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1.
FASEB J ; 37(4): e22833, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36921064

RESUMEN

Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory infiltration and demyelination in the central nervous system (CNS). IFN-gamma (IFN-γ), a critically important immunomodulator, has been widely studied in MS pathology. The confusing and complex effects of IFN-γ in MS patients and rodent models, however, cause us to look more closely at its exact role in MS. In this study, we identified the role of the IFN-γ signaling in the choroid plexus (CP) in the experimental autoimmune encephalomyelitis (EAE) model. We found that the IFN-γ signal was rapidly amplified when CNS immune cell infiltration occurred in the CP during the progressive stage. Furthermore, using two CP-specific knockdown strategies, we demonstrated that blocking the IFN-γ signal via knockdown of IFN-γR1 in the CP could protect mice against EAE pathology, as evidenced by improvements in clinical scores and infiltration. Notably, knocking down IFN-γR1 in the CP reduced the local expression of adhesion molecules and chemokines. This finding suggests that IFN-γ signaling in the CP may participate in the pathological process of EAE by preventing pathological T helper (Th) 17+ cells from infiltrating into the CNS. Finally, we showed that the unbalanced state of IFN-γ signaling between peripheral lymphocytes and the choroid plexus may determine whether IFN-γ has a protective or aggravating effect on EAE pathology. Above all, we discovered that IFN-γR1-mediated IFN-γ signaling in the CP was a vital pathway in the pathological process of EAE.


Asunto(s)
Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Ratones , Animales , Encefalomielitis Autoinmune Experimental/metabolismo , Plexo Coroideo/metabolismo , Plexo Coroideo/patología , Sistema Nervioso Central/metabolismo , Esclerosis Múltiple/metabolismo , Interferón gamma/metabolismo , Ratones Endogámicos C57BL
2.
Eur Radiol ; 34(4): 2546-2559, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37672055

RESUMEN

OBJECTIVES: To determine the value of conventional DWI, continuous-time random walk (CTRW), fractional order calculus (FROC), and stretched exponential model (SEM) in discriminating human epidermal growth factor receptor 2 (HER2) status of breast cancer (BC). METHODS: This prospective study included 158 women who underwent DWI, CTRW, FROC, and SEM and were pathologically categorized into the HER2-zero-expressing group (n = 10), HER2-low-expressing group (n = 86), and HER2-overexpressing group (n = 62). Nine diffusion parameters, namely ADC, αCTRW, ßCTRW, DCTRW, ßFROC, DFROC, µFROC, αSEM, and DDCSEM of the primary tumor, were derived from four diffusion models. These diffusion metrics and clinicopathologic features were compared between groups. Logistic regression was used to determine the optimal diffusion metrics and clinicopathologic variables for classifying the HER2-expressing statuses. Receiver operating characteristic (ROC) curves were used to evaluate their discriminative ability. RESULTS: The estrogen receptor (ER) status, progesterone receptor (PR) status, and tumor size differed between HER2-low-expressing and HER2-overexpressing groups (p < 0.001 to p = 0.009). The αCTRW, DCTRW, ßFROC, DFROC, µFROC, αSEM, and DDCSEM were significantly lower in HER2-low-expressing BCs than those in HER2-overexpressing BCs (p < 0.001 to p = 0.01). Further multivariable logistic regression analysis showed that the αCTRW was the single best discriminative metric, with an area under the curve (AUC) being higher than that of ADC (0.802 vs. 0.610, p < 0.05); the addition of ER status, PR status, and tumor size to the αCTRW improved the AUC to 0.877. CONCLUSIONS: The αCTRW could help discriminate the HER2-low-expressing and HER2-overexpressing BCs. CLINICAL RELEVANCE STATEMENT: Human epidermal growth factor receptor 2 (HER2)-low-expressing breast cancer (BC) might also benefit from the HER2-targeted therapy. Prediction of HER2-low-expressing BC or HER2-overexpressing BC is crucial for appropriate management. Advanced continuous-time random walk diffusion MRI offers a solution to this clinical issue. KEY POINTS: • Human epidermal receptor 2 (HER2)-low-expressing BC had lower αCTRW, DCTRW, ßFROC, DFROC, µFROC, αSEM, and DDCSEM values compared with HER2-overexpressing breast cancer. • The αCTRW was the single best diffusion metric (AUC = 0.802) for discrimination between the HER2-low-expressing and HER2-overexpressing breast cancers. • The addition of αCTRW to the clinicopathologic features (estrogen receptor status, progesterone receptor status, and tumor size) further improved the discriminative ability.


