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1.
J Neuropsychol ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738605

RESUMO

Moral identity is an important moral variable which has positive moral functions, such as contributing to prosocial behaviours, reducing antisocial behaviours, and resisting the risk factors of antisocial behaviours. However, little is known about the neural correlates of moral identity and the neural basis of the effect of moral identity on the risk factors of antisocial behaviours, including moral disengagement. In this study, we explored these issues in 142 college students by estimating the regional homogeneity (ReHo) through resting-state functional magnetic resonance imaging (fMRI). The whole-brain correlation analyses found that higher internalized moral identity was correlated with higher ReHo in the precuneus. Furthermore, the ReHo in the precuneus was negatively correlated with moral disengagement, suggesting positive moral functions of the neural mechanisms of moral identity. These findings deepen our understanding of individual differences in moral identity and provide inspiration for the education of moral identity and the intervention for moral disengagement from the perspective of the brain.

2.
J Hum Genet ; 69(7): 321-327, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38565611

RESUMO

Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex genetic etiology. This study aimed to analyze and identify pathogenic variants in a fetus with SCDO. Copy number variant sequencing and whole exome sequencing were performed on a Chinese fetus with SCDO, followed by bioinformatics analyses, in vitro functional assays and a systematic review on the reported SCDO cases with LFNG pathogenic variants. Ultrasound examinations in utero exhibited that the fetus had vertebral malformation, scoliosis and tethered cord, but rib malformation was not evident. We found a novel homozygous variant (c.1078 C > T, p.R360C) within the last exon of LFNG. The variant was predicted to cause loss of function of LFNG by in silico prediction tools, which was confirmed by an in vitro assay of LFNG enzyme activity. The systematic review listed a total of 20 variants of LFNG in SCDO. The mutational spectrum spans across all exons of LFNG except the last one. This study reported the first Chinese case of LFNG-related SCDO, revealing the prenatal phenotypes and expanding the mutational spectrum of the disorder.


Assuntos
Sequenciamento do Exoma , Humanos , Feminino , Feto/anormalidades , Gravidez , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Mutação , Meningomielocele/genética , Meningomielocele/diagnóstico por imagem , Variações do Número de Cópias de DNA , Povo Asiático/genética , População do Leste Asiático , Hérnia Diafragmática
3.
J Cardiovasc Transl Res ; 16(4): 778-792, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37284939

RESUMO

It is widely accepted that miRNAs play an important role in the pathogenesis of myocardial fibrosis. This study aimed to identify a new pathway of miR-212-5p in the activation of human cardiac fibroblasts (HCFs) induced by oxygen-glucose deprivation (OGD). First, we found that KLF4 protein was markedly decreased in OGD-induced HCFs. Then, bioinformatics analysis and verification experiments were used to identify the existence of an interaction of KLF4 with miR-212-5p. Functional experiments indicated that OGD significantly upregulated the expression of hypoxia inducible factor-1 alpha (HIF-1α) in HCFs, which positively regulated miR-212-5p transcription by binding to its promoter. MiR-212-5p inhibited the expression of Krüppel-like factor 4 (KLF4) protein by binding to the 3' untranslated coding regions (UTRs) of KLF4 mRNA. Inhibition of miR-212-5p effectively inhibited the activation of OGD-induced HCFs by upregulating KLF4 expression and inhibited cardiac fibrosis in vivo and in vitro.


Assuntos
MicroRNAs , Oxigênio , Humanos , Fator 4 Semelhante a Kruppel , Glucose , MicroRNAs/genética , MicroRNAs/metabolismo , Fibroblastos/metabolismo , Apoptose
4.
Aust Crit Care ; 36(5): 679-686, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36464525

