Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 278
Filtrar
1.
BMC Pediatr ; 24(1): 222, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561702

RESUMO

BACKGROUND AND OBJECTIVES: To investigate the relationship between body mass index (BMI) and blood biochemical indicators in early adolescence, and to provide ideas for early prevention of diseases and explore possible disease-related predictors. METHODS: 3125 participants aged 10 ∼ 14 years were selected from China from the survey of "China Nutrition and Health Surveillance ( 2016 ∼ 2017 ) ". Employing advanced statistical methods, including generalized linear models, heatmaps, hierarchical clustering, and generalized additive models, the study delved into the associations between BMI and various biochemical indicators. RESULTS: In early adolescence, indicators including systolic pressure, diastolic pressure, weight, height, BMI, hemoglobin, blood uric acid, serum creatinine, albumin, vitamin A presented increasing trends with the increase of age ( P < 0.05 ), whereas LDL-C, vitamin D, and ferritin showed decreasing trends with the increase of age ( P < 0.05 ). The increase in hemoglobin and blood uric acid levels with age was more pronounced in males compared to females ( P < 0.05 ). BMI was positively correlated with blood glucose, hemoglobin, triglyceride, LDL-C, blood uric acid, serum creatinine, ferritin, transferrin receptor, hs-CRP, total protein, vitamin A ( P < 0.05 ). There was a significant BMI × age interaction in the correlation analysis with LDL-C, transferrin receptor, serum creatinine, and hs-CRP ( P < 0.05 ). BMI was a risk factor for hypertension, hypertriglyceridemia, low high density lipoprotein cholesterolemia, and metabolic syndrome in all age groups ( OR > 1, P < 0.05 ). CONCLUSIONS: High BMI was a risk factor for hypertension, hypertriglyceridemia, low high density lipoprotein cholesterolemia, and MetS in early adolescents. With the focus on energy intake beginning in early adolescence, the maintenance of a healthy weight warrants greater attention.


Assuntos
Hipertensão , Hipertrigliceridemia , Masculino , Feminino , Humanos , Adolescente , Índice de Massa Corporal , Proteína C-Reativa/análise , LDL-Colesterol , Ácido Úrico , Creatinina , Vitamina A , Hipertensão/epidemiologia , Lipoproteínas HDL , Hemoglobinas/análise , Ferritinas , Receptores da Transferrina
2.
BMC Pediatr ; 24(1): 347, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769496

RESUMO

BACKGROUND: Among the neurological complications of influenza in children, the most severe is acute necrotizing encephalopathy (ANE), with a high mortality rate and neurological sequelae. ANE is characterized by rapid progression to death within 1-2 days from onset. However, the knowledge about the early diagnosis of ANE is limited, which is often misdiagnosed as simple seizures/convulsions or mild acute influenza-associated encephalopathy (IAE). OBJECTIVE: To develop and validate an early prediction model to discriminate the ANE from two common neurological complications, seizures/convulsions and mild IAE in children with influenza. METHODS: This retrospective case-control study included patients with ANE (median age 3.8 (2.3,5.4) years), seizures/convulsions alone (median age 2.6 (1.7,4.3) years), or mild IAE (median age 2.8 (1.5,6.1) years) at a tertiary pediatric medical center in China between November 2012 to January 2020. The random forest algorithm was used to screen the characteristics and construct a prediction model. RESULTS: Of the 433 patients, 278 (64.2%) had seizures/convulsions alone, 106 (24.5%) had mild IAE, and 49 (11.3%) had ANE. The discrimination performance of the model was satisfactory, with an accuracy above 0.80 from both model development (84.2%) and internal validation (88.2%). Seizures/convulsions were less likely to be wrongly classified (3.7%, 2/54), but mild IAE (22.7%, 5/22) was prone to be misdiagnosed as seizures/convulsions, and a small proportion (4.5%, 1/22) of them was prone to be misdiagnosed as ANE. Of the children with ANE, 22.2% (2/9) were misdiagnosed as mild IAE, and none were misdiagnosed as seizures/convulsions. CONCLUSION: This model can distinguish the ANE from seizures/convulsions with high accuracy and from mild IAE close to 80% accuracy, providing valuable information for the early management of children with influenza.


