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1.
World J Clin Cases ; 12(2): 383-391, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38313655

RESUMO

BACKGROUND: The SETD1B gene is instrumental in human intelligence and nerve development. Mutations in the SETD1B gene have been linked in recent studies to neurodevelopmental disorders, seizures, and language delay. CASE SUMMARY: This study aimed to analyze the clinical manifestations and treatment of three patients suffering from mental retardation, epilepsy, and language delay resulting from a new mutation in the SETD1B gene. Three individuals with these symptoms were selected, and their clinical symptoms, gene test results, and treatment were analyzed. This article discusses the impact of the SETD1B gene mutation on patients and outlines the treatment approach. Among the three patients (two females and one male, aged 8, 4, and 1, respectively), all exhibited psychomotor retardation, attention deficit, and hyperactivity disorder, and two had epilepsy. Antiepileptic treatment with sodium tripolyvalproate halted the seizures in the affected child, although mental development remained somewhat delayed. Whole exome sequencing revealed new mutations in the SETD1B gene for all patients, specifically with c.5473C>T (p.Arg1825trp), c.4120C>T (p.Gln1374*, 593), c.14_15insC (p.His5Hisfs*33). CONCLUSION: Possessing the SETD1B gene mutation may cause mental retardation accompanied by seizures and language delay. Although the exact mechanism is not fully understood, interventions such as drug therapy, rehabilitation training, and family support can assist patients in managing their symptoms and enhancing their quality of life. Furthermore, genetic testing supplies healthcare providers with more precise diagnostic and therapeutic guidance, informs families about genetic disease risks, and contributes to understanding disease pathogenesis and drug research and development.

2.
Epilepsia Open ; 9(1): 278-286, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37969060

RESUMO

OBJECTIVE: We aimed to find predictors for smartphone application-based ketogenic diet (KD) treatment effectiveness and safety. METHODS: The efficacy was evaluated according to the reduction in seizure frequency after the intervention of KD; safety was evaluated based on adverse effects. The ordinal logistic regression analysis was used to explore the influencing factors of efficacy. RESULTS: The study sample included 116 males and 65 females with a median age of 2.27 years. The baseline frequency of seizure was more than five times/day in 123 children, 50.83% of them received three or more antiepileptic drugs (AEDs). Seventy-two patients' KD initiation mode was outpatient, and 73 completed the 12-month follow-up. A total of 88 (48.62%) patients had reported a reduction in seizure ≥50%. Compared with 12 months, those who had received KD therapy for only 3 (P = 0.009) and 6 months (P = 0.005) were more likely to show negative outcomes. Outpatient initiation had better outcomes (P = 0.029) than inpatient initiation. For the number of AEDs applied, patients on two AEDs were more likely to achieve better outcomes (P = 0.001). Adverse events had been noted among 77 patients; BMI Z-score at KD initiation was associated with adverse effects (P = 0.003). SIGNIFICANCE: Our study suggested that outpatient initiation and long-term treatment of KD should be encouraged. PLAIN LANGUAGE SUMMARY: Our research shows that the KD is a helpful treatment for children with refractory epilepsy, reducing seizures by more than 50% in nearly half of the cases, with some experiencing complete seizure freedom. We used a smartphone app to improve communication between patients and their healthcare teams, resulting in a high retention, and app usage was linked to reduced adverse effects. We recommend early consideration of KD treatment for patients failing two AED, encourage outpatient initiation, and advocate for longer-term KD use.


Assuntos
Dieta Cetogênica , Epilepsia Resistente a Medicamentos , Aplicativos Móveis , Masculino , Feminino , Criança , Humanos , Pré-Escolar , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Dieta Cetogênica/efeitos adversos , Dieta Cetogênica/métodos , Smartphone , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Anticonvulsivantes/uso terapêutico
3.
Chem Biol Drug Des ; 103(1): e14389, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37955286