RESUMO

BACKGROUND: A smooth transition from the neonatal intensive care unit (NICU) to home is critical for establishing parents' competence as primary caregivers and ensuring infant health. In the clinical context with a restrictive visiting policy, family-centred care is challenging to implement, prohibiting a smooth transition of care for the families. According to Meleis' Transition Theory, parents might experience emotional change initiated by critical events during this transition. OBJECTIVES: The aim of this study was to understand parents' emotional experience of their preterm infant's birth to discharge home from the NICU to facilitate the care transition better. METHODS: This qualitative descriptive study using semistructured interviews was conducted between June and August 2020. Purposive sampling was used to recruit 17 parents (6 fathers and 11 mothers) from the NICU of a tertiary hospital in eastern China. Data were analysed using content analysis. RESULTS: The following three situational themes characterised by three-phase emotions related to 16 critical events were obtained from the data and were used to describe parents' experiences during the transition: Theme 1, Life falling apart; Theme 2, Feeling anxious and struggling with uncertainty; and Theme 3, Feeling both hopeful and inadequate at discharge. CONCLUSIONS: Parents of preterm infants have distinctive emotional experiences in each phase during their infants' transition from the NICU to home. Awareness of parents' critical events and emotional experiences in each phase could help NICU staff anticipate and provide timely and targeted support for parents. The next step is to develop a family-centred intervention for healthcare providers to better prepare parents for the transition from the NICU to home.


Assuntos
Recém-Nascido Prematuro , Alta do Paciente , Humanos , Recém-Nascido , Emoções , Recém-Nascido Prematuro/psicologia , Unidades de Terapia Intensiva Neonatal , Pais/psicologia , Pesquisa Qualitativa
5.
Aggress Behav ; 49(2): 101-109, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36334307

RESUMO

Cyber-aggression is a serious social problem worldwide. Its risks have been frequently explored, and violence exposure in daily life has been regarded as an important risk factor of cyber-aggression. However, the longitudinal association between violence exposure in daily life and cyber-aggression has not yet been examined, and the mechanisms underlying the link between violence exposure and cyber-aggression remain largely unclear. Based on the General Aggression Model and Script Theory, we explored the circular relation between violence exposure in daily life, hostile automatic thoughts, and cyber-aggression. The current study adopted a longitudinal design to address these issues among 941 college students. The results indicated violence exposure in daily life predicted hostile automatic thoughts and cyber-aggression 6 months later; hostile automatic thoughts predicted violence exposure and cyber-aggression 6 months later; and cyber-aggression predicted hostile automatic thoughts and violence exposure 6 months later. Moreover, each of them plays a mediating role in the association between the other two variables. These results support and expand the General Aggression Model and Script Theory that violence exposure, aggressive cognition, and aggression facilitate each other. This also provides theoretical guidance on reducing cyber-aggression in daily life.


Assuntos
Exposição à Violência , Humanos , Relações Interpessoais , Agressão , Hostilidade , Violência
6.
J Exp Biol ; 225(17)2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36004672

RESUMO

For small birds to survive during seasonal acclimatization in temperate zones, regulation of body mass and thermogenesis is crucial. To determine the role of temperature and photoperiod in seasonal changes in body mass and thermogenesis in Chinese hwameis (Garrulax canorus), we compared body mass, basal metabolic rate (BMR), energy intake and cellular metabolic capacity of the tissue (muscle) and/or organs (liver, kidney, heart and small intestine) in seasonally acclimatized and laboratory-acclimated hwameis. A significant seasonal influence on body mass and BMR (which peaked in winter) was found, and these variations were mirrored by exposing the housed birds to cold temperatures or a short photoperiod. The level of dry matter intake, gross energy intake and digestible energy intake was higher during winter, and in housed animals that were exposed to cold temperatures. These results suggest that by increasing energy intake and thermogenesis, Chinese hwameis can overcome winter thermoregulatory challenges. When compared with warm-acclimated birds, cold-acclimated birds displayed higher mass-specific and whole-organ state 4 respiration in the muscle, liver and kidney, and higher mass-specific and whole-organ cytochrome c oxidase activity in the liver. These data demonstrate that cellular thermogenesis partly underpins basal thermoregulation in Chinese hwameis. Cold temperature and short photoperiod can be used as helpful environmental cues during seasonal acclimatization. However, the role of temperature is more significant compared with that of photoperiod in Chinese hwameis; the changes in energy metabolism and thermoregulation induced by temperature appear to be intensified by photoperiod.


Assuntos
Passeriformes , Fotoperíodo , Aclimatação/fisiologia , Animais , Metabolismo Basal/fisiologia , Regulação da Temperatura Corporal , Peso Corporal/fisiologia , China , Metabolismo Energético , Passeriformes/fisiologia , Estações do Ano , Temperatura , Termogênese/fisiologia
7.
Chem Commun (Camb) ; 58(75): 10496-10499, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36043360

RESUMO

An electrooxidation strategy mediated by reactive oxygen species is proposed to realize the transformation of styrene to benzaldehyde on a Pt anode, with a high selectivity of ca. 89% and faradaic efficiency of 28.8%. Isotopic labelling, electron paramagnetic resonance and radical scavenging experiments revealed that OH˙ and O2-˙ species, formed in situ via anodic water oxidation, play a crucial role in the selective formation of benzaldehyde.

