurysms from the CTA images. The samples in the training dataset are used to train the CNN model, and those in the test dataset are used to assess the performance of the established system. Sensitivity, positive predictive value (PPV), and false positives are evaluated. The overall sensitivity and PPV of this system for detecting intracranial aneurysms from CTA images are 92.3% and 100%, respectively, and the segmentation sensitivity is 92.3%. The performance of the system in the detection of intracranial aneurysms is closely related to their size. The detection sensitivity for small intracranial aneurysms (≤ 3 mm) is 66.7%, whereas the sensitivity of detection for large (> 10 mm) and medium-sized (3-10 mm) intracranial aneurysms is 100%. The deep learning architecture with a 3D CNN model on the DeepMedic platform can reliably segment and detect intracranial aneurysms from CTA images with high sensitivity.


Assuntos
Aprendizado Profundo , Aneurisma Intracraniano , Humanos , Angiografia por Tomografia Computadorizada , Tomografia Computadorizada por Raios X/métodos , Angiografia Digital/métodos , Angiografia Cerebral/métodos , Sensibilidade e Especificidade
8.
Angew Chem Int Ed Engl ; 62(15): e202218886, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-36788706

RESUMO

The development of environment-friendly, step economic couplings to generate structurally diverse macrocyclic compounds is highly desirable but poses a marked challenge. Inspired by the C-H oxidation mechanism of cytochromes P450, an unprecedented and practical RhIII -catalyzed acylmethylation macrocyclization via C-H/O2 dual activation has been developed by us. The process of macrocyclization is facilitated by a synergic coordination from pyridine and ester group. Interestingly, the reaction mode derives from a three-component coupling which differs from established olefination and alkylation paths. Density functional theory (DFT) calculations and control experiments revealed the mechanism of this unique C-H/O2 dual activation. The newly achieved acylmethylation macrocyclic products and their derivatives showed a potent anti-H1N1 bioactivity, which may provide an opportunity for the discovery of novel anti-H1N1 macrocyclic leading compounds.


Assuntos
Influenza Humana , Ródio , Humanos , Catálise , Oxirredução , Alquilação
9.
Anal Chem ; 94(50): 17709-17715, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36475658

RESUMO

Heterocyclic nitrogen compounds play a vital role in luminescent materials, but most of them face the challenges of aggregation-caused quenching (ACQ) and poor water solubility. In this work, we present the nitrogen heterocyclic pentaphenylpyrrole (PentaPP) with an excellent aggregation-induced electrochemiluminescence (AIE-ECL) performance in the aqueous phase through the comparison of the elegant ECL luminophore 5,10,15,20-tetraphenylporphyrin (TPP). Further studies suggest that such unique AIE-ECL arises from its propeller-like noncoplanar structure and the large conjugation from the phenyl groups on the ring. In addition, the new ECL analysis could feature some advantages of AIE characteristic, water compatibility, and strong signal and finally achieve the ultrasensitive detection toward the explosive 2,4,6-trinitrophenol (TNP) with a lower detection limit (1.1 nM). This study does not only benefit to solve the two key problems mentioned before but also enriches the fundamentals and applications for ECL and pyrrole research.


Assuntos
Técnicas Biossensoriais , Pontos Quânticos , Técnicas Eletroquímicas , Medições Luminescentes , Água , Fotometria , Pontos Quânticos/química , Limite de Detecção
10.
PLoS Biol ; 17(8): e3000425, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31461438

RESUMO

Recurrent tumors originate from cancer stem cells (CSCs) that survive conventional treatments. CSCs consist of heterogeneous subpopulations that display distinct sensitivity to anticancer drugs. Such a heterogeneity presents a significant challenge in preventing tumor recurrence. In the current study, we observed that quiescent CUB-domain-containing protein 1 (CDCP1)+ CSCs are enriched after chemotherapy in mutant Kirsten rat sarcoma viral oncogene homolog (Kras) colorectal carcinomas (CRCs) and serve as a reservoir for recurrence. Mechanistically, glucose catabolism in CDCP1+ CSCs is routed to the oxidative pentose phosphate pathway (PPP); multiple cycling of carbon backbones in the oxidative PPP potentially maximizes NADPH reduction to counteract chemotherapy-induced reactive oxygen species (ROS) formation, thereby allowing CDCP1+ CSCs to survive chemotherapeutic attack. This is dependent on silent mating type information regulation 2 homolog 5 (Sirt5)-mediated inhibition of the glycolytic enzyme triosephosphate isomerase (TPI) through demalonylation of Lys56. Blocking demalonylation of TPI at Lys56 increases chemosensitivity of CDCP1+ CSCSs and delays recurrence of mutant Kras CRCs in vivo. These findings pinpoint a new therapeutic approach for combating mutant Kras CRCs.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Via de Pentose Fosfato/genética , Animais , Antígenos de Neoplasias/metabolismo , Antineoplásicos/farmacologia , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Glicólise , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , NADP/metabolismo , Células-Tronco Neoplásicas/fisiologia , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Via de Pentose Fosfato/fisiologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sirtuínas/metabolismo
11.
Toxicol Mech Methods ; 32(1): 27-36, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34412561

