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1.
Ecotoxicol Environ Saf ; 273: 116097, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38367605

RESUMO

BACKGROUND: Constrained by no proper way to assess cumulative exposure, the joint effect of air pollution cumulative exposure doses on childhood asthma and wheezing (AW) was not understood. OBJECTIVE: To assess the association between cumulative exposure to multiple air pollutants in early life and childhood AW. METHODS: We designed a nested case-control study based on the birth cohort in Jinan City. Children with AW followed up within 2 years after birth were treated as cases, and non-cases in this cohort were treated as the control source population, and the propensity score matching method was used to match each case to 5 controls. We calculated the individual cumulative outdoor exposure doses for each period using an inverse distance weighted model, alongside the complex Simpson's formula, accounting for outdoor time and respiratory volume. The Least absolute shrinkage and selection operator (Lasso) regression was performed to screen for covariates. To analyze the joint effects of pollutants, we employed the weighted quantile sum (WQS) regression model in conjunction with conditional logistic regression. RESULTS: 84 cases and 420 controls were included in this study. The odds ratio (OR) with 95% confidence interval (CI) of the impact of cumulative exposure (mg/m3) after birth on childhood AW was 1.78 (1.15-2.74) for SO2, 1.69 (1.11-2.57) for NO2, and 1.65 (1.09-2.52) for PM2.5, respectively. Furthermore, with each 25th percentile increase in the WQS index, the overall risk of cumulative doses for six pollutants exposure after birth on AW increased by an adjusted OR of 1.10 (1.03, 1.18), and SO2, PM2.5, and NO2 contributed the most to the WQS index. However, no statistically significant association was found between cumulative exposure to all pollutants before birth and childhood AW. CONCLUSIONS: There was a joint effect of the cumulative exposure dose of outdoor air pollutants after birth on AW in children aged 0-2 years. And traffic-related pollutants (SO2, PM2.5, and NO2) make a greater contribution to the joint effect.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Asma , Poluentes Ambientais , Criança , Humanos , Pré-Escolar , Poluentes Atmosféricos/análise , Sons Respiratórios , Dióxido de Nitrogênio , Estudos de Casos e Controles , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Asma/epidemiologia , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Material Particulado/análise
2.
J Transl Med ; 21(1): 733, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37848983

RESUMO

BACKGROUND: Maintaining the repair phenotype of denervated Schwann cells in the injured distal nerve is crucial for promoting peripheral nerve regeneration. However, when chronically denervated, the capacity of Schwann cells to support repair and regeneration deteriorates, leading to peripheral nerve regeneration and poor functional recovery. Herein, we investigated whether neurotrophin-3 (NT-3) could sustain the reparative phenotype of Schwann cells and promote peripheral nerve regeneration after chronic denervation and aimed to uncover its potential molecular mechanisms. METHODS: Western blot was employed to investigate the relationship between the expression of c-Jun and the reparative phenotype of Schwann cells. The inducible expression of c-Jun by NT-3 was examined both in vitro and in vivo with western blot and immunofluorescence staining. A chronic denervation model was established to study the role of NT-3 in peripheral nerve regeneration. The number of regenerated distal axons, myelination of regenerated axons, reinnervation of neuromuscular junctions, and muscle fiber diameters of target muscles were used to evaluate peripheral nerve regeneration by immunofluorescence staining, transmission electron microscopy (TEM), and hematoxylin and eosin (H&E) staining. Adeno-associated virus (AAV) 2/9 carrying shRNA, small molecule inhibitors, and siRNA were employed to investigate whether NT-3 could signal through the TrkC/ERK pathway to maintain c-Jun expression and promote peripheral nerve regeneration after chronic denervation. RESULTS: After peripheral nerve injury, c-Jun expression progressively increased until week 5 and then began to decrease in the distal nerve following denervation. NT-3 upregulated the expression of c-Jun in denervated Schwann cells, both in vitro and in vivo. NT-3 promoted peripheral nerve regeneration after chronic denervation, mainly by upregulating or maintaining a high level of c-Jun rather than NT-3 itself. The TrkC receptor was consistently presented on denervated Schwann cells and served as NT-3 receptors following chronic denervation. NT-3 mainly upregulated c-Jun through the TrkC/ERK pathway. CONCLUSION: NT-3 promotes peripheral nerve regeneration by maintaining the repair phenotype of Schwann cells after chronic denervation via the TrkC/ERK/c-Jun pathway. It provides a potential target for the clinical treatment of peripheral nerve injury after chronic denervation.