8.
Talanta ; 247: 123614, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35653861

RESUMO

With the development of new methods for the medical diagnosis, electrochemical sensors have attracted increasing attention. However, biofouling on the surface of the sensor significantly decreases sensor performance, thereby limiting the application of electrochemical sensors in complex biological fluids. Given the urgent need for anti-biofouling electrodes, a sensor based on a glass carbon electrode (GCE) modified with Ti3C2TX MXene and electrochemically reduced holey graphene (ERHG) was fabricated and demonstrated to have excellent electrochemical performance and anti-biofouling properties. ERHG provides abundant surface-active sites and imparts stability by hindering the agglomeration and oxidation of MXene. Furthermore, the excellent conductivity and hydrophilicity of MXene result in a high electron transfer rate and strong hydrophilicity. The MXene-ERHG/GCE sensor can detect dopamine with a wide linear range (0.2-125 µM) and a low detection limit of 0.044 µM in phosphate-buffer saline solution. Importantly, the hydrophilicity of MXene-ERHG reduces non-specific protein adsorption on the electrode surface, providing resistance to biofouling. After immersion in bovine serum albumin for 30 min, MXene-ERHG/GCE retained 85.90% of its initial peak current value, much higher than that of ERHG/GCE (17.75%). The MXene-ERHG/GCE sensor also showed good sensitivity for dopamine detection in serum and artificial cerebrospinal fluid (aCSF) containing bovine serum albumin. Moreover, MXene-ERHG/GCE exhibited excellent reproducibility and long-term stability in aCSF. The results demonstrate that MXene-ERHG/GCE has excellent anti-biofouling performance, and shows potential as an electrode material for application in biosensing.


Assuntos
Incrustação Biológica , Grafite , Incrustação Biológica/prevenção & controle , Carbono/química , Dopamina/análise , Técnicas Eletroquímicas/métodos , Eletrodos , Grafite/química , Reprodutibilidade dos Testes , Soroalbumina Bovina/química , Titânio/química
9.
Int J Cardiol ; 362: 85-92, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35618103

RESUMO

BACKGROUND: Multiple studies have shown that mental disorders are common risk factors for cardiovascular diseases (CVD). However, the relationship between psychological factors and atrial fibrillation (AF) incidence remains unclear. Therefore, we performed a systematic review and meta-analysis to assess the risk of AF due to psychological factors. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to January 2022. Relevant and eligible cohort studies were included. Random or fixed effect model was used to estimate the pooled hazard ratios (HRs) and 95% confidence intervals (CIs). For non-randomized studies, the risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Thirteen publications, including 5,329,908 participants, met our inclusion criteria. The incidence of AF was increased by 10% (HR = 1.10, 95% CI 1.02 to 1.19, I2 = 33.6%, P = 0.013, n = 235,599 in 6 studies) for patients with anxiety, by 15% (HR = 1.15, 95% CI 1.04 to 1.26, I2 = 40.2%, P = 0.04, n = 21,791 in 3 studies) for patients with anger, by 25% (HR = 1.25, 95% CI 1.12 to 1.39, I2 = 57.4%, P < 0.001, n = 5,160,247 in 6 studies) for patients with depression, and by 18% (HR = 1.18, 95% CI 1.05 to 1.32, I2 = 19.2%, P = 0.004, n = 51,664 in 4 studies) for people under work stress. CONCLUSIONS: Adverse psychological factors such as anxiety, anger, depression, and work stress may increase the risk of AF. Interventions to prevent mental disorders may reduce the growing global burden of AF and its associated healthcare costs. Given the current study's limitations, our findings need to be further confirmed by a larger prospective study.