RESUMO

The effect of Pulsatilla saponin A (PsA) on acute myocardial infarction (AMI) was unknown. This study targeted to examine the roles of PsA on hypoxia-triggered toxicity to H9c2 cells and reveal the potential mechanism. H9c2 cells were maintained under a hypoxic environment for 12 h to construct the AMI cell model and the cells were pretreated by PsA. Hypoxia triggered toxicity to H9c2 cells and the anti-toxicity effect of PsA was evaluated by CCK8, TUNEL, and Western blot. The levels of miR-24-3p and p16 in H9c2 cells, AMI group tissues, and their respective controls were assessed using qRT-PCR. The dual-luciferase assay was applied to verify the targeting mechanism of miR-24-3p on p16. Then the effects of miR-24-3p inhibitor or/and si-p16 on H9c2 cells treated with PsA under hypoxia were detected by CCK8, TUNEL, and Western blot. Flow cytometry was executed to determine the cell cycle. Hypoxia decreased viability and proliferation and increased apoptosis of H9c2 cells, which were ameliorated by PsA pretreatment. The level of miR-24-3p was diminished, but p16 expression was elevated in hypoxia-treated cells and AMI group tissues. MiR-24-3p could sponge p16 in hypoxia-treated cells. Furthermore, the impact of applying miR-24-3p inhibitor on PsA and hypoxia-treated cells could be reversed by si-p16. PsA relieved hypoxia-triggered cell toxicity via miR-24-3p/p16 axis. These findings provided some fresh insights into the potential therapeutic effects of the application of PsA in AMI.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , MicroRNAs , Infarto do Miocárdio , Saponinas/farmacologia , Apoptose , Linhagem Celular , Humanos , MicroRNAs/genética , Infarto do Miocárdio/tratamento farmacológico , Miócitos Cardíacos
12.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 51(6): 731-737, 2022 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-36915975

RESUMO

OBJECTIVE: To observe the clinical characteristics of mild and common COVID-19 patients infected with the Omicron variant, and to analyze related factors affecting the time to negative conversion of viral nucleic acid detection. METHODS: Clinical data of 1781 patients with coronavirus disease 2019 (COVID-19) admitted to a cabin hospital in Shanghai from April 12 to May 26, 2022, were retrospectively analyzed, including age, gender, height, weight, clinical symptoms, comorbid diseases, COVID-19 vaccination, treatment, and nucleic acid negative conversion time. Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of nucleic acid negative conversion time. RESULTS: Among the 1781 patients, 995 were male and 786 were female, with a median age of 39 (30, 52) years. There were 727 patients (40.8%) with overweight and obesity [body mass index (BMI) > 24 kg/cm 2) and 413 patients (23.2%) had comorbid diseases. 205 cases (11.5%) were not vaccinated while 1576 cases were vaccinated. There were 1233 cases (69.2%) with one or more symptoms. The main clinical symptoms were cough (60.3%), expectoration (50.4%) and fever (36.9%). 1444 cases (81.0%) were treated with Chinese medicine, 78 cases (4.4%) were treated with western medicine, 14 cases (0.8%) were treated with integrated Chinese and western medicine, and 245 cases (13.8%) did not receive any medical treatment. All patients improved and were discharged. The median nucleic acid negative conversion time was 10.3 (7.4, 12.4) d. Univariate and multivariate analysis showed that, age ≥ 60 years ( OR=1.537, 95% CI: 1.116 - 2.115, P<0.01), BMI > 24 kg/cm 2 ( OR=1.344, 95% CI: 1.106 - 1.634, P<0.01 ) and hypertension ( OR=1.518, 95% CI: 1.094 - 2.106, P<0.05) were independent risk factors for prolonged nucleic acid negative conversion. COVID-19 vaccination ( OR=0.548, 95% CI: 0.398 - 0.755, P<0.01) was a protective factor, that is, vaccination shortened the time for the nucleic acid test to become negative. CONCLUSIONS: The symptoms of the Omicron variant infection were relatively mild and occult. Age ≥ 60 years old, comorbid hypertension, no vaccination and BMI > 24 kg/cm 2 are independent influencing factors for prolonged nucleic acid negative conversion.


