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1.
Curr Med Sci ; 41(5): 953-960, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34693495

RESUMO

OBJECTIVE: The use of the traditional American Joint Committee on Cancer (AJCC) staging system alone has limitations in predicting the survival of gingiva squamous cell carcinoma (GSCC) patients. We aimed to establish a comprehensive prognostic nomogram with a prognostic value similar to the AJCC system. METHODS: Patients were identified from SEER database. Variables were selected by a backward stepwise selection method in a Cox regression model. A nomogram was used to predict cancer-specific survival rates for 3, 5 and 10 years in patients with GSCC. Several basic features of model validation were used to evaluate the performance of the survival model: consistency index (C-index), receiver operating characteristic (ROC) curve, calibration chart, net weight classification improvement (NRI), comprehensive discriminant improvement (IDI) and decision curve analysis (DCA). RESULTS: Multivariate analyses revealed that age, race, marital status, insurance, AJCC stage, pathology grade and surgery were risk factors for survival. In particular, the C-index, the area under the ROC curve (AUC) and the calibration plots showed good performance of the nomogram. Compared to the AJCC system, NRI and IDI showed that the nomogram has improved performance. Finally, the nomogram's 3-year and 5-year and 10-year DCA curves yield net benefits higher than traditional AJCC, whether training set or a validation set. CONCLUSION: We developed and validated the first GSCC prognosis nomogram, which has a better prognostic value than the separate AJCC staging system. Overall, the nomogram of this study is a valuable tool for clinical practice to consult patients and understand their risk for the next 3, 5 and 10 years.

2.
J Org Chem ; 86(17): 11862-11870, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34414760

RESUMO

α,ß-Deuterated amines are crucial for the development of deuterated drugs. We intend to introduce the novel tandem H/D exchange-single electron transfer (SET) reductive deuteration strategy with high pot- and reagent-economy by the synthesis of α,ß-deuterated amine using nitrile as the precursor. The H/D exchange of the -CH2CN group was achieved by D2O/Et3N, which were also the required reagents in the tandem SmI2-mediated SET reductive deuteration of the α-deuterated nitrile. The potential application of this method was further showcased by the synthesis of bevantolol-d4.


Assuntos
Aminas , Deutério , Transporte de Elétrons
3.
Ann Palliat Med ; 10(7): 7894-7904, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34353077

RESUMO

BACKGROUND: We performed a systematic review and meta-analysis to evaluate the therapeutic effects of arthroscopic debridement and proximal fibular osteotomy (AD & PFO) on medial tibial articular genu osteoarthritis (MTAGO), so as to provide a theoretical reference for clinical surgical analgesia for patients. METHODS: We searched and screened randomized controlled trials (RCTs) focusing on AD & PFO on MTAGO surgical analgesia published before December 31, 2020 in English databases including PubMed, Embase, Medline, Ovid, Springer, and Web of Science. The Cochrane Handbook for Systematic Reviews of Intervention 5.0.2 was adopted for bias risk assessment, and Review Manager 5.3 was used to conduct the meta-analysis. RESULTS: Twelve eligible studies were included, involving 765 research subjects. The meta-analysis results indicated that, relative to control group, satisfaction was markedly increased [mean difference (MD) =3.10; 95% confidence interval (CI), (1.48 to 6.51); Z=3; P=0.003], adverse reactions were reduced [MD =0.33; 95% CI, (0.08 to 1.32); Z=1.56; P=0.12] the hospital special surgery (HSS) score was lower [MD =5.37; 95% CI, (3.18 to 7.55); Z=4.82; P<0.00001], the visual analogue scale (VAS) score decreased [MD =-1.68; 95% CI, (-2.22 to -1.13); Z=6.01; P<0.00001], and the Knee Society score (KSS) was reduced [MD =6.16; 95% CI, (3.85 to 8.47); Z=5.23; P<0.00001]. However, the difference in the femoro-tibial (FT) angle between the control and study groups was not statistically considerable [MD =0.14; 95% CI, (-6.22 to 6.49); Z=0.04; P=0.97]. DISCUSSION: The combined adoption of AD & PFO for MTAGO surgical analgesia can reduce the HSS, KSS, and VAS scores of patients. The postoperative analgesia effect is good, and effectively reduces pain and adverse reactions in patients. Thus, it is suitable for analgesia in MTAGO.


