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1.
Biochim Biophys Acta Mol Basis Dis ; : 167352, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39004379

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx. Palate, lung, and nasal epithelium clone (PLUNC) has been identified as an early secreted protein that is specifically expressed in the nasopharynx. The aim of this study was to determine the role and mechanism of PLUNC in NPC. We used mRNA sequencing (seq) combined with ribosome-nascent chain complex (RNC)-seq to determine the biological role of PLUNC. The expression of epithelial-to-mesenchymal transition (EMT)-related molecules was detected by western blotting. Then, cell migration and invasion were detected by wound healing and Transwell chamber assays. NPC cells were injected into the tail vein of nude mice to explore the biological role of PLUNC in vivo. The sequencing results showed that PLUNC inhibited the progression of NPC and its expression was correlated with that of NOD-like receptors. Experiments confirmed that PLUNC inhibited the invasion and metastasis of NPC cells by promoting the ubiquitination degradation of NLRP3. PLUNC overexpression in combination with the treatment by MCC950, an inhibitor of NLRP3 inflammasome activation, was most effective in inhibiting NPC invasion and metastasis. In vivo experiments also confirmed that the combination of PLUNC overexpression and MCC950 treatment effectively inhibited the lung metastasis of NPC cells. In summary, our research suggested that PLUNC inhibited the invasion and metastasis of NPC by inhibiting NLRP3 inflammasome activation, and targeting the PLUNC-NLRP3 inflammasome axis could provide a new strategy for the diagnosis and treatment of NPC patients.

2.
Int Immunopharmacol ; 137: 112523, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38909500

RESUMO

BACKGROUND: APLNR is a G protein-coupled receptor and our previous study had revealed that APLNR could inhibit nasopharyngeal carcinoma (NPC) growth and metastasis. However, the role of APLNR in regulating PD-L1 expression and immune escape in NPC is unknown. METHODS: We analyzed the expression and correlation of APLNR and PD-L1 in NPC tissues and cells. We investigated the effect of APLNR on PD-L1 expression and the underlying mechanism in vitro and in vivo. We also evaluated the therapeutic potential of targeting APLNR in combination with PD-L1 antibody in a nude mouse xenograft model. RESULTS: We found that APLNR was negatively correlated with PD-L1 in NPC tissues and cells. APLNR could inhibit PD-L1 expression by binding to the FERM domain of JAK1 and blocking the interaction between JAK1 and IFNGR1, thus suppressing IFN-γ-mediated activation of the JAK1/STAT1 pathway. APLNR could also inhibit NPC immune escape by enhancing IFN-γ secretion and CD8+ T-cell infiltration and reducing CD8+ T-cell apoptosis and dysfunction. Moreover, the best effect was achieved in inhibiting NPC growth in nude mice when APLNR combined with PD-L1 antibody. CONCLUSIONS: Our study revealed a novel mechanism of APLNR regulating PD-L1 expression and immune escape in NPC and suggested that APLNR maybe a potential therapeutic target for NPC immunotherapy.


Assuntos
Antígeno B7-H1 , Camundongos Nus , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Evasão Tumoral , Antígeno B7-H1/metabolismo , Antígeno B7-H1/imunologia , Animais , Humanos , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/patologia , Linhagem Celular Tumoral , Evasão Tumoral/efeitos dos fármacos , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto , Regulação para Baixo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/imunologia , Camundongos Endogâmicos BALB C , Linfócitos T CD8-Positivos/imunologia , Feminino , Fator de Transcrição STAT1/metabolismo , Janus Quinase 1/metabolismo , Masculino , Interferon gama/metabolismo , Receptores de Interferon/genética , Receptores de Interferon/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
3.
Clin Kidney J ; 17(5): sfae111, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38783966