Assuntos
Fibrilação Atrial , Ansiedade , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Humanos , Incidência , Estudos Prospectivos , Fatores de Risco
10.
Bioengineered ; 13(5): 13055-13069, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35635053

RESUMO

Oral squamous cell carcinoma (OSCC) is a common cancer with high recurrence, metastasis rates and poor prognosis. Circular RNAs (circRNAs) take part in regulating OSCC. Herein, we examined the role of circ_0008068 in OSCC. The circ_0008068, Katanin p60 ATPase-containing subunit A-like 1 (KATNAL1) mRNA, microRNA-153-3p (miR-153-3p) and acylgycerol kinase (AGK) contents were indicated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Moreover, in vitro and in vivo assays were conducted to scrutinize the effects of circ_0008068 on OSCC. Additionally, the contact between miR-153-3p and circ_0008068 or AGK was assessed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Thereafter, we found that the appearance of circ_0008068 and AGK was increased, and miR-153-3p content was diminished in OSCC. Circ_0008068 lack subdued cell proliferation, migration, invasion, tube formation and glycolysis metabolism, but stimulated cell apoptosis in OSCC. In addition, circ_0008068 bound to miR-153-3p to modulate the expression of its target AGK. Besides, miR-153-3p was validated to act as a tumor suppressor in OSCC tumorigenesis by suppressing AGK. Additionally, circ_0008068 knockdown also attenuated tumor growth in nude mice. In all, circ_0008068 expedited the growth of OSCC by miR-153-3p/AGK axis.Abbreviations: OSCC: Oral squamous cell carcinoma; AGK: Acylgycerol kinase; CircRNA: Circular RNA; KATNAL1: Katanin p60 ATPase-containing subunit A-like 1; qRT-PCR: Quantitative real-time polymerase chain reaction; miRNAs/miRs: MicroRNAs; RIP: RNA immunoprecipitation; 3'UTR3': -untranslated region; HK2: Hexokinase 2; LDHA Lactate dehydrogenase A; IHC: Immunohistochemistry; CCK8: Cell counting kit-8; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase.


Assuntos
MicroRNAs , Neoplasias Bucais , RNA Circular , Carcinoma de Células Escamosas de Cabeça e Pescoço , Animais , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Katanina/genética , Camundongos , Camundongos Nus , MicroRNAs/genética , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Fosfotransferases (Aceptor do Grupo Álcool)/genética , RNA Circular/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
11.
Environ Sci Pollut Res Int ; 29(32): 49267-49278, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35217952

RESUMO

Activation of peroxymonosulfate (PMS) by Fe2+ is a green oxidation process for degradation of organic contaminants. However, the formation of iron mud and low PMS utilization lead to the decreased oxidation efficiency. In this work, commercial MoS2 particles were used as the catalyst for boosting the Fe2+/PMS process for carbamazepine (CBZ) removal. The CBZ removal efficiency by the MoS2/Fe2+/PMS process was significantly enhanced, increasing to 6.5 times that of the Fe2+/PMS process. The Fe3+ was reduced to Fe2+ by the exposed Mo4+ on the surface of MoS2, leading to the enhanced PMS utilization rate and increased Fe2+ concentration. The relative intensity of DMPO-HO• and DMPO- SO4-• followed the order of MoS2/PMS < Fe2+/PMS < MoS2/Fe2+/PMS, also suggesting the enhanced oxidation activity with the addition of MoS2 in the process of Fe2+/PMS. The commercial MoS2 had good stability shown by the CBZ removal efficiency remaining almost unchanged during 8-time cycling use. Finally, a possible CBZ degradation pathway was proposed for helping understand the oxidation mechanism of the MoS2/Fe2+/PMS process.


Assuntos
Molibdênio , Poluentes Químicos da Água , Carbamazepina , Peróxidos , Poluentes Químicos da Água/análise
12.
Sci Total Environ ; 815: 152694, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34995592

RESUMO

Recently, solar-driven seawater desalination based on air-water interfacial heating has triggered significant research interest due to its high water evaporation rate, high photothermal conversion efficiency, low energy consumption, simple operation and low cost. However, as the air-water interface temperature reaches as high as 40-70 °C, volatile organic compounds (VOCs) will volatilize into the condensed desalinated water and results in the polluted freshwater. In this work, anionic, cationic, and nonionic surfactants were applied for the first time to inhibit the phenolic compounds such as phenol, p-methylphenol and p-chlorophenol entering into the condensed freshwater. Results showed that the concentration of phenol could be reduced by the addition of cetyl trimethyl ammonium bromide (CTAB). The phenol's distillation concentration ratio (RD) reduced from 76% to 35% due to the electrostatic interaction and the micellar encapsulation between the CTAB and phenol. Moreover, parameters including CTAB dose, initial phenol concentration, solar intensity, pH, and salinity that affecting the RD were also investigated. Finally, a real seawater solar-driven distillation experiment also revealed that the water quality of freshwater was improved by the addition of CTAB. This work revealed that the surfactants such as CTAB can be potentially used to inhibit VOCs entering into the condensed freshwater during solar-driven seawater distillation.