Assuntos
Influenza Humana , Convulsões , Humanos , Influenza Humana/complicações , Influenza Humana/diagnóstico , Pré-Escolar , Estudos Retrospectivos , Feminino , Masculino , Estudos de Casos e Controles , Convulsões/diagnóstico , Convulsões/etiologia , Criança , Lactente , Diagnóstico Diferencial , China/epidemiologia , Encefalopatias/diagnóstico , Encefalopatias/etiologia , Algoritmo Florestas Aleatórias
3.
J Allergy Clin Immunol ; 152(3): 622-632, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37178731

RESUMO

BACKGROUND: Cough-variant asthma (CVA) may respond differently to antiasthmatic treatment. There are limited data on the heterogeneity of CVA. OBJECTIVE: We aimed to classify patients with CVA using cluster analysis based on clinicophysiologic parameters and to unveil the underlying molecular pathways of these phenotypes with transcriptomic data of sputum cells. METHODS: We applied k-mean clustering to 342 newly physician-diagnosed patients with CVA from a prospective multicenter observational cohort using 10 prespecified baseline clinical and pathophysiologic variables. The clusters were compared according to clinical features, treatment response, and sputum transcriptomic data. RESULTS: Three stable CVA clusters were identified. Cluster 1 (n = 176) was characterized by female predominance, late onset, normal lung function, and a low proportion of complete resolution of cough (60.8%) after antiasthmatic treatment. Patients in cluster 2 (n = 105) presented with young, nocturnal cough, atopy, high type 2 inflammation, and a high proportion of complete resolution of cough (73.3%) with a highly upregulated coexpression gene network that related to type 2 immunity. Patients in cluster 3 (n = 61) had high body mass index, long disease duration, family history of asthma, low lung function, and low proportion of complete resolution of cough (54.1%). TH17 immunity and type 2 immunity coexpression gene networks were both upregulated in clusters 1 and 3. CONCLUSION: Three clusters of CVA were identified with different clinical, pathophysiologic, and transcriptomic features and responses to antiasthmatics treatment, which may improve our understanding of pathogenesis and help clinicians develop individualized cough treatment in asthma.


Assuntos
Antiasmáticos , Asma , Feminino , Masculino , Humanos , Tosse , Estudos Prospectivos , Fenótipo , Antiasmáticos/uso terapêutico
4.
Biochem Biophys Res Commun ; 655: 1-10, 2023 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-36907112

RESUMO

OBJECTIVE: A study has been conducted to investigate the relationship between DDX3X and nucleus pulposus (NP) pyroptosis. METHODS: DDX3X and pyroptosis-related proteins (Caspase-1, Full-length GSDMD, Cleaved GSDMD) were measured in compression-induced human NP cells and tissue. DDX3X was overexpressed or knocked down by gene transfection. The expressions of NLRP3, ASC, and pyroptosis-related proteins were detected by Western blot assay. IL-1ß and IL-18 were detected by ELISA. HE staining and immunohistochemistry were used to observe the expression of DDX3X, NLRP3, and Caspase-1 in the rat model of compression-induced disc degeneration. RESULTS: DDX3X, NLRP3, and Caspase-1 were highly expressed in degenerated NP tissue. Overexpression of DDX3X induced pyroptosis in NP cells and increased levels of NLRP3, IL-1ß, IL-18, and pyroptosis-related proteins. Knockdown of DDX3X showed an opposite trend to overexpression of DDX3X. The NLRP3 inhibitor CY-09 effectively prevented the up-regulation of the expression of IL-1ß, IL-18, ASC, Pro-caspase-1, Full-length GSDMD, and Cleaved GSDMD. Increased expression of DDX3X, NLRP3, and Caspase-1 was observed in the rat model of compression-induced disc degeneration. CONCLUSION: Our study showed that DDX3X mediates pyroptosis of NP cells by upregulating NLRP3 expression, which ultimately leads to intervertebral disc degeneration (IDD). This discovery deepens the understanding of IDD pathogenesis and provides a promising and novel therapeutic target for IDD.


Assuntos
Degeneração do Disco Intervertebral , Núcleo Pulposo , Humanos , Ratos , Animais , Núcleo Pulposo/metabolismo , Interleucina-18/metabolismo , Piroptose , Degeneração do Disco Intervertebral/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Caspase 1/metabolismo , Inflamassomos/metabolismo , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo
5.
Pharmacol Res ; 196: 106919, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37722517