Asunto(s)
Neoplasias de la Mama , Receptor ErbB-2 , Femenino , Humanos , Neoplasias de la Mama/patología , Estudios Prospectivos , Receptores de Progesterona , Imagen de Difusión por Resonancia Magnética , Receptores de Estrógenos/metabolismo
3.
AJR Am J Roentgenol ; 222(4): e2330603, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38265001

RESUMEN

BACKGROUND. Breast cancer HER2 expression has been redefined using a three-tiered system, with HER2-zero cancers considered ineligible for HER2-targeted therapy, HER2-low cancers considered candidates for novel HER2-targeted drugs, and HER2-positive cancers treated with traditional HER2-targeted medications. OBJECTIVE. The purpose of this study was to assess MRI radiomics models for a three-tiered classification of HER2 expression of breast cancer. METHODS. This retrospective study included 592 patients with pathologically confirmed breast cancer (mean age, 47.0 ± 18.0 [SD] years) who underwent breast MRI at either of a health system's two hospitals from April 2016 through June 2022. Three-tiered HER2 status was pathologically determined. Radiologists assessed the conventional MRI features of tumors and manually segmented the tumors on multiparametric sequences (T2-weighted images, DWI, ADC maps, and T1-weighted delayed contrast-enhanced images) to extract radiomics features. Least absolute shrinkage and selection operator analysis was used to develop two radiomics signatures, to differentiate HER2-zero cancers from HER2-low or HER2-positive cancers (task 1) as well as to differentiate HER2-low cancers from HER2-positive cancers (task 2). Patients from hospital 1 were randomly assigned to a discovery set (task 1: n = 376; task 2: n = 335) or an internal validation set (task 1: n = 161; task 2: n = 143); patients from hospital 2 formed an external validation set (task 1: n = 55; task 2: n = 50). Multivariable logistic regression analysis was used to create nomograms combining radiomics signatures with clinicopathologic and conventional MRI features. RESULTS. AUC, sensitivity, and specificity in the discovery, internal validation, and external validation sets were as follows: for task 1, 0.89, 99.4%, and 69.0%; 0.86, 98.6%, and 76.5%; and 0.78, 100.0%, and 0.0%, respectively; for task 2, 0.77, 93.8%, and 32.3%; 0.75, 92.9%, and 6.8%; and 0.77, 97.0%, and 29.4%, respectively. For task 1, no nomogram was created because no clinicopathologic or conventional MRI feature was associated with HER2 status independent of the MRI radiomics signature. For task 2, a nomogram including an MRI radiomics signature and three pathologic features (histologic grade of III, high Ki-67 index, and positive progesterone receptor status) that were independently associated with HER2-low expression had an AUC of 0.87, 0.83, and 0.80 in the three sets. CONCLUSION. MRI radiomics features were used to differentiate HER2-zero from HER2-low cancers or HER2-positives cancers as well as to differentiate HER2-low cancers from HER2-positive cancers. CLINICAL IMPACT. MRI radiomics may help select patients for novel or traditional HER2-targeted therapies, particularly those patients with ambiguous results of immunohistochemical staining results or limited access to fluorescence in situ hybridization.


Asunto(s)
Neoplasias de la Mama , Imagen por Resonancia Magnética , Receptor ErbB-2 , Humanos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Femenino , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Receptor ErbB-2/metabolismo , Adulto , Anciano , Diagnóstico Diferencial , Interpretación de Imagen Asistida por Computador/métodos , Radiómica
4.
Cell Mol Life Sci ; 80(5): 129, 2023 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-37086384

RESUMEN

Ufmylation is a recently identified small ubiquitin-like modification, whose biological function and relevant cellular targets are poorly understood. Here we present evidence of a neuroprotective role for Ufmylation involving Autophagy-related gene 9 (Atg9) during Drosophila aging. The Ufm1 system ensures the health of aged neurons via Atg9 by coordinating autophagy and mTORC1, and maintaining mitochondrial homeostasis and JNK (c-Jun N-terminal kinase) activity. Neuron-specific expression of Atg9 suppresses the age-associated movement defect and lethality caused by loss of Ufmylation. Furthermore, Atg9 is identified as a conserved target of Ufm1 conjugation mediated by Ddrgk1, a critical regulator of Ufmylation. Mammalian Ddrgk1 was shown to be indispensable for the stability of endogenous Atg9A protein in mouse embryonic fibroblast (MEF) cells. Taken together, our findings might have important implications for neurodegenerative diseases in mammals.