RESUMO

Twenty-one new coumarin Mannich base derivatives (11a-u) were synthesized, which exhibited antiproliferation activities in HepG2 (liver cancer), A549 (lung cancer), MCF-7 (breast cancer), and HT-29 (colon cancer). Most of the target compounds showed the most potent activity against HepG2 cells compared with other cancer cells, compound 11g showed the strongest antiproliferative activity (2.10 µM) against HepG2, even superior to the positive control drug 5-FU(5.49 µM). The nitric oxide (NO) release of all compounds in HepG2 cells was determined, of which compound 11g showed high levels of NO release (10.8 µM). Notably, the solubility of compound 11g increased 13-fold compared with the lead 8. The preliminary cytotoxicity studies suggest that 11g had little effect on LO2 cells(normal liver cells, >50 µM). The effect of compound 11g on the apoptosis of HepG2 cells was also studied, and the results showed that the induction effect of compound 11g on apoptosis is a concentration-dependent manner. Our results indicate that compound 11g might be a promising lead for further studies.


Assuntos
Antineoplásicos , Bases de Mannich , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Bases de Mannich/farmacologia , Cumarínicos/farmacologia , Antineoplásicos/farmacologia , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Óxido Nítrico , Linhagem Celular Tumoral , Apoptose
4.
Comput Biol Med ; 169: 107840, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38157773

RESUMO

Medical image segmentation is a fundamental and critical step in many image-guided clinical approaches. Recent success of deep learning-based segmentation methods usually relies on a large amount of labeled data, which is particularly difficult and costly to obtain, especially in the medical imaging domain where only experts can provide reliable and accurate annotations. Semi-supervised learning has emerged as an appealing strategy and been widely applied to medical image segmentation tasks to train deep models with limited annotations. In this paper, we present a comprehensive review of recently proposed semi-supervised learning methods for medical image segmentation and summarize both the technical novelties and empirical results. Furthermore, we analyze and discuss the limitations and several unsolved problems of existing approaches. We hope this review can inspire the research community to explore solutions to this challenge and further advance the field of medical image segmentation.


Assuntos
Processamento de Imagem Assistida por Computador , Aprendizado de Máquina Supervisionado
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(10): 1217-1221, 2023 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-37730220

RESUMO

OBJECTIVE: To explore the correlation between clinical manifestations of Limb-girdle muscular dystrophy autosomal recessive 9 FKRP-related (R9 FKRP-related) and variants of the FKRP gene. METHODS: Two children who had presented at the Children's Hospital of Nanjing Medical University respectively due to increased serum myocardial zymogram and hepatic dysfunction on September 30, 2018 and August 3, 2018 were selected as the study subjects. Clinical data of the children were collected. Both children were suspected for Duchenne or Becker muscular dystrophy for asymptomatic high creatine kinase (CK) levels. Peripheral blood samples of the children and their parents were collected for whole exome sequencing, and candidate variants were validated by Sanger sequencing. RESULTS: Genetic testing revealed that both children have carried compound heterozygous variants of the FKRP gene. The c.545A>G and c.941C>T variants in child 1 have been reported previously, among which the c.545A>G is a hot spot mutation in the Chinese population. Child 2 has carried c.602T>C and c.961G>A variants, both of which were unreported previously. CONCLUSION: Both children have met the diagnostic criteria for LGMD R9 FKRP-related. Carriers of the c.545A>G variant may present milder symptoms. Compared with patients carrying null variants, carriers of compound heterozygous missense variants may present with a milder phenotype, manifesting as asymptomatic high CK level.


Assuntos
Distrofia Muscular do Cíngulo dos Membros , Distrofia Muscular de Duchenne , Humanos , Criança , Povo Asiático/genética , Testes Genéticos , Distrofia Muscular do Cíngulo dos Membros/genética , Pentosiltransferases/genética
6.
Sci Rep ; 13(1): 15366, 2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37717091

RESUMO

An accurate estimation of earth pressure on retaining walls is imperative to achieving its design. This paper presents an analytical method framework that considers the effect of plant transpiration relative to the traditional calculation approaches. Specifically, a closed-form solution for one-dimensional steady unsaturated flow considering plant transpiration is incorporated into a representation of effective stress to obtain the changes in matric suction, and effective stress. The representations are used to extend Hooke's law and Rankine's earth pressure theory to determine at-rest, active, and passive earth pressures. Subsequently, the analytical method is used in a series of analysis case studies on the influence of root architecture types, transpiration rates, and soil types on earth pressure, to reveal that it can rapidly obtain the earth pressure. Notably, the effect of plant transpiration on earth pressure is significant. Furthermore, it is found that soil types and transpiration rates have a larger influence than root architecture types. Collectively, the research not only reveals the effect of plant on earth pressure for retaining wall, but also provides a theoretical basis for further exploration of the contribution of plants to the stability of retaining wall.