RESUMO

Community-acquired pneumonia (CAP) is one of the most common infectious diseases, and its morbidity and mortality increase with age. Resistance and mutations development make the use of anti-infective therapy challenging. Chinese patent medicines (CPMs) are often used to treat CAP in China and well tolerable. However, currently there are no evidence-based guideline for the treatment of CAP with CPMs, and the misuse of CPMs is common. Therefore, we established a guideline panel to develop this guideline. We identified six clinical questions through two rounds of survey, and we then systematically searched relevant evidence and performed meta-analyses, evidence summaries and GRADE decision tables to draft recommendations, which were then voted on by a consensus panel using the Delphi method. Finally, we developed ten recommendations based on evidence synthesis and expert consensus. For the treatment of severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Xuebijing injection, Shenfu injection, and Shenmai injection respectively. For the treatment of non-severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Lianhua Qingwen capsule/granule, Qingfei Xiaoyan Pill and Shufeng Jiedu capsule respectively. CPMs have great potential to help in the fight against CAP worldwide, but more high-quality studies are still needed to strengthen the evidence.

6.
Eur Radiol ; 33(1): 11-22, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35771245

RESUMO

OBJECTIVE: The stratification of microsatellite instability (MSI) status assists clinicians in making treatment decisions for colorectal cancer (CRC) patients. This study aimed to establish a CT-based radiomics signature to predict MSI status in patients with CRC. METHODS: A total of 837 CRC patients who underwent preoperative enhanced CT and had available MSI status data were recruited from two hospitals. Radiomics features were extracted from segmented tumours, and a series of data balancing and feature selection strategies were used to select MSI-related features. Finally, an MSI-related radiomics signature was constructed using a genetic algorithm-enhanced artificial neural network model. Combined and clinical models were constructed using multivariate logistic regression analyses by integrating the clinical factors with or without the signature. A Kaplan-Meier survival analysis was conducted to explore the prognostic information of the signature in patients with CRC. RESULTS: Ten features were selected to construct a signature which showed robust performance in both the internal and external validation cohorts, with areas under the curves (AUC) of 0.788 and 0.775, respectively. The performance of the signature was comparable to that of the combined model (AUCs of 0.777 and 0.767, respectively) and it outperformed the clinical model constituting age and tumour location (AUCs of 0.768 and 0.623, respectively). Survival analysis demonstrated that the signature could stratify patients with stage II CRC according to prognosis (HR: 0.402, p = 0.029). CONCLUSIONS: This study built a robust radiomics signature for identifying the MSI status of CRC patients, which may assist individualised treatment decisions. KEY POINTS: • Our well-designed modelling strategies helped overcome the problem of data imbalance caused by the low incidence of MSI. • Genetic algorithm-enhanced artificial neural network-based CT radiomics signature can effectively distinguish the MSI status of CRC patients. • Kaplan-Meier survival analysis demonstrated that our signature could significantly stratify stage II CRC patients into high- and low-risk groups.


Assuntos
Neoplasias Colorretais , Instabilidade de Microssatélites , Humanos , Estudos Retrospectivos , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/genética , Redes Neurais de Computação , Tomografia Computadorizada por Raios X
7.
Eur Radiol ; 33(10): 6861-6871, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37171490

RESUMO

OBJECTIVES: The aim of this study is to evaluate the feasibility of clinicopathological characteristics and computed tomography (CT) morphological features in predicting lymph node metastasis (LNM) for patients with T1 colorectal cancer (CRC). METHODS: A total of 144 patients with T1 CRC who underwent CT scans and surgical resection were retrospectively included in our study. The clinicopathological characteristics and CT morphological features were assessed by two observers. Univariate and multiple logistic regression analyses were used to identify significant LNM predictive variables. Then a model was developed using the independent predictive factors. The predictive model was subjected to bootstrapping validation (1000 bootstrap resamples) to calculate the calibration curve and relative C-index. RESULTS: LNM were found in 30/144 patients (20.83%). Four independent risk factors were determined in the multiple logistic regression analysis, including presence of necrosis (adjusted odds ratio [OR] = 10.32, 95% confidence interval [CI] 1.96-54.3, p = 0.004), irregular outer border (adjusted OR = 5.94, 95% CI 1.39-25.45, p = 0.035), and heterogeneity enhancement (adjusted OR = 7.35, 95% CI 3.11-17.38, p = 0.007), as well as tumor location (adjusted ORright-sided colon = 0.05 [0.01-0.60], p = 0.018; adjusted ORrectum = 0.22 [0.06-0.83], p = 0.026). In the internal validation cohort, the model showed good calibration and good discrimination with a C-index of 0.89. CONCLUSIONS: There are significant associations between lymphatic metastasis status and tumor location as well as CT morphologic features in T1 CRC, which could help the doctor make decisions for additional surgery after endoscopic resection. KEY POINTS: • LNM more frequently occurs in left-sided T1 colon cancer than in right-sided T1 colon and rectal cancer. • CT morphologic features are risk factors for LNM of T1 CRC, which may be related to fundamental biological behaviors. • The combination of tumor location and CT morphologic features can more effectively assist in predicting LNM in patients with T1 CRC, and decrease the rate of unnecessary extra surgeries after endoscopic resection.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Humanos , Metástase Linfática/patologia , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Neoplasias do Colo/patologia , Fatores de Risco , Linfonodos/patologia
8.
Br J Nutr ; 130(10): 1657-1664, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-36944362

