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1.
J Cell Mol Med ; 28(18): e70072, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39294741

RESUMEN

Hepatocellular carcinoma (HCC) remains the most prevalent form of primary liver cancer, characterized by late detection and suboptimal response to current therapies. The tumour microenvironment, especially the role of M2 macrophages, is pivotal in the progression and prognosis of HCC. We applied the machine learning algorithm-CIBERSORT, to quantify cellular compositions within the HCC TME, focusing on M2 macrophages. Gene expression profiles were analysed to identify key molecules, with ATP6V1E1 as a primary focus. We employed Gene Set Enrichment Analysis (GSEA) and Kaplan-Meier survival analysis to investigate the molecular pathways and prognostic significance of ATP6V1E1. A prognostic model was developed using multivariate Cox regression analysis based on ATP6V1E1-related molecules, and functional impacts were assessed through cell proliferation assays. M2 macrophages were the dominant cell type in the HCC TME, significantly correlating with adverse survival outcomes. ATP6V1E1 was robustly associated with advanced disease stages and poor prognostic features such as vascular invasion and elevated alpha-fetoprotein levels. GSEA linked high ATP6V1E1 expression to critical oncogenic pathways, including immunosuppression and angiogenesis, and reduced activity in metabolic processes like bile acid and fatty acid metabolism. The prognostic model stratified HCC patients into distinct risk categories, showing high predictive accuracy (1-year AUC = 0.775, 3-year AUC = 0.709 and 5-year AUC = 0.791). In vitro assays demonstrated that ATP6V1E1 knockdown markedly inhibited the proliferation of HCC cells. The study underscores the significance of M2 macrophages and ATP6V1E1 in HCC, highlighting their potential as therapeutic and prognostic targets.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Aprendizaje Automático , Macrófagos , Microambiente Tumoral , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Humanos , Macrófagos/metabolismo , Microambiente Tumoral/genética , Pronóstico , Regulación Neoplásica de la Expresión Génica , ATPasas de Translocación de Protón Vacuolares/genética , ATPasas de Translocación de Protón Vacuolares/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Masculino , Línea Celular Tumoral , Proliferación Celular , Femenino , Estimación de Kaplan-Meier , Algoritmos , Persona de Mediana Edad
2.
Mol Med ; 30(1): 150, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39272008

RESUMEN

Cis-dichlorodiammineplatinum(II) (CDDP), while widely utilized in tumor therapy, results in toxic side effects that patients find intolerable. The specific mechanism by which CDDP inflicts ovarian damage remains unclear. This study aimed to explore the involvement of ferrostatin-1 (FER-1) and ferroptosis in CDDP-induced ovarian toxicity. This study established models of CDDP-induced injury in granulosa cells (GCs) and rat model of premature ovarian failure (POF). CCK-8 assessed the effects of CDDP and FER-1 on GC viability. FerroOrange and Mito-FerroGreen, DCFH-DA and MitoSox-Red, Rhodamine 123 and Transmission electron microscopy (TEM) measured Fe2+, reactive oxygen species (ROS), mitochondrial membrane potential and the mitochondrial morphology in GC cells, respectively. Serum hormone levels; organ indices; malondialdehyde, superoxide dismutase, and glutathione analyses; and western blotting were performed to examine ferroptosis's role in vitro. Molecular docking simulation was evaluated the interaction between FER-1 and GPX4 or FER-1 and NRF2. Molecular docking simulations were conducted to evaluate the interactions between FER-1 and GPX4, as well as FER-1 and NRF2. The findings revealed that CDDP-induced ovarian toxicity involved iron accumulation, increased ROS accumulation, and mitochondrial dysfunction, leading to endocrine disruption and tissue damage in rats. These changes correlated with NRF2, HO-1, and GPX4 levels. However, FER-1 decreased the extent of ferroptosis. Thus, ferroptosis appears to be a crucial mechanism of CDDP-induced ovarian injury, with GPX4 as potential protective targets.