7.
World J Clin Cases ; 11(14): 3340-3350, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37274027

RESUMO

BACKGROUND: Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL1) is a rare autosomal recessive severe neurometabolic disease. The aim of this study was to investigate the clinical characteristics and genetic pathogenicity of PEBEL1 caused by rare NAXE (or APOA1BP)-related defects. CASE SUMMARY: The patient was a girl aged 2 years and 10 mo. She was hospitalized due to walking disorder for > 40 d. The clinical manifestations were ataxia, motor function regression, hypotonia, and eyelid ptosis. Within 1 mo of hospitalization, she developed sigh breathing, respiratory failure, cerebellar edema and brain hernia, and finally she died. Changes were found in cranial imaging, including cerebellar edema accompanied by symmetrical myelopathy. Through whole exome sequencing, we detected NAXE compound heterozygous variation (NM 144772.3) c.733A>C (p. Lys245Gln, dbSNP: rs770023429) and novel variation c.370G>T (p.Gly124Cys) in the germline gene. The clinical features and core phenotypes of this case were consistent with 18 previously reported cases of PEBEL1. CONCLUSION: This is the first case of NAXE-related PEBEL1 with severe clinical phenotype in Mainland China. The p.Gly124Cys mutation discovered in this case has enriched the pathogenic variation spectrum of NAXE.

8.
Front Neurol ; 14: 1146349, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37181559

RESUMO

Objective: To compare the efficacy and safety of inpatient and outpatient initiation ketogenic diet (KD) protocol of pediatric refractory epilepsy. Methods: Eligible children with refractory epilepsy were randomly assigned to receive KD with inpatient and outpatient initiation. The generalized estimation equation (GEE) model was used to analyze the longitudinal variables of seizure reduction, ketone body, weight, height, body mass index (BMI), and BMI Z-score at different follow-up times between the two groups. Results: Between January 2013 and December 2021, 78 and 112 patients were assigned to outpatient and inpatient KD initiation groups, respectively. There were no statistical differences between the two groups based on baseline demographics and clinical characteristics (all Ps > 0.05). The GEE model indicated that the rate of reduction of seizures≥50% in the outpatient initiation group was higher than that of the inpatient initiation group (p = 0.049). A negative correlation was observed between the seizure reduction and blood ketone body at 1, 6, and 12 months (all Ps < 0.05). There were no significant differences in height, weight, BMI, and BMI Z-score between the two groups over the 12-month period by the GEE models (all Ps > 0.05). Adverse events were reported by 31 patients (43.05%) in the outpatient KD initiation group and 46 patients (42.20%) in the inpatient KD initiation group, but these differences were not statistically significant (p = 0.909). Conclusion: Our study shows that outpatient KD initiation is a safe and effective treatment for children with refractory epilepsy.

9.
Plants (Basel) ; 12(7)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37050124

RESUMO

Despite increasing evidence of kin recognition in natural and crop plants, there is a lack of knowledge of kin recognition in herbicide-resistant weeds that are escalating in cropping systems. Here, we identified a penoxsulam-resistant barnyardgrass biotype with the ability for kin recognition from two biotypes of penoxsulam-susceptible barnyardgrass and normal barnyardgrass at different levels of relatedness. When grown with closely related penoxsulam-susceptible barnyardgrass, penoxsulam-resistant barnyardgrass reduced root growth and distribution, lowering belowground competition, and advanced flowering and increased seed production, enhancing reproductive effectiveness. However, such kin recognition responses were not occurred in the presence of distantly related normal barnyardgrass. Root segregation, soil activated carbon amendment, and root exudates incubation indicated chemically-mediated kin recognition among barnyardgrass biotypes. Interestingly, penoxsulam-resistant barnyardgrass significantly reduced a putative signaling (-)-loliolide production in the presence of closely related biotype but increased production when growing with distantly related biotype and more distantly related interspecific allelopathic rice cultivar. Importantly, genetically identical penoxsulam-resistant and -susceptible barnyardgrass biotypes synergistically interact to influence the action of allelopathic rice cultivar. Therefore, kin recognition in plants could also occur at the herbicide-resistant barnyardgrass biotype level, and intraspecific kin recognition may facilitate cooperation between genetically related biotypes to compete with interspecific rice, offering many potential implications and applications in paddy systems.

10.
Front Nutr ; 9: 968868, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105574

RESUMO

Objective: To compare the serum 25-OH-VitD levels, the major marker of vitamin D (VitD) status, between healthy children and children with epilepsy before initiation of and during anti-seizure medications (ASMs) treatment and to evaluate the potential influence factors on 25-OH-VitD levels. Another major aim was to assess the potential role of VitD supplementation. Methods: For comparison, we finally enrolled and collected data from 6,338 healthy children presenting to Health Care Department and 648 children visiting primary care pediatricians with symptoms of epilepsy in Children's Hospital of Nanjing Medical University from January 2019 to June 2021. The demographic and biochemical characteristics of each child were extracted from the hospital information system. Results: Serum 25-OH-VitD levels in 648 children with epilepsy were significantly lower than those of 6,338 healthy children (P < 0.0001), and the percentage of VitD insufficiency and deficiency status in pediatric patients was 49.19%. Of note, the serum 25-OH-VitD levels in children with newly diagnosed epilepsy before receiving any ASMs treatment were also significantly lower than those in healthy controls. Interestingly, ASMs therapy, alone or in combination, did not consistently reduce baseline serum VitD levels in children with epilepsy. The lower serum VitD levels in pediatric patients than those in healthy children might be related to the disease itself, rather than the ASMs treatment. As expected, VitD supplementation substantially increased the serum 25-OH-VitD levels (P < 0.0001). More critically, children with epilepsy receiving VitD supplementation achieved good seizure control in our study. Significance: In this retrospective study, the childhood epilepsy before initiation of and during ASMs treatment decreased the serum 25-OH-VitD concentrations, suggesting a clear association between epileptic disease and the risk of VitD deficiency. ASMs coadministration and long-term valproic acid treatment did not worse VitD-deficiency status, but in the small group receiving VitD supplementation, there was a significant improvement in reduction of seizure frequency. Therefore, pediatric clinicians are urged to raise public awareness of epilepsy-associated VitD deficiency.

11.
Front Endocrinol (Lausanne) ; 13: 890218, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35957827

RESUMO

Background: Many studies have shown that diabetes is often closely related to oral squamous cell carcinoma (OSCC) occurrence and metastasis. Heat shock protein 70 (Hsp70) is a molecular chaperone related to diabetes complications. This study aims to investigate the role of Hsp70 in OSCC in expression of invadopodia-associated proteins. Methods: The expressions and correlation of HSP70, Hif1α, MMP2, MMP14, and cortactin were examined using bioinformatics analysis and verified by OSCC tissue microarrays. Assay in vitro was performed to analyze cell migration capacity after treatment with or without the HSP70 inhibitor. Results: The expressions of invadopodia-associated proteins were enhanced in OSCC tissues compared with paracarcinoma tissues and partially correlated with HSP70. Inhibiting HSP70 significantly decreased the cell viability, proliferation, and migration of OSCC cells. Conclusions: HSP70 may be involved in invadopodia-associated proteins in OSCC cells, which provides a promising method for treatment of OSCC metastasis.


Assuntos
Proteínas de Choque Térmico HSP70 , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Podossomos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Movimento Celular/genética , Movimento Celular/fisiologia , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Metástase Neoplásica/genética , Metástase Neoplásica/fisiopatologia , Podossomos/metabolismo , Podossomos/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
12.
Comput Med Imaging Graph ; 99: 102088, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35780703

RESUMO

Recently, deep convolutional neural networks have achieved great success for medical image segmentation. However, unlike segmentation of natural images, most medical images such as MRI and CT are volumetric data. In order to make full use of volumetric information, 3D CNNs are widely used. However, 3D CNNs suffer from higher inference time and computation cost, which hinders their further clinical applications. Additionally, with the increased number of parameters, the risk of overfitting is higher, especially for medical images where data and annotations are expensive to acquire. To issue this problem, many 2.5D segmentation methods have been proposed to make use of volumetric spatial information with less computation cost. Despite these works lead to improvements on a variety of segmentation tasks, to the best of our knowledge, there has not previously been a large-scale empirical comparison of these methods. In this paper, we aim to present a review of the latest developments of 2.5D methods for volumetric medical image segmentation. Additionally, to compare the performance and effectiveness of these methods, we provide an empirical study of these methods on three representative segmentation tasks involving different modalities and targets. Our experimental results highlight that 3D CNNs may not always be the best choice. Despite all these 2.5D methods can bring performance gains to 2D baseline, not all the methods hold the benefits on different datasets. We hope the results and conclusions of our study will prove useful for the community on exploring and developing efficient volumetric medical image segmentation methods.


Assuntos
Imageamento por Ressonância Magnética , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos
13.
J Int Med Res ; 50(5): 3000605221099013, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35549527

RESUMO

ß-thalassemia (ß-thal) is one of the most prevalent inherited blood disorders in Ganzhou, south China. Next-generation sequencing was used to screen for thalassemia carriers in the general population. During the screening, we identified a novel ß-thal variant in a 46-year-old Chinese man, which was validated by Sanger sequencing. Based on the patient's clinical data, this novel mutation was classified as severe ß0. However, the patient was mildly anemic (hemoglobin, 89 g/L), which was inconsistent with typical ß0 carrier characteristics. On further evaluation, quantitative PCR indicated the presence of six α genes, while molecular analysis and pedigree analysis revealed the coexistence of αααanti3.7 and αααanti4.2. Therefore, we report a novel ß-thal variant combined with six α genes. We describe the patient's clinical phenotype and the process of molecular diagnosis. This case extends the spectrum of thalassemia variants.


Assuntos
Globinas beta , Talassemia beta , Alelos , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Fenótipo , Globinas beta/genética , Talassemia beta/diagnóstico , Talassemia beta/genética
14.
Front Pediatr ; 10: 822096, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35273928

RESUMO

Background: O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant systemic disorder characterized by global developmental delay caused by mutations in the KMT2E gene. The aim of this study was to investigate the role of KMT2E mutations as a cause of ODLURO syndrome in a Chinese boy. Methods: We reported the clinical course of a Chinese boy who was diagnosed with ODLURO syndrome by the whole exome sequencing. We extracted genomic DNA of the proband and parents, gene variations were screened using whole-exome sequencing, followed by validation using direct Sanger sequencing. The effect of mRNA splicing variants were analyzed through a minigene splice assay and in vitro reverse transcription PCR (RT-PCR). Results: The proband presented with recurrent seizures and developmental delay. Using genetic analysis, we identified that the proband carried a de novo heterozygous splicing variant (c.1248+1G>T) in the KMT2E gene. In vivo transcript analysis showed that the proband did not carry any KMT2E mRNA transcript, while a specific exon11-exon13 (440 bp) transcript was detected in the unaffected parents. The in vitro minigene splice assay conducted in HEK293 cells confirmed that the c.1248+1G>T variant resulted in exon 12 skipping, which in turn caused an alteration in KMT2E mRNA splicing. The mutant transcript created a premature stop codon at the 378 amino acid position that could have been caused nonsense-mediated mRNA decay (NMD). Conclusion: We verified the pathogenic effect of the KMT2E c.1248+1G>T splicing variant, which disturbed normal mRNA splicing and caused mRNA decay. Our findings suggest that splice variants play an important role in the molecular basis of ODLURO, and that careful molecular profiling of these patients could play an essential role in tailoring of personalized treatment options soon.

16.
Micromachines (Basel) ; 12(11)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34832834

RESUMO

Digital microfluidic (DMF) has been a unique tool for manipulating micro-droplets with high flexibility and accuracy. To extend the application of DMF for automatic and in-site detection, it is promising to introduce colorimetric sensing based on gold nanoparticles (AuNPs), which have advantages including high sensitivity, label-free, biocompatibility, and easy surface modification. However, there is still a lack of studies for investigating the movement and stability of AuNPs for in-site detection on the electrowetting-based digital microfluidics. Herein, to demonstrate the ability of DMF for colorimetric sensing with AuNPs, we investigated the electrowetting property of the AuNPs droplets on the hydrophobic interface of the DMF chip and examined the stability of the AuNPs on DMF as well as the influence of evaporation to the colorimetric sensing. As a result, we found that the electrowetting of AuNPs fits to a modified Young-Lippmann equation, which suggests that a higher voltage is required to actuate AuNPs droplets compared with actuating water droplets. Moreover, the stability of AuNPs was maintained during the processing of electrowetting. We also proved that the evaporation of droplets has a limited influence on the detections that last several minutes. Finally, a model experiment for the detection of Hg2+ was carried out with similar results to the detections in bulk solution. The proposed method can be further extended to a wide range of AuNPs-based detection for label-free, automatic, and low-cost detection of small molecules, biomarkers, and metal ions.

17.
Front Neurol ; 10: 995, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31616359

RESUMO

Introduction: Acute cerebellar ataxia (ACA) is the most common form of pediatric ataxia. Changes in gut flora can modulate the nervous system, influencing brain function via the gut-brain axis (GBA). This study aimed to illustrate the relationship between intestinal microbiota and ACA. Method: A total of 30 and 12 children were randomly sampled from history of intestinal surgery (HOIS) and no intestinal surgery groups (NHOIS), respectively. In addition, 10 healthy children who sought physical examination in Children's Hospital of Nanjing Medical University were recruited as a control group. The stool samples were 16S rRNA detected. Results: We observed that many ACA children had intestinal surgery history prior to the onset of ACA. The 16S rRNA sequencing indicated that HOIS and control groups were well-distinguished by principal component analysis. The discrepancy between HOIS and NHOIS groups were also displayed by principal component analysis score plot. However, no differences were found between NHOIS and control groups. The results of student's t-test were consistent with principal component analysis. A total of nine different genera were identified between HOIS and control groups. Five genera and a phylum showed significant differences between HOIS and NHOIS groups. Conclusion: Altered genera and phyla associated with ACA were identified. Our findings provide new insight into treating and preventing ACA.

18.
Chem Biol Interact ; 308: 339-349, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31170387

RESUMO

Magnolol, the most abundant bioactive constituent of the Chinese herb Magnolia officinalis, has been found with multiple biological activities, including anti-oxidative, anti-inflammatory and enzyme-regulatory activities. In this study, the inhibitory effects and inhibition mechanism of magnolol on human carboxylesterases (hCEs), the key enzymes responsible for the hydrolytic metabolism of a variety of endogenous esters as well as ester-bearing drugs, have been well-investigated. The results demonstrate that magnolol strongly inhibits hCE1-mediated hydrolysis of various substrates, whereas the inhibition of hCE2 by magnolol is substrate-dependent, ranging from strong to moderate. Inhibition of intracellular hCE1 and hCE2 by magnolol was also investigated in living HepG2 cells, and the results showed that magnolol could strongly inhibit intracellular hCE1, while the inhibition of intracellular hCE2 was weak. Inhibition kinetic analyses and docking simulations revealed that magnolol inhibited both hCE1 and hCE2 in a mixed manner, which could be partially attributed to its binding at two distinct ligand-binding sites in each carboxylesterase, including the catalytic cavity and the regulatory domain. In addition, the potential risk of the metabolic interactions of magnolol via hCE1 inhibition was predicted on the basis of a series of available pharmacokinetic data and the inhibition constants. All these findings are very helpful in deciphering the metabolic interactions between magnolol and hCEs, and also very useful for avoiding deleterious interactions via inhibition of hCEs.