RESUMO

In recent years, obesity is a growing pandemic in the world and has likely contributed to increasing the incidence of obesity-related diseases. Fat mass and obesity-associated gene (FTO) is the first gene discovered which has a close connection with fat. Recent studies suggested that FTO gene has played an important role in the molecular mechanisms of many diseases. Obesity is considered to be a hereditary disease and can evoke many kinds of diseases, including polycystic ovary syndrome (PCOS), type 2 diabetes mellitus (T2DM), cancer, etc., whose exact possible molecular mechanisms responsible for the effect of FTO on obesity and obesity-related diseases remain largely unknown. In this review, we comprehensively discuss the correlation between FTO gene and obesity, cancer, PCOS, T2DM, as well as the molecular mechanism involved in these diseases.


Assuntos
Diabetes Mellitus Tipo 2 , Obesidade , Síndrome do Ovário Policístico , Feminino , Humanos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/genética , Genótipo , Obesidade/genética , Síndrome do Ovário Policístico/genética , Polimorfismo de Nucleotídeo Único , Proteínas
9.
Mol Biol Rep ; 50(5): 4527-4534, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36848006

RESUMO

Follicles consist of specialized somatic cells that encase a single oocyte. Follicle development is a process regulated by a variety of endocrine, paracrine, and secretory factors that work together to select follicles for ovulation. Zinc is an essential nutrient for the human body and is involved in many physiological processes, such as follicle development, immune response, homeostasis, oxidative stress, cell cycle progression, DNA replication, DNA damage repair, apoptosis, and aging. Zinc deficiency can lead to blocked oocyte meiotic process, cumulus expansion, and follicle ovulation. In this mini-review, we summarize the the role of zinc in follicular development.


Assuntos
Células da Granulosa , Zinco , Feminino , Humanos , Células da Granulosa/metabolismo , Zinco/metabolismo , Corpo Humano , Folículo Ovariano , Oócitos
10.
Nutr Neurosci ; 26(10): 1011-1018, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36062834

RESUMO

Objectives: This study aimed to investigate the association between sugar-sweetened beverages (SSB) consumption (including individual SSB) and cognitive function from the National Health and Nutrition Examination Survey (NHANES) and Food Patterns Equivalents Database (FPED) and whether it is age-dependent.Methods: Older adults aged 60 years old and over were included during the NHANES 2011-2014. SSB consumption was defined as the amount of added sugar obtained by connecting the NHANES and FPED. Cognitive function tests included the consortium to establish a registry for Alzheimer's disease test, Animal Fluency Test and Digit Symbol Substitution Test. We calculated z-score using the average of the total standardized scores on three cognitive tests to estimate the level of whole cognition. Multi-variable linear regression models and interaction analysis were conducted in this study.Results: For individual SSB types, increased carbonated soft drinks, sweetened tea, fruit drinks, energy drinks, and sport drinks were all significantly linked to declined cognitive function (P < 0.05), respectively. Nevertheless, interaction effects by age groups were not significant (P for interaction > 0.05).Discussion: SSB consumption (including individual SSB) was negatively associated with cognitive function, which was not age-dependent. Future studies may advance the knowledge in the field considering the association between SSB consumption and cognitive function.


Assuntos
Bebidas Energéticas , Bebidas Adoçadas com Açúcar , Animais , Bebidas/efeitos adversos , Bebidas Adoçadas com Açúcar/efeitos adversos , Inquéritos Nutricionais , Bebidas Gaseificadas , Cognição
11.
BMC Pregnancy Childbirth ; 23(1): 624, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37648962