Assuntos
COVID-19 , Hipertensão , Ácidos Nucleicos , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , COVID-19/epidemiologia , Vacinas contra COVID-19 , Estudos Retrospectivos , China , Hipertensão/epidemiologia
13.
Bioorg Med Chem ; 47: 116358, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34479103

RESUMO

Bruton tyrosine kinase (BTK) is a key kinase in the B cell antigen receptor signal transduction pathway, which is involved in the regulation of the proliferation, differentiation and apoptosis of B cells. BTK has become a significant target for the treatment of hematological malignancies and autoimmune diseases. Ibrutinib, the first-generation BTK inhibitor, has made a great contribution to the treatment of B cell malignant tumors, but there are still some problems such as resistance or miss target of site mutation. Therefore, there is an imperative need to develop novel BTK inhibitors to overcome these problems. Besides, proteolysis targeting chimera (PROTAC) technology has been successfully applied to the development of BTK degradation agents, which has opened a fresh way for the BTK targeted treatment. This paper reviews the biological function of BTK, the discovery and development of BTK targeted drugs as a promising cancer therapy. It mainly reviews the binding sites and structural characteristics of BTK, structure-activity relationships, activity and drug resistance of BTK inhibitors, as well as potential treatment strategies to overcome the resistance of BTK, which provides a reference for the rational design and development of new powerful BTK inhibitors.


Assuntos
Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Antineoplásicos/farmacologia , Desenvolvimento de Medicamentos , Inibidores de Proteínas Quinases/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Tirosina Quinase da Agamaglobulinemia/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química
14.
Twin Res Hum Genet ; 24(1): 22-28, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33775270

RESUMO

The purpose of our study was to elucidate the functions of miR-30c-5p on adenomyosis for exploring novel treatment strategies. We first detected the expression of miR-30c-5p in clinical adenomyotic tissues and isolated endometrial cells from adenomyotic tissues. Next, gain and loss-of-function assays were performed to detect the effect of miR-30c-5p on adenomyotic endometrial cells. Further, luciferase assay and real-time polymerase chain reaction as well as western blot were conducted to investigate the potential target of miR-30c-5p; and transwell assay, wound-healing assay and CCK-8 assay were used to evaluate the effects of miR-30c-5p and its target on regulating biological functions of adenomyotic endometrial cells. Our results found that miR-30c-5p was down-regulated in both adenomyosis tissues and adenomyotic epithelial cells, which correlated with dysmenorrhea, longer duration of symptoms and more menstrual bleeding. Moreover, the overexpression of miR-30c-5p inhibited the proliferation, migration and invasion of adenomyotic epithelial cells, where miR-30c-5p knockdown had an opposite effect. Furthermore, we confirmed mitogen-activated protein kinase 1 (MAPK1) was one of the direct targets of miR-30c-5p, indicating its important role in miR-30c-5p-mediated suppression of proliferation, invasion and migration in adenomyotic epithelial cells. This study showed that the interaction of miR-30c-5p with MAPK1 can regulate the proliferation, invasion and migration in adenomyotic epithelial cells.


Assuntos
Adenomiose , MicroRNAs , Adenomiose/genética , Movimento Celular/genética , Proliferação de Células/genética , Células Epiteliais , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Proteína Quinase 1 Ativada por Mitógeno
15.
Molecules ; 26(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299525

RESUMO

FAK is a nonreceptor intracellular tyrosine kinase which plays an important biological function. Many studies have found that FAK is overexpressed in many human cancer cell lines, which promotes tumor cell growth by controlling cell adhesion, migration, proliferation, and survival. Therefore, targeting FAK is considered to be a promising cancer therapy with small molecules. Many FAK inhibitors have been reported as anticancer agents with various mechanisms. Currently, six FAK inhibitors, including GSK-2256098 (Phase I), VS-6063 (Phase II), CEP-37440 (Phase I), VS-6062 (Phase I), VS-4718 (Phase I), and BI-853520 (Phase I) are undergoing clinical trials in different phases. Up to now, there have been many novel FAK inhibitors with anticancer activity reported by different research groups. In addition, FAK degraders have been successfully developed through "proteolysis targeting chimera" (PROTAC) technology, opening up a new way for FAK-targeted therapy. In this paper, the structure and biological function of FAK are reviewed, and we summarize the design, chemical types, and activity of FAK inhibitors according to the development of FAK drugs, which provided the reference for the discovery of new anticancer agents.