Assuntos
Compostos de Bifenilo/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , Lignanas/metabolismo , Sítios de Ligação , Biocatálise , Compostos de Bifenilo/química , Hidrolases de Éster Carboxílico/antagonistas & inibidores , Domínio Catalítico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Células Hep G2 , Humanos , Hidrólise , Cinética , Lignanas/química , Simulação de Acoplamento Molecular
19.
Eur J Pharmacol ; 853: 381-387, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31009636

RESUMO

Diabetic retinopathy is a common complication of diabetes that affects the retina due to a sustained high blood sugar level. Recent studies have demonstrated that high glucose-driven oxidative stress plays an important role in the microvascular complications of retina in diabetes. Oxidative stress occurs due to the excess of reactive oxygen species, which causes oxidative damage to retina, leading to the leak of tiny blood vessels, or acts as signaling molecules to trigger neovascularization, resulting in new fragile vessels. NADPH oxidase (NOX) is a key enzymatic source of reactive oxygen species in the retina, and it is involved in the early as well as the advanced stage of diabetic retinopathy. To date, at least 7 NOX isoforms, including NOX1 to NOX5, dual oxidase1 and dual oxidase 2, have been identified. It has been shown that NOX isoforms exert different roles in the pathogenesis of diabetic retinopathy. Intervention of NOX by its inhibitors or modulators shows beneficial effect on improving the retinal functions in the models of diabetic retinopathy in vivo or in vitro. Thereby, NOX might be a potential target for the therapy of diabetic retinopathy. The present review focuses on the role of NOX, particularly the NOX isoforms, in promoting the development of diabetic retinopathy. In addition, NOX isoforms as potential targets for therapy of diabetic retinopathy are also discussed.


Assuntos
Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/enzimologia , Terapia de Alvo Molecular/métodos , NADPH Oxidases/metabolismo , Animais , Humanos
20.
J Child Neurol ; 33(14): 909-917, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30303442

RESUMO

The present study examined whether serum biomarkers can predict the prognosis of childhood epilepsy, including seizure frequency, electroencephalographic (EEG) changes, and cognitive impairment. We measured serum concentrations of high mobility group protein B1 (HMGB1), interleukin-1ß (IL-1ß), S100 calcium-binding protein B (S-100B), glial fibrillary acidic protein (GFAP), and α1-antichymotrypsin (AACT) in 180 children with new-onset epilepsy and 40 healthy children. Cognitive evaluations were performed 18 months after the initial seizure episodes at diagnosis (ie, baseline visit). The relationship between serum biomarkers and epilepsy prognosis was investigated using Pearson correlation coefficients, logistic regression analyses, and receiver operating characteristic curves. Sixty-seven patients had generalized tonic-clonic seizures, 92 had focal motor seizures, and 21 had epileptic spasms. Serum concentrations of HMGB1, IL-1ß, S-100B, and GFAP were significantly higher in the epilepsy group within 24 hours of a seizure episode than in the control group. Furthermore, HMGB1 and IL-1ß were significant predictors of epilepsy prognosis. Receiver operating characteristic curve analysis revealed that HMGB1 could more accurately predict seizure frequency than IL-1ß; when the serum concentration of HMGB1 was >9.625 ng/mL, there was 80.6% sensitivity and 92.5% specificity for predicting seizure frequency reduction. In conclusion, HMGB1 and IL-1ß have a predictive value for epilepsy prognosis in children.


Assuntos
Epilepsia/sangue , Proteína HMGB1/sangue , Interleucina-1beta/sangue , Adolescente , Criança , Pré-Escolar , Eletroencefalografia , Epilepsia/diagnóstico por imagem , Feminino , Seguimentos , Proteína Glial Fibrilar Ácida/sangue , Humanos , Lactente , Recém-Nascido , Inteligência/fisiologia , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Fatores de Tempo , alfa 1-Antiquimotripsina/sangue
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