Asunto(s)
Cisplatino , Ciclohexilaminas , Ferroptosis , Simulación del Acoplamiento Molecular , Fenilendiaminas , Especies Reactivas de Oxígeno , Animales , Femenino , Ferroptosis/efectos de los fármacos , Ciclohexilaminas/farmacología , Ratas , Especies Reactivas de Oxígeno/metabolismo , Cisplatino/efectos adversos , Fenilendiaminas/farmacología , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Ovario/efectos de los fármacos , Ovario/metabolismo , Ovario/patología , Insuficiencia Ovárica Primaria/inducido químicamente , Insuficiencia Ovárica Primaria/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo
3.
Heliyon ; 10(17): e36822, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39281521

RESUMEN

Background: Long non-coding RNAs (lncRNAs) are implicated in a variety of regulatory functions within tumors, yet their specific roles in glioma remain underexplored. Methods: We extracted glioma patient data from The Cancer Genome Atlas and UCSC Xena database for analysis using R, focusing on genomic characterization, biological enrichment, immune evaluation, and the development of a predictive model employing machine learning techniques. Additionally, we conducted cell culture and proliferation assays. Results: Our analysis revealed that the lncRNA SLC16A1-AS1 plays a pivotal role in glioma pathogenesis and prognosis. We observed that abnormal expression of SLC16A1-AS1 varied with tumor grade, IDH mutation status, and histological type, correlating with worse survival outcomes. Genomically, SLC16A1-AS1 was associated with Tumor Mutational Burden and other prognostic biomarkers. The expression of this lncRNA was also linked to the activation of critical biological pathways and appeared to modulate the immune microenvironment, enhancing the presence of immune cells and checkpoints, which may be predictive of immunotherapy outcomes. Our predictive model, constructed from genes associated with SLC16A1-AS1, accurately forecasted glioma prognosis, strongly correlating with survival and treatment responses. In vitro experiments further demonstrated that SLC16A1-AS1 significantly influences glioma cell proliferation, invasion, and migration, underscoring its role in tumor aggression and its potential as a therapeutic target. Conclusions: This study underscores the significant influence of SLC16A1-AS1 on glioma progression and prognosis, with its expression correlating with tumor traits and immune responses. The findings highlight the potential of targeting SLC16A1-AS1 in therapeutic strategies aimed at mitigating glioma aggressiveness.

4.
Ann Med ; 56(1): 2399317, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39239799

RESUMEN

OBJECTIVE: Clinical validity of genome sequencing (GS) (>30×) has been preliminarily verified in the post-natal setting. This study is to investigate the potential utility of trio-GS as a prenatal test for diagnosis of central nervous system (CNS) anomalies. METHODS: We performed trio-based GS on a prospective cohort of 17 foetuses with CNS abnormalities. Single nucleotide variation (SNV), small insertion and deletion (Indel), copy number variation (CNV), structural variant (SV), and regions with absence of heterozygosity (AOH) were analyzed and classified according to ACMG guidelines. RESULTS: Trio-GS identified diagnostic findings in 29.4% (5/17) of foetuses, with pathogenic variants found in SON, L1CAM, KMT2D, and ASPM. Corpus callosum (CC) and cavum septum pellucidum (CSP) abnormalities were the most frequent CNS abnormalities (47.1%, 8/17) with a diagnostic yield of 50%. A total of 29.4% (5/17) foetuses had variants of uncertain significance (VUS). Particularly, maternal uniparental disomy 16 and a de novo mosaic 4p12p11 duplication were simultaneously detected in one foetus with abnormal sulcus development. In addition, parentally inherited chromosomal inversions were identified in two foetuses. CONCLUSION: GS demonstrates its feasibility in providing genetic diagnosis for foetal CNS abnormalities and shows the potential to expand the application to foetuses with other ultrasound anomalies in prenatal diagnosis.


Asunto(s)
Variaciones en el Número de Copia de ADN , Diagnóstico Prenatal , Humanos , Femenino , Embarazo , Estudios Prospectivos , Diagnóstico Prenatal/métodos , Secuenciación Completa del Genoma , Adulto , Malformaciones del Sistema Nervioso/genética , Malformaciones del Sistema Nervioso/diagnóstico , Malformaciones del Sistema Nervioso/diagnóstico por imagen , Feto/anomalías , Feto/diagnóstico por imagen , Sistema Nervioso Central/anomalías , Sistema Nervioso Central/diagnóstico por imagen , Sistema Nervioso Central/embriología , Masculino
5.
J Food Sci ; 89(6): 3829-3846, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38745368

RESUMEN

Lonicera japonica Thunb. (LJT) is known for its valuable medicinal properties that highlight its potential application in the pharmaceutical and health food industry. We predict that LJT polyphenols by network pharmacology may be involved in immunomodulation, and the study of LJT polyphenols regulating immunity is still insufficient; therefore, we experimentally found that LJT enhances immunity by promoting the proliferation and phagocytic activity of RAW246.7 cells. A model of an immunosuppressed mouse was constructed using cyclophosphamide-induced, and LJT was extracted for the intervention. We found that LJT restored immune homeostasis in immune deficiency mice by inhibiting the abnormal apoptosis in lymphocytes, enhancing natural killer cell cytotoxicity, promoting T lymphocyte proliferation, and increasing the CD4+ and CD8+ T lymphocytes in quantity. Moreover, LJT treatment modulates immunity by significantly downregulating lipopolysaccharide-induced inflammation and oxidative stress levels. We verified the immunomodulatory function of LJT through both cell and animal experiments. The combination of potential-protein interactions and molecular docking later revealed that LJT polyphenols were associated with immunomodulatory effects on MAPK1; together, LJT intervention significantly modulates the immune, with the activation of MAPK1 as the underlying mechanism of action, which provided evidence for the utilization of LJT as a nutraceutical in immune function.


Asunto(s)
Inmunomodulación , Lonicera , Farmacología en Red , Extractos Vegetales , Lonicera/química , Animales , Ratones , Extractos Vegetales/farmacología , Farmacología en Red/métodos , Inmunomodulación/efectos de los fármacos , Células RAW 264.7 , Simulación del Acoplamiento Molecular , Polifenoles/farmacología , Proliferación Celular/efectos de los fármacos , Masculino , Apoptosis/efectos de los fármacos , Ratones Endogámicos BALB C
6.
Front Genet ; 14: 1237912, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37662847

RESUMEN

Objective: To investigate the positive rate of chromosomal and monogenic etiologies and pregnancy outcomes in fetuses with hyperechoic kidney, and to provide more information for genetic counseling and prognosis evaluation. Methods: We performed a retrospective analysis of 25 cases of hyperechoic kidney diagnosed prenatal in the Second Affiliated Hospital of Harbin Medical University and Harbin Red Cross Central Hospital (January 2017-December 2022). Furthermore, we conducted a meta-analysis of a series of hyperechoic kidneys (HEK) in the literature to assess the incidence of chromosomal and monogenic etiologies, mortality, and pooled odds ratio (OR) estimates of the association between the incidence of these outcomes and other associated ultrasound abnormalities. Results: 25 fetuses of HEK were enrolled in the cohort study, including 14 with isolated hyperechoic kidney (IHK) and 11 with non-isolated hyperechoic kidney (NIHK). Chromosomal aneuploidies were detected in 4 of 20 patients (20%). The detection rate of pathogenic or suspected pathogenic copy number variations (CNVs) was 29% (4/14) for IHK and 37% (4/11) for NIHK. Whole exome sequencing (WES) was performed in 5 fetuses, and pathogenic genes were detected in all of them. The rate of termination of pregnancy was 56% in HEK. 21 studies including 1,178 fetuses were included in the meta-analysis. No case of abnormal chromosome karyotype or (intrauterine death)IUD was reported in fetuses with IHK. In contrast, the positive rate of karyotype in NIHK was 22% and that in HEK was 20%, with the ORs of 0.28 (95% CI 0.16-0.51) and 0.25, (95% CI 0.14-0.44), respectively. The positive rate of (chromosome microarray analysis) CMA in IHK was 59% and that in NIHK was 32%, with the ORs of 1.46 (95% CI 1.33-1.62) and 0.48 (95% CI, 0.28-0.85), respectively. The positive rate of monogenic etiologies in IHK was 31%, with the OR of 0.80 (95% CI 0.25-2.63). In IHK, the termination rate was 21% and neonatal mortality was 13%, with the ORs of 0.26 (95% CI, 0.17-0.40), 1.72 (95% CI, 1.59-1.86), and that in NIHK was 63%, 0.15 (95% CI, 0.10-0.24); 11%, 0.12 (95% CI, 0.06-0.26), respectively. The intrauterine mortality in NIHK group was 2%, with the OR of 0.02 (95% CI, 0.01-0.05). HNF1B variant has the highest incidence (26%) in IHK. Conclusion: The positive rate of karyotype was 20% in HEK and 22% in NIHK. The positive rate of CMA was 32% in NIHK and 59% in IHK. The positive rate of IHK monogenic etiologies was 31%. HNF1B gene variation is the most common cause of IHK. The overall fetal mortality rate of NIHK is significantly higher than that of IHK. The amount of amniotic fluid, kidney size and the degree of corticomedullary differentiation have a great impact on the prognosis, these indicators should be taken into consideration to guide clinical consultation and decision-making.

7.
Materials (Basel) ; 16(18)2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37763556

RESUMEN

High-velocity oxygen fuel (HVOF) spraying is a promising technique for depositing protective coatings. The performances of HVOF-sprayed coatings are affected by in-flight particle properties, such as temperature and velocity, that are controlled by the spraying parameters. However, obtaining the desired coatings through experimental methods alone is challenging, owing to the complex physical and chemical processes involved in the HVOF approach. Compared with traditional experimental methods, a novel method for optimizing and predicting coating performance is presented herein; this method involves combining machine learning techniques with thermal spray technology. Herein, we firstly introduce physics-informed neural networks (PINNs) and convolutional neural networks (CNNs) to address the overfitting problem in small-sample algorithms and then apply the algorithms to HVOF processes and HVOF-sprayed coatings. We proposed the PINN and CNN hierarchical neural network to establish prediction models for the in-flight particle properties and performances of NiCr-Cr3C2 coatings (e.g., porosity, microhardness, and wear rate). Additionally, a random forest model is used to evaluate the relative importance of the effect of the spraying parameters on the properties of in-flight particles and coating performance. We find that the particle temperature and velocity as well as the coating performances (porosity, wear resistance, and microhardness) can be predicted with up to 99% accuracy and that the spraying distance and velocity of in-flight particles exert the most substantial effects on the in-flight particle properties and coating performance, respectively. This study can serve as a theoretical reference for the development of intelligent HVOF systems in the future.

8.
Eur J Obstet Gynecol Reprod Biol ; 289: 140-144, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37660509

RESUMEN

We report a case of a fetus with 46,XX testicular disorder of sex development detected prenatally. This fetus was found abnormally due to non-invasive prenatal testing. Amniocentesis revealed SRY gene on the X chromosome of the fetus. The related literature was reviewed, and the advantages and limitations of various prenatal diagnostic techniques were discussed. The combination of non-invasive prenatal testing and various prenatal diagnostic techniques has enabled more fetuses with sex reversal to be detected.


Asunto(s)
Genes sry , Diagnóstico Prenatal , Femenino , Embarazo , Humanos , Amniocentesis , Desarrollo Sexual , Feto
9.
Int Immunopharmacol ; 123: 110762, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37562295

RESUMEN

OBJECTIVE: The purpose of this study was to identify potential predictors of clinical outcome in severe COVID-19 patients and to investigate the relationship between immunological parameters and duration of illness. METHODS: This single-center study retrospectively recruited 73 patients with severe or critical COVID-19. Immunological indicators include white blood cell count, neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio, and circulating inflammatory mediators were observed for their association with disease severity, mortality and duration of illness of COVID-19. RESULTS: Serum inflammatory mediators levels of C-reactive protein (P = 0.015), interleukin 6 (IL-6) (P < 0.001), CX3CL1 (P < 0.001), D-dimer (P < 0.001) and procalcitonin (PCT) (P < 0.001) were increased in critical illness patients compared to those severe COVID-19 patients. CX3CL1 has the highest C-index (0.75) to predict in-hospital mortality in patients with COVID-19. Furthermore, this study shows for the first time that the duration of illness in severe COVID-19 patients is associated with serum levels of CX3CL1 (P = 0.037) and D-dimer (P = 0.014). CONCLUSION: CX3CL1, D-dimer, PCT, and IL-6 could effectively predict mortality in severe COVID-19 patients. In addition, only the circulating levels of CX3CL1 and D-dimer were significantly associated with duration of illness.


Asunto(s)
COVID-19 , Humanos , Estudios Retrospectivos , Interleucina-6 , Biomarcadores , Proteína C-Reactiva/análisis , Polipéptido alfa Relacionado con Calcitonina , Índice de Severidad de la Enfermedad
10.
J Intell ; 11(7)2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37504776

RESUMEN

Many theories of motivation suggest that motivation and academic achievement reinforce each other over time, yet few longitudinal studies have examined behavioral pathways that may mediate interplay from motivation to achievement. Moreover, empirical studies so far have mostly focused on Western countries. In this study, we first examined whether students' value of education, as a measure of motivation, is reciprocally related to achievement (class rank and self-rated performance) in a sample of junior high schoolers in an East-Asian country (N = 3445, Korean Youth Panel Study). We tested this reciprocity using different statistical models. Second, we investigated whether the relation between motivation and achievement was mediated by time invested in learning. Reciprocal effects between value of education and academic achievement were found in classic cross-lagged panel models, but only unilateral effects (from achievement to value of education) were found when we used random-intercept and random-curve cross-lagged panel models. Adding the time investment variable, the reciprocal effect between value of education, time investment, and academic achievement was found with the random intercept model. In conclusion, the reciprocity between of motivation and achievement are more elusive than previous research suggested; further studies should be dedicated to scrutinizing its existence with various statistical models.

11.
Endocrine ; 82(2): 335-342, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37308773

RESUMEN

BACKGROUND: Iodine is an essential element for the biosynthesis of thyroid-stimulating hormone (TSH). Both excessive and deficient iodine are major risk factors for thyroid diseases, including thyroid dysfunction, thyroid nodules, and thyroid autoimmunity (TAI). This study aimed to elucidate the relationship between iodine status and the prevalence of thyroid diseases through a national cross-sectional epidemiological survey in Jiangxi province (China). METHODS: This population-based, cross-sectional study enrolled 2636 Chinese local inhabitants who aged over 18 years old from April to August in 2015. Physical examination was performed and biochemical indices, urinary iodine concentration (UIC), and TSH level were measured. The Chi-square test, nonparametric test, and 4 multivariate logistic regression models adjusted for risk factors were applied to analysis. Spearman correlation coefficients were calculated to investigate the relationship between iodine intake level and the prevalence of thyroid diseases. RESULTS: The median UIC was 176.4 µg/L, and a significant difference was found in median UIC between men (182.45 µg/L) and women (169.25 µg/L) (P = 0.03). Among these study subjects, 14.4%, 44.5%, 26.1%, and 15.0% had deficient, adequate, more than adequate, and excessive iodine concentrations, respectively. The prevalence rates of hyperthyroidism, subclinical hyperthyroidism, hypothyroidism, subclinical hypothyroidism, thyroid nodules, and TAI were 0.91%, 0.57%, 0.34% and 7.89%, 9.45%, and 12.7%, respectively. Significant differences were found in iodine status, waist circumstance, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), TSH, thyroid nodules, and TAI between men and women (P < 0.05). Compared with those with adequate UIC, subjects with excessive UIC had higher prevalence rates of thyroid dysfunction (odds ratio (OR) = 1.74, 95% confidence interval (CI): 1.40-2.54) and thyroid nodules (OR = 3.33, 95%CI 1.32-8.42). In addition, subjects with deficient and excessive UIC were at the higher risk of TAI compared with those with adequate UIC (OR = 1.68, 95%CI: 1.19-2.60; OR = 1.52, 95%CI: 1.04-2.96, respectively). UIC was positively correlated with the prevalence rates of thyroid nodules (r = -0.44, P < 0.01) and TAI (r = -0.055, P < 0.01). On the contrary, UIC was negatively correlated with the risk of thyroid dysfunction (r = -0.24, P > 0.05). CONCLUSION: Adult inhabitants from Jiangxi province in the TIDE study were in the adequate iodine status. Excessive iodine status was noted as a risk factor for thyroid dysfunction and thyroid nodules. In addition, both iodine deficiency and excessive iodine were risk factors for TAI.


Asunto(s)
Hipertiroidismo , Hipotiroidismo , Yodo , Enfermedades de la Tiroides , Nódulo Tiroideo , Masculino , Adulto , Humanos , Femenino , Persona de Mediana Edad , Estudios Transversales , Nódulo Tiroideo/epidemiología , Tiroxina , Prevalencia , Enfermedades de la Tiroides/epidemiología , Enfermedades de la Tiroides/inducido químicamente , Hipotiroidismo/epidemiología , Hipotiroidismo/inducido químicamente , Tirotropina , China/epidemiología
12.
Exp Ther Med ; 24(6): 746, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36561974

RESUMEN

Evodiamine (EVO) is one of the main components extracted from Evodia rutaecarpa and has been reported to inhibit tumor growth by inhibiting proliferation and inducing apoptosis. Although the anticancer activity of evodiamine has been confirmed, the exact mechanism remains to be elucidated. In the present study, cancer stem-like cells (CSCs) were successfully enriched from A549 cells by being cultured in serum-free medium and characterized by detecting stemness markers. Expectedly, the addition of EVO inhibited proliferation, migration and invasion in A549 cells, demonstrating its inhibitory effects on the malignant behaviors of A549 cells. In CSCs derived from A549 cells, EVO treatment promoted cell proliferation while inhibiting migration and invasion. By detecting the hallmarks of the epithelial-mesenchymal transition (EMT), including E-cadherin, Vimentin, Slug and Snail via western blotting, it was revealed that EVO treatment inactivated the EMT process and potentially led to the loss of self-renewal capacity of CSCs and promoted proliferation. By activating the EMT using TGF-ß pretreatment, EVO treatment downregulated the hallmarks of the EMT and led to inactivation of the EMT, indicating its potential mechanism of regulating CSCs via the EMT pathway. The findings suggested that modulation of the self-renewal capacity of CSCs may affect malignant cancer behaviors following surgery. EVO exerts inhibitory effects not only on cancer cells but also on CSCs in non-small-cell lung cancer, and therefore could be used as a promising drug targeting CSCs.

13.
Front Immunol ; 13: 1037318, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36405716

RESUMEN

Background: Alzheimer's disease is the most common neurodegenerative disease worldwide. Metabolic syndrome is the most common metabolic and endocrine disease in the elderly. Some studies have suggested a possible association between MetS and AD, but few studied genes that have a co-diagnostic role in both diseases. Methods: The microarray data of AD (GSE63060 and GSE63061 were merged after the batch effect was removed) and MetS (GSE98895) in the GEO database were downloaded. The WGCNA was used to identify the co-expression modules related to AD and MetS. RF and LASSO were used to identify the candidate genes. Machine learning XGBoost improves the diagnostic effect of hub gene in AD and MetS. The CIBERSORT algorithm was performed to assess immune cell infiltration MetS and AD samples and to investigate the relationship between biomarkers and infiltrating immune cells. The peripheral blood mononuclear cells (PBMCs) single-cell RNA (scRNA) sequencing data from patients with AD and normal individuals were visualized with the Seurat standard flow dimension reduction clustering the metabolic pathway activity changes each cell with ssGSEA. Results: The brown module was identified as the significant module with AD and MetS. GO analysis of shared genes showed that intracellular transport and establishment of localization in cell and organelle organization were enriched in the pathophysiology of AD and MetS. By using RF and Lasso learning methods, we finally obtained eight diagnostic genes, namely ARHGAP4, SNRPG, UQCRB, PSMA3, DPM1, MED6, RPL36AL and RPS27A. Their AUC were all greater than 0.7. Higher immune cell infiltrations expressions were found in the two diseases and were positively linked to the characteristic genes. The scRNA-seq datasets finally obtained seven cell clusters. Seven major cell types including CD8 T cell, monocytes, T cells, NK cell, B cells, dendritic cells and macrophages were clustered according to immune cell markers. The ssGSEA revealed that immune-related gene (SNRPG) was significantly regulated in the glycolysis-metabolic pathway. Conclusion: We identified genes with common diagnostic effects on both MetS and AD, and found genes involved in multiple metabolic pathways associated with various immune cells.