Assuntos
Osteoartrite do Joelho , Desbridamento , Fíbula , Humanos , Osteoartrite do Joelho/cirurgia , Osteotomia , Tíbia/cirurgia
4.
Front Neurosci ; 15: 690743, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335167

RESUMO

Objectives: The purpose of this study was to (1) explore the changes in topological properties of static and dynamic brain functional networks after nasopharyngeal carcinoma (NPC) radiotherapy (RT) using rs-fMRI and graph theoretical analysis, (2) explore the correlation between cognitive function and changes in brain function, and (3) add to the understanding of the pathogenesis of radiation brain injury (RBI). Methods: Fifty-four patients were divided into 3 groups according to time after RT: PT1 (0-6 months); PT2 (>6 to ≤12 months); and PT3 (>12 months). 29 normal controls (NCs) were included. The subjects' topological properties were evaluated by graph-theoretic network analysis, the functional connectivity of static functional networks was calculated using network-based statistics, and the dynamic functional network matrix was subjected to cluster analysis. Finally, correlation analyses were conducted to explore the relationship between the altered network parameters and cognitive function. Results: Assortativity, hierarchy, and network efficiency were significantly abnormal in the PT1 group compared with the NC or PT3 group. The small-world variance in the PT3 group was smaller than that in NCs. The Nodal ClustCoeff of Postcentral_R in the PT2 group was significantly smaller than that in PT3 and NC groups. Functional connectivities were significantly reduced in the patient groups. Most of the functional connectivities of the middle temporal gyrus (MTG) were shown to be significantly reduced in all three patient groups. Most of the functional connectivities of the insula showed significantly reduced in the PT1 and PT3 groups, and most of the functional connectivities in brain regions such as frontal and parietal lobes showed significantly reduced in the PT2 and PT3 groups. These abnormal functional connectivities were correlated with scores on multiple scales that primarily assessed memory, executive ability, and overall cognitive function. The frequency F of occurrence of various states in each subject differed significantly, and the interaction effect of group and state was significant. Conclusion: The disruption of static and dynamic functional network stability, reduced network efficiency and reduced functional connectivity may be potential biomarkers of RBI. Our findings may provide new insights into the pathogenesis of RBI from the perspective of functional networks.

5.
Research (Wash D C) ; 2021: 9783432, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34250494

RESUMO

Sensors capable of monitoring dynamic mechanics of tendons throughout a body in real time could bring systematic information about a human body's physical condition, which is beneficial for avoiding muscle injury, checking hereditary muscle atrophy, and so on. However, the development of such sensors has been hindered by the requirement of superior portability, high resolution, and superb conformability. Here, we present a wearable and stretchable bioelectronic patch for detecting tendon activities. It is made up of a piezoelectric material, systematically optimized from architectures and mechanics, and exhibits a high resolution of 5.8 × 10-5 N with a linearity parameter of R 2 = 0.999. Additionally, a tendon real-time monitoring and healthcare system is established by integrating the patch with a micro controller unit (MCU), which is able to process collected data and deliver feedback for exercise evaluation. Specifically, through the patch on the ankle, we measured the maximum force on the Achilles tendon during jumping which is about 16312 N, which is much higher than that during normal walking (3208 N) and running (5909 N). This work not only provides a strategy for facile monitoring of the variation of the tendon throughout the body but also throws light on the profound comprehension of human activities.

6.
Nat Commun ; 12(1): 3583, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34117225

RESUMO

Construction of C-C bonds via reductive coupling of aldehydes and ketones is hindered by the highly negative reduction potential of these carbonyl substrates, particularly ketones, and this renders the formation of ketyl radicals extremely endergonic. Here, we report the efficient activation of carbonyl compounds by the formation of specific host-guest interactions in a hydroxyl-decorated porous photocatalyst. MFM-300(Cr) exhibits a band gap of 1.75 eV and shows excellent catalytic activity and stability towards the photoreductive coupling of 30 different aldehydes and ketones to the corresponding 1,2-diols at room temperature. Synchrotron X-ray diffraction and electron paramagnetic resonance spectroscopy confirm the generation of ketyl radicals via confinement within MFM-300(Cr). This protocol removes simultaneously the need for a precious metal-based photocatalyst or for amine-based sacrificial agents for the photochemical synthesis.