Assuntos
Regeneração Nervosa , Neurotrofina 3 , Traumatismos dos Nervos Periféricos , Células de Schwann , Humanos , Axônios/metabolismo , Denervação , Sistema de Sinalização das MAP Quinases , Regeneração Nervosa/genética , Regeneração Nervosa/fisiologia , Neurotrofina 3/genética , Neurotrofina 3/metabolismo , Traumatismos dos Nervos Periféricos/genética , Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos dos Nervos Periféricos/terapia , Receptores Proteína Tirosina Quinases/metabolismo , Células de Schwann/metabolismo
3.
Crit Rev Food Sci Nutr ; : 1-15, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37243343

RESUMO

High pressure processing (HPP) offers the benefits of safety, uniformity, energy-efficient, and low waste, which is widely applied for microbial inactivation and shelf-life extension for foods. Over the past forty years, HPP has been extensively researched in the food industry, enabling the inactivation or activation of different enzymes in future food by altering their molecular structure and active site conformation. Such activation or inactivation of enzymes effectively hinders the spoilage of food and the production of beneficial substances, which is crucial for improving food quality. This paper reviews the mechanism in which high pressure affects the stability and activity of enzymes, concludes the roles of key enzymes in the future food processed using high pressure technologies. Moreover, we discuss the application of modified enzymes based on high pressure, providing insights into the future direction of enzyme evolution under complex food processing conditions (e.g. high temperature, high pressure, high shear, and multiple elements). Finally, we conclude with prospects of high pressure technology and research directions in the future. Although HPP has shown positive effects in improving the future food quality, there is still a pressing need to develop new and effective combined processing methods, upgrade processing modes, and promote sustainable lifestyles.

4.
Environ Res ; 226: 115687, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36925033

RESUMO

BACKGROUND: Given differences in vulnerability of children in early life, a life course approach to asthma and wheezing (AW) in young children caused by ozone (O3) is not fully understood. METHODS: We conducted a birth cohort in Jinan, China from 2018 to 2021 to elucidate the onset model of childhood AW due to O3 exposure. An inverse distance weighted model was used for individual exposure assessment. The time-dependent Cox proportional-hazard model and logistic model were used to investigate the effects of O3 exposure on AW. Principal component analysis, interaction analysis, and distributed lag model were used to analyze the life course approach. RESULTS: The cumulative incidence rate for AW among 6501 children aged 2 was 1.4%. A high level of O3 was related to AW (HR: 2.10, 95% CI: 1.31, 3.37). Only O3 exposure after birth was associated with AW, with an OR of 1.82 (1.08, 3.12), after adjusting for the effect before birth. Furthermore, adjusting for other air pollutants, the HR for the individual effect of high O3 exposure on AW was 2.44 (1.53, 3.89). Interestingly, P values for interactions for O3 and the principal components of other pollutants, as well as the characteristic variable of open windows were less than 0.1. Moreover, an increase in the IQR of O3 exposure at the 31st to 37th weeks before birth and the 1st to 105th weeks after birth was associated with an increase in the HRs for AW. CONCLUSIONS: High-level of O3 exposure after birth could lead to AW among young children. Importantly, the AW onset model may include the risk factors accumulation and the sensitive period model. Specifically, there are two sensitive windows in early life, and the correlated insults between the high level of O3 and other pollutants as well as open windows in the asthma-inducing effect.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Asma , Poluentes Ambientais , Ozônio , Feminino , Humanos , Criança , Pré-Escolar , Ozônio/análise , Poluição do Ar/análise , Coorte de Nascimento , Estudos Prospectivos , Acontecimentos que Mudam a Vida , Sons Respiratórios/etiologia , Material Particulado/análise , Poluentes Atmosféricos/análise , Asma/induzido quimicamente , Asma/epidemiologia , China/epidemiologia , Poluentes Ambientais/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise
5.
J Nanobiotechnology ; 21(1): 231, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37475025