Assuntos
Destilação , Purificação da Água , Água Doce , Fenóis , Água do Mar , Tensoativos
13.
Chemosphere ; 280: 130618, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33964747

RESUMO

Currently, seawater desalination based on air-water interface solar heating has triggered significant research interests because it effectively makes use of the solar energy and avoids fossil fuel consumption. However, to prevent the volatile organic compounds (VOCs) from volatilizing with water vapor which later will liquefy and enter the condensed freshwater is still a challenge. In this work, a g-C3N4/MoS2 based floating solar still (CM-FSS) combined with thermal/light activation of persulfate (PS) at air-water interface was applied for clean freshwater production for the first time. The CM-FSS was composed of a g-C3N4/MoS2 top layer for solar absorption, simultaneous thermal/light activation of PS and then VOCs degradation at air-water interface, a floating layer of expandable polyethylene (EPE) foam for heat isolation, and a transport channel of air-laid paper (ALP) for seawater and PS solution delivery. The water evaporation rate of the CM-FSS was measured at 1.23 kg m-2 h-1 under 1 kW m-2, which is 4.09 times higher than that of pure water without an evaporator. With the assistance of g-C3N4/MoS2 photocatalytic degradation and thermal/light activation of PS at the air-water interface, a high removal efficiency of a selected model VOCs pollutant of nitrobenzene (NB) could reach to 98.2% in condensed freshwater. Finally, when real seawater samples were employed as source water for solar distillation, the typical water-quality indices such as salinity, turbidity, anions, cations and organics of the condensed freshwater were below the limit values of the Standards for Drinking Water Quality in WHO, US EPA and China.


Assuntos
Purificação da Água , Água , China , Molibdênio , Luz Solar
14.
J Adv Nurs ; 77(3): 1379-1390, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33249653

RESUMO

AIM: To describe the facilitating/inhibiting factors of preparation for preterm infant discharge and recommendations for increasing discharge readiness from parents' and healthcare providers' perspectives based on Meleis's Transitions Theory. DESIGN: A qualitative cross-sectional descriptive design. METHODS: We selected a purposive sample of 17 parents (9 fathers and 8 mothers) and 13 healthcare providers (10 nurses and 3 clinicians) from the neonatal intensive care unit of a tertiary hospital in Eastern China. Data were collected between May -July 2018. Data from audio-recorded semi-structured individual interviews were coded with content analysis both inductively and deductively. RESULTS: The analyses yielded four themes: personal conditions, community conditions, nursing therapeutics, and patterns of response. Parents and healthcare providers had unique opinions about the themes. CONCLUSION: Meleis's Transitions Theory seems to be an applicable and practicable framework for understanding the discharge preparation of parents with preterm infants and may be used to help healthcare providers to develop appropriate interventions on discharge preparation practice. IMPACT: To address the lack of discharge readiness of preterm infants in China and countries with a similar clinical context, healthcare providers should help parents play a more active role to promote their engagement in discharge preparation. In a wider global community, healthcare providers should consider parents' personal conditions and their practical needs in performing discharge preparation.


Assuntos
Recém-Nascido Prematuro , Alta do Paciente , China , Estudos Transversais , Pessoal de Saúde , Humanos , Lactente , Recém-Nascido , Pais , Pesquisa Qualitativa
15.
J Vis Exp ; (161)2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32744529

RESUMO

The interest on nitrogen-containing heterocycles has expanded rapidly in the synthetic community since they are important motifs for new drugs. Traditionally, they were synthesized through thermal cycloaddition reactions, whereas today, photocatalysis is preferred due to the mild and efficient conditions. With this focus, a new photocatalytic method for the synthesis of nitrogen-containing heterocycles is highly desired. Here, we report a protocol for the biosynthesis of cercosporin, which could function as a metal-free photocatalyst. We then illustrate cercosporin-photocatalyzed protocols for the synthesis of nitrogen-containing heterocycles 1,2,3-thiadiazoles through annulation of azoalkenes with KSCN, and synthesis of 1,4,5,6-tetrahydropyridazines [4+2] through cyclodimerization of azoalkenes under mild conditions, respectively. As a result, there is a new bridge between the microbial fermentation method and organic synthesis in a mild, cost-effective, environmentally friendly and sustainable manner.


Assuntos
Alcenos/química , Compostos Azo/química , Perileno/análogos & derivados , Técnicas de Química Sintética , Reação de Cicloadição , Metais/química , Nitrogênio/química , Perileno/química
16.
Sheng Wu Gong Cheng Xue Bao ; 36(7): 1346-1355, 2020 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-32748592

RESUMO

Cytochrome P450 monooxygenases as powerful biocatalysts catalyze a wide range of chemical reactions to facilitate exogenous substances metabolism and biosynthesis of natural products. In order to explore new catalytic reactions and increase the number of P450 biocatalysts used in synthetic biology, a new self-sufficient cytochrome P450 monooxygenase (P450(VpMO)), belongs to CYP116B class, was mined from Variovorax paradoxus S110 genome and expressed in Escherichia coli. Based on characterization of the enzymatic properties, it shows that the optimal pH and temperature for P450(VpMO) reaction activity are 8.0 and 45 °C, respectively. P450(VpMO) is relatively stable at temperatures below 35 °C. The Km and kcat of P450(VpMO) toward 4-Methoxyacetophenone are 0.458 mmol/L and 2.438 min⁻¹, respectively. Importantly, P450(VpMO) was able to catalyze the demethylation reaction for a range of substrates containing methoxy group. Its demethylation reactivity is reasonably better than other P450s belongs to CYP116B class, particularly, for 4-methoxyacetophenone with a great conversion efficiency at 91%, showing that P450(VpMO) could be used as a great biocatalyst candidate for further analysis.


Assuntos
Comamonadaceae , Sistema Enzimático do Citocromo P-450 , Biologia Sintética , Catálise , Comamonadaceae/enzimologia , Comamonadaceae/genética , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Expressão Gênica
17.
Oncol Rep ; 43(4): 1221-1233, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020227

RESUMO

Numerous studies have demonstrated that microRNAs (miRNAs) play a key role in human carcinogenesis and metastasis. For example, miR­299­5p has previously been revealed to be dysregulated in several human cancers. However, the biological function of miR­299­5p in breast cancer remains unclear. The present study demonstrated that miR­299­5p was downregulated in breast cancer tissues and cell lines. The restoration of miR­299­5p expression suppressed cell migration and invasion, whereas inhibition of miR­299­5p promoted cell migration and invasion. In addition, in vivo studies demonstrated that miR­299­5p overexpression was able to inhibit tumour metastasis in nude mice. Mechanistically, through bioinformatics analysis and a dual­luciferase assay, it was confirmed that miR­299­5p directly targets serine/threonine kinase 39 (STK39). Silencing STK39 inhibited cell metastasis and suppressed epithelial­mesenchymal transition markers and matrix metalloproteinase expression, whereas restoration of STK39 expression was able to reverse miR­299­5p­inhibited cell migration and invasion. Collectively, the results of the present study demonstrated that miR­299­5p supresses breast cancer cell migration and invasion by targeting STK39. These findings may provide novel insights into miR­299­5p and its potential diagnostic and therapeutic benefits in breast cancer.


Assuntos
Neoplasias da Mama/genética , Proliferação de Células/genética , MicroRNAs/genética , Proteínas Serina-Treonina Quinases/genética , Animais , Apoptose/genética , Neoplasias da Mama/patologia , Carcinogênese/genética , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Camundongos , Invasividade Neoplásica/genética , Metástase Neoplásica
18.
Bioinformatics ; 36(9): 2872-2880, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31950974