7.
Nanotechnology ; 32(37)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34098540

RESUMO

ZnO is considered to be one of the promising anode materials for lithium-ion batteries (LIBs), but the poor electronic conductivity and large volume variation during lithium-ion extraction and insertion process of ZnO seriously hinders its commercial application in LIBs. In this study, we synthesized a novel self-supporting porous ZnO nanobelt (PZB) arrays on Zn foils, in which Zn foils can be directly used as current collectors to promote electrically connection between the active materials and the current collectors. Furthermore, the well-aligned ZnO nanobelts have a thin thickness and uniform porous structure, which endue it well improved electrochemical performance. The PZB anodes display a high areal capacity of 5.91 mAh cm-2at current density of 0.5 mA cm-2at room temperature, and deliver an areal capacity of 1.73 mAh cm-2at -20 °C, indicating its excellent application potential especially at low temperatures, and it makes the porous ZnO nanobelts a practical anode material for LIBs.

8.
Technol Cancer Res Treat ; 20: 15330338211027912, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34190015

RESUMO

BACKGROUND: The aim of our study was to develop a nomogram model to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRC). METHODS: GSRC patients from 2004 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database and randomly assigned to the training and validation sets. Multivariate Cox regression analyses screened for OS and CSS independent risk factors and nomograms were constructed. RESULTS: A total of 7,149 eligible GSRC patients were identified, including 4,766 in the training set and 2,383 in the validation set. Multivariate Cox regression analysis showed that gender, marital status, race, AJCC stage, TNM stage, surgery and chemotherapy were independent risk factors for both OS and CSS. Based on the results of the multivariate Cox regression analysis, prognostic nomograms were constructed for OS and CSS. In the training set, the C-index was 0.754 (95% CI = 0.746-0.762) for the OS nomogram and 0.762 (95% CI: 0.753-0.771) for the CSS nomogram. In the internal validation, the C-index for the OS nomogram was 0.758 (95% CI: 0.746-0.770), while the C-index for the CSS nomogram was 0.762 (95% CI: 0.749-0.775). Compared with TNM stage and SEER stage, the nomogram had better predictive ability. In addition, the calibration curves also showed good consistency between the predicted and actual 3-year and 5-year OS and CSS. CONCLUSION: The nomogram can effectively predict OS and CSS in patients with GSRC, which may help clinicians to personalize prognostic assessments and clinical decisions.

9.
BMC Med Educ ; 21(1): 320, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090439

RESUMO

BACKGROUND: Self-regulated learning (SRL) is an important contributing element to the academic success of students. Literature suggests that the understanding of SRL among medical students is obscure as there is still some uncertainty about whether high performing medical students use SRL. This study explored the characteristics of high performing medical students from the SRL perspective to gain a better understanding of the application of SRL for effective learning. METHODS: Twenty-one students who scored at the 90th percentile in written knowledge-based assessment consented to participate in this study. Each student wrote a guided reflective journal and subsequently attended a semi-structured interview. Students were prompted to explain the rationales for their answers. The data were then analysed using thematic analysis to identify patterns among these students from the SRL perspective. Two coders analysed the data independently and discussed the codes to reach a consensus. RESULTS: High performing students set goals, made plans, and motivated themselves to achieve the goals. They put consistent efforts into their studies and applied effective learning strategies. They also employed coping mechanisms to deal with challenges. High performing students regularly evaluated their performance and adopted new strategies. CONCLUSIONS: This study reported that high performing students applied SRL and described the rationales of practice. Medical schools could design SRL-driven interventions to enhance the learning experiences of medical students. Recommendations are made for students on how to apply SRL.