RESUMO

Extracellular vesicles (EVs) are nano-sized, natural, cell-derived vesicles that contain the same nucleic acids, proteins, and lipids as their source cells. Thus, they can serve as natural carriers for therapeutic agents and drugs, and have many advantages over conventional nanocarriers, including their low immunogenicity, good biocompatibility, natural blood-brain barrier penetration, and capacity for gene delivery. This review first introduces the classification of EVs and then discusses several currently popular methods for isolating and purifying EVs, EVs-mediated drug delivery, and the functionalization of EVs as carriers. Thereby, it provides new avenues for the development of EVs-based therapeutic strategies in different fields of medicine. Finally, it highlights some challenges and future perspectives with regard to the clinical application of EVs.


Assuntos
Sistemas de Liberação de Medicamentos , Vesículas Extracelulares , Sistemas de Liberação de Medicamentos/métodos , Vesículas Extracelulares/metabolismo , Proteínas , Transporte Biológico
6.
Med Sci Monit ; 29: e941937, 2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37864329

RESUMO

BACKGROUND Lumbar disc herniation (LDH) at L4-L5 impacts paravertebral muscle morphology. Intervertebral disc degeneration is linked to paravertebral muscle changes, affecting LDH treatment outcomes. This study explored L4-L5 LDH paravertebral muscle alterations, specifically in the erector spinae, multifidus, and psoas major, using Michigan State University's classification to guide LDH treatment. MATERIAL AND METHODS The study enrolled 160 patients, including 39 normal patients and 121 L4-L5 LDH patients. Patients with LDH were grouped according to MSU classification and compared to the normal group according to demographics and imaging changes. RESULTS In patients with L4-L5 herniation in Zone B, the FI of the ES muscle at L3-L4 level, L4-L5 level, and L5-S1 level was higher than that of normal people (P=0.018, P=0.043, P=0.010, respectively), and there was no difference between FI of MF and normal people. The Zone B patients also had a smaller CSA of the ES muscle at L4-L5 level than that in the normal group (P=0.049). Patients in the Zone C group were older than those in the normal group (P=0.014). The CSA of the PM of patients with Grade 3 herniation differed from that of the normal group at the L4-L5 and L5-S1 level. They were higher than in normal people at L4-L5 level (P=0.011) and lower at L5-S1 level (P=0.028). CONCLUSIONS In patients with L4-L5 herniation in Zone B, the FI of ES at L3-S1 level was higher than in normal people, and the CSA at L4-L5 level was smaller than in normal people. In patients with Grade3 herniation, PM CSA was larger at L4-L5 level and smaller at L5-S1 level than in normal people.


Assuntos
Degeneração do Disco Intervertebral , Deslocamento do Disco Intervertebral , Humanos , Michigan , Universidades , Vértebras Lombares , Imageamento por Ressonância Magnética/métodos , Músculos Psoas
7.
BMC Genomics ; 23(1): 59, 2022 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-35033021

RESUMO

BACKGROUND: Ischemic stroke (IS) is a principal contributor to long-term disability in adults. A new cell death mediated by iron is ferroptosis, characterized by lethal aggregation of lipid peroxidation. However, a paucity of ferroptosis-related biomarkers early identify IS until now. This study investigated potential ferroptosis-related gene pair biomarkers in IS and explored their roles in immune infiltration. RESULTS: In total, we identified 6 differentially expressed ferroptosis-related genes (DEFRGs) in the metadata cohort. Of these genes, 4 DEFRGs were incorporated into the competitive endogenous RNA (ceRNA) network, including 78 lncRNA-miRNA and 16 miRNA-mRNA interactions. Based on relative expression values of DEFRGs, we constructed gene pairs. An integrated scheme consisting of machine learning algorithms, ceRNA network, and gene pair was proposed to screen the key DEFRG biomarkers. The receiver operating characteristic (ROC) curve witnessed that the diagnostic performance of DEFRG pair CDKN1A/JUN was superior to that of single gene. Moreover, the CIBERSORT algorithm exhibited immune infiltration landscapes: plasma cells, resting NK cells, and resting mast cells infiltrated less in IS samples than controls. Spearman correlation analysis confirmed a significant correlation between plasma cells and CDKN1A/JUN (CDKN1A: r = - 0.503, P < 0.001, JUN: r = - 0.330, P = 0.025). CONCLUSIONS: Our findings suggested that CDKN1A/JUN could be a robust and promising gene-pair diagnostic biomarker for IS, regulating ferroptosis during IS progression via C9orf106/C9orf139-miR-22-3p-CDKN1A and GAS5-miR-139-5p/miR-429-JUN axes. Meanwhile, plasma cells might exert a vital interplay in IS immune microenvironment, providing an innovative insight for IS therapeutic target.