RESUMO

BACKGROUND: Aneuploidy pregnancy is a severe major birth defect and causes about 50% spontaneous miscarriages with unknown etiology. To date, only a few epidemiological studies with small sample sizes have investigated the risk factors for aneuploidy pregnancy. TP53, MDM2, and miR-34b/c genes are implicated in tumorigenesis with aneuploidy, yet the function of their polymorphisms in aneuploidy pregnancy susceptibility needs to be clarified. OBJECTIVE: To elucidate the association of TP53 rs1042522 G > C, MDM2 rs2279744 309 T > G, and miR-34b/c rs4938723 T > C specific polymorphisms with aneuploidy pregnancy. METHODS: In the retrospective case-control study, 330 aneuploidies pregnancy women and 813 normal pregnancy controls were recruited between January 2018 and April 2022 at the First People's Hospital of Yunnan Province, Kunming, China. Three functional polymorphisms, the TP53 rs1042522 G > C (Arg72Pro), MDM2 rs2279744 309 T > G, and miR-34b/c rs4938723 T > C, were genotyped using the snapshot method. RESULTS: The frequency distribution of three genotypic variants was not different between case and control pregnant women and was similar to with Hardy-Weinberg Equilibrium (HWE). However, in the younger subgroup (less than 35 years old), a significant difference was detected in allele and recessive model (p = 0.01). In the advanced age subgroup (more than or equal to 35 years old), G of MDM2 rs2279744 T > G revealed a significantly higher frequency in cases than controls (p = 0.045), and miR-34b/c rs4938723 T > C revealed a significant difference under the dominant model (p = 0.03), but no significant differences were observed in other models and in both younger and older subgroup (p > 0.05, respectively). These results suggest that individual polymorphisms were not associated with aneuploidy pregnancy, combined with age, they may serve as a risk factor for aneuploidy pregnancy. CONCLUSION: Combination of TP53 rs1042522 G > C, MDM2 rs2279744 T > G, and miR-34b/c rs4938723 T > C polymorphisms with maternal age may be related to aneuploidy pregnancy susceptibility. These findings might elaborate on the genetic etiology of aneuploidy pregnancy.


Assuntos
Aneuploidia , MicroRNAs , Gravidez , Humanos , Feminino , Adulto , Estudos de Casos e Controles , China , Estudos Retrospectivos , MicroRNAs/genética , Proteína Supressora de Tumor p53/genética , Proteínas Proto-Oncogênicas c-mdm2/genética
12.
BMC Public Health ; 23(1): 2423, 2023 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-38053120

RESUMO

BACKGROUND AND AIM: The health implications of BMI and MetS in lactating women are significant. This study aims to investigate the relationship between risk of Mets in lactation and BMI in four stages: pre-pregnancy, prenatal period, 42 days postpartum, and current lactation. METHODS AND RESULTS: A total of 1870 Lactating Women within 2 years after delivery were included from "China Child and Lactating Mother Nutrition Health Surveillance (2016-2017)". Logistic regression model and Restricted cubic spline (RCS) were used to estimate the relationship between BMI and risk of MetS. ROC analysis was used to determine the threshold for the risk of MetS. Chain mediating effect analysis was used to verify the mediating effect. BMI of MetS group in all stages were higher than non-MetS group (P < 0.0001). There were significant positive correlations between BMI in each stage and ORs of MetS during lactation (P < 0.05). The best cut-off values for BMI in the four stages were 23.47, 30.49, 26.04 and 25.47 kg/m2. The non-linear spline test at BMI in 42 days postpartum, current and MetS in lactation was statistically significant (P non-linear = 0.0223, 0.0003). The mediation effect of all chains have to work through lactation BMI. The total indirect effect accounted for 80.95% of the total effect. CONCLUSIONS: The risk of MetS in lactating women is due to a high BMI base before pregnancy and postpartum. High BMI in all stages of pregnancy and postpartum were risk factors for MetS in lactation. BMI during lactation plays a key role in the risk of MetS.


Assuntos
Síndrome Metabólica , Feminino , Humanos , Gravidez , Índice de Massa Corporal , Aleitamento Materno , População do Leste Asiático , Lactação , Síndrome Metabólica/epidemiologia
13.
Food Microbiol ; 112: 104246, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36906310

RESUMO

This study aimed to investigate the time-course effect of Lactobacillus plantarum NJAU-01 in scavenging exogenous hydrogen peroxide (H2O2). The results showed that L. plantarum NJAU-01 at 107 CFU/mL was able to eliminate a maximum of 4 mM H2O2 within a prolonged lag phase and resume to proliferate during the following culture. Redox state in the start-lag phase (0 h, without the addition of H2O2), indicated by glutathione and protein sulfhydryl, was impaired in the lag phase (3 h and 12 h) and then gradually recovered during subsequent growing stages (20 h and 30 h). By using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and proteomics analysis, a total of 163 proteins such as PhoP family transcriptional regulator, glutamine synthetase, peptide methionine sulfoxide reductase, thioredoxin reductase, ribosomal proteins, acetolactate synthase, ATP binding subunit ClpX, phosphoglycerate kinase, UvrABC system protein A and UvrABC system protein B were identified as differential proteins across the entire growth phase. Those proteins were mainly involved in H2O2 sensing, protein synthesis, repairing proteins and DNA lesions, amino sugar and nucleotide sugar metabolism. Our data suggest that biomolecules of L. plantarum NJAU-01 are oxidized to passively consume H2O2 and are restored by the enhanced protein and/or gene repair systems.