Assuntos
Educação de Graduação em Medicina , Estudantes de Medicina , Competência Clínica , Humanos , Aprendizagem , Pesquisa Qualitativa
10.
Adv Mater ; 33(24): e2101891, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33963783

RESUMO

Touch sensing is among the most important sensing capabilities of a human, and the same is true for smart robotics. Current research on tactile sensors is mainly concentrated on electronic skin (e-skin), but e-skin is prone to be easily dirtied, damaged, and disturbed after repeated usage, which greatly limits its practical applications in robotics. Here, by mimicking the way that animals explore the environment using hair-based sensors, a bendable biomimetic whisker mechanoreceptor (BWMR) is designed for robotic tactile sensing. Owing to the advantages of triboelectric nanogenerator technology, the BWMR can convert external mechanical stimuli into electrical signals without a power supply, which is conducive to its widespread applications in robots. Because of the leverage effect of the whisker, the BWMR can distinguish an exciting force of 1.129 µN by amplifying external weak signals, which can be further improved by increasing the whisker length. Real-time sensing is demonstrated using a BWMR, exhibiting its potential for robotic tactile systems.

11.
Pest Manag Sci ; 77(9): 3910-3920, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33871901

RESUMO

BACKGROUND: Succinate dehydrogenase inhibitors (SDHIs) play an increasingly important role in controlling plant diseases. However, the similar structures of SDHIs result in rapid development of cross-resistance development and a clear bottleneck of poor activity against oomycetes, therefore the need to seek new SDHI fungicides with novel structures is urgent. RESULTS: Innovative pyrazolyl oxime ethers were designed by replacing amide with oxime ether based on the succinate dehydrogenase (SDH) structure, and 19 pairs of Z- and E-isomers were efficiently prepared for the discovery of SDHI compounds with a novel bridge. Their biological activities against four fungi and two oomycetes were evaluated, and substantial differences were observed between the Z- and E- isomers of the title compounds. Furthermore, most of these compounds exhibited remarkable activities against Rhizoctonia solani with EC50 values of less than 10 mg L-1 in vitro, and bioassay in vivo further confirmed that E-I-6 exhibited good protective efficacy (76.12%) at 200 mg L-1 . In addition, Z-I-12 provided better activity against the oomycetes Pythium aphanidermatum and Phytophthora capsici (EC50  = 1.56 and 0.93 mg L-1 ) than those of boscalid. Moreover, E-I-12 exhibited excellent SDH inhibition (IC50  = 0.21 mg L-1 ) thanks to its good binding ability to the SDH by hydrogen-bonding interactions, π-cation interaction and hydrophobic interactions. CONCLUSION: Novel pyrazolyl oxime ethers have the potential as SDHI compounds for future development, and the strategy of replacing an amide bond with oxime ether may offer an alternative option in SDHI fungicide discovery.


Assuntos
Fungicidas Industriais , Oomicetos , Antifúngicos/farmacologia , Éteres/farmacologia , Fungicidas Industriais/farmacologia , Oximas/farmacologia , Rhizoctonia , Relação Estrutura-Atividade , Succinato Desidrogenase/metabolismo
12.
Chem Commun (Camb) ; 57(42): 5195-5198, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-33908475

RESUMO

A highly chemoselective reductive deuteration of acyl fluorides to provide α,α-dideuterio alcohols with exquisite levels of deuterium incorporation was developed using SmI2 and D2O as the deuterium source. This method introduces acyl fluorides as attractive radical precursors for the generation of reactive acyl-type fluoride ketyls that should find widespread application in many synthetic strategies involving single electron transfer processes.

13.
Cereb Cortex ; 31(9): 4169-4179, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-33825870

RESUMO

One prominent theory in neuroscience and psychology assumes that cortical regions for language are left hemisphere lateralized in the human brain. In the current study, we used a novel technique, quantitative magnetic resonance imaging (qMRI), to examine interhemispheric asymmetries in language regions in terms of macromolecular tissue volume (MTV) and quantitative longitudinal relaxation time (T1) maps in the living human brain. These two measures are known to reflect cortical myeloarchitecture from the microstructural perspective. One hundred and fifteen adults (55 male, 60 female) were examined for their myeloarchitectonic asymmetries of language regions. We found that the cortical myeloarchitecture of inferior frontal areas including the pars opercularis, pars triangularis, and pars orbitalis is left lateralized, while that of the middle temporal gyrus, Heschl's gyrus, and planum temporale is right lateralized. Moreover, the leftward lateralization of myelination structure is significantly correlated with language skills measured by phonemic and speech tone awareness. This study reveals for the first time a mixed pattern of myeloarchitectonic asymmetries, which calls for a general theory to accommodate the full complexity of principles underlying human hemispheric specialization.