Assuntos
Isquemia Encefálica , Ferroptose , AVC Isquêmico , MicroRNAs , Acidente Vascular Cerebral , Isquemia Encefálica/genética , Biologia Computacional , Marcadores Genéticos , Humanos , Acidente Vascular Cerebral/genética
8.
Small ; 18(27): e2201300, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35678523

RESUMO

The treatment of diabetic wounds remains challenging due to the excess levels of oxidative stress, vulnerability to bacterial infection, and persistent inflammation response during healing. The development of hydrogel wound dressings with ideal anti-inflammation, antioxidant, and anti-infective properties is an urgent clinical requirement. In the present study, an injectable thermosensitive niobium carbide (Nb2 C)-based hydrogel (Nb2 C@Gel) with antioxidative and antimicrobial activity is developed to promote diabetic wound healing. The Nb2 C@Gel system is composed of Nb2 C and a PLGA-PEG-PLGA triblock copolymer. The fabricated Nb2 C nanosheets (NSs) show good biocompatibility during in vitro cytotoxicity and hemocompatibility assays and in vivo toxicity assays. In vitro experiments show that Nb2 C NSs can efficiently eliminate reactive oxygen species (ROS), thus protecting cells in the wound from oxidative stress damage. Meanwhile, Nb2 C NSs also exhibit good near-infrared (NIR) photothermal antimicrobial activity against both Staphylococcus aureus and Escherichia coli. In vivo results demonstrate that Nb2 C@Gel promotes wound healing by attenuating ROS levels, reducing oxidative damage, eradicating bacterial infection under NIR irradiation, and accelerating angiogenesis. To summarize, the Nb2 C@Gel system, with its ROS-scavenging, photothermal antimicrobial and hemostatic activities, can be a promising and effective strategy for the treatment of diabetic wounds.


Assuntos
Infecções Bacterianas , Diabetes Mellitus , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antioxidantes , Escherichia coli , Humanos , Hidrogéis , Nióbio , Espécies Reativas de Oxigênio , Cicatrização
9.
J Pharmacol Exp Ther ; 383(3): 227-237, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36116794

RESUMO

A positive response to scalene muscle block (SMB) is an important indication for the diagnosis of thoracic outlet syndrome. Lidocaine injection is commonly used in clinical practice in SMB, although there have been some cases of misdiagnosis. Botulinum toxin A (BTX-A) is one of the therapeutic agents in SMB, but whether it is also indicated for SMB diagnosis is controversial. To evaluate the muscle block efficiency of these two drugs, the contraction strength was repeatedly recorded on tibialis anterior muscle in rats. It was found that at a safe dosage, 2% lidocaine performed best at 40 µL, but it still exhibits an unsatisfactory partial blocking efficiency. Moreover, neither lidocaine injection in combination with epinephrine or dexamethasone nor multiple locations injection could improve the blocking efficiency. On the other hand, injections of 3, 6, and 12 U/kg BTX-A all showed almost complete muscle block. Gait analysis showed that antagonistic gastrocnemius muscle, responsible for heel rising, was paralyzed for nonspecific blockage in the 12 U/kg BTX-A group, but not in the 3 U/kg or 6 U/kg BTX-A group. Cleaved synaptosomal associated protein 25 (c-SNAP 25) was stained to test the transportation of BTX-A, and was additionally observed in the peripheral muscles in 6 and 12 U/kg groups. c-SNAP 25, however, was barely detectable in the spinal cord after BTX-A administration. Therefore, our results suggest that low dosage of BTX-A may be a promising option for the diagnostic SMB of thoracic outlet syndrome. SIGNIFICANCE STATEMENT: Muscle block is important for the diagnosis and treatment of thoracic outlet syndrome and commonly performed with lidocaine. However, misdiagnosis was observed sometimes. Here, we found that intramuscular injection of optimal dosage lidocaine only partially blocked the muscle contraction in rats, whereas low-dosage botulinum toxin, barely used in diagnostic block, showed almost complete block without affecting the central nervous system. This study suggests that botulinum toxin might be more suitable for muscle block than lidocaine in clinical practice.