Assuntos
Antineoplásicos/farmacologia , Descoberta de Drogas , Proteína-Tirosina Quinases de Adesão Focal/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Animais , Antineoplásicos/química , Proteína-Tirosina Quinases de Adesão Focal/química , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Modelos Moleculares , Terapia de Alvo Molecular , Neoplasias/metabolismo , Inibidores de Proteínas Quinases/química
16.
Molecules ; 26(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34443487

RESUMO

The chalcone and quinoline scaffolds are frequently utilized to design novel anticancer agents. As the continuation of our work on effective anticancer agents, we assumed that linking chalcone fragment to the quinoline scaffold through the principle of molecular hybridization strategy could produce novel compounds with potential anticancer activity. Therefore, quinoline-chalcone derivatives were designed and synthesized, and we explored their antiproliferative activity against MGC-803, HCT-116, and MCF-7 cells. Among these compounds, compound 12e exhibited a most excellent inhibitory potency against MGC-803, HCT-116, and MCF-7 cells with IC50 values of 1.38, 5.34, and 5.21 µM, respectively. The structure-activity relationship of quinoline-chalcone derivatives was preliminarily explored in this report. Further mechanism studies suggested that compound 12e inhibited MGC-803 cells in a dose-dependent manner and the cell colony formation activity of MGC-803 cells, arrested MGC-803 cells at the G2/M phase and significantly upregulated the levels of apoptosis-related proteins (Caspase3/9 and cleaved-PARP) in MGC-803 cells. In addition, compound 12e could significantly induce ROS generation, and was dependent on ROS production to exert inhibitory effects on gastric cancer cells. Taken together, all the results suggested that directly linking chalcone fragment to the quinoline scaffold could produce novel anticancer molecules, and compound 12e might be a valuable lead compound for the development of anticancer agents.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Chalconas/síntese química , Chalconas/farmacologia , Desenho de Fármacos , Quinolinas/síntese química , Quinolinas/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Chalconas/química , Humanos , Quinolinas/química , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
17.
Opt Express ; 28(21): 31872-31881, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33115151

RESUMO

This paper proposes a novel cholesteric liquid crystal (CLC) film-based dual-probe fiber sensor to monitor volatile organic compound (VOC) gas. The sensor consists of a 2×2 multimode fiber coupler, in which the two output fiber ends are covered by two types of CLC films (CLCF) with different pitches. It can be observed that the reflection peak wavelengths of CLCs shift to the red side as the VOC gas concentration increases. The sensitivities of the two CLCFs are 8.435 nm·L/mmol and 14.867 nm·L/mmol to acetone, 14.586 nm·L/mmol and 29.303 nm·L/mmol to ethanol, respectively. In addition, the dependence of the peak wavelength shift of CLCF on the total concentration of the acetone and ethanol mixed gas at different mixing ratios is measured. The linear relationships between the peak shift of CLCFs, the total mixed gas concentration and acetone/ethanol ratio are calculated using the least-squares method. Therefore, this proposed dual-probe fiber optic sensor can distinguish the concentrations of acetone and ethanol in a mixed gas of acetone and ethanol.

18.
Langmuir ; 36(26): 7483-7493, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32543868

RESUMO

Understanding photocurrent conversion of layered double hydroxide (LDH) materials will be a key step in the future application of these materials to light-capturing molecular devices. In the present study, ultrathin nickel-iron layered double hydroxide/dye (NF-LDH/dye) Langmuir-Blodgett (LB) semiconductor films were prepared using an LB device and deposited on an indium tin oxide (ITO) substrate as a photoanode. The photoelectric conversion efficiency of the prepared LB semiconductor film materials was tested. A comparative experiment was performed to effectively explore the photoelectric conversion performances of the LB semiconductor film materials. Specifically, the NF-LDH cast film electrode, the dye cast film electrode, and an ultrathin composite LB film electrode were used as typical samples to explore photoelectric conversion performances. The electrochemical workstation was used to study the photocurrent density, linear scanning voltammetry curve, and electrochemical impedance spectroscopy of LB film electrodes with different layers. The results show that the film electrode cast by LDH alone or dye alone produces weak photocurrent. The photoelectric conversion efficiency of the LB film electrode is enhanced due to the different dyes' molecular structures and/or aggregations on the surface of LDH with various morphological patterns. The combined NF-LDH/dye composite LB film photoelectrode can generate a photocurrent that is 2-5 times stronger than the raw material, and the stable use efficiency is more than 92%. Present obtained composite LB films demonstrated a uniform morphology and good photoelectric conversion ability. This work provides a useful reference for the field of LDH semiconductor optoelectronic devices and solar cells.

