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1.
Biomed Opt Express ; 15(4): 2498-2516, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38633068

RESUMO

Comprehensive visualization and accurate extraction of tumor vasculature are essential to study the nature of glioma. Nowadays, tissue clearing technology enables 3D visualization of human glioma vasculature at micron resolution, but current vessel extraction schemes cannot well cope with the extraction of complex tumor vessels with high disruption and irregularity under realistic conditions. Here, we developed a framework, FineVess, based on deep learning to automatically extract glioma vessels in confocal microscope images of cleared human tumor tissues. In the framework, a customized deep learning network, named 3D ResCBAM nnU-Net, was designed to segment the vessels, and a novel pipeline based on preprocessing and post-processing was developed to refine the segmentation results automatically. On the basis of its application to a practical dataset, we showed that the FineVess enabled extraction of variable and incomplete vessels with high accuracy in challenging 3D images, better than other traditional and state-of-the-art schemes. For the extracted vessels, we calculated vascular morphological features including fractal dimension and vascular wall integrity of different tumor grades, and verified the vascular heterogeneity through quantitative analysis.

2.
Front Immunol ; 15: 1376838, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590521

RESUMO

Background: Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system. Currently, the pathological mechanisms of MS are not fully understood, but research has suggested that iron metabolism disorder may be associated with the onset and clinical manifestations of MS. Methods and materials: The study utilized publicly available databases and bioinformatics techniques for gene expression data analysis, including differential expression analysis, weighted correlation network analysis, gene enrichment analysis, and construction of logistic regression models. Subsequently, Mendelian randomization was used to assess the causal relationship between different iron metabolism markers and MS. Results: This study identified IREB2, LAMP2, ISCU, ATP6V1G1, ATP13A2, and SKP1 as genes associated with multiple sclerosis (MS) and iron metabolism, establishing their multi-gene diagnostic value for MS with an AUC of 0.83. Additionally, Mendelian randomization analysis revealed a potential causal relationship between transferrin saturation and MS (p=2.22E-02; OR 95%CI=0.86 (0.75, 0.98)), as well as serum transferrin and MS (p=2.18E-04; OR 95%CI=1.22 (1.10, 1.36)). Conclusion: This study comprehensively explored the relationship between iron metabolism and MS through integrated bioinformatics analysis and Mendelian randomization methods. The findings provide important insights for further research into the role of iron metabolism disorder in the pathogenesis of MS and offer crucial theoretical support for the treatment of MS.


Assuntos
Distúrbios do Metabolismo do Ferro , Esclerose Múltipla , Humanos , Esclerose Múltipla/genética , Genes Reguladores , Transferrinas , Ferro
3.
Physiol Behav ; 279: 114530, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38552706

RESUMO

Depression is a serious mental illness. Previous studies found that early life stress (ELS) plays a vital role in the onset and progression of depression. However, relevant studies have not yet been able to explain the specific effects of early stress on stress-induced depression sensitivity and individual behavior during growth. Therefore, we constructed a maternal separation (MS) model and administered chronic social frustration stress at different stages of their growth while conducting metabolomics analysis on the hippocampus of mice. Our results showed that the immobility time of mice in the forced swimming test was significantly reduced at the end of MS. Meanwhile, mice with MS experience significantly decreased total movement distance in the open field test and sucrose preference ratio in the sucrose preference test when subjected to chronic social defeat stress (CSDS) during adolescence. In adulthood, the results were the opposite. In addition, we found that level changes in metabolites such as Beta-alanine, l-aspartic acid, 2-aminoadipic acid, and Glycine are closely related to behavioral changes. These metabolites are mainly enriched in Pantothenate, CoA biosynthesis, and Beta Alanine metabolism pathways. Our experiment revealed that the effects of ELS vary across different age groups. It will increase an individual's sensitivity to depression when facing CSDS in adolescence, but it will reduce their sensitivity to depression when facing CSDS in adulthood. This may be achieved by regulating the hippocampus's Pantothenate and CoA biosynthesis and Beta Alanine metabolism pathways represented by Beta-alanine, l-Aspartic acid, 2-aminoadipic acid, and Glycine metabolites.


