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1.
Front Immunol ; 15: 1374931, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38562930

RESUMEN

Background: Clear cell renal cell carcinomas (ccRCCs) epitomize the most formidable clinical subtype among renal neoplasms. While the impact of tumor-associated fibroblasts on ccRCC progression is duly acknowledged, a paucity of literature exists elucidating the intricate mechanisms and signaling pathways operative at the individual cellular level. Methods: Employing single-cell transcriptomic analysis, we meticulously curated UMAP profiles spanning substantial ccRCC populations, delving into the composition and intrinsic signaling pathways of these cohorts. Additionally, Myofibroblasts were fastidiously categorized into discrete subpopulations, with a thorough elucidation of the temporal trajectory relationships between these subpopulations. We further probed the cellular interaction pathways connecting pivotal subpopulations with tumors. Our endeavor also encompassed the identification of prognostic genes associated with these subpopulations through Bulk RNA-seq, subsequently validated through empirical experimentation. Results: A notable escalation in the nFeature and nCount of Myofibroblasts and EPCs within ccRCCs was observed, notably enriched in oxidation-related pathways. This phenomenon is postulated to be closely associated with the heightened metabolic activities of Myofibroblasts and EPCs. The Myofibroblasts subpopulation, denoted as C3 HMGA1+ Myofibroblasts, emerges as a pivotal subset, displaying low differentiation and positioning itself at the terminal point of the temporal trajectory. Intriguingly, these cells exhibit a high degree of interaction with tumor cells through the MPZ signaling pathway network, suggesting that Myofibroblasts may facilitate tumor progression via this pathway. Prognostic genes associated with C3 were identified, among which TUBB3 is implicated in potential resistance to tumor recurrence. Finally, experimental validation revealed that the knockout of the key gene within the MPZ pathway, MPZL1, can inhibit tumor activity, proliferation, invasion, and migration capabilities. Conclusion: This investigation delves into the intricate mechanisms and interaction pathways between Myofibroblasts and ccRCCs at the single-cell level. We propose that targeting MPZL1 and the oxidative phosphorylation pathway could serve as potential key targets for treating the progression and recurrence of ccRCC. This discovery paves the way for new directions in the treatment and prognosis diagnosis of ccRCC in the future.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Miofibroblastos/metabolismo , Recurrencia Local de Neoplasia , Neoplasias Renales/patología , Perfilación de la Expresión Génica , Fosfoproteínas/genética , Péptidos y Proteínas de Señalización Intracelular/genética
2.
Front Psychol ; 15: 1225011, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38655219

RESUMEN

Studies have shown that product scarcity appeals affect consumers' perceived scarcity, willingness to pay, and other responses, and that scarcity appeal has the potential to cause consumers to pay higher attention to the product. However, there is a lack of research on the psychological responses of consumers to scarcity appeal from the perspective of perceived green washing. In this paper, three experiments are conducted to demonstrate the impact of product scarcity appeals on consumers' purchase intentions. The research shows that when green products use product scarcity appeals as a strategy, consumers' purchase intentions are affected, but consumers' information processing about the product is the most important determinant. Perceived green washing mediates the negative effect of product scarcity appeals on green product purchase intentions. And impression management motives moderate the negative effect of product scarcity appeals on green product purchase intentions. The findings of the study not only help companies to effectively adopt the right advertising strategies to improve their marketing effectiveness, but also help them to explore the market for green products.

3.
Front Immunol ; 15: 1368685, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38510250

RESUMEN

Background: Glioblastoma (GBM), with its high recurrence and mortality rates, makes it the deadliest neurological malignancy. Oxidative phosphorylation is a highly active cellular pathway in GBM, and NFYB is a tumor-associated transcription factor. Both are related to mitochondrial function, but studies on their relationship with GBM at the single-cell level are still scarce. Methods: We re-analyzed the single-cell profiles of GBM from patients with different subtypes by single-cell transcriptomic analysis and further subdivided the large population of Glioma cells into different subpopulations, explored the interrelationships and active pathways among cell stages and clinical subtypes of the populations, and investigated the relationship between the transcription factor NFYB of the key subpopulations and GBM, searching for the prognostic genes of GBM related to NFYB, and verified by experiments. Results: Glioma cells and their C5 subpopulation had the highest percentage of G2M staging and rGBM, which we hypothesized might be related to the higher dividing and proliferating ability of both Glioma and C5 subpopulations. Oxidative phosphorylation pathway activity is elevated in both the Glioma and C5 subgroup, and NFYB is a key transcription factor for the C5 subgroup, suggesting its possible involvement in GBM proliferation and recurrence, and its close association with mitochondrial function. We also identified 13 prognostic genes associated with NFYB, of which MEM60 may cause GBM patients to have a poor prognosis by promoting GBM proliferation and drug resistance. Knockdown of the NFYB was found to contribute to the inhibition of proliferation, invasion, and migration of GBM cells. Conclusion: These findings help to elucidate the key mechanisms of mitochondrial function in GBM progression and recurrence, and to establish a new prognostic model and therapeutic target based on NFYB.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/patología , Fosforilación Oxidativa , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Factores de Transcripción/metabolismo , Factor de Unión a CCAAT/metabolismo
4.
Front Immunol ; 15: 1351287, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38482016