Assuntos
Lactobacillus plantarum , Lactobacillus plantarum/metabolismo , Peróxido de Hidrogênio/farmacologia , Proteômica , Oxirredução , Proteínas de Bactérias/genética
14.
Phytother Res ; 37(2): 717-730, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36216328

RESUMO

Airway remodeling is one of the hallmarks of chronic obstructive pulmonary disease (COPD) and is closely related to the dysregulation of epithelial-mesenchymal transition (EMT). Smad3, an important transcriptional regulator responsible for transducing TGF-ß1 signals, is a promising target for EMT modulation. We found that ligustilide (Lig), a novel Smad3 covalent inhibitor, effectively inhibited airway remodeling in cigarette smoke (CS) combined with lipopolysaccharide (LPS)-induced COPD mice. Oral administration of an alkynyl-modified Lig probe was used to capture and trace target proteins in mouse lung tissue, revealing Smad3 in airway epithelium as a key target of Lig. Protein mass spectrometry and Smad3 mutation analysis via in-gel imaging indicated that the epoxidized metabolite of Lig covalently binds to the MH2 domain of Smad3 at Cys331/337. This irreversible bonding destroys the interaction of Smad3-SARA, prevents Smad3 phosphorylation activation, and subsequently suppresses the nuclear transfer of p-Smad3, the EMT process, and collagen deposition in TGF-ß1-stimulated BEAS-2B cells and COPD mice. These findings provide experimental support that Lig attenuates COPD by repressing airway remodeling which is attributed to its suppression on the activation of EMT process in the airway epithelium via targeting Smad3 and inhibiting the recruitment of the Smad3-SARA heterodimer in the TGF-ß1/Smad3 pathway.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Fator de Crescimento Transformador beta1 , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Remodelação das Vias Aéreas , Pulmão/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Epitélio/metabolismo , Transição Epitelial-Mesenquimal , Proteína Smad3/metabolismo
15.
Phytother Res ; 37(9): 4282-4297, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37282760

RESUMO

Transient receptor potential vanilloid 4 (TRPV4) plays a role in regulating pulmonary fibrosis (PF). While several TRPV4 antagonists including magnolol (MAG), have been discovered, the mechanism of action is not fully understood. This study aimed to investigate the effect of MAG on alleviating fibrosis in chronic obstructive pulmonary disease (COPD) based on TRPV4, and to further analyze its mechanism of action on TRPV4. COPD was induced using cigarette smoke and LPS. The therapeutic effect of MAG on COPD-induced fibrosis was evaluated. TRPV4 was identified as the main target protein of MAG using target protein capture with MAG probe and drug affinity response target stability assay. The binding sites of MAG at TRPV4 were analyzed using molecular docking and small molecule interaction with TRPV4-ankyrin repeat domain (ARD). The effects of MAG on TRPV4 membrane distribution and channel activity were analyzed by co-immunoprecipitation, fluorescence co-localization, and living cell assay of calcium levels. By targeting TRPV4-ARD, MAG disrupted the binding between phosphatidylinositol 3 kinase γ and TRPV4, leading to hampered membrane distribution on fibroblasts. Additionally, MAG competitively impaired ATP binding to TRPV4-ARD, inhibiting TRPV4 channel opening activity. MAG effectively blocked the fibrotic process caused by mechanical or inflammatory signals, thus alleviating PF in COPD. Targeting TRPV4-ARD presents a novel treatment strategy for PF in COPD.