Assuntos
Depressão , Privação Materna , Camundongos , Animais , Depressão/etiologia , Depressão/metabolismo , Ácido 2-Aminoadípico/metabolismo , Ácido 2-Aminoadípico/farmacologia , Hipocampo/metabolismo , Glicina/farmacologia , Sacarose/farmacologia , beta-Alanina/metabolismo , beta-Alanina/farmacologia , Estresse Psicológico/metabolismo , Comportamento Animal/fisiologia , Modelos Animais de Doenças
4.
Front Immunol ; 15: 1339649, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348026

RESUMO

Background: There is increasing evidence that the types of immune cells are associated with various neurodegenerative diseases. However, it is currently unclear whether these associations reflect causal relationships. Objective: To elucidate the causal relationship between immune cells and neurodegenerative diseases, we conducted a two-sample Mendelian randomization (MR) analysis. Materials and methods: The exposure and outcome GWAS data used in this study were obtained from an open-access database (https://gwas.mrcieu.ac.uk/), the study employed two-sample MR analysis to assess the causal relationship between 731 immune cell features and four neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). All immune cell data was obtained from Multiple MR methods were used to minimize bias and obtain reliable estimates of the causal relationship between the variables of interest and the outcomes. Instrumental variable selection criteria were restricted to ensure the accuracy and effectiveness of the causal relationship between species of immune cells and the risk of these neurodegenerative diseases. Results: The study identified potential causal relationships between various immune cells and different neurodegenerative diseases. Specifically, we found that 8 different types of immune cells have potential causal relationships with AD, 1 type of immune cells has potential causal relationships with PD, 6 different types of immune cells have potential causal relationships with ALS, and 6 different types of immune cells have potential causal relationships with MS. Conclusion: Our study, through genetic means, demonstrates close causal associations between the specific types of immune cells and AD, PD, ALS and MS, providing useful guidance for future clinical researches.


Assuntos
Doença de Alzheimer , Esclerose Lateral Amiotrófica , Esclerose Múltipla , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doenças Neurodegenerativas/genética , Esclerose Lateral Amiotrófica/genética , Doença de Alzheimer/genética , Doença de Parkinson/genética , Causalidade , Esclerose Múltipla/genética
5.
Am J Epidemiol ; 193(4): 580-595, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37946325

RESUMO

There's a paucity of robust normal fractional limb and organ volume standards from a large and diverse ethnic population. The Fetal 3D Study was designed to develop research and clinical applications for fetal soft tissue and organ volume assessment. The NICHD Fetal Growth Studies (2009-2013) collected 2D and 3D fetal volumes. In the Fetal 3D Study (2015-2019), sonographers performed longitudinal 2D and 3D measurements for specific fetal anatomical structures in research ultrasounds of singletons and dichorionic twins. The primary aim was to establish standards for fetal body composition and organ volumes, overall and by maternal race/ethnicity, and determine whether these standards vary for twins versus singletons. We describe the study design, methods, and details about reviewer training. Basic characteristics of this cohort, with their corresponding distributions of fetal 3D measurements by anatomical structure, are summarized. This investigation is responsive to critical data gaps in understanding serial changes in fetal subcutaneous fat, lean body mass, and organ volume in association with pregnancy complications. In the future, this cohort can answer critical questions regarding the potential influence of maternal characteristics, lifestyle factors, nutrition, and biomarker and chemical data on longitudinal measures of fetal subcutaneous fat, lean body mass, and organ volumes.


Assuntos
National Institute of Child Health and Human Development (U.S.) , Cuidado Pré-Natal , Gravidez , Feminino , Estados Unidos , Humanos , Estudos de Coortes , Idade Gestacional , Desenvolvimento Fetal , Composição Corporal , Ultrassonografia Pré-Natal
6.
Int Wound J ; 21(1): e14403, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37735819

RESUMO

This analysis systematically reviewed the efficacy of evidence-based care on diabetic foot ulcers. A computerised literature search was conducted for randomised controlled studies (RCTs) of evidence-based care interventions for the treatment of diabetic foot ulcers using the PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM) and Wanfang databases from the date of inception of each database to June 2023. The articles were independently screened, data were extracted by two researchers, and the quality of each study was assessed using the Cochrane bias assessment tool. Meta-analysis of the data was performed using RevMan 5.4 software. Twenty-five RCTs with a total of 2272 patients were included. Meta-analysis showed that, compared with other care methods, evidence-based care significantly improved the treatment efficacy of diabetic foot ulcers (odds ratio: 3.91, 95% confidence interval [CI]: 2.76 to 5.53, p < 0.001) and significantly reduced their fasting plasma glucose (mean difference [MD]: -1.10, 95% CI: -1.24 to -0.96, p < 0.001), 2-h postprandial glucose (2hPG) (MD: -1.69, 95% CI: -2.07 to -1.31, p < 0.001) and glycated haemoglobin (HbA1c) (MD: -0.71, 95% CI: -0.94 to -0.48, p < 0.001). Evidence-based care intervention is effective at reducing FPG, 2hPG and HbA1c levels and improving treatment efficacy in patients with diabetic foot ulcers.


Assuntos
Diabetes Mellitus , Pé Diabético , Humanos , Pé Diabético/terapia , Medicina Baseada em Evidências , Hemoglobinas Glicadas , Resultado do Tratamento , China
7.
Sci Rep ; 13(1): 21606, 2023 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-38062190

RESUMO

This study aimed to investigate the relationship between hypertension and Alzheimer's disease (AD) and demonstrate the key role of stroke in this relationship using mediating Mendelian randomization. AD, a neurodegenerative disease characterized by memory loss, cognitive impairment, and behavioral abnormalities, severely affects the quality of life of patients. Hypertension is an important risk factor for AD. However, the precise mechanism underlying this relationship is unclear. To investigate the relationship between hypertension and AD, we used a mediated Mendelian randomization method and screened for mediating variables between hypertension and AD by setting instrumental variables. The results of the mediated analysis showed that stroke, as a mediating variable, plays an important role in the causal relationship between hypertension and AD. Specifically, the mediated indirect effect value for stroke obtained using multivariate mediated MR analysis was 54.9%. This implies that approximately 55% of the risk of AD owing to hypertension can be attributed to stroke. The results suggest that the increased risk of AD owing to hypertension is mediated through stroke. The finding not only sheds light on the relationship between hypertension and AD but also indicates novel methods for the prevention and treatment of AD. By identifying the critical role of stroke in the link between hypertension and AD, this study provides insights into potential interventions that could mitigate the impact of hypertension on AD. This could help develop personalized treatments and help improve the quality of life of patients with AD who suffer from hypertension.


Assuntos
Doença de Alzheimer , Hipertensão , Doenças Neurodegenerativas , Acidente Vascular Cerebral , Humanos , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Análise da Randomização Mendeliana , Qualidade de Vida , Hipertensão/complicações , Hipertensão/genética , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único
8.
Eur J Med Chem ; 259: 115696, 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37542990

RESUMO

Glycyrrhizin (GL) is one of the antagonists of highly conserved nuclear protein (HMGB1). The researches have shown that the glycosyl of GL is an important pharmacophore for GL binding to HMGB1, and it is the determinant factor for mechanism of action. To get the HMGB1 inhibitors with higher activity and good pharmacokinetic properties, two classes of GL analogues containing C-N glycoside bond were synthesized, and their anti-inflammatory, anti-oxidative stress and anti-septic kidney injury were evaluated. The results are as follows. First, in the anti-inflammatory assay, all the compounds inhibited NO release in some degree; among them, compound 6 displayed the strongest NO inhibitory effect with IC50 value of 15.9 µM, and compound 15 with IC50 of 20.2 µM. The two compounds not only decreased IL-1ß and TNF-α levels in RAW264.7 cells and HK-2 cells, but also downregulated the levels of NLRP3, P-NF-κB p65 and HMGB1 in activated HK-2 cells in a dose-dependent manner. Second, in the renal protection assay with H2O2-stimulated HK-2 cell line, they reduced MDA level and increased SOD in HK-2 cells; additionally, they also inhibited the HK-2 cell apoptosis and downregulated the Caspase-1 p20 level. Third, in the in vivo activity tests of the septic mouse, they also showed good activities just like in vitro, decreasing the IL-1ß, TNF-α, MDA, blood creatinine (Scr) and urea nitrogen (BUN) in serum, and increasing SOD levels in a dose-dependent manner. The immunoblotting results showed the two compounds downregulated the levels of HMGB1, P-NF-κB p65, NLRP3 and Caspase-1 p20 protein. All in all, the two compounds improved the renal injury of septic mice, and alleviated the tube wall structure damage and renal tubular dilation in kidney, which further proved by H&E staining. This suggests the two compounds have septic acute kidney injury activity, and they will be potential therapeutic drugs for septic acute kidney injury.


Assuntos
Injúria Renal Aguda , Proteína HMGB1 , Sepse , Camundongos , Animais , Ácido Glicirrízico/farmacologia , Ácido Glicirrízico/uso terapêutico , NF-kappa B/metabolismo , Proteína HMGB1/metabolismo , Proteína HMGB1/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Peróxido de Hidrogênio , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Sepse/tratamento farmacológico , Sepse/metabolismo , Caspases , Superóxido Dismutase
9.
Open Life Sci ; 18(1): 20220675, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37589011

RESUMO

With the continuous development of the pharmaceutical industry, people have always paid attention to the safety and effectiveness of drugs, including innovative drugs and generic drugs. For pharmaceutical companies as manufacturers, drug development is a very lengthy process that requires high costs, millions of man-hours, thousands of trials, and the mobilization of hundreds of researchers. Therefore, efforts need to be made to develop drugs with high safety and effectiveness. Drug research and development plays an important role today. Based on this, this article applied computer molecular simulation embedded technology and artificial intelligence technology to drug research and development. First, the problems faced in the research and development of anti-inflammatory disease-dependent tumor drugs were introduced, and then the applications of computer molecular simulation embedded technology and artificial intelligence technology in drug research and development were analyzed. Subsequently, the application of artificial intelligence in drug research and development teaching was analyzed, and a teaching system based on computer molecular simulation embedded technology and artificial intelligence was designed. Finally, the application effects of computer molecular simulation embedded technology and artificial intelligence technology were analyzed, and a feasible conclusion was drawn. The use of computer molecular simulation embedded technology and artificial intelligence technology can greatly improve the efficiency of drug research and development, and the research and development safety of imatinib mesylate has been improved by 7%. On the other hand, it can improve students' learning interest and stimulate their learning interest, and students' drug research and development capabilities have been improved. Drug research and development for inflammatory-dependent tumors has good application prospects.

10.
Bioorg Chem ; 138: 106609, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37207595

RESUMO

Cardiac tissue suffers much from sepsis, and the incidence of myocardial injury is high in septic patients. The treatment of sepsis myocardial injury (SMI) has been the focus of clinical medicine. Salidroside shows myocardial cell protection, anti-oxidation and anti- inflammation effects, and it is thought as one of the potential compounds to treat sepsis myocardial injury. However, its anti-inflammatory activity is lower and its pharmacokinetic properties are not ideal, which is far from clinical application. Here, a series of salidroside analogs were synthesized, and their bioactivities were evaluated from several aspects, including their anti-oxidant and anti-inflammatory activities in vitro and anti-sepsis myocardial injury activities in vivo. Of all the compounds which synthesized, compounds 2 and 3 exhibited stronger anti-inflammatory activities than the others; after treating LPS-stimulated RAW264.7 or H9c2 cells with each of them, the levels of IL-1ß, IL-6 and TNF-α were down-regulated in a dose-dependent manner. In the anti-oxidative stress injury test, compounds 2 and 3 not only markedly increased the survival rate of cells, and but also improved the cellular oxidative stress-related indicators MDA, SOD and cell damage marker LDH in a dose-dependent manner. In the LPS-induced septic rat myocardial injury models (in vivo), the two compounds also showed good bioactivities. They also reduced the expression of IL-1ß, IL-6 and TNF-α, and blocked cell damage by suppressing overhauled oxidation in septic rats. In addition, the myocardial injury was significantly improved and the inflammatory infiltration was reduced after treatment with the two compounds. In conclusion, the salidroside analogs (2 and 3) showed promising therapeutical effect on septic myocardial injury in LPS-model rats, and they could be good candidates for clinical trials against inflammation and septic myocardial injury.


Assuntos
Sepse , Fator de Necrose Tumoral alfa , Ratos , Animais , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Sepse/tratamento farmacológico , Inflamação
12.
J Neuropathol Exp Neurol ; 82(5): 376-389, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-37023472

RESUMO

In recent years, tissue clearing has revolutionized the way we view biological materials. This has resulted in considerable advances in neuropathology and brain imaging. Its application to gliomas has the potential to increase understanding of tumor architecture, reveal mechanisms of tumor invasion, and provide valuable insights into diagnostics and treatments. This review outlines numerous tissue-clearing applications and recent developments in glioma research and delineates the limitations of existing technology and potential applications in experimental and clinical oncology.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Glioma/diagnóstico por imagem , Glioma/patologia , Encéfalo/patologia , Imageamento Tridimensional , Microambiente Tumoral
13.
PLoS One ; 18(3): e0282791, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36928064

RESUMO

BACKGROUND: Customized fetal growth charts assume birthweight at term to be normally distributed across the population with a constant coefficient of variation at earlier gestational ages. Thus, standard deviation used for computing percentiles (e.g., 10th, 90th) is assumed to be proportional to the customized mean, although this assumption has never been formally tested. METHODS: In a secondary analysis of NICHD Fetal Growth Studies-Singletons (12 U.S. sites, 2009-2013) using longitudinal sonographic biometric data (n = 2288 pregnancies), we investigated the assumptions of normality and constant coefficient of variation by examining behavior of the mean and standard deviation, computed following the Gardosi method. We then created a more flexible model that customizes both mean and standard deviation using heteroscedastic regression and calculated customized percentiles directly using quantile regression, with an application in a separate study of 102, 012 deliveries, 37-41 weeks. RESULTS: Analysis of term optimal birthweight challenged assumptions of proportionality and that values were normally distributed: at different mean birthweight values, standard deviation did not change linearly with mean birthweight and the percentile computed with the normality assumption deviated from empirical percentiles. Composite neonatal morbidity and mortality rates in relation to birthweight < 10th were higher for heteroscedastic and quantile models (10.3% and 10.0%, respectively) than the Gardosi model (7.2%), although prediction performance was similar among all three (c-statistic 0.52-0.53). CONCLUSIONS: Our findings question normality and constant coefficient of variation assumptions of the Gardosi customization method. A heteroscedastic model captures unstable variance in customization characteristics which may improve detection of abnormal growth percentiles. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00912132.


Assuntos
Desenvolvimento Fetal , Cuidado Pré-Natal , Feminino , Humanos , Recém-Nascido , Gravidez , Peso ao Nascer , Feto , Idade Gestacional , Valores de Referência , Ultrassonografia Pré-Natal
14.
J Biophotonics ; 16(5): e202200357, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36633394

RESUMO

The 3D visualization based on tissue clearing technology allows us to have a deeper understanding of the 3D spatial information of deep molecules in the tissue. Tissue clearing and bacterial labeling methods have been used for in situ 3D microbiota imaging, and we have developed a pipeline for 3D visualization of in situ microbiota in human gliomas. Anti-LPS antibodies are appropriate to label and characterize bacteria in situ within tumors. However, autofluorescence (AF) is common in biological tissues, especially in brain tissues filled with lipofuscin-like (LF) substances. This natural fluorescent signal is usually considered to be a problem because it affects the 3D visualization of fluorescent signals in bacterial LPS staining. Here, we used Sudan Black B (SBB) to mask the AF of human glioma tissue and explored in detail the optimal quencher concentration, which allows 3D visualization of intratumoral bacteria to reduce AF and maintain the intensity of intratumoral bacteria-specific LPS fluorescent signals.


Assuntos
Corantes , Glioma , Humanos , Coloração e Rotulagem , Glioma/diagnóstico por imagem , Bactérias
16.
Am J Obstet Gynecol ; 228(2): 224.e1-224.e16, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35952840

RESUMO

BACKGROUND: Prenatal omega-3 fatty acid supplementation, particularly docosahexaenoic acid and eicosapentaenoic acid, has been associated with greater birthweight in clinical trials; however, its effect on fetal growth throughout gestation is unknown. OBJECTIVE: This study aimed to examine the association between first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation and growth trajectories of estimated fetal weight and specific fetal biometrics measured longitudinally from the second trimester of pregnancy to delivery. STUDY DESIGN: In a multisite, prospective cohort of racially diverse, low-risk pregnant women, we used secondary data analysis to examine fetal growth trajectories in relation to self-reported (yes or no) first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation. Fetal ultrasonographic measurements, including abdominal circumference, biparietal diameter, femur length, head circumference, and humerus length, were measured at enrollment (8-13 weeks) and up to 5 follow-up visits. Estimated fetal weight and head circumference-to-abdominal circumference ratio (a measure of growth symmetry) were calculated. Fetal growth trajectories were modeled for each measure using a linear mixed model with cubic splines. If significant differences in fetal growth trajectories between groups were observed (global P<.05), weekly comparisons were performed to determine when in gestation these differences emerged. Analyses were adjusted for maternal sociodemographics, parity, infant sex, total energy consumption, and diet quality score. All analyses were repeated using dietary docosahexaenoic acid and eicosapentaenoic acid intake, dichotomized at the recommended cutoff for pregnant and lactating women (≥0.25 vs <0.25 g/d), among women who did not report supplement intake in the first trimester of pregnancy were repeated. RESULTS: Among 1535 women, 143 (9%) reported docosahexaenoic acid and eicosapentaenoic acid supplementation in the first trimester of pregnancy. Overall, first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation was associated with statistically significant differences (P-value <.05) in fetal growth trajectories during pregnancy. Specifically, estimated fetal weight was larger among women with docosahexaenoic acid and eicosapentaenoic acid supplementation than among those without supplementation (global P=.028) with significant weekly differences in median estimated fetal weight most apparent between 38 to 41 weeks of gestation (median estimated fetal weight difference at 40 weeks of gestation, 114 g). Differences in fetal growth trajectories for abdominal circumference (P=.003), head circumference (P=.003), and head circumference-to-abdominal circumference ratio (P=.0004) were also identified by supplementation status. In weekly comparisons, docosahexaenoic acid and eicosapentaenoic acid supplement use was associated with larger median abdominal circumference (changed from 2 to 9 mm) in midpregnancy onward (19 to 41 weeks), larger median head circumference between 30 to 33 weeks of gestation, and smaller median head circumference-to-abdominal circumference ratio in the second and third trimesters of pregnancy. There was no specific weekly difference in fetal femur length or humerus length by docosahexaenoic acid and eicosapentaenoic acid supplementation. First-trimester dietary sources of docosahexaenoic acid and eicosapentaenoic acid among women with no first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation (n=1392) were associated with differences in fetal biparietal diameter (P=.043), but not other metrics of fetal growth. At the recommended dietary docosahexaenoic acid and eicosapentaenoic acid levels compared with below-recommended levels, biparietal diameter was larger between 38 to 41 weeks of gestation. CONCLUSION: In this racially diverse pregnancy cohort, first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation was associated with significant increases in fetal growth, specifically greater estimated fetal abdominal circumference in the second and third trimesters of pregnancy.


Assuntos
Ácidos Graxos Ômega-3 , Gravidez , Feminino , Humanos , Peso Fetal , Primeiro Trimestre da Gravidez , Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico , Estudos Prospectivos , Lactação , Desenvolvimento Fetal , Suplementos Nutricionais , Ultrassonografia Pré-Natal
17.
Neuro Endocrinol Lett ; 43(6): 293-302, 2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36586129

RESUMO

The association between amyotrophic lateral sclerosis (ALS) and primary progressive aphasia (PPA) is rarely seen in patients. A case of ALS-PPA with a possible reticulon 2 (RTN2) mutation was reported in this study. Moreover, we systematically reviewed the previous reports of 28 ALS cases with progressive non-fluent aphasia (PNFA) and semantic dementia (SD) to identified the unique pathologic features and strong heritability of ALS-PPA. There is a different heritability among the ALS-SD, ALS-PNFA, and the ALS-unclassified PPA groups (p=0.003). Males are more prone to have ALS-PPA than females in all the three groups (p=0.028). PPA-ALS usually starts with cognitive impairment, and the onset most often involves the bulbar. In addition, chromosome 9 open reading frame 72(C9ORF72) and TANK-binding kinase 1 (TBK1) are important pathogenic genes of PPA-ALS. Overall, heritability is of high certainty in ALS-SD, ALS-PNFA, and the ALS-unclassified PPA groups. TAR (Trans-Activator Regulatory) DNA-binding Protein 43 (TDP43) is a 100% predictive pathologic protein of ALS-PPA. C9ORF72 and TBK1 are important pathogenic genes of PPA-ALS.


Assuntos
Esclerose Lateral Amiotrófica , Afasia Primária Progressiva , Demência Frontotemporal , Masculino , Feminino , Humanos , Proteína C9orf72/genética , Demência Frontotemporal/genética , Demência Frontotemporal/patologia , Demência Frontotemporal/psicologia , Mutação
18.
RSC Med Chem ; 13(11): 1391-1409, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36439975

RESUMO

Bile acids (BAs) containing both hydrophilic hydroxyl and carboxyl groups and hydrophobic methyl and steroid nuclei can promote the absorption of fat and other substances in the intestine, and they are synthesized by cholesterol in the liver and then returned to the liver through enteric liver circulation. Because there are many BA receptors on the cell membrane of colon tissues, BAs can improve the specific delivery and transport of medicines to colon tissues. Moreover, BAs have a certain anticancer and inflammation activity by themselves. Based on this theory, a series of BA derivatives against colon cancer including cholic acid (CA), chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA) and lithocholic acid (LCA) were designed and synthesized, and their antitumor activity was evaluated. For in vitro anti-tumor tests, all the compounds displayed cell proliferative inhibition to nine human malignant tumor cell lines to some degree, and in particular they showed stronger inhibition to the colon cancer cells than the other cell lines. Among them, four compounds (4, 5, 6, and 7) showed stronger activity than the other compounds as well as the positive control 5-FU against HCT116 cells, and their IC50 was between 21.32 µmol L-1 and 28.90 µmol L-1; cell clone formation and migration tests showed that they not only effectively inhibited the formation of HCT116 cell colonies, but also inhibited the HCT116 cell migration and invasion; moreover, they induced apoptosis, arrested the mitotic process at the G2/M phase of the cell cycle, reduced the mitochondrial membrane potential, increased the intracellular ROS levels, and reduced the expression of Bcl-2 and p-STAT3 in HCT 116 cells. In addition, they also displayed intermediate anti-inflammatory activity by inhibiting inflammatory mediators NO and downregulating TNF-α expression, which also is one of the causes of colon cancer. This suggests that they deserve to be further investigated as candidates for colon cancer treatment drugs.

19.
Int Immunopharmacol ; 113(Pt A): 109381, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36327874

RESUMO

BACKGROUND: Renal damage is one of the typical clinical manifestations of systemic lupus erythematosus (SLE) and few effective markers can be used to predict SLE with renal damage. Additionally, the relationship among AhR, B cells and SLE with renal damage is poorly understood. METHOD: A case-control study was performed, and the clinical and laboratory data were acquired from medical records. Flow cytometry was used to analyze the expression of AhR in B cells. RESULTS: Both the proportion of B cells in peripheral blood lymphocytes and AhR in B cells were significantly higher in SLE patients than in healthy controls. AhR in B cells was negatively correlated with complement 3 and 4 levels but was positively correlated with SLEDAI-2 K, erythrocyte sedimentation rate, C-reactive protein and absolute lymphocyte count. Furthermore, more SLE patients suffered from renal damage and arthritis in the high-AhR B-cell group than in the low-AhR B-cell group. Interestingly, AhR in B cells was significantly increased in SLE with renal damage compared with SLE without renal damage, but no significant difference was observed between SLE with arthritis and SLE without arthritis. In addition, the area under the curve for AhR in B cells was 0.815, and its optimal cut-off level was 3.05 %, which provided a 83.3 % sensitivity and a 70.0 % specificity in predicting SLE with renal damage. CONCLUSION: AhR in B cells was correlated with SLE disease activity, and it may be a potential marker for predicting SLE with renal damage.


Assuntos
Artrite , Lúpus Eritematoso Sistêmico , Humanos , Estudos de Casos e Controles , Linfócitos B/metabolismo , Contagem de Linfócitos , Biomarcadores
20.
Metabolites ; 12(10)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36295798

RESUMO

Glycyrrhiza glabra L., known as licorice, is one of the most famous herbs in the world. In this study, we investigated the phytochemical and antitumor activities of G. glabra, especially its anti-colorectal cancer activities. G. glabra was extracted with 70% methanol, and the ethyl acetate layer was separated by silica gel, ODS, LH-20 column chromatography, and semi-preparative HPLC to obtain the compounds. The structures were determined by NMR and MS methods. Three new compounds named licopyranol A-C (1-3), and eighteen known compounds (4-21) were isolated. Compounds with an isoprenyl group or dimethylpyran ring showed better antitumor activities. Licopyranol A (1) and glycyrol (5) both inhibited the proliferation, reduced clone formation and promoted apoptosis of RKO cells. The Western blotting assays showed that glycyrol significantly reduced the expression of E-cadherin, ß-catenin, c-Myc, and GSK-3ß proteins in RKO cells, suggesting that glycyrol may inhibit the growth of colorectal cancer RKO cells via the Wnt/ß-catenin signaling pathway.

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