Assuntos
Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Síndrome do Desfiladeiro Torácico , Ratos , Animais , Toxinas Botulínicas Tipo A/farmacologia , Lidocaína/farmacologia , Injeções Intramusculares , Músculo Esquelético
10.
Environ Res ; 214(Pt 1): 113879, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35835165

RESUMO

The concentration of ozone (O3) in the environment is gradually increasing, but there are limited reports on the exposure to O3 during pregnancy on the risk of adverse birth outcomes. Our study aimed to examine the causal and independent effect of O3 exposure during pregnancy on the risk of preterm birth (PTB) and to identify the critical window. Based on the baseline population of the birth cohort in Jinan, northern China, we obtained the individual exposure for each subject during pregnancy of ambient 8-h moving average O3 through the inverse distance weighting model. The effect of O3 exposure during pregnancy on PTB was evaluated through the time-dependent Cox proportional-hazard models. And we assessed the causal relationship by controlling unknown confounding factors using the instrumental variable (IV) analysis, estimated the independent effect by principal component analysis, and identified the critical window period of exposure through the distributed lag model. Among 6501 subjects, 285 mothers delivered prematurely. The median (IQR) of O3 concentration during pregnancy was 109.51 (23.54) µg/m3. The high level of O3 exposure (>173.64 µg/m³) increased the risk of PTB, with HR of 1.92 (95% CI: 1.38-2.66). Furthermore, the HR (95% CI) of the O3 estimated value calculated by the IV (wind speed) on the risk of PTB was 2.63 (1.41-4.88). In addition, the high level of O3 exposure was associated with the risk of PTB in the 13th-18th gestational weeks. Therefore, the high level of O3 exposure during pregnancy may independently increase the risk of PTB, which may be a causal effect. The 13th to 18th week of gestation is a critical window for preventing this risk.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Ozônio , Nascimento Prematuro , China , Feminino , Humanos , Recém-Nascido , Exposição Materna , Material Particulado , Gravidez
11.
Environ Res ; 204(Pt C): 112286, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34743895

RESUMO

BACKGROUND: The relationship between prenatal exposure to sulfur dioxide (SO2) and childhood wheezing and asthma is unclear. OBJECTIVE: To explore the association between prenatal exposure to SO2 and childhood wheeze and asthma. To investigate the effects for the exposure during different pregnancy trimesters. METHODS: We conducted a cross-sectional study firstly in Jinan City to get the prevalence of wheeze and asthma on children aged 18 months to 3 years. And then, we designed a case-control study based on population to evaluate the association between prenatal SO2 exposure and childhood asthma and wheezing. Based on the starting and ending date of pregnancy and specific residential addresses, the individual concentrations of SO2 during pregnancy was evaluated using an inverse distance weighted model. RESULTS: The prevalence of wheeze and asthma on children aged 18 months to 3 years was 2.07% in our cross-sectional study. 236 cases and 1445 controls were available for exposure estimates. The OR (95% CI) of 1.296 (1.130-1.491) was significant after adjusting for the covariates. In the first and third trimesters, the effects were enhanced to 1.602 (1.275-2.022) and 1.448 (1.179-1.783) in the multi-pollutant model with adjusting the effects of other trimesters. Coincidentally, the SO2 exposure level of the case in the first trimester was higher than that in the second and third trimesters (P < 0.001); however, there was no significant difference in exposure levels of the case between the second and third trimesters of pregnancy (P = 0.381). CONCLUSION: Prenatal exposure to higher concentration of SO2 could increase the risk of asthma and wheezing in younger children. The first trimester might be just the window for the toxic effect, while the third trimester was the sensitive window for the effect of SO2 exposure during pregnancy on childhood asthma.