Asunto(s)
Enfermedad de Alzheimer , Síndrome Metabólico , Enfermedades Neurodegenerativas , Humanos , Anciano , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Síndrome Metabólico/genética , Leucocitos Mononucleares/metabolismo , Algoritmos , Aprendizaje Automático , Biomarcadores , Proteínas Nucleares snRNP
15.
Front Immunol ; 13: 1037739, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36389847

RESUMEN

Molting is one of the most important biological processes of crustacean species, and a number of molecular mechanisms facilitate this complex procedure. However, the understanding of the immune mechanisms underlying crustacean molting cycle remains very limited. This study performed transcriptome sequencing in hemolymph and hepatopancreas of the swimming crab (Portunus trituberculatus) during the four molting stages: post-molt (AB), inter-molt (C), pre-molt (D), and ecdysis (E). The results showed that there were 78,572 unigenes that were obtained in the hemolymph and hepatopancreas of P. trituberculatus. Further analysis showed that 98 DEGs were involved in immunity response of hemolymph and hepatopancreas, and most of the DEGs participated in the process of signal transduction, pattern recognition proteins/receptors, and antioxidative enzymes system. Specifically, the key genes and pathway involved in signal transduction including the GPCR126, beta-integrin, integrin, three genes in mitogen-activated protein kinase (MAPK) signaling cascade (MAPKKK10, MAPKK4, and p38 MAPK), and four genes in Toll pathway (Toll-like receptor, cactus, pelle-like kinase, and NFIL3). For the pattern recognition proteins/receptors, the lowest expression level of 11 genes was found in the E stage, including C-type lectin receptor, C-type lectin domain family 6 member A and SRB3/C in the hemolymph, and hepatopancreatic lectin 4, C-type lectin, SRB, Down syndrome cell adhesion molecule homolog, Down syndrome cell adhesion molecule isoform, and A2M. Moreover, the expression level of copper/zinc superoxide dismutase isoform 4, glutathione peroxidase, glutathione S-transferase, peroxiredoxin, peroxiredoxin 6, and dual oxidase 2 in stage C or stage D significantly higher than that of stage E or stage AB. These results fill in the gap of the continuous transcriptional changes that are evident during the molting cycle of crab and further provided valuable information for elucidating the molecular mechanisms of immune regulation during the molting cycle of crab.


Asunto(s)
Fenómenos Biológicos , Braquiuros , Síndrome de Down , Animales , Braquiuros/genética , Braquiuros/metabolismo , Transcriptoma , Muda/genética , Natación , Lectinas Tipo C/metabolismo , Integrinas/metabolismo , Moléculas de Adhesión Celular/metabolismo
16.
Artículo en Inglés | MEDLINE | ID: mdl-36360947

RESUMEN

Cognitive and psychological conditions in childhood will have an important impact on adult life. There is relatively little literature on the impact of educational expectations on children's cognition and psychological health from the perspective of urban and rural differences. Based on the cohort data of the CFPS from 2012 and 2016, this study screened a total of 994 children aged 10-15 to study the effects of parents' educational expectations and children's educational expectations on children's cognition and depression. The results show that both parents' educational expectations and children's educational expectations have a positive impact on children's cognition. Parents' educational expectations and children's educational expectations have negative effects on children's depression. When parents' educational expectations are greater than their children's educational expectations, educational expectations have a negative impact on children's cognition and a positive impact on children's depression. In both urban and rural samples, parents' educational expectations and children's educational expectations have a positive impact on children's cognition and a negative impact on children's depression. However, the impact of educational expectations on children's cognition and depression was greater in rural areas than in urban areas. When parents' educational expectations are greater than their children's educational expectations, educational expectations in urban areas have no effect on children's cognition.


Asunto(s)
Depresión , Trastornos Mentales , Niño , Adulto , Humanos , Depresión/epidemiología , Depresión/psicología , Motivación , Escolaridad , Cognición
17.
Artículo en Inglés | MEDLINE | ID: mdl-36361348

RESUMEN

This study aimed to (1) explore the configuration of vocational identity status among emerging adults with and without hearing impairment using latent profile analysis, and (2) investigate the relationships between vocational identity status and self-esteem and subjective well-being. In total, 408 students without disabilities and 432 with hearing impairments from two Chinese higher institutions participated in the study. The Vocational Identity Status Assessment, Rosenberg Self-Esteem scale, Satisfaction with Life Scale, and Positive and Negative Affect were used to assess the major variables. The results derived five latent profiles (achieved, foreclosed, searching moratorium, undifferentiated, and diffused) of vocational identity in the present sample. The students were over-represented in undifferentiated profiles and under-represented in achieved and foreclosed ones. Hearing impairment significantly affected vocational identity status profile membership. The results showed that emerging adults with achievement and foreclosure statuses displayed healthy psychological outcomes, having the highest self-esteem, life satisfaction, and positive affect, and the lowest negative affect. In contrast, the diffused group showed the most disturbing pattern with the lowest self-esteem, life satisfaction, and positive affect, and the highest negative affect. The research findings reveal some notable issues in vocational identity status for emerging Chinese adults, raising concerns about the influence of hearing impairment on vocational identity formation, and provide implications for Chinese society to facilitate college students' career development process to promote their vocational identity status and enhance their self-esteem and subjective well-being.


Asunto(s)
Pérdida Auditiva , Autoimagen , Adulto , Humanos , Logro , Rehabilitación Vocacional , China
18.
Child Adolesc Psychiatry Ment Health ; 16(1): 79, 2022 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-36209100

RESUMEN

There is a significant delay between parents having concerns and receiving a formal assessment and Autism Spectrum Disorder (ASD) diagnosis. Telemedicine could be an effective alternative that shortens the waiting time for parents and primary health providers in ASD screening and diagnosis. We conducted a systematic review examining the uses of telemedicine technology for ASD screening, assessment, or diagnostic purposes and to what extent sample characteristics and psychometric properties were reported. This study searched four databases from 2000 to 2022 and obtained 26 studies that met the inclusion criteria. The 17 applications used in these 26 studies were divided into three categories based on their purpose: screening, diagnostic, and assessment. The results described the data extracted, including study characteristics, applied methods, indicators seen, and psychometric properties. Among the 15 applications with psychometric properties reported, the sensitivity ranged from 0.70 to 1, and the specificity ranged from 0.38 to 1. The present study highlights the strengths and weaknesses of current telemedicine approaches and provides a basis for future research. More rigorous empirical studies with larger sample sizes are needed to understand the feasibility, strengths, and limitations of telehealth technologies for screening, assessing, and diagnosing ASD.

19.
Front Genet ; 13: 910556, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35774506

RESUMEN

Preeclampsia is the leading cause of morbidity and mortality for mothers and newborns worldwide. Despite extensive efforts made to understand the underlying pathology of preeclampsia, there is still no clinically useful effective tool for the early diagnosis of preeclampsia. In this study, we conducted a retrospectively multicenter discover-validation study to develop and validate a novel biomarker for preeclampsia diagnosis. We identified 38 differentially expressed genes (DEGs) involved in preeclampsia in a case-control study by analyzing expression profiles in the discovery cohort. We developed a 5-mRNA signature (termed PE5-signature) to diagnose preeclampsia from 38 DEGs using recursive feature elimination with a random forest supervised classification algorithm, including ENG, KRT80, CEBPA, RDH13 and WASH9P. The PE5-signature showed high accuracy in discriminating preeclampsia from controls with a receiver operating characteristic area under the curve value (AUC) of 0.971, a sensitivity of 0.842 and a specificity of 0.950. The PE5-signature was then validated in an independent case-control study and achieved a reliable and robust predictive performance with an AUC of 0.929, a sensitivity of 0.696, and a specificity of 0.946. In summary, we have developed and validated a five-mRNA biomarker panel as a risk assessment tool to assist in the detection of preeclampsia. This gene panel has potential clinical value for early preeclampsia diagnosis and may help us better understand the precise mechanisms involved.

20.
Curr Oncol ; 29(8): 5247-5261, 2022 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-35892986

RESUMEN

The lack of new drugs and resistance to existing drugs are serious problems in gastric cancer(GC) treatment. The research found polyphenols possess anti-Helicobacter pylori(Hp) and antitumor activities and may be used in the research and development of drugs for cancer prevention and treatment. However, polyphenols are affected by their chemical structures and physical properties, which leads to relatively low bioavailability and bioactivity in vivo. The intestinal flora can improve the absorption, utilization, and biological activity of polyphenols, whereas polyphenol compounds can increase the richness of the intestinal flora, reduce the activity of carcinogenic bacteria, stabilize the proportion of core flora, and maintain homeostasis of the intestinal microenvironment. Our review summarizes the gastrointestinal flora-mediated mechanisms of polyphenol against GC.


Asunto(s)
Microbioma Gastrointestinal , Neoplasias Gástricas , Disponibilidad Biológica , Humanos , Polifenoles/farmacología , Polifenoles/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Microambiente Tumoral
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