RESUMO

Background: IgG4-associated kidney disease (IgG4-RKD) encompasses a spectrum of disorders, predominantly featuring tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy (MGN). The limited understanding of the co-occurrence of IgG4-RD-TIN with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) poses a diagnostic and therapeutic challenge. Methods: We examined 49 cases, comprising 21 cases of IgG4-RD-TIN (group A), 10 cases of IgG4-RD-TIN accompanied with MGN (group B), and 18 cases of IgG4-RD-TIN concurrent with AAV (group C), at the First Affiliated Hospital of Zhejiang University, China, from June 2015 to December 2022. Results: The mean age and gender of the three IgG4-RKD subtypes were not statistically significant. IgG4-RD-TIN exhibited higher serum creatinine and a higher incidence of hypocomplementemia (group A 47.6%, group B 30%, group C 16.7%). IgG4-RD-TIN-MGN was characterized by proteinuria (group A 0.3 g/d, group B 4.0 g/d, group C 0.8 g/d, P < 0.001) and hypoalbuminemia. IgG4-RD-TIN-AAV exhibited hypohemoglobinemia (group A 103.45 g/l, group B 119.60 g/l, group C 87.94 g/l, P < 0.001) and a high level of urine erythrocytes. The primary treatment for IgG4-RD-TIN was steroids alone, whereas IgG4-RD-TIN-MGN and IgG4-RD-TIN-AAV necessitated combination therapy. Group A experienced two relapses, whereas groups B and C had no relapses. There was no significant difference in patient survival among the three groups, and only two cases in group C suffered sudden death. Conclusions: This study provides valuable insights into clinical manifestations, auxiliary examination features, pathological characteristics, and prognosis of IgG4-RD-TIN, IgG4-RD-TIN-MGN, and IgG4-RD-TIN concurrent AAV. Large-scale studies are required to validate these findings.

4.
J Cancer ; 15(11): 3452-3465, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38817853

RESUMO

Background: S100A8/S100A9 belong to the S100 calcium-binding protein family and play an essential role in the progression of chronic inflammation in diseases. It also regulates various biological processes such as tumor cell survival, apoptosis, and invasive metastasis. The extracellular form of S100A8/S100A9 functions by modulating cellular oxidative metabolism and facilitating inflammation-to-cancer progression. This modulation occurs through specific binding to receptors like RAGE and TLR4 and activation of signaling pathways including STAT3 and NF-κB. In tumor cells, S100A8 and S100A9 induce phenotypic changes by influencing calcium ion concentrations and other pathways. However, the precise function of high S100A8/S100A9 expression in colorectal cancer cells remains unclear. Methods: To explore the role of S100A8/S100A9 in colorectal cancer, we used immunohistochemistry and data from GEO and TCGA databases to analyze its expression in colorectal cancer cells, normal intestinal mucosa, and adjacent tissues. Functional models of high S100A8/S100A9 expression in colorectal cancer cells were established through transfection with overexpression plasmids. Protein microarrays, enzyme-linked immunosorbent assays (ELISAs), and real-time PCR were employed to assess the expression and secretion of 40 cytokines. MTT and Transwell invasion assays were conducted to evaluate changes in cell proliferation, invasion, and chemotaxis. Finally, tail vein and subcutaneous tumorigenesis assays assessed cell proliferation and migration in vivo. Results: We observed significantly higher expression of S100A8/S100A9 in colorectal cancer epithelial cells compared to normal intestinal mucosa and adjacent tissues. Overexpression of S100A8/S100A9 in mouse colon cancer cells CT26.WT led to differential increases in the secretion levels of various cytokines (CXCL5, CXCL11, GM-CSF, G-CSF, IL1a, IL1b, sTNF RI, and CCL3). Additionally, this overexpression activated signaling pathways such as STAT3, NF-κB, and ERK-MAPK. The synthesis and secretion of inflammatory factors could be inhibited by using NF-κB and ERK-MAPK pathway inhibitors. Moreover, S100A8 promotes the proliferation and invasion of colon cancer cells. Notably, the CXCR2 inhibitor (SB265610) effectively reversed the phenotypic changes induced by the CXCL5/CXCR2 biological axis. Conclusions: Our findings indicate that increased expression of S100A8 and S100A9 in colon cancer epithelial cells enhances the secretion of inflammatory factors by activating NF-κB, ERK-MAPK, and other signaling pathways. S100A8 facilitates colon cancer cell proliferation, invasion, and metastasis through the CXCL5/CXCR2 biological axis.