Assuntos
Asma , Efeitos Tardios da Exposição Pré-Natal , Asma/induzido quimicamente , Asma/epidemiologia , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Humanos , Lactente , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Sons Respiratórios , Dióxido de Enxofre/toxicidade
12.
Curr Microbiol ; 78(8): 3058-3067, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34156543

RESUMO

Isolation of culturable actinobacteria from coastal wetlands and screening of their potential biological activities are important for the development of new marine natural products. We collected and isolated 109 actinobacteria from the Sanggou Bay and the Swan Lake wetlands, in the coast of Weihai, China. Of the 109 isolates, 104 had antimicrobial activity against at least one indicator strain. The 35 strains with the strongest inhibitory effects were chosen for the screening of the biosynthesis gene clusters of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS). Four strains with the PKS gene, six strains with the NRPS gene, and three strains with both genes were detected. Eight of the 13 strains with PKS or NRPS genes belong to the genera Streptomyces, and other strains belonged to genus Micromonospora, Nocardiopsis, Rhodococcus, Saccharomonospora, and Staphylococcus. Our results reveal that the culturable actinobacteria isolated from coastal wetlands showed broad-spectrum antimicrobial activities, and some strains with antimicrobial activities possessed PKS and NRPS genes. Thus, culturable actinobacteria from coastal wetlands may contain potential new bioactive substances.


Assuntos
Actinobacteria , Anti-Infecciosos , Actinobacteria/genética , China , Filogenia , RNA Ribossômico 16S , Áreas Alagadas
13.
BMC Med Inform Decis Mak ; 21(1): 115, 2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33820531

RESUMO

BACKGROUND: Screening carotid B-mode ultrasonography is a frequently used method to detect subjects with carotid atherosclerosis (CAS). Due to the asymptomatic progression of most CAS patients, early identification is challenging for clinicians, and it may trigger ischemic stroke. Recently, machine learning has shown a strong ability to classify data and a potential for prediction in the medical field. The combined use of machine learning and the electronic health records of patients could provide clinicians with a more convenient and precise method to identify asymptomatic CAS. METHODS: Retrospective cohort study using routine clinical data of medical check-up subjects from April 19, 2010 to November 15, 2019. Six machine learning models (logistic regression [LR], random forest [RF], decision tree [DT], eXtreme Gradient Boosting [XGB], Gaussian Naïve Bayes [GNB], and K-Nearest Neighbour [KNN]) were used to predict asymptomatic CAS and compared their predictability in terms of the area under the receiver operating characteristic curve (AUCROC), accuracy (ACC), and F1 score (F1). RESULTS: Of the 18,441 subjects, 6553 were diagnosed with asymptomatic CAS. Compared to DT (AUCROC 0.628, ACC 65.4%, and F1 52.5%), the other five models improved prediction: KNN + 7.6% (0.704, 68.8%, and 50.9%, respectively), GNB + 12.5% (0.753, 67.0%, and 46.8%, respectively), XGB + 16.0% (0.788, 73.4%, and 55.7%, respectively), RF + 16.6% (0.794, 74.5%, and 56.8%, respectively) and LR + 18.1% (0.809, 74.7%, and 59.9%, respectively). The highest achieving model, LR predicted 1045/1966 cases (sensitivity 53.2%) and 3088/3566 non-cases (specificity 86.6%). A tenfold cross-validation scheme further verified the predictive ability of the LR. CONCLUSIONS: Among machine learning models, LR showed optimal performance in predicting asymptomatic CAS. Our findings set the stage for an early automatic alarming system, allowing a more precise allocation of CAS prevention measures to individuals probably to benefit most.


Assuntos
Doenças das Artérias Carótidas , Registros Eletrônicos de Saúde , Teorema de Bayes , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Humanos , Aprendizado de Máquina , Estudos Retrospectivos
14.
J Cell Mol Med ; 23(2): 1622-1627, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30484953

RESUMO

Disabled-1 (Dab1) is best known as an adaptor protein regulating neuron migration and lamination during development. However, the exact function of Dab1 in breast cancer is unknown. In this study, we examined the expression of Dab1 in 38 breast cancer paraffin sections, as well as 60 paired frozen breast cancer and their adjacent tissues. Our results showed that Dab1 was reduced in breast cancer, and its compromised expression correlated with triple negative breast cancer phenotype, poor differentiation, as well as lymph node metastasis. Functional analysis in breast cancer cell lines demonstrated that Dab1 promoted cell apoptosis, which, at least partially, depended on its regulation of NF-κB/Bcl-2/caspase-9 pathway. Our study strongly suggests that Dab1 may be a potential tumour suppressor gene in breast cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias da Mama/genética , Proteínas do Tecido Nervoso/genética , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Neoplasias da Mama/patologia , Caspase 9/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Células MCF-7 , Pessoa de Meia-Idade , NF-kappa B/genética , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Fator de Transcrição RelA/genética , Neoplasias de Mama Triplo Negativas/patologia , Proteína X Associada a bcl-2/genética
15.
Acta Pharmacol Sin ; 40(4): 522-529, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29921888

RESUMO

Silkworm cocoon was recorded to cure carbuncle in the Compendium of Materia Medica. Previous studies have demonstrated that the supplemental silk protein sericin exhibits anticancer activity. In the present study, we investigated the effects of silk fibroin peptide (SFP) extracted from silkworm cocoons against human lung cancer cells in vitro and in vivo and its possible anticancer mechanisms. SFP that we prepared had high content of glycine (~ 30%) and showed a molecular weight of ~ 10 kDa. Intragastric administration of SFP (30 g/kg/d) for 14 days did not affect the weights, vital signs, routine blood indices, and blood biochemical parameters in mice. MTT assay showed that SFP dose-dependently inhibited the growth of human lung cancer A549 and H460 cells in vitro with IC50 values of 9.921 and 9.083 mg/mL, respectively. SFP also dose-dependently suppressed the clonogenic activity of the two cell lines. In lung cancer H460 xenograft mice, intraperitoneal injection of SFP (200 or 500 mg/kg/d) for 40 days significantly suppressed the tumor growth, but did not induce significant changes in the body weight. We further examined the effects of SFP on cell cycle and apoptosis in H460 cells using flow cytometry, which revealed that SFP-induced cell cycle arrest at the S phase, and then promoted cell apoptosis. We demonstrated that SFP (20-50 mg/mL) dose-dependently downregulates Bcl-2 protein expression and upregulates Bax protein in H460 cells during cell apoptosis. The results suggest that SFP should be studied further as a novel therapeutic agent for the treatment of lung cancer.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Fibroínas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Peptídeos/farmacologia , Células A549 , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Fibroínas/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/química , Relação Estrutura-Atividade
16.
J Cell Mol Med ; 22(6): 3259-3263, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29575613

RESUMO

Single-chain variable fragment (scFv) antibodies are the smallest immunoglobulins with high antigen-binding affinity. We have previously reported that fibroblast growth factor 1 played pivotal roles in cancer development and generated a mouse scFv (mscFv1C9) could effectively prohibit cancer cell proliferation in vitro and in vivo. Here, we further humanized this scFv (hscFv1C9) using a structure-guided complementarity determining region grafting strategy. The purified hscFv1C9 maintained similar antigen-binding affinity and specificity as mscFv1C9, and it was capable of inhibiting growth of different tumours in vitro and in vivo. These data strongly suggested that hscFv1C9 has antitumour potentials.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Fator 1 de Crescimento de Fibroblastos/antagonistas & inibidores , Glioma/tratamento farmacológico , Anticorpos de Cadeia Única/farmacologia , Sequência de Aminoácidos/genética , Animais , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais Humanizados/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Feminino , Fator 1 de Crescimento de Fibroblastos/química , Fator 1 de Crescimento de Fibroblastos/genética , Fator 1 de Crescimento de Fibroblastos/imunologia , Glioma/genética , Glioma/patologia , Xenoenxertos , Humanos , Camundongos , Anticorpos de Cadeia Única/imunologia
17.
J Basic Microbiol ; 58(1): 60-67, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29105800

RESUMO

A total of 216 killer yeasts Saccharomyces cerevisiae, isolated from wine, were evaluated in controlling Colletotrichum gloeosporioides, a pre-harvest anthracnose agent of grape. Three of these yeast isolates were tested positive for antagonizing C. gloeosporioides and were further evaluated for their mechanisms as biological control agents (BCAs): production of antifungal compounds, production of hydrolytic enzymes, inhibition of C. gloeosporioides conidia germination, colonization on grape berry, and efficiency in controlling anthracnose of grape. The results showed that all three S. cerevisiae isolates produced antifungal compounds, inhibited C. gloeosporioides conidia germination and produced ß-1,3-glucanase and chitinase. All isolates colonized grape berry in large quantities and controlled C. gloeosporioides when artificially inoculated on grape berry. Among the three isolates, application of isolate GA8 resulted in 69.7% of disease reductions for C. gloeosporioides on grape berry. The antagonistic isolates of S. cerevisiae could represent important BCAs of anthracnose of grape caused by C. gloeosporioides that are responsible for economic losses in viticulture.


Assuntos
Agentes de Controle Biológico/isolamento & purificação , Colletotrichum/fisiologia , Saccharomyces cerevisiae/fisiologia , Vitis/microbiologia , Vinho/microbiologia , Antibiose , Antifúngicos/isolamento & purificação , Agentes de Controle Biológico/metabolismo , Quitinases/biossíntese , Glucana 1,3-beta-Glucosidase/biossíntese , Doenças das Plantas/microbiologia , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/isolamento & purificação
18.
Mol Pharm ; 14(9): 3013-3024, 2017 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-28703594

RESUMO

In the present study, a new coamorphous phase (CAP) of bioactive herbal ingredient curcumin (CUR) with high solubilitythe was screened with pharmaceutically acceptable coformers. Besides, to provide basic information for the best practice of physiological and pharmaceutical preparations of CUR-based CAP, the interaction between CUR-based CAP and bovine serum albumin (BSA) was studied at the molecular level in this paper. CAP of CUR and piperazine with molar ratio of 1:2 was prepared by EtOH-assisted grinding. The as-prepared CAP was characterized by powder X-ray diffraction, modulated temperature differential scanning calorimetry, thermogravimetric analysis, Fourier-transform infrared, and solid-state 13C nuclear magnetic resonance. The 1:2 CAP stoichioimetry was sustained by C═O···H hydrogen bonds between the N-H group of the piperazine and the C═O group of CUR; piperazine stabilized the diketo structure of CUR in CAP. The dissolution rate of CUR-piperazine CAP in 30% ethanol-water was faster than that of CUR; the t50 values were 243.1 min for CUR and 4.378 min for CAP. Furthermore, interactions of CUR and CUR-piperazine CAP with BSA were investigated by fluorescence spectroscopy and density functional theory (DFT) calculation. The binding constants (Kb) of CUR and CUR-piperazine CAP with BSA were 10.0 and 9.1 × 103 L mol-1 at 298 K, respectively. Moreover, DFT simulation indicated that the interaction energy values of hydrogen-bonded interaction in the tryptophan-CUR and tryptophan-CUR-piperazine complex were -26.1 and -17.9 kJ mol-1, respectively. In a conclusion, after formation of CUR-piperazine CAP, the interaction forces between CUR and BSA became weaker.


Assuntos
Curcumina/química , Piperazinas/química , Soroalbumina Bovina/química , Espectrometria de Fluorescência/métodos , Animais , Bovinos , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Piperazina , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
20.
Sensors (Basel) ; 17(12)2017 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-29232907

RESUMO

Intelligent Transportation Systems (ITSs) can be applied to inform and incentivize travellers to help them make cognizant choices concerning their trip routes and transport modality use for their daily travel whilst achieving more sustainable societal and transport authority goals. However, in practice, it is challenging for an ITS to enable incentive generation that is context-driven and personalized, whilst supporting multi-dimensional travel goals. This is because an ITS has to address the situation where different travellers have different travel preferences and constraints for route and modality, in the face of dynamically-varying traffic conditions. Furthermore, personalized incentive generation also needs to dynamically achieve different travel goals from multiple travellers, in the face of their conducts being a mix of both competitive and cooperative behaviours. To address this challenge, a Rule-based Incentive Framework (RIF) is proposed in this paper that utilizes both decision tree and evolutionary game theory to process travel information and intelligently generate personalized incentives for travellers. The travel information processed includes travellers' mobile patterns, travellers' modality preferences and route traffic volume information. A series of MATLAB simulations of RIF was undertaken to validate RIF to show that it is potentially an effective way to incentivize travellers to change travel routes and modalities as an essential smart city service.

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