Asunto(s)
Envejecimiento , Proteínas Relacionadas con la Autofagia , Encéfalo , Proteínas de Drosophila , Drosophila , Animales , Ratones , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Envejecimiento/genética , Envejecimiento/metabolismo , Proteínas Relacionadas con la Autofagia/genética , Proteínas Relacionadas con la Autofagia/metabolismo , Encéfalo/metabolismo , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Fibroblastos/metabolismo , Mamíferos/metabolismo , Proteínas de la Membrana/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
5.
Acta Biochim Biophys Sin (Shanghai) ; 56(5): 663-674, 2024 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-38557898

RESUMEN

Adoptive cell therapies involve infusing engineered immune cells into cancer patients to recognize and eliminate tumor cells. Adoptive cell therapy, as a form of living drug, has undergone explosive growth over the past decade. The recognition of tumor antigens by the T-cell receptor (TCR) is one of the natural mechanisms that the immune system used to eliminate tumor cells. TCR-T cell therapy, which involves introducing exogenous TCRs into patients' T cells, is a novel cell therapy strategy. TCR-T cell therapy can target the entire proteome of cancer cells. Engineering T cells with exogenous TCRs to help patients combat cancer has achieved success in clinical trials, particularly in treating solid tumors. In this review, we examine the progress of TCR-T cell therapy over the past five years. This includes the discovery of new tumor antigens, protein engineering techniques for TCR, reprogramming strategies for TCR-T cell therapy, clinical studies on TCR-T cell therapy, and the advancement of TCR-T cell therapy in China. We also propose several potential directions for the future development of TCR-T cell therapy.


Asunto(s)
Antígenos de Neoplasias , Inmunoterapia Adoptiva , Neoplasias , Receptores de Antígenos de Linfocitos T , Linfocitos T , Humanos , Neoplasias/terapia , Neoplasias/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/genética , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/tendencias , Antígenos de Neoplasias/inmunología , Linfocitos T/inmunología , Animales , Ingeniería de Proteínas/métodos
6.
Perfusion ; : 2676591241244983, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565217

RESUMEN

INTRODUCTION: We set out to investigate whether the use of Histidine-Tryptophan-Ketoglutarate (HTK) solution or del Nido cardioplegia is linked to an increased incidence of postoperative acute kidney injury (AKI) in patients undergoing coronary artery bypass surgery (CABG). METHODS: A retrospective study was carried out at our center, with a total of 478 patients included in the analysis. Among them, 268 patients were administered the del Nido solution (DN) while 210 patients received the HTK solution. The primary focus of this study was to assess the occurrence of postoperative AKI and the need for renal replacement therapy (RRT). Multivariable logistic regression was used to examine the relationship between the type of cardioplegia used and adverse kidney outcomes. Additionally, serum levels of sodium, potassium, and ionized calcium were monitored during cardiopulmonary bypass (CPB). RESULTS: The incidence of AKI was significantly higher in the HTK group compared to the DN group [(48/220 (21.81%) vs. 24/186 (12.90%), p = .049], although the rate of RRT did not show a statistically significant difference (9/48, 18.75% vs. 6/24, 25%, p = .538). Multivariate logistic regression analysis revealed that HTK was a significant risk factor for AKI. Furthermore, serum sodium and calcium levels were found to decrease following HTK cardioplegic infusion. Conclusion: Our study provides compelling evidence of the impact of cardioplegic solutions on postoperative AKI rates. It underscores the importance of optimizing cardiac arrest protocols. These findings warrant further prospective investigations into the influence of cardioplegic solutions on electrolyte imbalances and postoperative AKI rates.

7.
Purinergic Signal ; 19(1): 135-144, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35167016

RESUMEN

The choroid plexus (CP) is one of the key gateways regulating the entry of peripheral immune cells into the CNS. However, the neuromodulatory mechanisms of maintaining its gateway activity are not fully understood. Here, we identified adenosine A2A receptor (A2AR) activity as a regulatory signal for the activity of CP gateway under physiological conditions. In association with a tightly closed CP gateway, we found that A2AR was present at low density in the CP. The RNA-seq analysis revealed that the A2AR antagonist KW6002 affected the expression of the cell adhesion molecules' (CAMs) pathway and cell response to IFN-γ in the CP. Furthermore, blocking or activating A2AR signaling in the CP resulted in a decreased and an increased, respectively, expression of lymphocyte trafficking determinants and disruption of the tight junctions (TJs). Furthermore, A2AR signaling regulates the CP permeability. Thus, A2AR activity in the CP may serve as a therapeutic target for remodeling the immune homeostasis in the CNS with implications for the treatment of neuroimmunological disorders.


Asunto(s)
Plexo Coroideo , Receptor de Adenosina A2A , Receptor de Adenosina A2A/metabolismo , Plexo Coroideo/metabolismo , Adenosina/metabolismo , Transducción de Señal
8.
Sensors (Basel) ; 14(11): 20687-701, 2014 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-25372616

RESUMEN

Recharging implantable electronics from the outside of the human body is very important for applications such as implantable biosensors and other implantable electronics. In this paper, a recharging method for implantable biosensors based on a wearable incoherent light source has been proposed and simulated. Firstly, we develop a model of the incoherent light source and a multi-layer model of skin tissue. Secondly, the recharging processes of the proposed method have been simulated and tested experimentally, whereby some important conclusions have been reached. Our results indicate that the proposed method will offer a convenient, safe and low-cost recharging method for implantable biosensors, which should promote the application of implantable electronics.


Asunto(s)
Técnicas Biosensibles/instrumentación , Suministros de Energía Eléctrica , Transferencia de Energía/fisiología , Iluminación/instrumentación , Modelos Biológicos , Prótesis e Implantes , Fenómenos Fisiológicos de la Piel , Simulación por Computador , Diseño Asistido por Computadora , Diseño de Equipo , Análisis de Falla de Equipo , Humanos
9.
J Cardiothorac Surg ; 19(1): 262, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654307

RESUMEN

BACKGROUND: The relationship between venous congestion in cardiopulmonary bypass (CPB) and acute kidney injury (AKI) in cardiac surgery has not utterly substantiated. This study aimed at investigate the relationship between CVP in CPB and the occurrence of AKI. METHODS: We retrospectively reviewed 2048 consecutive patients with cardiovascular disease undergoing cardiac procedure with CPB from January 2018 to December 2022. We used the median CVP value obtained during CPB for our analysis and patients were grouped according to this parameter. The primary outcomes were AKI and renal replacement therapy(RRT). Multivariable logistic regression was used to explore the association between CVP and AKI. RESULTS: A total of 2048 patients were enrolled in our study and divided into high CVP group (CVP ≥ 6.5 mmHg) and low CVP group (CVP < 6.5 mmHg) according to the median CVP value. Patients in high CVP group had the high AKI and RRT rate when compared to the low CVPgroup[(367/912,40.24%)vs.(408/1136,35.92%),P = 0.045;(16/912,1.75%vs.9/1136;0.79%), P = 0.049]. Multivariate logistic regression analysis displayed CVP played an indispensable part in development of renal failure in surgical. CONCLUSIONS: Elevated CVP(≥ 6.5mmH2OmmHg) in CPB during cardiac operation is associated with an increased risk of AKI in cardiovascular surgery patients. Clinical attention should be paid to the potential role of CVP in predicting the occurrence of AKI.


Asunto(s)
Lesión Renal Aguda , Procedimientos Quirúrgicos Cardíacos , Puente Cardiopulmonar , Presión Venosa Central , Humanos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/fisiopatología , Masculino , Femenino , Puente Cardiopulmonar/efectos adversos , Estudios Retrospectivos , Presión Venosa Central/fisiología , Persona de Mediana Edad , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Anciano , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Factores de Riesgo , Terapia de Reemplazo Renal
10.
Viruses ; 16(1)2024 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-38257818

RESUMEN

Pigs play important roles in agriculture and bio-medicine; however, porcine viral infections have caused huge losses to the pig industry and severely affected the animal welfare and social public safety. During viral infections, many non-coding RNAs are induced or repressed by viruses and regulate viral infection. Many viruses have, therefore, developed a number of mechanisms that use ncRNAs to evade the host immune system. Understanding how ncRNAs regulate host immunity during porcine viral infections is critical for the development of antiviral therapies. In this review, we provide a summary of the classification, production and function of ncRNAs involved in regulating porcine viral infections. Additionally, we outline pathways and modes of action by which ncRNAs regulate viral infections and highlight the therapeutic potential of artificial microRNA. Our hope is that this information will aid in the development of antiviral therapies based on ncRNAs for the pig industry.


Asunto(s)
MicroARNs , Virosis , Porcinos , Animales , Virosis/tratamiento farmacológico , Virosis/veterinaria , ARN no Traducido/genética , Agricultura , Antivirales/farmacología , Antivirales/uso terapéutico
11.
Medicine (Baltimore) ; 102(43): e35493, 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37904441

RESUMEN

Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) that is highly aggressive and hypoxic compared with other subtypes. The role of hypoxia-inducible factor 1α (HIF-1α) as a key hypoxic transcription factor in oncogenic processes has been extensively studied. Recently, it has been shown that HIF-1α regulates the complex biological processes of TNBC, such as glycolysis, angiogenesis, invasion and metastasis, BC stem cells enrichment, and immune escape, to promote TNBC survival and development through the activation of downstream target genes. This article discusses the expression of the HIF-1α transcription factor in TNBC and the Hypoxia-mediated activation of hypoxia-inducible factor-1α in triple-negative BC. It offers a fresh approach to clinical research and treatment for TNBC.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Hipoxia , Glucólisis , Línea Celular Tumoral
12.
Clin Exp Med ; 23(6): 2141-2150, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36737488

RESUMEN

BACKGROUND: Selective internal radiation therapy (SIRT) is a developing technique and its efficacy and modality of application in hepatocellular carcinoma (HCC) are still controversial. This network meta-analysis aims to determine whether the efficacy and safety of SIRT alone and in combination are superior to that of sorafenib. METHODS: Four databases (PubMed, Embase, Cochrane Library, and Web of Science) were searched before August 2022. Cochrane Randomized Trial Risk of Bias Assessment Tool and the Newcastle-Ottawa scale were used to assess the quality. The outcomes of interest included overall survival (OS), progression-free survival (PFS), and adverse events (AEs). RESULTS: A total of 9 eligible trials involving 1954 patients were included, and SIRT ranked first among the three treatment modalities in terms of both OS (probability, 52.3%) and PFS (probability, 68.6%). The combination of SIRT and sorafenib did not improve OS or PFS in patients with HCC. Although the combination of SIRT and sorafenib did not raise the risk of grade 3 or higher AEs, it may have introduced more AEs than either alone. CONCLUSIONS: SIRT alone was found to be superior to sorafenib and the combination of the two in improving OS or PFS in patients with non-surgical HCC, especially in patients with combined portal vein tumor thrombus. The AEs induced by SIRT were different from those of sorafenib, but the overall toxicity was manageable, the combination of the two may cause an increase in the types of AEs that occur.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/radioterapia , Sorafenib/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/radioterapia , Teorema de Bayes , Metaanálisis en Red
13.
J Vis Exp ; (196)2023 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-37395567

RESUMEN

The choroid plexus (ChP) serves as a critical gateway for immune cell infiltration into the central nervous system (CNS) under both physiological and pathological conditions. Recent research has shown that regulating ChP activity may offer protection against CNS disorders. However, studying the biological function of the ChP without affecting other brain regions is challenging due to its delicate structure. This study presents a novel method for gene knockdown in ChP tissue using adeno-associated viruses (AAVs) or cyclization recombination enzyme (Cre) recombinase protein consisting of TAT sequence (CRE-TAT). The results demonstrate that after injecting AAV or CRE-TAT into the lateral ventricle, the fluorescence was exclusively concentrated in the ChP. Using this approach, the study successfully knocked down the adenosine A2A receptor (A2AR) in the ChP using RNA interference (RNAi) or Cre/locus of X-overP1 (Cre/LoxP) systems, and showed that this knockdown could alleviate the pathology of experimental autoimmune encephalomyelitis (EAE). This technique may have important implications for future research on the ChP's role in CNS disorders.


Asunto(s)
Plexo Coroideo , Encefalomielitis Autoinmune Experimental , Animales , Humanos , Plexo Coroideo/metabolismo , Plexo Coroideo/patología , Encefalomielitis Autoinmune Experimental/metabolismo , Encéfalo/patología , Sistema Nervioso Central/metabolismo
14.
Medicine (Baltimore) ; 102(1): e32533, 2023 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-36607847

RESUMEN

Since the 1950s, hypoxia has been recognized as a crucial characteristic of cancer cells and their microenvironment. Indeed, hypoxia promotes the growth, survival, and metastasis of cancer cells. In the early 1990s, we found that as many phenomena in hypoxia can occur through hypoxia-inducible factor-1α (HIF1α). HIF1α is known as an angiogenesis converter in hypoxia, which promotes tumorigenesis, development, immune escape, recurrence, etc; This page goes into great detail on how HIF1α is activated during hypoxia and how the 2 signaling channels interact. It specifically emphasizes the significance of reactive oxygen species, the function of the PI3K/the serine/threonine kinase Akt/mammalian target of rapamycin cascade, and outlines the similarities between the 2 important factors (reactive oxygen species and PI3K/the serine/threonine kinase Akt/mammalian target of rapamycin cascade), nuclear factor κB, for HIF1α Important implications, in an effort to offer fresh views for the treatment of head and neck squamous cell carcinoma and HIF1α research.