19.
J Cardiovasc Electrophysiol ; 30(6): 910-917, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30907035

RESUMO

OBJECTIVE: Early atrial fibrillation (AF) recurrences are common and have been shown to predict AF recurrences late after AF ablation during follow-up. Neiguan point acupuncture has been recognized to be therapeutic in treating AF in clinical practice. METHODS AND RESULTS: Eighty-five patients were enrolled in succession due to persistent AF. All patients were randomized divided into control group and acupuncture group. In the control group (n = 45), amiodarone was orally taken from the first day after pulmonary vein isolation (PVI). In the acupuncture group (n = 40), patients were treated with Neiguan point acupuncture for 7 days and amiodarone was prescribed as same as the control group after PVI. The levels of inflammatory factors were analyzed before operation, 1 week after the operation and 3 months later. After 3 months, the acupuncture group had a lower rate of early recurrences than the control group (5/40 [12.5%] vs 15/45 [33.3%], P = 0.039). The inflammatory factors level in the two groups were significantly increased after ablation. However, compared with the control group, the levels of TNF-α, IL-6, CRP, TGF-ß1, MMP2 in the acupuncture group significantly lower (P < 0.05). In a multivariate analysis, acupuncture was an independent factor associated with a lower rate of early recurrences during the blanking period (odds ratio, 0.17; 95% confidence interval, 0.05-0.63; P = 0.008). CONCLUSION: Neiguan point acupuncture combined with amiodarone is superior to amiodarone alone in reducing early recurrences of patients with persistent AF after PVI. The efficacy of Neiguan acupuncture therapy on the early recurrence is associated with the decreased inflammation factors.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Amiodarona/uso terapêutico , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/terapia , Ablação por Cateter , Frequência Cardíaca/efeitos dos fármacos , Veias Pulmonares/efeitos dos fármacos , Veias Pulmonares/cirurgia , Potenciais de Ação , Terapia por Acupuntura/efeitos adversos , Idoso , Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , China , Terapia Combinada , Feminino , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Veias Pulmonares/fisiopatologia , Recidiva , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento
20.
Neurocrit Care ; 30(1): 81-87, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29995185

RESUMO

BACKGROUND: Prognostic significance of serum calcium level in patients with intracerebral hemorrhage is not well studied. The aim of the study was to identify if a relationship between admission serum calcium level and prognosis exists in patients with intracerebral hemorrhage. METHODS: A total of 1262 confirmed intracerebral hemorrhage patients were included. Demographic data, medical history, medicine history, laboratory data, imaging data, clinical score, and progress note were collected from their medical records. All images of head computed tomography were reanalyzed. Ninety-day prognosis was recorded, and poor outcome was defined as death or major disability caused by intracerebral hemorrhage. RESULTS: During the 90-day follow-up period, 504 patients died and 226 patients suffered from major disability. Death and major disability were combined as poor prognosis. The remaining 532 patients showed good prognosis. Admission serum calcium level was lower in the patients with poor prognosis than in the patients with good prognosis (2.41 ± 0.23 mmol/l, 2.55 ± 0.26 mmol/l, P < 0.001). Admission INR and hematoma volume were higher in the patients with poor prognosis than in the patients with good prognosis (INR: 1.74 ± 0.29, 1.70 ± 0.29, P = 0.029; hematoma volume: 11.6 ± 4.4 ml, 10.7 ± 4.1 ml, P < 0.001). There was no difference in admission APTT level between the two prognosis groups (28.4 ± 5.6 s, 27.8 ± 5.4 s, P = 0.056). A multivariate COX regression analysis reported that admission serum calcium level ≤ 2.41 mmol/l was associated with the increased risk of poor prognosis (death or major disability) in the patients (HR 1.45, 95% CI 1.32-1.60). In addition, there was a significant linear association of serum calcium level with coagulation function markers and hematoma volume on admission (APTT: r = - 0.091, P = 0.001; INR: r = - 0.063, P = 0.025; hematoma volume: r = -0.108, P < 0.001). CONCLUSIONS: Admission serum calcium level might be a prognostic marker for intracerebral hemorrhage. Potential mechanism involved calcium-induced coagulation function abnormality.


Assuntos
Cálcio/sangue , Hemorragia Cerebral/sangue , Hemorragia Cerebral/diagnóstico , Avaliação de Resultados em Cuidados de Saúde , Idoso , Biomarcadores/sangue , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Prognóstico
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