Assuntos
Antineoplásicos , Doença Pulmonar Obstrutiva Crônica , Fibrose Pulmonar , Humanos , Repetição de Anquirina , Fibrose Pulmonar/metabolismo , Canais de Cátion TRPV/metabolismo , Simulação de Acoplamento Molecular , Fibrose
16.
Int J Vitam Nutr Res ; 93(2): 142-153, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34233510

RESUMO

Background: The impact of the dietary B vitamins intakes on the development of depression has been scarcely investigated. Thus, this study aimed to examine the associations of dietary B vitamins intakes with the risk of depression in American adults. Methods: The data we used in this study were from the National Health and Nutrition Examination Survey (NHANES) 2007-2014. We used the Logistic regression models to analyze the associations of the dietary intakes of B vitamins with the risk of depression. Results: 17,732 individuals (8,623 males and 9,109 females) were enrolled in the study and they were all 18 or older. Compared to the lowest quartile of dietary intake, the ORs (95%CIs) of the highest quartile were 0.64 (0.50-0.82), 0.78 (0.62-0.97), 0.60 (0.47-0.78), 0.65 (0.50-0.84), and 0.71 (0.54-0.95) for vitamin B1, vitamin B2, niacin, vitamin B6, and vitamin B12, respectively. Compared to the people whose dietary intakes below the RDA in the model 2, those with intake meeting the RDA of vitamin B1 (OR: 0.68; 95%CI: 0.56-0.84), niacin (OR: 0.65; 95%CI: 0.51-0.81), B6 (OR: 0.65; 95%CI: 0.52-0.81), or B12 (OR: 0.65; 95%CI: 0.48-0.88) had a lower risk of depression, severally. We also found a nonlinear negative association between dietary vitamin B1, vitamin B2, niacin, vitamin B6, and vitamin B12 intakes and the risk of depression in the dose-response analyses, severally. Conclusions: Our results suggested that dietary vitamin B1, vitamin B2, niacin, vitamin B6, and vitamin B12 intakes may be inversely associated with the risk of depression.


Assuntos
Niacina , Complexo Vitamínico B , Masculino , Feminino , Adulto , Humanos , Inquéritos Nutricionais , Depressão/epidemiologia , Vitamina B 12 , Riboflavina , Vitamina B 6 , Vitamina A , Vitamina K , Ingestão de Alimentos , Tiamina , Ácido Fólico
17.
Molecules ; 28(13)2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37446662

RESUMO

Gentian is a traditional Chinese herb with heat-clearing, damp-drying, inflammation-alleviating and digestion-promoting effects, which is widely used in clinical practice. However, there are many species of gentian. According to the pharmacopoeia, Gentiana manshurica Kitag, Gentiana scabra Bge, Gentiana triflora Pall and Gentianarigescens Franch are included. Therefore, accurately identifying the species of gentian is important in clinical use. In recent years, with the advantages of low cost, convenience, fast analysis and high sensitivity, infrared spectroscopy (IR) has been extensively used in herbal identification. Unlike one-dimensional spectroscopy, a two-dimensional correlation spectrum (2D-COS) can improve the resolution of the spectrum and better highlight the details that are difficult to detect. In addition, the residual neural network (ResNet) is an important breakthrough in convolutional neural networks (CNNs) for significant advantages related to image recognition. Herein, we propose a new method for identifying gentian-related species using 2D-COS combined with ResNet. A total of 173 gentian samples from seven different species are collected in this study. In order to eliminate a large amount of redundant information and improve the efficiency of machine learning, the extracted feature band method was used to optimize the model. Four feature bands were selected from the infrared spectrum, namely 3500-3000 cm-1, 3000-2750 cm-1, 1750-1100 cm-1 and 1100-400 cm-1, respectively. The one-dimensional spectral data were converted into synchronous 2D-COS images, asynchronous 2D-COS images, and integrative 2D-COS images using Matlab (R2022a). The identification strategy for these three 2D-COS images was based on ResNet, which analyzes 2D-COS images based on single feature bands and full bands as well as fused feature bands. According to the results, (1) compared with the other two 2D-COS images, synchronous 2D-COS images are more suitable for the ResNet model, and (2) after extracting a single feature band 1750-1100 cm-1 to optimize ResNet, the model has the best convergence performance, the accuracy of training, test and external validation is 1 and the loss value is only 0.155. In summary, 2D-COS combined with ResNet is an effective and accurate method to identify gentian-related species.