5.
ISME J ; 18(1)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38423525

RESUMO

Gut microbiota are important in the adaptation of phytophagous insects to their plant hosts. However, the interaction between gut microbiomes and pioneering populations of invasive insects during their adaptation to new hosts, particularly in the initial phases of invasion, has been less studied. We studied the contribution of the gut microbiome to host adaptation in the globally recognized invasive pest, Hyphantria cunea, as it expands its range into southern China. The southern population of H. cunea shows effective adaptation to Metasequoia glyptostroboides and exhibits greater larval survival on Metasequoia than the original population. Genome resequencing revealed no significant differences in functions related to host adaptation between the two populations. The compatibility between southern H. cunea populations and M. glyptostroboides revealed a correlation between the abundance of several gut bacteria genera (Bacteroides, Blautia, and Coprococcus) and H. cunea survival. Transplanting the larval gut microbiome from southern to northern populations enhanced the adaptability of the latter to the previously unsuitable plant M. glyptostroboides. This research provides evidence that the gut microbiome of pioneering populations can enhance the compatibility of invasive pests to new hosts and enable more rapid adaptation to new habitats.


Assuntos
Microbioma Gastrointestinal , Mariposas , Animais , Larva , Genoma , Bactérias/genética
6.
Cell Oncol (Dordr) ; 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37962808

RESUMO

PURPOSE: Nasopharyngeal carcinoma (NPC) is an aggressive head and neck disease with a high incidence of distant metastases. Enlargeosomes are cytoplasmic organelles marked by, desmoyokin/AHNAK. This study aimed to evaluate the expression of AHNAK in NPC and its effect on enlargeosomes and to investigate the correlation between AHNAK expression levels and clinical NPC patient characteristics. METHODS: Primary nasopharyngeal carcinoma (NPC) and NPC specimens were evaluated by analyzing public data, and immunohistochemistry. Systematic in vitro and in vivo experiments were performed using different NPC-derived cell lines and mouse models. RESULTS: In this study, we detected AHNAK and Annexin A2(ANXA2), a protein coating the surface of enlargeosomes, in NPC samples. We found that AHNAK was down-regulated. Down-regulation of AHNAK was associated with poor overall survival in NPC patients. Moreover, transcription factor FOSL1-mediated transcriptional repression was responsible for the low expression of AHNAK by recruiting EZH2. Whereas Annexin A2 was upregulated in human NPC tissues. Upregulation of Annexin A2 was associated with lymph node metastasis and distant metastasis in NPC patients. Functional studies confirmed that silencing of AHNAK enhanced the growth, invasion, and metastatic properties of NPC cells both in vitro and in vivo. In terms of mechanism, loss of AHNAK led to an increase of annexin A2 protein level in NPC cells. Silencing ANXA2 restored NPC cells' migrative and invasive ability upon loss of AHNAK. CONCLUSION: Here, we report AHNAK as a tumor suppressor in NPC, which may act through annexin A2 oncogenic signaling in enlargeosome, with potential implications for novel approaches to NPC treatment.

7.
Ren Fail ; 45(2): 2251587, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37724549

RESUMO

INTRODUCTION: Coagulation disorders play a key role in chronic kidney disease, and the formation or elevation of plasma D-dimer levels reflects activation of the coagulation system. However, its relationship with the severity and progression of kidney disease in IgA nephropathy (IgAN) remains unclear. METHODS: We assessed 1818 patients with IgAN diagnosed between 2002 and 2019 at the First Affiliated Hospital, Zhejiang University School of Medicine. Plasma D-dimer levels were measured at the time of the renal biopsy. The association between plasma D-dimer levels and kidney disease progression events, defined as a 50% decline in eGFR and end-stage kidney disease (ESKD), was tested using restricted cubic splines and Cox proportional hazard models. RESULTS: The median plasma D-dimer level was 220 (170-388.5) µg/L FEU, which was significantly higher than healthy controls 170 (170-202) µg/L FEU. Plasma D-dimer levels were positively correlated with proteinuria (r = 0.211, p < 0.001) and serum galactose-deficient IgA1 (r = 0.226, p = 0.004) and negatively correlated with eGFR (r=-0.127, p < 0.001) and Oxford T (p < 0.001) and C (p = 0.004) scores. After a median follow-up of 25.67 (13.03-47.44) months, 126 (6.93%) patients experienced composite kidney disease progression events. Higher plasma D-dimer levels were associated with an increased risk of kidney disease progression events (hazard ratio, 1.73; 95% confidence interval [95% CI], 1.40-2.23) per ln-transformed plasma D-dimer (p < 0.001), after adjustment for sex, age, proteinuria, Mean arterial pressure (MAP) and Oxford classification scores. In reference to the first tertile of plasma D-dimer, hazard ratios were 1.48 (95% CI, 0.76-2.88) for the second tertile, 3.03 (95% CI, 1.58-5.82) for the third tertile. CONCLUSIONS: High plasma D-dimer levels were associated with the progression of kidney disease severity in IgA nephropathy.


Assuntos
Glomerulonefrite por IGA , Humanos , Glomerulonefrite por IGA/diagnóstico , Estudos de Coortes , Proteinúria , Progressão da Doença
8.
Front Cell Dev Biol ; 11: 1204033, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37397250

RESUMO

Yes-associated protein (YAP) is a transcriptional regulator that affects cell proliferation, organ size and tissue development and regeneration, and has therefore, been an important object of study. In recent years, there has been an increasing research focus on YAP in inflammation and immunology, and the role of YAP in the development of inflammation and in immune escape by tumors has been progressively elucidated. Because YAP signaling involves a variety of different signal transduction cascades, the full range of functions in diverse cells and microenvironments remains incompletely understood. In this article, we discuss the complex involvement of YAP in inflammation, the molecular mechanisms through which it exercises pro- and anti-inflammatory effects under different conditions, and the progress achieved in elucidating the functions of YAP in inflammatory diseases. A thorough understanding of YAP signaling in inflammation will provide a foundation for its use as a therapeutic target in inflammatory diseases.

9.
J Cancer ; 14(10): 1751-1762, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37476195

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignant tumor of the head and neck with high metastatic and invasive nature. Super enhancers (SEs) control the expression of cell identity genes and oncogenes during tumorigenesis. As a glycosaminoglycan in the tumor microenvironment, hyaluronan (HA) is associated with cancer development. High expression of hyaluronan synthase 3 (HAS3) resulted in HA deposition, which promoted the growth of cancer cell. However, its role in NPC development remains elusive. We demonstrated that the levels of HAS3 mRNA or protein were increased in NPC cell lines. Transcription of HAS3 is associated with SE. Disruption of SE by bromodomain containing 4 (BRD4) inhibitor JQ1 resulted in downregulation of HAS3 and inhibition of cell proliferation and invasiveness in NPC cells. Inhibition of HA synthesis by HAS inhibitor 4-MU suppressed cell growth and invasion of NPC cells, whereas HA treatment exerted opposite effects. Genetically silencing HAS3 in HK1 and FaDu NPC cells attenuated cell proliferation and mobility, while re-expression of HAS3 enhanced malignant potential of CNE1 and CNE2 NPC cells. Furthermore, loss of HAS3 impaired metastatic potential of HK1 cells in nude mice. Mechanistically, inhibition of HA synthesis by chemical inhibitor or silencing HAS3 led to reduction of the levels of phosphorylation of EGFR, AKT, and ERK proteins. In contrast, exogenous HA treatment or forced expression of HAS3 activated EGFR/AKT/ERK signaling cascade. This study suggested that HAS3 is driven by SE and overexpressed in NPC. High expression of HAS3 promotes the malignant features of NPC via activation of EGFR/AKT/ERK signaling pathway.

11.
Sci China Life Sci ; 66(11): 2515-2526, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37071289

RESUMO

Cancer is one of the leading causes of human death worldwide. Treatment of cancer exhausts significant medical resources, and the morbidity and mortality caused by cancer is a huge social burden. Cancer has therefore become a serious economic and social problem shared globally. As an increasingly prevalent disease in China, cancer is a huge challenge for the country's healthcare system. Based on recent data published in the Journal of the National Cancer Center on cancer incidence and mortality in China in 2016, we analyzed the current trends in cancer incidence and changes in cancer mortality and survival rate in China. And also, we examined several key risk factors for cancer pathogenesis and discussed potential countermeasures for cancer prevention and treatment in China.


Assuntos
Neoplasias , Humanos , Neoplasias/epidemiologia , Neoplasias/prevenção & controle , Incidência , Fatores de Risco , Taxa de Sobrevida , China/epidemiologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-37018680

RESUMO

Precisely and automatically detecting the cough sound is of vital clinical importance. Nevertheless, due to privacy protection considerations, transmitting the raw audio data to the cloud is not permitted, and therefore there is a great demand for an efficient, accurate, and low-cost solution at the edge device. To address this challenge, we propose a semi-custom software-hardware co-design methodology to help build the cough detection system. Specifically, we first design a scalable and compact convolutional neural network (CNN) structure that generates many network instances. Second, we develop a dedicated hardware accelerator to perform the inference computation efficiently, and then we find the optimal network instance by applying network design space exploration. Finally, we compile the optimal network and let it run on the hardware accelerator. The experimental results demonstrate that our model achieves 88.8% classification accuracy, 91.2% sensitivity, 86.5% specificity, and 86.5% precision, while the computation complexity is only 1.09M multiply-accumulation (MAC). Additionally, when implemented on a lightweight field programmable gate array (FPGA), the complete cough detection system only occupies 7.9K lookup tables (LUTs), 12.9K flip-flops (FFs), and 41 digital signal processing (DSP) slices, providing 8.3 GOP/s actual inference throughput and total power dissipation of 0.93 W. This framework meets the needs of partial application and can be easily extended or integrated into other healthcare applications.

13.
Cereb Cortex ; 33(3): 557-566, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-35348655

RESUMO

Subjective cognitive decline (SCD) is a preclinical asymptomatic stage of Alzheimer's disease (AD). Accurate diagnosis of SCD represents the greatest challenge for current clinical practice. The multimodal magnetic resonance imaging (MRI) features of 7 brain networks and 90 regions of interests from Chinese and ANDI cohorts were calculated. Machine learning (ML) methods based on support vector machine (SVM) were used to classify SCD plus and normal control. To assure the robustness of ML model, above analyses were repeated in amyloid ß (Aß) and apolipoprotein E (APOE) ɛ4 subgroups. We found that the accuracy of the proposed multimodal SVM method achieved 79.49% and 83.13%, respectively, in Chinese and ANDI cohorts for the diagnosis of the SCD plus individuals. Furthermore, adding Aß pathology and ApoE ɛ4 genotype information can further improve the accuracy to 85.36% and 82.52%. More importantly, the classification model exhibited the robustness in the crossracial cohorts and different subgroups, which outperforms any single and 2 modalities. The study indicates that multimodal MRI imaging combining with ML classification method yields excellent and powerful performances at categorizing SCD due to AD, suggesting potential for clinical utility.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Peptídeos beta-Amiloides , Imageamento por Ressonância Magnética/métodos , Aprendizado de Máquina , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/genética , Apolipoproteínas E/genética
14.
Front Med (Lausanne) ; 9: 922193, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36507530

RESUMO

Background: Minimal change disease (MCD) has a high recurrence rate, but currently, no biomarker can predict its recurrence. To this end, this study aimed at identifying potential serum cytokines as valuable biomarkers for predicting the risk of MCD recurrence. Materials and methods: Raybiotech 440 cytokine antibody microarray was used to detect the serum samples of eight relapsed, eight non-relapsed MCD patients after glucocorticoid treatment, and eight healthy controls. The differentially expressed cytokines were confirmed by enzyme-linked immunosorbent assay (ELISA) with serum samples from 29 non-relapsed and 35 relapsed MCD patients. The study used the receiver operating characteristic (ROC) curve analysis to investigate the sensitivity and specificity of a serum biomarker for predicting the MCD relapse. Results: Serum IL-12p40 levels increased significantly in the relapsed group. The Area Under the ROC Curve (AUC) of IL-12p40 was 0.727 (95%CI: 0.597-0.856; P < 0.01). The RNA-sequencing analysis and qPCR assay performed on the IL-12 treated mouse podocytes and the control group showed increased expression of podocyte damage genes, such as connective tissue growth factor (CTGF), matrix metallopeptidase 9 (MMP9), secreted phosphoprotein 1 (SPP1), and cyclooxygenase-2 (COX-2) in the former group. Conclusion: IL-12p40 may serve as a new biomarker for predicting the risk of MCD recurrence after glucocorticoid treatment, and it may be involved in the pathogenesis and recurrence of MCD.

15.
Comput Math Methods Med ; 2022: 6517965, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36245838

RESUMO

Obstructive sleep apnea (OSA) is caused by repeated blockage of the upper respiratory airways during sleep. The traditional evaluation methods for OSA severity are yet limited. This study aimed to screen gene signatures to effectively evaluate OSA severity. Expression profiles of peripheral blood mononuclear cells in the different severities of OSA patients were accessed from Gene Expression Omnibus (GEO) database. A total of 446 differentially expressed genes (DEGs) were screened among the varying severities of OSA samples by analysis of variance (ANOVA) test. A total of 1,152 DEGs were screened between the pre- and post-treatment OSA samples by using t test. Overlap of the two groups of DEGs was selected (88 DEGs) for Metascape enrichment analysis. Afterwards, Mfuzz package was used to perform soft clustering analysis on these 88 genes, by which 6 clusters were obtained. It was observed that the gene expression condition of the cluster 3 was positively associated with OSA severity degree; also, the gene expression condition in cluster 4 was negatively correlated with OSA severity. A total of 10 gene markers related to OSA progression were selected from cluster 3 and cluster 4. Their expression levels and correlation were analyzed. The marker genes in cluster 3 and cluster 4 were examined, finding that most genes were significantly correlated with apnea hypopnea index (AHI). An accurate and objective assessment of the severity of OSA is of great significance for formulating follow-up treatment strategies for patients with OSA. In this paper, a set of marker genes that can detect the severity of OSA were screened by bioinformatics methods, which could be jointly used with the traditional OSA diagnostic index to achieve a more reliable OSA severity evaluation.


Assuntos
Leucócitos Mononucleares , Apneia Obstrutiva do Sono , Análise por Conglomerados , Marcadores Genéticos , Humanos , Polissonografia , Sono , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/genética
16.
Genes Dis ; 9(6): 1757-1758, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36157500

RESUMO

[This corrects the article DOI: 10.1016/j.gendis.2020.07.005.][This corrects the article DOI: 10.1016/j.gendis.2021.09.001.].

17.
Cell Death Dis ; 13(8): 711, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35974000

RESUMO

Lung cancer remains one of the most common malignancies and the leading cause of cancer-related death worldwide. Forkhead box protein A1 (FOXA1) is a pioneer factor amplified in lung adenocarcinoma (LUAD). However, its role in LUAD remains elusive. In this study, we found that expression of FOXA1 enhanced LUAD cell survival in nutrients deprived conditions through inhibiting autophagic cell death (ACD). FOXA1 bound to the imprinting control region of insulin-like growth factor 2 (IGF2) and interacted with DNA methyltransferase 1 (DNMT1), leading to initiation of DNMT1-mediated loss of imprinting (LOI) of IGF2 and autocrine of IGF2. Blockage of IGF2 and its downstream insulin-like growth factor 1 receptor (IGF1R) abolished the protective effect of FOXA1 on LUAD cells in nutrients deprived conditions. Furthermore, FOXA1 suppressed the expression of the lysosomal enzyme glucocerebrosidase 1 (GBA1), a positive mediator of ACD, through ubiquitination of GBA1 enhanced by IGF2. Notably, FOXA1 expression in A549 cells reduced the efficacy of the anti-angiogenic drug nintedanib to inhibit xenograft tumor growth, whereas a combination of nintedanib with IGF1R inhibitor linsitinib or mTORC1 inhibitor rapamycin enhanced tumor control. Clinically, high expression level of FOXA1 protein was associated with unfavorable prognosis in LUAD patients of advanced stage who received bevacizumab treatment. Our findings uncovered a previously unrecognized role of FOXA1 in mediating loss of imprinting of IGF2, which confer LUAD cells enhanced survival ability against nutrients deprivation through suppressing autophagic cell death.


Assuntos
Adenocarcinoma de Pulmão , Morte Celular Autofágica , Fator 3-alfa Nuclear de Hepatócito , Fator de Crescimento Insulin-Like II , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Impressão Genômica , Fator 3-alfa Nuclear de Hepatócito/genética , Humanos , Fator de Crescimento Insulin-Like II/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Nutrientes
18.
Sensors (Basel) ; 22(16)2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-36015811

RESUMO

The multi-satellites cooperative transmission can effectively increase the data rate that can be achieved by internet of things (IoT) terminals. However, the dynamic characteristics brought by low Earth orbit (LEO) satellites will seriously decrease the data rate and make the data rate fluctuate. In this paper, dual-stream transmission and downlink power control for multiple LEO satellites-assisted IoT networks are investigated. To mitigate the effects of the frequency offset caused by different LEO satellites, a multi-satellites synchronization scheme is proposed. Then, different power control schemes are given to resist the data rate fluctuation during the transmission. The simulation results show that the proposed schemes can effectively compensate for the varied frequency offset and keep the data rate stable.

19.
Artigo em Inglês | MEDLINE | ID: mdl-35800002

RESUMO

Background: Vertigo is a cardinal symptom of posterior circulation infarction (POCI). Acupuncture is demonstrated to have a beneficial effect on posterior circulation infarction vertigo (PCIV). However, the mechanism of acupuncture therapy is not clarified. This study aims to assess the cerebral blood flow velocity modulation and clinical efficacy of acupuncture for PCIV patients. Methods: We conducted this systematic review for clinical randomized controlled trials (RCTs) regarding acupuncture on PCIV. The study duration was from September 2020 to September 2021. We searched the PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP. The publication date was set from inception to August 31, 2020. Based on the inclusion and exclusion criteria, two researchers independently screened literature and extracted data including basic study information, intervention details, outcome details, and adverse events. Outcome measures included the blood flow velocities of vertebrobasilar arteries and the Clinical Effective Rate of posterior circulation infarction vertigo. Pooled data were presented as standardized mean differences (SMDs) and relative risks (RR), with 95% confidence intervals (CIs). The meta-analysis was conducted using Review Manager software version 5.3.0. Results: A total of 20 eligible RCTs (1541 participants) were included in this review, which compared acupuncture therapy (1 RCT) or acupuncture combined with pharmaceutical therapy (19 RCTs) to pharmaceutical therapy in patients with posterior circulation infarction vertigo. 7 studies assessed the blood flow velocities of the basilar artery examined by Transcranial Doppler (TCD), 8 studies assessed the bilateral vertebral arteries, and 13 studies evaluated the Clinical Effective Rate of posterior circulation infarction vertigo. Meta-analysis results showed that blood flow velocities of the basilar artery (SMD = 0.58, 95% CI = 0.40-0.76; P < 0.05), left vertebral artery (SMD = 0.48, 95% CI = 0.22-0.73; P < 0.05), and right vertebral artery (SMD = 0.44, 95% CI = 0.19-0.69; P < 0.05) were significantly higher in the acupuncture group compared with the control group. Clinical Effective Rate (RR = 1.22, 95% CI = 1.15-1.29; P = 0.792) was significantly better in the acupuncture group compared with the control group. Conclusions: This study shows that acupuncture therapy is useful in improving the blood flow velocity of vertebrobasilar arteries and Clinical Effective Rate in patients with posterior circulation infarction vertigo. However, double-blind, sham-controlled trials with large sample sizes are required to support our conclusions.

20.
Cell Death Dis ; 13(6): 544, 2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35688814

RESUMO

Ferroptosis is a type of cell death that depends on iron and reactive oxygen species (ROS). The accumulation of iron and lipid peroxidation primarily initiates oxidative membrane damage during ferroptosis. The core molecular mechanism of ferroptosis includes the regulation of oxidation and the balance between damage and antioxidant defense. Tumor cells usually contain a large amount of H2O2, and ferrous/iron ions will react with excessive H2O2 in cells to produce hydroxyl radicals and induce ferroptosis in tumor cells. Here, we reviewed the latest studies on the regulation of ferroptosis in tumor cells and introduced the tumor-related signaling pathways of ferroptosis. We paid particular attention to the role of noncoding RNA, nanomaterials, the role of drugs, and targeted treatment using ferroptosis drugs for mediating the ferroptosis process in tumor cells. Finally, we discussed the currently unresolved problems and future research directions for ferroptosis in tumor cells and the prospects of this emerging field. Therefore, we have attempted to provide a reference for further understanding of the pathogenesis of ferroptosis and proposed new targets for cancer treatment.


Assuntos
Ferroptose , Neoplasias , Humanos , Peróxido de Hidrogênio , Ferro/metabolismo , Peroxidação de Lipídeos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Espécies Reativas de Oxigênio/metabolismo
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