14.
Cell Death Dis ; 12(3): 228, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658485

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is prevalent clinically and can lead to more serious chronic liver disease. However, the pathological mechanism is still unclear, and thus, there are no approved drugs on the market. Transcriptional coactivator WW domain-binding protein 2 (WBP2) is a newly discovered oncogene that has an important relationship with the occurrence and development of breast cancer and mediates the interaction between Wnt and various other signaling pathways. The expression level of WBP2 was decreased in NAFLD. Overexpression of WBP2 with AAV in vivo alleviated liver fat deposition and insulin resistance induced by a high-fat diet (HFD). Knockdown of WBP2 with AAV aggravated HFD-induced fatty liver and insulin resistance. In vitro experiments showed that in the human normal hepatocyte cell line LO2 and primary hepatocytes isolated from mice, overexpression of WBP2 reduced fat deposition, and knocking out or knocking down WBP2 aggravated PA-induced fat deposition. Through mass spectrometry, we found that WBP2 can bind to AMPKß1, and by mutating AMPKß1, we found that WBP2 can induce phosphorylation of AMPKß1 at S108 and then activate the AMPK pathway to affect lipid metabolism. The effect of WBP2 on NAFLD provides a possible new direction for future research on NAFLD.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Resistência à Insulina , Fígado/enzimologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Transativadores/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Técnicas de Transferência de Genes , Células HEK293 , Humanos , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/enzimologia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Fosforilação , Transdução de Sinais , Transativadores/genética , Regulação para Cima
15.
Int Ophthalmol ; 41(7): 2505-2512, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33772700

RESUMO

OBJECTIVE: The purpose of this study was to screen target miRNA related to RB and explore the expression levels of target miRNA in RB and its potential value of diagnosis. METHODS: The Affymetrix GeneChip miRNA 4.0 Array was used to screen the differential miRNAs in the plasma of 5 RB patients before and after intravenous chemotherapy, and the most significant down-regulated miRNA was selected for target miRNA. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is used to verify the expression levels of plasma target miRNA in 30 RB patients. Then, qRT-PCR was performed to further verify the expression of target miRNA in plasma of RB patients and RB tumor tissues. Finally, receiver-operating-characteristic (ROC) curve and the area under the ROC curve (AUC) were used to evaluate the diagnostic power of plasma target miRNA. RESULTS: The miRNA Array obtain 8 core miRNAs, 1 up-regulated and 7 down-regulated, of which miR-6089 was the most significantly down-regulated. Plasma miR-6089 levels were significantly up-regulated in RB patients. Besides, in RB tumor tissues, miR-6089 levels were also obviously up-regulated. After intravenous chemotherapy, the expression of plasma miR-6089 was significantly decreased. Furthermore, ROC curve analysis showed that miR-6089 in the plasma had a good sensitivity and specificity for distinguishing RB from the healthy control group. CONCLUSIONS: MiR-6089 may be considered as a novel potential diagnostic biomarker for RB. TRIAL REGISTRATION NUMBER: ChiCTR2000040154; date of registration: 2020/11/22; retrospectively registered.


Assuntos
MicroRNAs , Neoplasias da Retina , Retinoblastoma , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Humanos , MicroRNAs/genética , Curva ROC , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/genética , Retinoblastoma/diagnóstico , Retinoblastoma/genética
16.
ACS Appl Mater Interfaces ; 13(9): 11205-11214, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33645227

RESUMO

Equipping wearable electronics with special functions will endow them with more additional values and more comprehensive practical performance. Here, we report an ultraviolet (UV)-protective, self-cleaning, antibacterial, and self-powered all-nanofiber-based triboelectric nanogenerator (TENG) for mechanical energy harvesting and self-powered sensing, which is fabricated with Ag nanowires (NWs)/TPU nanofibers and the TiO2@PAN networks through a facile electrospinning method. Due to the added TiO2 nanoparticles (NPs), the TENG presents excellent UV-protective performance, including the ultraviolet protection factor (UPF) of ∼204, the transmittance of UVA (TUVA) of ∼0.0574%, and the transmittance of UVB (TUVB) ∼0.107%. Furthermore, under solar lighting for 25 min, most surface contamination can be degraded, and the decreased power output would be recovered. Owing to the coupled effects of TiO2 NPs and Ag NWs, the TENG shows excellent antibacterial activity against Staphylococcus aureus. Due to the micro-to-nano hierarchical porous structure, the all-nanofiber-based TENG can serve as self-powered pedometers for detecting and tracking human motion behaviors. As a multifunctional self-powered device, the TENG prompts various applications in the fields of micro/nanopower sources, human movement monitoring, and human-machine interfaces, potentially providing an alternative energy solution and a multifunctional interactive platform for the next-generation wearable electronics.


Assuntos
Antibacterianos/farmacologia , Locomoção , Monitorização Fisiológica/métodos , Nanofibras/química , Nanofios/química , Dispositivos Eletrônicos Vestíveis , Resinas Acrílicas/química , Fontes de Energia Elétrica , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Monitorização Fisiológica/instrumentação , Poliuretanos/química , Prata/química , Staphylococcus aureus/efeitos dos fármacos , Luz Solar , Titânio/química , Titânio/efeitos da radiação
17.
Cardiol Res Pract ; 2021: 8838151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33552599

RESUMO

Objectives: To verify the protective effect of phosphocreatine on myocardium in an ischemic model and the possible mechanism of action. Methods: The model of myocardial ischemia/reperfusion (I/R) was established by the ligation balloon method. 30 SD rats were randomly divided into three groups, n = 10 in each group. Sham operation group: the coronary artery was not blocked and observed for 120 minutes. The ischemia/reperfusion (I/R) group was given ischemia for 30 minutes and ischemia reperfusion for 90 minutes. Phosphocreatine (PCr) group: after 30 minutes of ischemia, the rats were intraperitoneally injected with PCr (200 mg/kg) for 90 minutes. The animal groups of myocardial ischemia/reperfusion model in vitro were the same as those in vivo. The heart was removed by thoracotomy and washed immediately in H-K buffer solution. Then, the heart was installed on the Langendorff instrument. The concentration of PCr perfusion fluid in the PCr group was 10 mmol/L. The changes in coronary blood flow in isolated myocardium were recorded. The heart rate and electrocardiogram were recorded by RM6240BT. At the end of the experiment, myocardial pathological sections and Cx43 immunofluorescence staining were made, and the contents of malondialdehyde (MDA) in myocardial tissue were detected. Results: Phosphocreatinine treatment improved the myocardial ischemia model, performance in electrocardiogram (ECG) changes (ST segment apparent), and histological changes (decrease in necrotic myocardial cells, inflammatory cell infiltration, and a reduction in myocardial edema). At the same time, MDA decreased, while coronary blood flow and Cx43 expression significantly improved. Conclusions: Phosphocreatine can improve the electrocardiogram and restore histologic changes in ischemic myocardium and coronary blood flow. The postulated mechanism is by inhibiting the generation of free oxygen radicals and restoring the expression of Cx43 protein.

18.
Nanoscale ; 13(7): 4278-4294, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33595027

RESUMO

Colorectal cancer is one of the malignant tumors with high morbidity and lethality. Its efficient diagnosis and treatment has important significance. In this study, the orthotopic cancer model mouse, which could perfectly simulate clinical inflammatory colorectal cancer, was constructed by chemical induction. Based on this model, a new pH/ultrasonic dual-response, step-targeting and precisely controlled-release enteric-coated granule was designed for the combined sonodynamic (SDT)-chemotherapy. The enteric-coated granule was fabricated by enwrapping carboxymethyl chitosan (CMC) on folic acid-modified phospholipid (SLB-FA) encapsulating mesoporous silicon-coated gold nanoparticles loaded with chlorin (Ce6) and doxorubicin hydrochloride (DOX), titled as Au@mSiO2/Ce6/DOX/SLB-FA@CMC (GMCDS-FA@CMC). The diameter of the Au@mSiO2/Ce6/DOX/SLB-FA (GMCDS-FA) nanoprobe was 61.21 nm and that of the GMCDS-FA@CMC enteric-coated granule was 1.1 µm. MTT results showed that the cell survival rate was still as high as 76.55 ± 1.27% when the concentration of GMCDS-FA was up to 200 µg mL-1, which can indicate the low cytotoxicity of the nanoprobe. According to CT imaging, the enteric-coated granule had the highest concentration in the colorectum of the orthotopic cancer mouse after 7-9 h with oral administration, and was nearly metabolized out of the body after 24 h. The in vitro and in vivo experiments showed that the targeting enteric-coated granule had the best effect of treatment and desired prognosis after combined SDT-chemotherapy.


Assuntos
Neoplasias Colorretais , Nanopartículas Metálicas , Nanopartículas , Animais , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/tratamento farmacológico , Doxorrubicina/farmacologia , Ácido Fólico , Ouro , Concentração de Íons de Hidrogênio , Camundongos , Ultrassom
19.
J Org Chem ; 86(3): 2907-2916, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33486945

RESUMO

Selective introduction of the deuterium atom into the α-position of amines is important for the development of all types of novel deuterated drugs and agrochemicals due to the pervasive presence of amines. In this study, we report the first general single-electron-transfer reductive deuteration of both ketoximes and aldoximes using SmI2 as an electron donor and D2O as a deuterium source for the synthesis of α-deuterated primary amines with excellent levels of deuterium incorporations (>95% [D]). This protocol exhibits excellent chemoselectivity and tolerates a variety of functional groups. The potential application of this new method was showcased in the synthesis of deuterated drugs, such as rimantadine-d4, the tebufenpyrad analogue, derivatives of nabumetone and pregnenolone, and a series of building blocks for the rapid and general assembly of deuterated drugs and pesticides.


Assuntos
Aminas , Oximas , Deutério
20.
Biochem Pharmacol ; 184: 114403, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33388284

RESUMO

Chlorpromazine (CPZ), an FDA-approved phenothiazine derivative used to treat schizophrenia and other psychiatric disorders, has been demonstrated to have potential anti-tumor effects. However, the potential effects of CPZ on human oral cancer cells and the underlying molecular mechanisms remain unknown. In this study, treatment of human oral cancer cells with CPZ inhibited their proliferation and induced G2/M phase arrest. Treatment with CPZ induced apoptosis through the extrinsic death receptor and the intrinsic mitochondrial pathways. In addition, the induction of autophagy was observed by the formation of autophagosomes, the expression of autophagy-related proteins and activation of the PI3K/Akt/mTOR/p70S6K pathway. The CPZ-induced cell death was reversed by the pan-caspase inhibitor Z-VAD-FMK, by the autophagy inhibitor 3-MA and by the knockdown of LC3B using a shRNA (shLC3B), suggesting that autophagy promoted CPZ-induced apoptosis. Finally, CPZ significantly suppressed tumor growth in both a zebrafish oral cancer xenotransplantation model and in a murine model of 4-nitroquinoline-1-oxide (4NQO)-induced oral cancer. Overall, this evidence demonstrated that CPZ is a novel promising strategy for the treatment of oral cancer.


Assuntos
Autofagia/efeitos dos fármacos , Clorpromazina/farmacologia , Neoplasias Bucais/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Antipsicóticos/farmacologia , Autofagia/fisiologia , Linhagem Celular Tumoral , Vesículas Extracelulares/efeitos dos fármacos , Vesículas Extracelulares/fisiologia , Fase G2/efeitos dos fármacos , Humanos , Camundongos Endogâmicos BALB C , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Peixe-Zebra
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