Assuntos
Gentiana , Gentiana/química , Redes Neurais de Computação , Espectrofotometria Infravermelho , Aprendizado de Máquina , Temperatura Alta
18.
Respir Res ; 23(1): 243, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36096782

RESUMO

BACKGROUND: Asthma is a heterogeneous disease with variable symptoms, which presents with cough either as the sole or predominant symptom with or without wheezing. We compared the clinical and pathophysiological characteristics of cough predominant asthma (CPA), cough variant asthma (CVA) and classic asthma (CA) in order to determine any differential phenotypic traits. METHODS: In 20 clinics across China, a total of 2088 patients were finally recruited, including 327 CVA, 1041 CPA and 720 CA patients. We recorded cough and wheezing visual analogue scale, Leicester cough questionnaire (LCQ) and asthma control test scores. Fractional exhaled nitric oxide (FeNO), induced sputum cell counts, and capsaicin cough challenge were also measured and compared. RESULTS: CPA patients more frequently presented with cough as the initial symptom, and laryngeal symptoms (p < 0.001), had less symptoms related with rhinitis/sinusitis and gastroesophageal reflux (p < 0.05) than CA patients. Comorbidities including rhinitis and gastroesophageal reflux were similar, while the proportion of COPD and bronchiectasis was higher in CA patients. There were no differences in FeNO levels, sputum eosinophil and neutrophil counts, FEV1 (%pred) decreased from CVA to CPA to CA patients (p < 0.001). Cough sensitivity was higher in CVA and CPA compared to CA (p < 0.001), and was positively correlated with LCQ scores. CONCLUSIONS: CVA, CPA and CA can be distinguished by the presence of laryngeal symptoms, cough sensitivity and airflow obstruction. Asthma-associated chronic cough was not associated with airway inflammation or comorbidities in our cohort. Trial registration The Chinese Clinical Trial Registration Center, ChiCTR-POC-17011646, 13 June 2017.


Assuntos
Asma , Refluxo Gastroesofágico , Rinite , Asma/complicações , Asma/diagnóstico , Asma/epidemiologia , Tosse/diagnóstico , Tosse/epidemiologia , Humanos , Óxido Nítrico , Fenótipo , Estudos Prospectivos , Sons Respiratórios , Rinite/complicações , Inquéritos e Questionários
19.
Reprod Biol Endocrinol ; 20(1): 80, 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35597951

RESUMO

SCOPE: Male fertility and sperm quality are negatively affected by psychological stress. Chronic restraint stress (CRS) is a common psychological stress that has a negative effect on sperm. Betaine (BET), an active ingredient isolated from Lycium barbarum, has anti-oxidant, anti-inflammatory and other pharmacological activities. This study aims to explore whether betaine has a therapeutic effect on sperm deformity and vitality under CRS and its mechanism. METHODS AND RESULTS: Chronic restraint stress was induced in 8-week-old male C57BL/6 J mice by fixation for 6 h a day for 35 days. Mice were intraperitoneally injected with betaine (BET) or normal saline (NS) for 14 days. Thirty-five days later, the animals were sacrificed. The results showed that the detrimental effects of CRS on testes as evident by disrupted histoarchitecture, increased oxidative stress, inflammation and apoptosis that compromised male fertility. BET injections can reverse these symptoms. CONCLUSIONS: BET can improve spermatogenesis dysfunction caused by CRS, which may provide potential dietary guidance.


Assuntos
Betaína , Testículo , Animais , Betaína/metabolismo , Betaína/farmacologia , Betaína/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Espermatogênese , Testículo/metabolismo
20.
Genet Res (Camb) ; 2022: 2917881, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36245555

RESUMO

Background: We aimed to investigate the associations of various genetic variants in the nicotine metabolism pathway with smoking cessation (SC) in the Chinese Han population. Method: A case-control study was conducted where 363 successful smoking quitters were referred to as cases, and 345 failed smoking quitters were referred to as controls. A total of 42 genetic variants in 10 genes were selectedand genotyped. The weighted gene score was applied to analyze the whole gene effect. Logistic regression was used to explore associations of each genetic variant and gene score with smoking cessation. Results: Our study found that the variants CYP2A6∗4, rs11726322, rs12233719, and rs3100 were associated with a higher probability of quitting smoking, while rs3760657 was associated with a lower probability of quitting smoking. Moreover, the gene scores of CYP2D6, FMO3, UGT2B10, UGT1A9, UGT2B7, and UGT2B15 were shown to exert a positive effect, while the gene score of CYP2B6 was detected to exert a negative effect on successful smoking cessation. Conclusion: This study revealed that genetic variants in the nicotine metabolic pathway were associated with smoking cessation in the Chinese Han population.


Assuntos
Abandono do Hábito de Fumar , Estudos de Casos e Controles , Citocromo P-450 CYP2B6 , Citocromo P-450 CYP2D6 , Glucuronosiltransferase/genética , Humanos , Nicotina/genética , Nicotina/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA