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OBJECTIVE: The objective of this study was to identify the risk factors that influence metastasis and prognosis in patients with nodular melanoma (NM), as well as to develop and validate a prognostic model using artificial intelligence (AI) algorithms. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for 4,727 patients with NM based on the inclusion/exclusion criteria. Their clinicopathological characteristics were retrospectively reviewed, and logistic regression analysis was utilized to identify risk factors for metastasis. This was followed by employing Multilayer Perceptron (MLP), Adaptive Boosting (AB), Bagging (BAG), logistic regression (LR), Gradient Boosting Machine (GBM), and eXtreme Gradient Boosting (XGB) algorithms to develop metastasis models. The performance of the six models was evaluated and compared, leading to the selection and visualization of the optimal model. Through integrating the prognostic factors of Cox regression analysis with the optimal models, the prognostic prediction model was constructed, validated, and assessed. RESULTS: Logistic regression analyses identified that marital status, gender, primary site, surgery, radiation, chemotherapy, system management, and N stage were all independent risk factors for NM metastasis. MLP emerged as the optimal model among the six models (AUC = 0.932, F1 = 0.855, Accuracy = 0.856, Sensitivity = 0.878), and the corresponding network calculator (https://shimunana-nm-distant-m-nm-m-distant-8z8k54.streamlit.app/) was developed. The following were examined as independent prognostic factors: MLP, age, marital status, sequence number, laterality, surgery, radiation, chemotherapy, system management, T stage, and N stage. System management and surgery emerged as protective factors (HR < 1). To predict 1-, 3-, and 5-year overall survival (OS), a nomogram was created. The validation results demonstrated that the model exhibited good discrimination and consistency, as well as high clinical usefulness. CONCLUSION: The developed prediction model more effectively reflects the prognosis of patients with NM and differentiates between the risk level of patients, serving as a useful supplement to the classical American Joint Committee on Cancer (AJCC) staging system and offering a reference for clinically stratified individualized treatment and prognosis prediction. Furthermore, the model enables clinicians to quantify the risk of metastasis in NM patients, assess patient survival, and administer precise treatments.
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Inteligencia Artificial , Melanoma , Humanos , Melanoma/patología , Melanoma/mortalidad , Femenino , Masculino , Pronóstico , Persona de Mediana Edad , Factores de Riesgo , Anciano , Estudios Retrospectivos , Metástasis de la Neoplasia , Programa de VERF , Adulto , Algoritmos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/terapia , Modelos LogísticosRESUMEN
The incidence of Parkinson's disease (PD) rises rapidly with the increase of age. With the advent of global aging, the number of patients with PD is rising along with the elderly population, especially in China. Previously, we found that Yishen chuchan decoction (YCD), prescribed based on clinical experience, has the potential of alleviating symptoms, delaying the progression, and controlling the development of PD. Nonetheless, the underlying mechanistic role is yet to be explored. Aim: This research examined the possible therapeutic effects of YCD in alleviating PD via a systematic approach with network pharmacology and experimental validation, aiming at providing a new understanding of traditional Chinese medicine management regarding PD. Methods: The chemical structure and properties of YCD were adopted from Traditional Chinese Medicine System Pharmacology Database (TCMSP), SwissADME, PubChem, and PubMed. The potential targets for YCD and PD were identified using Swiss Target Prediction, GeneCard, PubChem, and UniProt. The herbal-component-target network was created via the Cytoscape software. Moreover, by using the STRING database, the protein-protein interaction (PPI) network was screened. Gene function GO and KEGG pathway enrichment analyses were performed via the Metascape database. YCD-medicated Rat Serum from Sprague-Dawley (SD) Rats was prepared, and SH-SY5Y cells were preconditioned with rotenone to develop the PD model. To examine the impact of YCD on these cells and explore the mechanistic role of the p38 mitogen-activated protein kinase (MAPK) pathway, the cells were pretreated with either serum or a p38 MAPK pathway inhibitor. This study employed the Cell Counting Kit (CCK)-8 assay and Hoechst 33,342 staining to evaluate the viability and morphological changes induced by the YCD-medicated rat serum on rotenone-treated SH-SY5Y cells. Apoptosis was assessed by Flow cytometry. Immunofluorescence staining assessed the microtubule-associated protein 2 (MAP2) level. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the concentrations of inflammatory mediators interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Also, reactive oxygen species (ROS) and superoxide dismutase (SOD) levels were determined. Western Blotting measured the expression of total and phospho-p38 MAPK (p-p38). Results: This study identified 65 active components in YCD, which were found to target 801 specific genes. By screening, 63 potential core targets were identified from a pool of 172 overlapping targets between PD and YCD. These targets were examined by GO and KEGG analyses revealing their substantial correlation to MAPK, PI3K-Akt signaling pathways, positively controlling protein phosphorylation, and pathways of neurodegenerative diseases. SH-SY5Y cells were treated with 2 µM rotenone for 48 h, which reduced cell viability to 50 %, and reduced MAP2 expression, increased the rate of apoptosis, oxidative stress, inflammation, and p-p38 expressions. YCD-medicated rat serum significantly improved the viability, reduced the apoptosis rate, and increased the MAP2 expression. YCD-medicated serum increased SOD, reduced ROS and suppressed IL-6, IL-1ß and TNF-α levels, thus inhibiting oxidative stress and inflammation in rotenone-treated SH-SY5Y cells. Moreover, YCD-medicated serum substantially lowered the p-p38 expression induced by rotenone. SB203580, a specific inhibitor of p38 MAPK, could also inhibit the p-p38 expression, apoptosis, and restore morphological damage of cells, also improve inflammation and oxidative stress. Conclusion: YCD enhanced cell viability and reduced apoptosis rate, inflammation, and oxidative stress in vitro. These beneficial effects could potentially involve the suppression of p38 pathway and suppressed the phosphorylation of p38 MAPK.
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With a significant increase in the obesity epidemic in China, addressing adolescent obesity should be highlighted as a priority. The current qualitative study aims to explore the perspectives of key stakeholders regarding adolescent obesity, providing guidance for developing effective obesity interventions for Chinese adolescents. A total of 12 focus group discussions were convened with a range of representative stakeholders including adolescents (n = 37), parents (n = 28), and school staff (n = 21) from sample schools. Semi-structured topic guides were used for data collection. All data were transcribed verbatim and analyzed thematically. From multiple stakeholder perspectives, we finally identified 3 overarching themes (Understanding adolescent obesity, Key healthy lifestyles, and Barriers to obesity prevention practices) and 8 sub-themes. While participants had mixed perceptions of status and prevalence of adolescent obesity, all acknowledged the serious health consequences associated with it. As significant modifiable risk factors, unhealthy diet and physical activity were identified to be prevalent among Chinese teenagers and lead to excessive weight gain. However, a variety of individual, environmental and sociocultural factors hindered the implementation of healthy lifestyles, affecting adolescent obesity prevention and control. Given adolescent obesity is a complex, multifactorial and multilevel public issue, comprehensive lifestyle interventions are recommended that synergistically engage multiple stakeholders across key communities to fight the ongoing obesity epidemic.
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Grupos Focales , Obesidad Infantil , Investigación Cualitativa , Humanos , Adolescente , Masculino , China/epidemiología , Femenino , Obesidad Infantil/prevención & control , Obesidad Infantil/epidemiología , Ejercicio Físico , Padres/psicología , Factores de Riesgo , Estilo de Vida Saludable , Participación de los Interesados , DietaRESUMEN
The endoplasmic reticulum (ER) is a key organelle in eukaryotic cells, responsible for a wide range of vital functions, including the modification, folding, and trafficking of proteins, as well as the biosynthesis of lipids and the maintenance of intracellular calcium homeostasis. A variety of factors can disrupt the function of the ER, leading to the aggregation of unfolded and misfolded proteins within its confines and the induction of ER stress. A conserved cascade of signaling events known as the unfolded protein response (UPR) has evolved to relieve the burden within the ER and restore ER homeostasis. However, these processes can culminate in cell death while ER stress is sustained over an extended period and at elevated levels. This review summarizes the potential role of ER stress and the UPR in determining cell fate and function in various diseases, including cardiovascular diseases, neurodegenerative diseases, metabolic diseases, autoimmune diseases, fibrotic diseases, viral infections, and cancer. It also puts forward that the manipulation of this intricate signaling pathway may represent a novel target for drug discovery and innovative therapeutic strategies in the context of human diseases.
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Circular RNAs (circRNAs) have emerged as key regulators of cancer occurrence and progression, as well as promising biomarkers for cancer diagnosis and prognosis. However, the potential mechanisms of circRNAs implicated in lymph node (LN) metastasis of gastric cancer remain unclear. Herein, we identify a novel N6-methyladenosine (m6A) modified circRNA, circPAK2, which is significantly upregulated in gastric cancer tissues and metastatic LN tissues. Functionally, circPAK2 enhances the migration, invasion, lymphangiogenesis, angiogenesis, epithelial-mesenchymal transition (EMT), and metastasis of gastric cancer in vitro and in vivo. Mechanistically, circPAK2 is exported by YTH domain-containing protein 1 (YTHDC1) from the nucleus to the cytoplasm in an m6A methylation-dependent manner. Moreover, increased cytoplasmic circPAK2 interacts with Insulin-Like Growth Factor 2 mRNA-Binding Proteins (IGF2BPs) and forms a circPAK2/IGF2BPs/VEGFA complex to stabilize VEGFA mRNA, which contributes to gastric cancer vasculature formation and aggressiveness. Clinically, high circPAK2 expression is positively associated with LN metastasis and poor prognosis in gastric cancer. This study highlights m6A-modified circPAK2 as a key regulator of LN metastasis of gastric cancer, thus supporting circPAK2 as a promising therapeutic target and prognostic biomarker for gastric cancer.
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Adenosina , Metástasis Linfática , ARN Circular , Proteínas de Unión al ARN , Transducción de Señal , Neoplasias Gástricas , Factor A de Crecimiento Endotelial Vascular , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Metástasis Linfática/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Animales , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Transducción de Señal/genética , Ratones , Masculino , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Pronóstico , Femenino , Ratones DesnudosRESUMEN
BACKGROUND: This study aimed to develop a novel six-gene expression biomarker panel to enhance the early detection and risk stratification of peritoneal recurrence and micrometastasis in locally advanced gastric cancer (LAGC). METHODS: We used genome-wide transcriptome profiling and rigorous bioinformatics to identify a six-gene expression biomarker panel. This panel was validated across multiple clinical cohorts using both tissue and liquid biopsy samples to predict peritoneal recurrence and micrometastasis in patients with LAGC. RESULTS: Through genome-wide expression profiling, we identified six mRNAs and developed a risk prediction model using 196 samples from a surgical specimen training cohort. This model, incorporating a 6-mRNA panel with clinical features, demonstrated high predictive accuracy for peritoneal recurrence in gastric cancer patients, with an AUC of 0.966 (95% CI: 0.944-0.988). Transitioning from invasive surgical or endoscopic biopsy to noninvasive liquid biopsy, the model retained its predictive efficacy (AUC = 0.963; 95% CI: 0.926-1.000). Additionally, the 6-mRNA panel effectively differentiated patients with or without peritoneal metastasis in 95 peripheral blood specimens (AUC = 0.970; 95% CI: 0.936-1.000) and identified peritoneal micrometastases with a high efficiency (AUC = 0.941; 95% CI: 0.874-1.000). CONCLUSIONS: Our study provides a novel gene expression biomarker panel that significantly enhances early detection of peritoneal recurrence and micrometastasis in patients with LAGC. The RSA model's predictive capability offers a promising tool for tailored treatment strategies, underscoring the importance of integrating molecular biomarkers with clinical parameters in precision oncology.
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Biomarcadores de Tumor , Perfilación de la Expresión Génica , Micrometástasis de Neoplasia , Recurrencia Local de Neoplasia , Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Biopsia Líquida/métodos , Femenino , Micrometástasis de Neoplasia/genética , Masculino , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/genética , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica/métodos , Persona de Mediana Edad , Transcriptoma , AncianoRESUMEN
BACKGROUND: Gastric cancer (GC) is a prevalent malignant tumor of the gastrointestinal (GI) system. However, the lack of reliable biomarkers has made its diagnosis, prognosis, and treatment challenging. Immunogenic cell death (ICD) is a type of programmed cell death that is strongly related to the immune system. However, its function in GC requires further investigation. METHOD: We used multi-omics and multi-angle approaches to comprehensively explore the prognostic features of ICD in patients with stomach adenocarcinoma (STAD). At the single-cell level, we screened genes associated with ICD at the transcriptome level, selected prognostic genes related to ICD using weighted gene co-expression network analysis (WGCNA) and machine learning, and constructed a prognostic model. In addition, we constructed nomograms that incorporated pertinent clinical features and provided effective tools for prognostic prediction in clinical settings. We also investigated the sensitivity of the risk subgroups to both immunotherapy and drugs. Finally, in addition to quantitative real-time polymerase chain reaction, immunofluorescence was used to validate the expression of ICD-linked genes. RESULTS: Based on single-cell and transcriptome WGCNA analyses, we identified 34 ICD-related genes, of which 11 were related to prognosis. We established a prognostic model using the least absolute shrinkage and selection operator (LASSO) algorithm and identified dissimilarities in overall survival (OS) and progression-free survival (PFS) in risk subgroups. The nomograms associated with the ICD-related signature (ICDRS) demonstrated a good predictive value for clinical applications. Moreover, we detected changes in the tumor microenvironment (TME), including biological functions, mutation landscapes, and immune cell infiltration, between the high- and low-risk groups. CONCLUSION: We constructed an ICD-related prognostic model that incorporated features related to cell death. This model can serve as a useful tool for predicting the prognosis of GC, targeted prevention, and personalized medicine.
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BACKGROUND: The involvement of quality of life as the UNAIDS fourth 90 target to monitor the global HIV response highlighted the development of patient-reported outcome (PRO) measures to help address the holistic needs of people living with HIV/AIDS (PLWHA) beyond viral suppression. This study developed and tested preliminary measurement properties of a new patient-reported outcome (PROHIV-OLD) measure designed specifically to capture influences of HIV on patients aged 50 and older in China. METHODS: Ninety-three older people living with HIV/AIDS (PLWHA) were interviewed to solicit items and two rounds of patient cognitive interviews were conducted to modify the content and wording of the initial items. A validation study was then conducted to refine the initial instrument and evaluate measurement properties. Patients were recruited between February 2021 and November 2021, and followed six months later after the first investigation. Classical test theory (CTT) and item response theory (IRT) were used to select items using the baseline data. The follow-up data were used to evaluate the measurement properties of the final instrument. RESULTS: A total of 600 patients were recruited at the baseline. Of the 485 patients who completed the follow-up investigation, 483 were included in the validation sample. The final scale of PROHIV-OLD contained 25 items describing five dimensions (physical symptoms, mental status, illness perception, family relationship, and treatment). All the PROHIV-OLD dimensions had satisfactory reliability with Cronbach's alpha coefficient, McDonald's ω, and composite reliability of each dimension being all higher than 0.85. Most dimensions met the test-retest reliability standard except for the physical symptoms dimension (ICC = 0.64). Confirmatory factor analysis supported the structural validity of the final scale, and the model fit index satisfied the criterion. The correlations between dimensions of PROHIV-OLD and MOS-HIV met hypotheses in general. Significant differences on scores of the PROHIV-OLD were found between demographic and clinical subgroups, supporting known-groups validity. CONCLUSIONS: The PROHIV-OLD was found to have good feasibility, reliability and validity for evaluating health outcome of Chinese older PLWHA. Other measurement properties such as responsiveness and interpretability will be further examined.
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Síndrome de Inmunodeficiencia Adquirida , Calidad de Vida , Humanos , Persona de Mediana Edad , Anciano , Calidad de Vida/psicología , Encuestas y Cuestionarios , Reproducibilidad de los Resultados , Medición de Resultados Informados por el Paciente , China , Psicometría/métodosRESUMEN
Objective: Acute ischemic stroke (AIS) brings an increasingly heavier economic burden nowadays. Prolonged length of stay (LOS) is a vital factor in healthcare expenditures. The aim of this study was to predict prolonged LOS in AIS patients based on an interpretable machine learning algorithm. Methods: We enrolled AIS patients in our hospital from August 2017 to July 2019, and divided them into the "prolonged LOS" group and the "no prolonged LOS" group. Prolonged LOS was defined as hospitalization for more than 7 days. The least absolute shrinkage and selection operator (LASSO) regression was applied to reduce the dimensionality of the data. We compared the predictive capacity of extended LOS in eight different machine learning algorithms. SHapley Additive exPlanations (SHAP) values were used to interpret the outcome, and the most optimal model was assessed by discrimination, calibration, and clinical utility. Results: Prolonged LOS developed in 149 (22.0%) of the 677 eligible patients. In eight machine learning algorithms, prolonged LOS was best predicted by the Gaussian naive Bayes (GNB) model, which had a striking area under the curve (AUC) of 0.878 ± 0.007 in the training set and 0.857 ± 0.039 in the validation set. The variables sorted by the gap values showed that the strongest predictors were pneumonia, dysphagia, thrombectomy, and stroke severity. High net benefits were observed at 0%-76% threshold probabilities, while good agreement was found between the observed and predicted probabilities. Conclusions: The model using the GNB algorithm proved excellent for predicting prolonged LOS in AIS patients. This simple model of prolonged hospitalization could help adjust policies and better utilize resources.
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Accidente Cerebrovascular Isquémico , Humanos , Tiempo de Internación , Accidente Cerebrovascular Isquémico/terapia , Teorema de Bayes , Modelos Estadísticos , Pronóstico , Algoritmos , Aprendizaje AutomáticoRESUMEN
BACKGROUND: Aortic dissection (AD) is one of the crucial and common cardiovascular diseases, and pyroptosis is a novel cell delivery mechanism that is probably involved in the pathogenesis of various cardiovascular diseases. However, no study has investigated the role of pyroptosis in AD. METHODS: We obtained two AD datasets, GSE153434 and GSE190635, from the Gene Expression Omnibus database. The differential expression of AD-related genes was determined by differential analysis, and their enrichment analysis was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Additionally, a protein-protein interaction network was established. Next, potential biomarkers were screened by Lasso regression analysis, and a neural network model was constructed. Finally, the potential biomarkers were validated by constructing a mouse model of AD. RESULTS: A total of 1033 differentially expressed related genes were distinguished and these genes were mainly associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase signaling pathways. The Lasso regression results showed five potential biomarkers, namely platelet endothelial cell adhesion molecule-1 (PECAM1), caspase 4 (CASP4), mixed lineage kinase domain-like pseudokinase (MLKL), APAF1-interacting protein (APIP), and histone deacetylase 6 (HDAC6) and successfully constructed a neural network model to predict AD occurrence. The results showed that CASP4 and MLKL were highly expressed, whereas PECAM1 and HDAC6 were lowly expressed in AD samples, and no statistically significant difference was observed in APIP expression in AD samples. CONCLUSION: Pyroptosis plays a crucial role in AD occurrence and development. Moreover, the five potential biomarkers identified in the present study can act as targets for the early diagnosis of AD in patients.
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Disección Aórtica , Enfermedades Cardiovasculares , Animales , Ratones , Humanos , Piroptosis/genética , Fosfatidilinositol 3-Quinasas , Redes Neurales de la Computación , Disección Aórtica/genética , Biomarcadores , Biología ComputacionalRESUMEN
Objective: Magnoflorine (Mag) has been reported to have anxiolytics, anti-cancer, and anti-inflammatory properties. In this study, we aim to investigate the effects of Mag on the rheumatoid arthritis (RA) and explore the underlying mechanism using a collagen-induced arthritis (CIA) mouse model and a lipopolysaccharide (LPS)-stimulated macrophage inflammation model. Methods: The in vivo effects of Mag on CIA were studied by inducing CIA in a mouse model using DBA/1J mice followed by treatment with vehicle, methotrexate (MTX, 1 mg/kg/d), and Mag (5 mg/kg/d, 10 mg/kg/d, and 20 mg/kg/d), and the in vitro effects of Mag on macrophages were examined by stimulation of RAW264.7 cells line and peritoneal macrophages (PMs) by LPS in the presence of different concentrations of Mag. Network pharmacology and molecular docking was then performed to predict the the binding ability between Mag and its targets. Inflammatory mediators were assayed by quantitative real-time PCR and enzyme linked immunosorbent assay (ELISA). Signaling pathway changes were subsequently determined by Western blotting and immunohistochemistry (IHC). Results: In vivo experiments demonstrated that Mag decreased arthritis severity scores, joints destruction, and macrophages infiltration into the synovial tissues of the CIA mice. Network pharmacology analysis revealed that Mag interacted with TNF-α, IL-6, IL-1ß, and MCP-1. Consistent with this, analysis of the serum, synovial tissue of the CIA mice, and the supernatant of the cultured RAW264.7 cells and PMs showed that Mag suppressed the expression of TNF-α, IL-6, IL-1ß, MCP-1, iNOS, and IFN-ß. Furthermore, Mag attenuated the phosphorylation of p65, IκBα, ERK, JNK, and p38 MAPKs in the synovial tissues of the CIA mice and LPS-stimulated RAW 264.7 cells. Conclusion: Mag may exert anti-arthritic and anti-inflammatory effects by inhibiting the activation of NF-κB and MAPK signaling pathways.
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Gastric cancer is one of the top causes of cancer-related death globally. Although novel treatment strategies have been developed, attempts to eradicate gastric cancer have been proven insufficient. Oxidative stress is continually produced and continually present in the human body. Increasing evidences show that oxidative stress contributes significantly to the development of gastric cancer, either through initiation, promotion, and progression of cancer cells or causing cell death. As a result, the purpose of this article is to review the role of oxidative stress response and the subsequent signaling pathways as well as potential oxidative stress-related therapeutic targets in gastric cancer. Understanding the pathophysiology of gastric cancer and developing new therapies for gastric cancer depends on more researches focusing on the potential contributors to oxidative stress and gastric carcinogenesis.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , Estrés Oxidativo , Carcinogénesis , Transducción de Señal , Muerte CelularRESUMEN
Cancer is the second most common cause of mortality in the world. One of the unresolved difficult pathological mechanism issues in malignant tumors is the imbalance of substance and energy metabolism of tumor cells. Cells maintain life through energy metabolism, and normal cells provide energy through mitochondrial oxidative phosphorylation to generate ATP, while tumor cells demonstrate different energy metabolism. Neuroendocrine control is crucial for tumor cells' consumption of nutrients and energy. As a result, better combinatorial therapeutic approaches will be made possible by knowing the neuroendocrine regulating mechanism of how the neuroendocrine system can fuel cellular metabolism. Here, the basics of metabolic remodeling in tumor cells for nutrients and metabolites are presented, showing how the neuroendocrine system regulates substance and energy metabolic pathways to satisfy tumor cell proliferation and survival requirements. In this context, targeting neuroendocrine regulatory pathways in tumor cell metabolism can beneficially enhance or temper tumor cell metabolism and serve as promising alternatives to available treatments.
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Metabolismo Energético , Neoplasias , Humanos , Neoplasias/metabolismo , Fosforilación Oxidativa , Mitocondrias/metabolismo , Redes y Vías MetabólicasRESUMEN
Alzheimer's disease (AD) is a degenerative disease of the central nervous system, the most common type of dementia in old age, which causes progressive loss of cognitive functions such as thoughts, memory, reasoning, behavioral abilities and social skills, affecting the daily life of patients. The dentate gyrus of the hippocampus is a key area for learning and memory functions, and an important site of adult hippocampal neurogenesis (AHN) in normal mammals. AHN mainly consists of the proliferation, differentiation, survival and maturation of newborn neurons and occurs throughout adulthood, but the level of AHN decreases with age. In AD, the AHN will be affected to different degrees at different times, and its exact molecular mechanisms are increasingly elucidated. In this review, we summarize the changes of AHN in AD and its alteration mechanism, which will help lay the foundation for further research on the pathogenesis and diagnostic and therapeutic approaches of AD.
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Background: Cardiomyocyte death is an important pathophysiological basis for ischemic cardiomyopathy (ICM). Many studies have suggested that ferroptosis is a key link in the development of ICM. We performed bioinformatics analysis and experiment validation to explore the potential ferroptosis-related genes and immune infiltration of ICM. Methods: We downloaded the datasets of ICM from the Gene Expression Omnibus database and analyzed the ferroptosis-related differentially expressed genes (DEGs). Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and protein-protein interaction network were performed to analyze ferroptosis-related DEGs. Gene Set Enrichment Analysis was used to evaluate the gene enrichment signaling pathway of ferroptosis-related genes in ICM. Then, we explored the immune landscape of patients with ICM. Finally, the RNA expression of the top five ferroptosis-related DEGs was validated in blood samples from patients with ICM and healthy controls using qRT-PCR. Results: Overall, 42 ferroptosis-related DEGs (17 upregulated and 25 downregulated genes) were identified. Functional enrichment analysis indicated several enriched terms related to ferroptosis and the immune pathway. Immunological analysis suggested that the immune microenvironment in patients with ICM is altered. The immune checkpoint-related genes (PDCD1LG2, LAG3, and TIGIT) were overexpressed in ICM. The qRT-PCR results showed that the expression levels of IL6, JUN, STAT3, and ATM in patients with ICM and healthy controls were consistent with the bioinformatics analysis results from the mRNA microarray. Conclusion: Our study showed significant differences in ferroptosis-related genes and functional pathway between ICM patients and healthy controls. We also provided insight into the landscape of immune cells and the expression of immune checkpoints in patients with ICM. This study provides a new road for future investigation of the pathogenesis and treatment of ICM.
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Background: Non-small cell lung cancer (NSCLC) is still a slightly less orphan disease after immunotherapy, and routine treatment has low efficiency and adverse events. Ginseng is commonly used in the treatment of NSCLC. The purpose of this study is to assess the efficacy and hemorheological indexes of ginseng and its active components in patients with non-small cell lung cancer. Methods: A comprehensive literature search was performed in PubMed, the Cochrane Library, Medline (Ovid), the Web of Science, Embase, CKNI, Wan Fang, VIP, and SinoMed up to July 2021. Only randomized controlled trials evaluating ginseng in combination with chemotherapy versus chemotherapy alone in NSCLC patients were included. Primary outcomes included patients' condition after using ginseng or its active components. Secondary outcomes included changes in immune cells, cytokines, and secretions in serum. Data were extracted by two independent individuals, and the Cochrane Risk of Bias tool version 2.0 was applied for the included studies. Systematic review and meta-analysis were performed by RevMan 5.3 software. Results: The results included 1480 cases in 17 studies. The results of the integration of clinical outcomes showed that the treatment of ginseng (or combination of ginseng with chemotherapy) can improve the quality of life for patients with NSCLC. Analysis of immune cell subtypes revealed that ginseng and its active ingredients can upregulate the percentages of antitumor immunocyte subtypes and downregulate the accounts of immunosuppressive cells. In addition, a reduction of the inflammatory level and an increase of antitumor indicators in serum were reported. Meta-analysis showed that Karnofsky score: WMD = 16, 95% CI (9.52, 22.47); quality-of-life score: WMD = 8.55, 95%CI (6.08, 11.03); lesion diameter: WMD = -0.45, 95% CI (-0.75, -0.15); weight: WMD = 4.49, 95% CI (1.18, 7.80); CD3+: WMD = 8.46, 95% CI (5.71, 11.20); CD4+: WMD = 8.45, 95% CI (6.32, 10.57)+; CD8+: WMD = -3.76, 95% CI (-6.34, -1.18); CD4+/CD8+: WMD = 0.32, 95% CI (0.10, 0.53); MDSC: WMD = -2.88, 95% CI (-4.59, -1.17); NK: WMD = 3.67, 95% CI (2.63, 4.71); Treg: WMD = -1.42, 95% CI (-2.33, -0.51); CEA: WMD = -4.01, 95% CI (-4.12, -3.90); NSE: WMD = -4.00, 95% CI (-4.14, -3.86); IL-2: WMD = 9.45, 95% CI (8.08, 10.82); IL-4: WMD = -9.61, 95% CI (-11.16, -8.06); IL-5: WMD = -11.95, 95% CI (-13.51, -10.39); IL-6: WMD = -7.65, 95% CI (-8.70, -6.60); IL-2/IL-5: WMD = 0.51, 95% CI (0.47, 0.55); IFN-γ: WMD = 15.19, 95% CI (3.16, 27.23); IFN-γ/IL-4: WMD = 0.91, 95% CI (0.85, 0.97); VEGF: WMD = -59.29, 95% CI (-72.99, -45.58); TGF-α: WMD = -10.09, 95% CI (-12.24, -7.94); TGF-ß: WMD = -135.62, 95% CI (-147.00, -124.24); TGF-ß1: WMD = -4.22, 95% CI (-5.04, -3.41); arginase: WMD = -1.81, 95% CI (-3.57, -0.05); IgG: WMD = 1.62, 95% CI (0.18, 3.06); IgM: WMD = -0.45, 95% CI (-0.59, -0.31). All results are statistically significant. No adverse events were reported in the included articles. Conclusion: It is a reasonable choice to use ginseng and its active components as adjuvant therapy for NSCLC. Ginseng is helpful for NSCLC patients' conditions, immune cells, cytokines, and secretions in the serum.
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Background and Study Aims: Antiepileptic drugs are the first choice of treatment for patients with epilepsy. However, the withdrawal of antiepileptic drugs after seizure-free remains a significant focus for the majority of patients with epilepsy and their families. In this study, we evaluated the risk factors associated with relapse after drug withdrawal in patients with seizure free for 2 years. We aimed to guide patients in seizure-free to assess the risk of drug withdrawal. Patients and Methods: Through screening, 452 patients with epilepsy were included in the study.Patients were followed up for at least 2 years or more. Analyzed their clinical data by applying the χ2-test, Kaplan-Meier survival analysis and multivariate Cox regression analysis. Results: 423 patients completed follow-up, of which 304 cases recurred (71.9%).Related recurrence factors include age of onset, type of seizure, number of AEDs, seizure-free time before withdrawal, and electroencephalogram (EEG) results before drug withdrawal (P<0.05). The results of correlation analysis showed that age of onset, seizure frequency, seizure type, number of AEDs, the period from AEDs treatment to a seizure-free status, EEG results before drug withdrawal, and pre-medication course, were all significantly related to the recurrence of seizures after drug reduction and withdrawal (P<0.05). We identified a range of independent risk factors, including onset age, seizure frequency, Multiple AEDs and the period from AEDs treatment to a seizure-free status. Conclusion: The overall recurrence rate of epilepsy in our patient cohort was high, and the peak recurrence period was within one-year of drug withdrawal. Patients with partial seizures, a short seizure-free time before withdrawal, severe EEG abnormalities before drug reduction, and a long course of the disease, are prone to relapse. Patients with an older age at onset and a high frequency of attack, those taking multi-drug combination therapy, and those that take a long time to gain control, should be managed carefully to AEDs withdrawal.
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Increasing evidence reveals that delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) results from the combined effects of environmental and genetic factors. The main pathological feature of DEACMP was generalized demyelination of cerebral white matter. Myelin basic protein (MBP) levels in cerebrospinal fluid (CSF) and serum samples from DEACMP patients were elevated. This study investigated the association of MBP single nucleotide polymorphisms(SNPs) (rs470555, rs470724, rs4890785, rs595997, rs76452994, and rs921336) with DEACMP. We genotyped 416 DEACMP patients and 785 age, educational level, and sex-matched ACMP patients for rs470555, rs470724, rs4890785, rs595997, rs76452994, and rs921336 SNPs using the Agena MassArray. There were no significant differences in the allele frequency distribution, four genetic models, and genotype distributions between the DEACMP and ACMP groups for rs470555, rs470724, rs4890785, and rs595997. However, significant differences were observed for rs76452994 and rs921336. This study revealed that the MBP polymorphisms, rs470555, rs470724, rs4890785, and rs595997, were not associated with DEACMP. Based on the codominant, dominant, and overdominant genetic inheritability patterns, the MBP rs76452994 and rs921366 polymorphisms were associated with DEACMP. Furthermore, the G allele of rs76452994 and T allele of rs921336 could lead to higher DEACMP risk.
Asunto(s)
Encefalopatías , Intoxicación por Monóxido de Carbono , Humanos , Encefalopatías/complicaciones , Intoxicación por Monóxido de Carbono/complicaciones , Intoxicación por Monóxido de Carbono/genética , Genotipo , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Adolescent and young adult (AYA) cancer survivors (first diagnosed with cancer at age 15-39) are distinct within the cancer community due to their unique challenges and diverse psycho-behavioral characteristics. This study aimed to analyze psycho-behavioral pathways and further explore the mediating role of cognitive appraisals on AYA cancer survivors' quality of life (QoL). METHODS: Three hundred and eighty-nine AYA cancer survivors were eligible for analyses and recruited to self-administer questionnaires on QoL (the Chinese version of EORTC Quality of Life Questionnaire-C30 v3.0), resilience, coping, and appraisal on site. This study performed structural equation modeling (SEM) to examine pathways on QoL based on the Rapkin & Schwartz QoL Appraisal Model. RESULTS: The average age of participants (47.6% female) was 32.7 ± 4.1 years. The SEM results closely fit the measured data (RMSEA = 0.053, GFI = 0.955, CFI = 0.964, SRMR = 0.052). The final model showed direct negative effects of later clinical-stage, more comorbidities, and more Acceptance-Resignation coping on QoL; indirect positive effects of better resilience on QoL through less Acceptance-Resignation coping (ß = 0.286, P = 0.002). Appraisal mediated the effects of treatment and resilience on QoL (ß = -0.024, P = 0.038). Further, Calm, Peaceful, and Active appraisal patterns were associated with improved Cognitive Functioning (ß = 0.119, P = 0.009). CONCLUSION: Appraisal, coping, and resilience could significantly mediate the effects of cancer and its treatment on the QoL of AYA cancer survivors. Future interventions targeting cognitive appraisals and psycho-behaviors will be helpful. Figuring out what matters to such a unique population and how they appraise a cancer diagnosis through treatment trajectories could help nurses adjust support.
Asunto(s)
Supervivientes de Cáncer , Neoplasias , Humanos , Femenino , Adulto Joven , Adolescente , Adulto , Masculino , Calidad de Vida/psicología , Supervivientes de Cáncer/psicología , Neoplasias/psicología , Emociones , Adaptación Psicológica , Encuestas y CuestionariosRESUMEN
HJ11 is a novel traditional Chinese medicine developed from the appropriate addition and reduction of Si-Miao-Yong-An decoction, which has been commonly used to treat ischemia-reperfusion (I/R) injury in the clinical setting. However, the mechanism of action of HJ11 components remains unclear. Ferroptosis is a critical factor that promotes myocardial I/R injury, and the pathophysiological ferroptosis-mediated lipid peroxidation causes I/R injury. Therefore, this study explored whether HJ11 decoction ameliorates myocardial I/R injury by attenuating ACSL4-mediated ferroptosis. This study also explored the effect of ACSL4 expression on iron-dependent programmed cell death by preparing a rat model of myocardial I/R injury and oxygen glucose deprivation/reperfusion (OGD/R)-induced H9c2 cells. The results showed that HJ11 decoction improved cardiac function; attenuated I/R injury, apoptosis, oxidative stress, mitochondrial damage, and iron accumulation; and reduced infarct size in the myocardial I/R injury rat model. Additionally, HJ11 decoction suppressed the expression of ferroptosis-promoting proteins [Acyl-CoA synthetase long-chain family member 4 (ACSL4) and cyclooxygenase-2 (COX2)] but promoted the expression of ferroptosis-inhibiting proteins [ferritin heavy chain 1 (FTH1) and glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4)] in the myocardial tissues of the I/R injury rat model. Similar results were found with the OGD/R-induced H9c2 cells. Interestingly, ACSL4 knockdown attenuated iron accumulation, oxidative stress, and ferroptosis in the OGD/R-treated H9c2 cells. However, ACSL4 overexpression counteracted the inhibitory effect of the HJ11 decoction on OGD/R-triggered oxidative stress and ferroptosis in H9c2 cells. These findings suggest that HJ11 decoction restrained the development of myocardial I/R injury by regulating ACSL4-mediated ferroptosis. Thus, HJ11 decoction may be an effective medication to treat myocardial I/R injury.