RESUMEN

Background: Cervical carcinoma (CC) represents a prevalent gynecological neoplasm, with a discernible rise in prevalence among younger cohorts observed in recent years. Nonetheless, the intrinsic cellular heterogeneity of CC remains inadequately investigated. Methods: We utilized single-cell RNA sequencing (scRNA-seq) transcriptomic analysis to scrutinize the tumor epithelial cells derived from four specimens of cervical carcinoma (CC) patients. This method enabled the identification of pivotal subpopulations of tumor epithelial cells and elucidation of their contributions to CC progression. Subsequently, we assessed the influence of associated molecules in bulk RNA sequencing (Bulk RNA-seq) cohorts and performed cellular experiments for validation purposes. Results: Through our analysis, we have discerned C3 PLP2+ Tumor Epithelial Progenitor Cells as a noteworthy subpopulation in cervical carcinoma (CC), exerting a pivotal influence on the differentiation and progression of CC. We have established an independent prognostic indicator-the PLP2+ Tumor EPCs score. By stratifying patients into high and low score groups based on the median score, we have observed that the high-score group exhibits diminished survival rates compared to the low-score group. The correlations observed between these groups and immune infiltration, enriched pathways, single-nucleotide polymorphisms (SNPs), drug sensitivity, among other factors, further underscore their impact on CC prognosis. Cellular experiments have validated the significant impact of ATF6 on the proliferation and migration of CC cell lines. Conclusion: This study enriches our comprehension of the determinants shaping the progression of CC, elevates cognizance of the tumor microenvironment in CC, and offers valuable insights for prospective CC therapies. These discoveries contribute to the refinement of CC diagnostics and the formulation of optimal therapeutic approaches.


Asunto(s)
Carcinoma , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/genética , RNA-Seq , Pronóstico , Microambiente Tumoral/genética , Estudios Prospectivos , Análisis de Expresión Génica de una Sola Célula
5.
Int Ophthalmol ; 43(10): 3595-3600, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37355488

RESUMEN

PURPOSE: The purpose of this observational study was to determine whether ophthalmology residents know how to check Goldmann applanation tonometer (GAT) calibration. METHODS: The step-by-step technique for checking the calibration of a GAT was taken from the manufacturer's manual and developed into a mark sheet. Ophthalmology residents in years 2-8 of training from 11 hospitals were individually observed and assessed checking calibration of a GAT. Participation was voluntary. Contact between participants was minimised to prevent communication about the study. RESULTS: Sixty-eight per cent (n = 30) of eligible ophthalmology residents (years 2-8) from 11 hospitals (three teaching hospitals and eight local general hospitals) were observed checking GAT calibration. Only 33% (n = 10; 95% CI: 16-50%) of ophthalmology residents were able to correctly check GAT calibration. Those participants who were previously taught (p = 0.046) or assessed (p = 0.015) were more likely to be successful in GAT calibration. CONCLUSIONS: Most ophthalmology residents were unable to correctly check GAT calibration. Although better than previously published results, this observational study shows that further training and assessment is required for ophthalmology residents to learn the technique of checking GAT calibration.


Asunto(s)
Presión Intraocular , Oftalmología , Humanos , Tonometría Ocular/métodos , Calibración , Reproducibilidad de los Resultados
6.
Am J Transl Res ; 15(3): 2122-2139, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37056832

RESUMEN

OBJECTIVE: Endometrial cancer is one of the most common tumors of the female reproductive system, and the existing treatment options for advanced and metastatic endometrial cancer have certain limitations. The antitumor activity of luteolin has been gradually discovered. The purpose of this study was to predict the potential of luteolin in the treatment of endometrial cancer and to provide reference for future clinical drug use. METHODS: The target gene database of luteolin and differential gene dataset of uterine corpus endometrial carcinoma (UCEC) have been constructed to obtain the differential genes (DR-DEGs) for luteolin and UCEC. The Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis are performed at the same time. Genes associated with prognosis in DR-DEGs were screened and validated using univariate and multivariate COX risk regression analysis so as to construct a prognostic model. Genes are divided into high-risk and low-risk groups according to risk scores for survival analysis and the predictive effect of the model is evaluated. The role of immune function in UCEC is investigated by immune infiltration and immune checkpoint analysis Finally, Transwell experiment was conducted to investigate the effect of luteolin on the migration ability of endometrial cancer cells, and the expression changes of MMP1, IL-17 and VEGF were detected by q-PCR. RESULTS: Through the GO, KEGG and GSEA enrichment analysis, we have found a significant enrichment in "IL 17 signaling (IL-17) pathway", "oxidative stress response" and "HOMOLOGOUS_RECOMBINATION". Through multivariate COX risk regression analysis, four genes associated with the prognosis are harvested, including "PRSS1, MMP1, ERBB2 and NUF2" which belong to high-risk genes. Kaplan-Meier analysis shows that the survival rate in the high risk group is lower than that in the low risk group, and the receiver operating characteristic (ROC) curve reveals that the predictive effect of the model is good and stable (area under 1-year curve (AUC) 0.569, two-year AUC 0.628 and three-year AUC 0.653). Immune infiltration and immune checkpoint analysis suggest that "CD40", "T cells regulatory (Tregs)", "dendritic cells resting" and "dendritic cells activated" are correlated with survival and prognosis in UCEC patients. In in vitro experiments, we found that the migration ability of endometrial cancer cells was significantly reduced after luteolin treatment, and the expressions of MMP1, IL-17 and VEGF were all decreased. CONCLUSION: Through bioinformatic analysis, we found that luteolin could slow down the progression of UCEC by inhibiting the production of inflammatory mediators such as IL-17 and oxidative stress, and constructed genetic prognostic models associated with them: PRSS1, MMP1, ERBB2 and NUF2, respectively. In addition, we found that luteolin has an inhibitory effect on the migration of endometrial cancer cells and can reduce the expressions of MMP1, IL-17 and VEGF, thus easing the progression of endometrial cancer.

7.
BMC Endocr Disord ; 23(1): 33, 2023 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-36740666

RESUMEN

BACKGROUND: This study provides a systematic review and meta-analysis of randomized controlled trials, which examined the effect of the selenium supplementation on polycystic ovary syndrome (PCOS). METHODS: Confirmed studies related to selenium supplementation and PCOS were searched from the databases of EMBASE, PubMed and Web of Science. Data were reported as weighted mean difference (WMD) or standard mean difference (SMD) and associated 95% confidence intervals (CIs). Analysis was performed with Stata version 12.0. RESULTS: A total of 389 cases (selenium group n = 195, control group n = 194) were included in this studies. This meta-analysis showed that selenium supplementation has a positive effect on TAC, and supplementation of selenium does not significantly improve the level of BMI, Weight, LDL, HDL, Triglycerides, Total Testosterone, HOMA-IR, NO, GSH, MDA and FPG. CONCLUSION: Although selenium can improve TAC in PCOS patients, it has no significant effect on BMI, Total Testosterone, et al. In terms of the results of this meta-analysis, it is not recommended for patients with PCOS to use selenium as a regular trace element supplement. Based on the improving effect of selenium on TAC, supplementation of selenium may have a positive effect on improving follicle quality for some PCOS patients who have poor follicle quality caused by oxidative stress or who want to undergo IVF.


Asunto(s)
Síndrome del Ovario Poliquístico , Selenio , Femenino , Humanos , Selenio/uso terapéutico , Selenio/farmacología , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/complicaciones , Ensayos Clínicos Controlados Aleatorios como Asunto , Testosterona/uso terapéutico , Suplementos Dietéticos
8.
Reprod Sci ; 30(2): 576-589, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-35854199

RESUMEN

Necroptosis is one of the common modes of apoptosis, and it has an intrinsic association with cancer prognosis. However, the role of the necroptosis-related long non-coding RNA LncRNA (NRLncRNAs) in uterine corpora endometrial cancer (UCEC) has not yet been fully elucidated at present. Therefore, the present study is designed to investigate the potential prognostic value of necroptosis-related LncRNAs in UCEC. In the present study, the expression profiles and clinical data of UCEC patients were downloaded from TCGA database to identify the differentially expressed NRLncRNAs associated with overall survival. A LncRNA risk model was constructed via Cox regression analysis, and its prognostic value was evaluated. We have also further evaluated the relationships between the LncRNA features and the related cellular function, related pathways, immune status, and immune checkpoints m6A-related genes. Seven signatures, including PCAT19, CDKN2B-AS1, LINC01936, LINC02178, BMPR1B-DT, LINC00237, and TRPM2-AS, were established to assess the overall survival (OS) of the UCEC in the present study. Survival analysis and ROC curves indicated that the correlated signature has good predictable performance. The normogram could accurately predict the overall survival of the patients with an excellent clinical practical value. Enrichment analysis of gene sets indicated that risk signals were enriched in several immune-related pathways. In addition, the risk characteristics were significantly correlated with immune cells, immune function, immune cell infiltration, immune checkpoints, and some m6A-related genes. This study has identified seven necroptosis-related LncRNA signatures for the first time, providing a valuable basis for a more accurate prognostic prediction of UCEC.


Asunto(s)
Carcinoma Endometrioide , ARN Largo no Codificante , Femenino , Humanos , Pronóstico , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Necroptosis/genética , Análisis de Supervivencia
9.
Eye (Lond) ; 37(6): 1271-1274, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-35614342

RESUMEN

BACKGROUND/OBJECTIVES: To determine the incidence, proportion and location of periocular tumours in an English county over a five year period, and compare to other studies in the UK and worldwide. SUBJECTS/METHODS: A retrospective review of histopathology reports was performed for all periocular excision biopsies of malignancies from the county's three main hospitals over a 5-year period. These hospitals cover a population of just over one million. Tumours were classified according to type and location. RESULTS: 1220 lesions were included in this study. Right-sided lesions were more common than left. The incidence of basal cell carcinoma was 22 per 100,000 and squamous cell carcinoma 1.3 per 100,000, which were found most commonly on the lower eyelid and eyebrow respectively. The incidences of all other types of lesions were less than 0.5 per 100,000 per year. CONCLUSIONS: The incidence of periocular basal cell carcinomas in the predominantly elderly Caucasian population was at least three times the published national average. The high incidence of periocular tumours in this North East Anglian county is set to increase further as the proportion of over 65 year olds in the population is predicted to nearly double within two decades.


Asunto(s)
Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias de los Párpados , Neoplasias Cutáneas , Anciano , Humanos , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/patología , Neoplasias de los Párpados/patología , Párpados/cirugía , Estudios Retrospectivos , Neoplasias Cutáneas/patología
10.
Front Immunol ; 14: 1288137, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38274828

RESUMEN

Background: Glioblastoma (GBM), a prevalent malignant neoplasm within the neuro-oncological domain, has been a subject of considerable scrutiny. Macrophages, serving as the principal immunological constituents, profoundly infiltrate the microenvironment of GBM. However, investigations elucidating the intricate immunological mechanisms governing macrophage involvement in GBM at the single-cell level remain notably limited. Methods: We conducted a comprehensive investigation employing single-cell analysis, aiming to redefine the intricate cellular landscape within both the core and peripheral regions of GBM tumors. Our analytical focus extended to the profound study of macrophages, elucidating their roles within the context of oxidative stress, intercellular information exchange, and cellular trajectories concerning GBM and its assorted subpopulations. We pursued the identification of GBM prognostic genes intricately associated with macrophages. Utilizing experimental research to investigate the relevance of MANBA in the context of GBM. Results: Our investigations have illuminated the central role of macrophages in the intricate interplay among various subpopulations within the GBM microenvironment. Notably, we observed a pronounced intensity of oxidative stress responses within macrophages when compared to their GBM counterparts in other subpopulations. Moreover, macrophages orchestrated intricate cellular communication networks, facilitated by the SPP1-CD44 axis, both internally and with neighboring subpopulations. These findings collectively suggest the potential for macrophage polarization from an M1 to an M2 phenotype, contributing to immune suppression within the tumor microenvironment. Furthermore, our exploration unearthed GBM prognostic genes closely associated with macrophages, most notably MANBA and TCF12. Remarkably, MANBA appears to participate in the modulation of neuroimmune functionality by exerting inhibitory effects on M1-polarized macrophages, thereby fostering tumor progression. To bolster these assertions, experimental validations unequivocally affirmed the promotional impact of MANBA on GBM, elucidated through its capacity to curb cell proliferation, invasiveness, and metastatic potential. Conclusion: These revelations represent a pivotal step towards unraveling the intricate immunological mechanisms governing the interactions between macrophages and diverse subpopulations within the GBM milieu. Furthermore, they lay the foundation for the development of an innovative GBM prognostic model, with MANBA at its epicenter, and underscore the potential for novel immunotherapeutic targets in the ongoing pursuit of enhanced treatment modalities for this formidable malignancy.


Asunto(s)
Glioblastoma , Humanos , Glioblastoma/patología , Línea Celular Tumoral , Macrófagos , Comunicación Celular , Perfilación de la Expresión Génica , Microambiente Tumoral/genética
11.
Front Psychol ; 13: 1051856, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36438390

RESUMEN

Firms increasingly use comparative advertising in green marketing to convey information of green products to consumers, but there is still a lack of research on the effect and mechanism of comparative advertising in the green products field. Across four experimental studies, we show that comparative advertising facilitates consumers' purchase intention of green products (PIGP), because comparative advertising lead to higher perceived diagnosticity of Information. Yet, comparative advertising does not always bring high intention to buy green products. When using egoistic appeals, the perceived diagnosticity of information and purchase intention of green products were higher in comparative advertising than in non-comparative advertising. When utilizing altruistic appeals, there was no significant difference between the two kinds of advertising. In addition, individual differences of consumers also affect the effect of comparative advertising. The positive effect of comparative advertising on the purchase intention of green products is weakened for consumers with high green involvement. Our findings advance existing knowledge about the use of comparative advertising in green marketing and provide enlightening suggestions for how firms can promote consumers to buy green products.

12.
Sci Rep ; 12(1): 18813, 2022 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-36335189

RESUMEN

N-7 methylguanine (m7G) is one of the most common RNA base modifications in post-transcriptional regulation, which participates in multiple processes such as transcription, mRNA splicing and translation during the mRNA life cycle. However, its expression and prognostic value in uterine corpus endometrial carcinoma (UCEC) have not been systematically studied. In this paper, the data such as gene expression profiles, clinical data of UCEC patients, somatic mutations and copy number variants (CNVs) are obtained from the cancer genome atlas (TCGA) and UCSC Xena. By analyzing the expression differences of m7G-related mRNA in UCEC and plotting the correlation network maps, a risk score model composed of four m7G-related mRNAs (NSUN2, NUDT3, LARP1 and NCBP3) is constructed using least absolute shrinkage and selection operator (LASSO), univariate and multivariate Cox regression in order to identify prognosis and immune response. The correlation of clinical prognosis is analyzed between the m7G-related mRNA and UCEC via Kaplan-Meier method, receiver operating characteristic (ROC) curve, principal component analysis (PCA), t-SNE, decision curve analysis (DCA) curve and nomogram etc. It is concluded that the high risk is significantly correlated with (P < 0.001) the poorer overall survival (OS) in patients with UCEC. It is one of the independent risk factors affecting the OS. Differentially expressed genes are identified by R software in the high and low risk groups. The functional analysis and pathway enrichment analysis have been performed. Single sample gene set enrichment analysis (ssGSEA), immune checkpoints, m6A-related genes, tumor mutation burden (TMB), stem cell correlation, tumor immune dysfunction and rejection (TIDE) scores and drug sensitivity are also used to study the risk model. In addition, we have obtained 3 genotypes based on consensus clustering, which are significantly related to (P < 0.001) the OS and progression-free survival (PFS). The deconvolution algorithm (CIBERSORT) is applied to calculate the proportion of 22 tumor infiltrating immune cells (TIC) in UCEC patients and the estimation algorithm (ESTIMATE) is applied to work out the number of immune and matrix components. In summary, m7G-related mRNA may become a potential biomarker for UCEC prognosis, which may promote UCEC occurrence and development by regulating cell cycles and immune cell infiltration. It is expected to become a potential therapeutic target of UECE.


Asunto(s)
Carcinoma Endometrioide , Neoplasias Endometriales , Femenino , Humanos , Pronóstico , Neoplasias Endometriales/patología , Regulación Neoplásica de la Expresión Génica , Carcinoma Endometrioide/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo
13.
Front Pharmacol ; 13: 953874, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36210802

RESUMEN

Background: Using bioinformatics analysis and experimental operations, we intend to analyze the potential mechanism of action of capsaicin target gene GATA1 in the treatment of uterine corpus endometrial carcinoma (UCEC) and develop a prognostic model for the disease to validate this model. Methods: By obtaining capsaicin and UCEC-related DR-DEGs, the prognosis-related gene GATA1 was screened. The survival analysis was conducted via establishing high and low expression groups of GATA1. Whether the GATA1 could be an independent prognostic factor for UCEC, it was also validated. The therapeutic mechanism of capsaicin-related genes in UCEC was further investigated using enrichment analysis and immune methods as well as in combination with single-cell sequencing data. Finally, it was validated by cell experiments. Results: GATA1, a high-risk gene associated with prognosis, was obtained by screening. Kaplan-Meier analysis showed that the survival of the high expression group was lower than that of low expression group. ROC curves showed that the prediction effect of the model was good and stable (1-year area under curve (AUC): 0.601; 2-years AUC: 0.575; 3-years AUC: 0.610). Independent prognosis analysis showed that the GATA1 can serve as an independent prognostic factor for UCEC. Enrichment analysis showed that "neuroactive Ligand - receptor interaction and TYPE I DIABETES MELLITUS" had a significant enrichment effect. Single-cell sequencing showed that the GATA1 was significantly expressed in mast cells. Cell experiments showed that the capsaicin significantly reduced the UCEC cell activity and migration ability, as well as inhibited the expression of GATA1. Conclusion: This study suggests that the capsaicin has potential value and application prospect in the treatment of UCEC. It provides new genetic markers for the prognosis of UCEC patients.

14.
Sci Rep ; 12(1): 16773, 2022 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-36202899

RESUMEN

Necroptosis is a kind of programmed necrosis mode that plays a double-edged role in tumor progression. However, the role of necroptosis-related Messenger RNA (mRNA) in predicting the prognosis and immune response of cervical squamous carcinoma and adenocarcinoma (CESC) has not been fully studied. Firstly, the incidence of somatic mutation rate and copy number variation for 74 necroptosis-related mRNAs (NRmRNAs) were analyzed. Secondly, CESC patients were divided into four stable clusters based on the consensus clustering results and analyzed for correlations with a series of clinical factors. Subsequently, a total of 291 The Cancer Genome Atlas samples were randomly divided into either training or validation cohorts. A Cox proportional hazard model consisting of three NRmRNAs (CXCL8, CLEC9A, and TAB2) was constructed by univariate, least absolute shrinkage and selection operator and multivariate COX regression analysis to identify the prognosis and immune response. Its performance and stability were further validated in another testing dataset (GSE44001) from Gene Expression Omnibus database. The results of the receiver operating characteristic curve, principal component analysis, t-SNE, and nomogram indicated that the prognostic model we constructed can serve as an independent prognostic factor. The combination of the prognostic model and the classic TNM staging system could improve the performance in predicting the survival of CESC patients. In addition, differentially expressed genes from high and low-risk patients are screened by R software for functional analysis and pathway enrichment analysis. Besides, single-sample gene set enrichment analysis revealed that tumor-killing immune cells were reduced in the high-risk group. Moreover, patients in the low-risk group are more likely to benefit from immune checkpoint inhibitors. The analysis of tumor immune dysfunction and exclusion scores, M6A-related genes, stem cell correlation and Tumor mutational burden data with clinical information has quantified the expression levels of NRmRNAs between the two risk subgroups. According to tumor immune microenvironment scores, Spearman's correlation analysis, and drug sensitivity, immunotherapy may have a higher response rate and better efficacy in patients of the low-risk subgroup. In conclusion, we have reported the clinical significance of NRmRNAs for the prognosis and immune response in CESC patients for the first time. Screening of accurate and effective prognostic markers is important for designing a multi-combined targeted therapeutic strategy and the development of individualized precision medicine.


Asunto(s)
Adenocarcinoma , Neoplasias Óseas , Neoplasias de la Mama , Carcinoma de Células Escamosas , Neoplasias del Cuello Uterino , Carcinoma de Células Escamosas/genética , Variaciones en el Número de Copia de ADN , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico , Necroptosis , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Microambiente Tumoral/genética , Neoplasias del Cuello Uterino/genética
15.
Medicine (Baltimore) ; 101(37): e30021, 2022 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-36123943

RESUMEN

BACKGROUND: By using network pharmacology and molecular docking technology, we have explored the mechanism of action of Sanqi in the treatment of endometriosis (EMS), in order to provide reference for clinical studies of Chinese medicine treatment of Ems and Chinese medicine pharmacology. METHODS: There are 123 intersecting targets between the active ingredients of Sanqi and disease targets. In the Protein-Protein Interaction network, Jun proto-oncogene, AP-1 transcription factor subunit, tumor necrosis factor, interleukin 6, etc., are the core proteins. The top 20 genes ranked by degree have been analyzed according to the Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analysis, and 20 pathways have been identified. RESULTS: On the Kyoto Encyclopedia of Genes and Genomes pathway, the most important part is the phosphatidylinositol 3'-kinase-Akt signaling pathway, and on the Gene Ontology pathway, it is the Heme binding. The top 3 targets docked to quercetin have a certain affinity when it is docked to their degree value. Among the chemical components of Sanqi, quercetin has the most targets, suggesting that it may play a major role in the treatment of EMS. CONCLUSION: The results of molecular docking provide further evidence of the potential role of Sanqi for EMS. Overall, our study provides a new direction for the treatment of EMS and provides the basis for Sanqi as a drug for the treatment of EMS.


Asunto(s)
Endometriosis , Medicamentos Herbarios Chinos , Endometriosis/tratamiento farmacológico , Femenino , Hemo , Humanos , Interleucina-6 , Simulación del Acoplamiento Molecular , Farmacología en Red , Fosfatidilinositoles , Proteínas Proto-Oncogénicas c-akt , Quercetina , Tecnología , Factor de Transcripción AP-1 , Factores de Necrosis Tumoral
16.
Sci Rep ; 12(1): 16285, 2022 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-36175606

RESUMEN

Necroptosis, a programmed form of necrotic cell death, plays critical regulatory roles in the progression and metastatic spread of cancers such as cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, there are few articles systematically analyzing the necroptosis-related long non-coding RNAs (NRlncRNAs) correlated with CESC patients. Both RNA-sequencing and clinical data of CESC patients are downloaded from TCGA database in this study. Pearson correlation analysis, least absolute shrinkage, operator algorithm selection and Cox regression model are employed to screen and create a risk score model of eleven-NRlncRNAs (MIR100HG, LINC00996, SNHG30, LINC02688, HCG15, TUBA3FP, MIAT, DBH-AS1, ERICH6-AS1SCAT1, LINC01702) prognostic. Thereafter, a series of tests are carried out in sequence to evaluate the model for independent prognostic value. Gene set enrichment analytic paper, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analytic paper make it clear that immune-related signaling pathways are very rich in the high-risk subgroup. Additionally, the prognostic risk score model is correlated to immune cell infiltration, potential immune checkpoint, immune function, immune micro-environmental and m6A-related gene. Mutation frequency in mutated genes and survival probability trend are higher in the low-risk subgroup in most of test cases when compared to the high-risk subgroup. This study constructs a renewed prognostic model of eleven-NRlncRNAs, which may make some contribution to accurately predicting the prognosis and the immune response from CESC patients, and improve the recognition of CESC patients and optimize customized treatment regimens to some extent.


Asunto(s)
Adenocarcinoma , Carcinoma de Células Escamosas , ARN Largo no Codificante , Neoplasias del Cuello Uterino , Femenino , Humanos , Carcinoma de Células Escamosas/genética , Inmunidad , Necroptosis/genética , Pronóstico , ARN Largo no Codificante/genética , Neoplasias del Cuello Uterino/genética
17.
Medicine (Baltimore) ; 101(32): e30006, 2022 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-35960093

RESUMEN

BACKGROUND: The role of antioxidant intervention in polycystic ovary syndrome (PCOS) patients has been increasingly investigated in recent years. In order to further clarify whether antioxidant therapy is beneficial for PCOS patients and the emphasis of its effects, this study provides a systematic review and meta-analysis of randomized controlled trials examining the effect of antioxidant intervention on PCOS. METHODS: Enrolled study designs related to antioxidant interventions and PCOS, published from 1999 to 2020, were searched from EMBASE, PubMed, and Web of Science databases to sort out proven studies on antioxidant interventions and PCOS. Data were reported as weighted mean difference (WMD) or standard mean difference with associated confidence intervals of 95%. The analysis was conducted using Stata version 16.0. RESULTS: Twenty-three studies were included in total. Antioxidant intervention had a positive impact on homeostasis model assessment of insulin resistance (WMD = -0.37, P = .011) and Triglycerides (WMD = -25.51, P < .001). And antioxidant intervention did not improve testosterone levels significantly (WMD = -0.20, P = .2611). Subgroup analysis showed that except for the D-chiro-inosito subgroup, no difference in body mass index was observed between the intervention group and the control group. CONCLUSIONS: This meta-analysis demonstrates the efficacy of antioxidant intervention in patients with PCOS, demonstrating that antioxidant intervention has a significant effect on insulin resistance and lipid metabolism improvement. However, antioxidant intervention therapy has no discernible impact on testosterone levels or body mass index. Omega-3 may be a more effective antioxidant intervention for PCOS. In addition, this meta-analysis provides important reference opinions and treatment recommendations for PCOS.


Asunto(s)
Resistencia a la Insulina , Síndrome del Ovario Poliquístico , Antioxidantes/uso terapéutico , Índice de Masa Corporal , Femenino , Humanos , Síndrome del Ovario Poliquístico/complicaciones , Testosterona/uso terapéutico
18.
Medicine (Baltimore) ; 101(26): e29765, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35776991

RESUMEN

BACKGROUND: In recent years, the role of metformin in girls with precocious puberty (PP) has been increasingly frequently studied. The objective of this present study is to assess the effect of metformin on low birth weight girls with precocious puberty (LBW-PP girls). METHODS: We search the confirmed studies about circulating metformin and PP from the databases of EMBASE, PubMed, and Web of Science. Data were reported as weighted mean difference (WMD) and associated 95% confidence intervals (CIs). Analysis was performed by Review Manager 5.3 and Stata version 12.0. RESULTS: A total of 205 cases (metformin group n = 102, untreated group n = 103) were included in this study. The meta-analysis of randomized controlled trials (RCTs) suggested that metformin had statistically significant effects on testosterone (P = .001), androstenedione (P = .022), bone mineral density (BMD; P = .151), triglycerides (P ≤ .001), body mass index Z score (BMI Z score; P ≤ .001), dehydroepiandrosterone-sulfate (DHEAS; P = .053), sex hormone-binding globulin (SHBG; P = .049), high-density lipoprotein (HDL) cholesterol (P ≤ .001), low-density lipoprotein (LDL) cholesterol (P = .021), fat mass (P ≤ .001), lean mass (P = .025), and fasting insulin (P = .002). CONCLUSION: This meta-analysis provided evidence of the efficacy of metformin in girls with LBW-PP girls, which proved that metformin could improve metabolism and reduce weight. Metformin had a positive effect on preventing LBW-PP girls from developing into obesity and polycystic ovarian syndrome. In addition, this meta-analysis provided important reference opinions and directions for the treatment of LBW-PP girls.


Asunto(s)
Metformina , Pubertad Precoz , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Recién Nacido de Bajo Peso , Recién Nacido , Metaanálisis como Asunto , Metformina/uso terapéutico , Pubertad Precoz/tratamiento farmacológico , Revisiones Sistemáticas como Asunto
19.
BMC Complement Med Ther ; 22(1): 150, 2022 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-35672846

RESUMEN

Endometrial carcinoma is one of the two cancers with rising mortality and morbidity in recent years. In the light of many controversies about its treatment, it is urgent to construct a new prognostic model and to find out new therapeutic directions. As a small drug molecule widely used in clinical treatment and experimental research in China, puerarin has recently been proven to have obvious anti-cancer effects in multiple cancer cells. In this study, bioinformatics analysis and experimental validation were used to explore the potential mechanism of puerarin for endometrial carcinoma and construct a prognostic model. A total of 22 drug-related differential genes were found by constructing a database of drug targets and disease genes. The protein-protein interaction network was constructed for GO and KEGG enrichment analysis to initially explore the potential mechanism of its therapeutic effects. To construct the prognostic model, validation was performed by risk regression analysis and LASSO analysis. Finally, two prognostic genes-PIM1 and BIRC5 were determined to establish high and low risk groups. Kaplan-Meier analysis displayed a higher survival rate in the low-risk group than in the high-risk group. ROC curves indicated the stable and good effect in prediction (one-year AUC is 0.626; two-year AUC is 0.620; three-year AUC is 0.623). The interrelationship between immunity and its disease was explored by immune infiltration analysis. Finally, the potential effect of puerarin on endometrial carcinoma cells was further verified by experiments.


Asunto(s)
Biología Computacional , Neoplasias Endometriales , Biomarcadores de Tumor/genética , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genética , Femenino , Humanos , Isoflavonas , Farmacología en Red
20.
BMJ Case Rep ; 15(3)2022 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-35260395

RESUMEN

We present a previously undescribed case of a persistent hypotony maculopathy secondary to an iatrogenic cyclodialysis cleft created during XEN-45 gel stent insertion. We present this case as a further analysis of the Karimi et al case of cyclopexy by the corresponding surgeon. Following right XEN-45 implantation, our patient developed immediate and persistent postoperative hypotony for 4 weeks. Gonioscopy revealed a small cyclodialysis cleft at the 1-2 o'clock position. The cyclodialysis cleft was sealed with direct gonioscopic argon laser cyclopexy. Two months after laser treatment and total of 6 months post XEN-45 insertion, right eye visual acuity returned to 6/4 with intraocular pressure 11 mm Hg without any glaucoma medication. Here, we present details of the non-invasive safe and successful management of hypotony maculopathy secondary to the cleft using Argon laser gonio cyclopexy, with no requirement of return to theatre.


Asunto(s)
Hendiduras de Ciclodiálisis , Lesiones Oculares , Degeneración Macular , Hipotensión Ocular , Argón , Cuerpo Ciliar/cirugía , Lesiones Oculares/complicaciones , Lesiones Oculares/cirugía , Humanos , Enfermedad Iatrogénica , Presión Intraocular , Rayos Láser , Degeneración Macular/complicaciones , Hipotensión Ocular/etiología , Hipotensión Ocular/cirugía
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