RESUMO

MOTIVATION: Quantitative structure-activity relationship (QSAR) and drug-target interaction (DTI) prediction are both commonly used in drug discovery. Collaboration among pharmaceutical institutions can lead to better performance in both QSAR and DTI prediction. However, the drug-related data privacy and intellectual property issues have become a noticeable hindrance for inter-institutional collaboration in drug discovery. RESULTS: We have developed two novel algorithms under secure multiparty computation (MPC), including QSARMPC and DTIMPC, which enable pharmaceutical institutions to achieve high-quality collaboration to advance drug discovery without divulging private drug-related information. QSARMPC, a neural network model under MPC, displays good scalability and performance and is feasible for privacy-preserving collaboration on large-scale QSAR prediction. DTIMPC integrates drug-related heterogeneous network data and accurately predicts novel DTIs, while keeping the drug information confidential. Under several experimental settings that reflect the situations in real drug discovery scenarios, we have demonstrated that DTIMPC possesses significant performance improvement over the baseline methods, generates novel DTI predictions with supporting evidence from the literature and shows the feasible scalability to handle growing DTI data. All these results indicate that QSARMPC and DTIMPC can provide practically useful tools for advancing privacy-preserving drug discovery. AVAILABILITY AND IMPLEMENTATION: The source codes of QSARMPC and DTIMPC are available on the GitHub: https://github.com/rongma6/QSARMPC_DTIMPC.git. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Descoberta de Drogas , Privacidade , Algoritmos , Desenvolvimento de Medicamentos
19.
Biomed Pharmacother ; 113: 108742, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30851545

RESUMO

Caries, pulpitis, and trauma are the main causes of dental pulp damage. The regeneration capacity of dental pulp declines with age. Lin28 is a conserved RNA-binding protein in higher eukaryotes that regulates several important cellular functions associated with development, glucose metabolism, differentiation, and pluripotency. Conditional reactivation of Lin28 gene in adult mice markedly accelerates the wound-healing process in injured digits. However, little is known about its functions and molecular mechanism in human dental pulp. The aim of this study was to investigate the effects and mechanism of overexpression of Lin28 gene on the proliferation of human dental pulp cells (HDPCs). For this purpose, a number of molecular and biochemical analytical techniques, including the ethynyl-2'-deoxyuridine (EdU) incorporation assay, RNA-protein immunoprecipitation (RIP) analysis, and luciferase assays, were used for detailed characterization. In addition, factors regulating HDPCs activation were explored through gain-of-function and loss-of-function analyses. The results demonstrate that Lin28 promotes cell proliferation and the S-G2/M transition of HDPCs and directly binds to a group of cell cycle regulatory mRNAs in HDPCs. Through bioinformatics analysis and luciferase assays, we confirmed that let-7a targets IGF2BP2. Silencing of IGF2BP2 showed similar cellular and molecular effects as let-7a. Similarly, restoration of IGF2BP2 counteracted the effects of let-7a expression. In conclusion, Lin28 promotes cell proliferation by regulation of both mRNA translation (let-7-independent) and miRNA biogenesis (let-7-dependent). Lin28 can promote the expression of pro-proliferative genes by directly enhancing their translation to maintain a tight control over HDPC proliferation.


Assuntos
Polpa Dentária/citologia , MicroRNAs/genética , Proteínas de Ligação a RNA/genética , Adolescente , Diferenciação Celular/genética , Proliferação de Células/genética , Criança , Biologia Computacional/métodos , Desoxiuridina/análogos & derivados , Desoxiuridina/metabolismo , Inativação Gênica , Humanos , Imunoprecipitação , RNA Mensageiro/metabolismo , Regulação para Cima , Adulto Jovem
20.
Toxicol Appl Pharmacol ; 322: 89-96, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28284858

RESUMO

Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF. The action potential duration (APD) was remarkably prolonged under the concentration range of 12.5-50.0mM ethanol in guinea pig atrial myocytes. Ultra-rapid delayed rectified potassium currents (IKv1.5) were markedly inhibited by 12.5-50.0mM ethanol in a concentration-dependent manner. Ethanol with 50.0mM could inhibit rapid delayed rectifier potassium currents (IhERG). Ethanol under 6.25-50.0mM did not affect on inward rectifier potassium currents (IKir2.1). Collectively, the present study provided an evidence that moderate ethanol intake can prolong the APD of atrial myocytes by inhibition of IKv1.5 and IhERG, which contributed to preventing the development and duration of AF.


Assuntos
Antiarrítmicos/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Etanol/administração & dosagem , Canal de Potássio Kv1.5/antagonistas & inibidores , Miócitos Cardíacos/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/administração & dosagem , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Fibrilação Atrial/fisiopatologia , Cães , Relação Dose-Resposta a Droga , Cobaias , Células HEK293 , Humanos , Canal de Potássio Kv1.5/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Miócitos Cardíacos/fisiologia
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