Asunto(s)
Neoplasias de Cabeza y Cuello , Proteínas Proto-Oncogénicas c-akt , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Especies Reactivas de Oxígeno , Subunidad alfa del Factor 1 Inducible por Hipoxia , Proteínas Serina-Treonina Quinasas , Hipoxia , Serina-Treonina Quinasas TOR , Fosfatidilinositol 3-Quinasas , Serina , Microambiente Tumoral
15.
Medicine (Baltimore) ; 102(14): e33158, 2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-37026902

RESUMEN

The actin 2/3 complex (Arp2/3) regulates actin polymerization and nucleation of actin filaments, is associated with cell motility, and has been shown to play a key role in the invasion and migration of cancer cells. nucleation-promoting factor (NPF) such as N-WASP (neural-WASP famly verprolin-homologous protein family), WAVE (WASP famly verprolin-homologous protein family), and WASH (WASP and Scar homologue) undergo conformational changes upon receipt of multiple upstream signals including Rho family GTPases, cdc42 (Cell division control protein 42 homolog), and phosphatidylinositol 4,5-bisphosphate (PtdIns 4,5 P2) to bind and activate the Arp2/3 complex. Once activated, the Arp2/3 complex forms actin-based membrane protrusions necessary for cancer cells to acquire an invasive phenotype. Therefore, how to influence the invasion and migration of cancer cells by regulating the activity of the Arp2/3 complex has attracted great research interest in recent years. Several studies have explored the effects of phosphorylation modifications of cortactin and several NPFs (Nucleation Promoting Factor) including N-WASP and WAVE on the activity of the Arp2/3 complex and ultimately on cancer cell invasiveness, and have attempted to suggest new strategies for antiinvasive therapy as a result. Other studies have highlighted the potential of targeting genes encoding partial or complete proteins of the Arp2/3 complex as a therapeutic strategy to prevent cancer cell invasion and metastasis. This article reviews the role of the Arp2/3 complex in the development, invasion, and metastasis of different types of cancer and the mechanisms regulating the activity of the Arp2/3 complex.


Asunto(s)
Complejo 2-3 Proteico Relacionado con la Actina , Neoplasias , Complejo 2-3 Proteico Relacionado con la Actina/metabolismo , Actinas/metabolismo , Proteína 2 Relacionada con la Actina , Proteína 3 Relacionada con la Actina , Familia de Proteínas del Síndrome de Wiskott-Aldrich/metabolismo
16.
Sensors (Basel) ; 12(10): 13567-82, 2012 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-23202010

RESUMEN

Simulation based on the finite-element (FE) method plays an important role in the investigation of intra-body communication (IBC). In this paper, a finite-element model of the whole body model used for the IBC simulation is proposed and verified, while the FE simulation of the galvanic coupling IBC with different signal transmission paths has been achieved. Firstly, a novel finite-element method for modeling the whole human body is proposed, and a FE model of the whole human body used for IBC simulation was developed. Secondly, the simulations of the galvanic coupling IBC with the different signal transmission paths were implemented. Finally, the feasibility of the proposed method was verified by using in vivo measurements within the frequency range of 10 kHz-5 MHz, whereby some important conclusions were deduced. Our results indicate that the proposed method will offer significant advantages in the investigation of the galvanic coupling intra-body communication.


Asunto(s)
Redes de Comunicación de Computadores/instrumentación , Respuesta Galvánica de la Piel/fisiología , Cuerpo Humano , Monitoreo Ambulatorio/instrumentación , Simulación por Computador , Diseño de Equipo , Análisis de Elementos Finitos , Humanos , Monitoreo Ambulatorio/métodos , Telemetría/instrumentación , Telemetría/métodos
17.
J Anim Sci ; 100(11)2022 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-36056742

RESUMEN

This study was conducted to systematically assess and compare the fluctuations in crude protein (CP), crude fat (CF), and mineral content of staged (larva to adult) Drosophila (fruit fly) to that of a market-purchased black soldier fly larvae (BSFL) product. Results suggested that the relative CP content by dry matter ranged from 40.11% to 53.73% during Drosophila development, significantly higher (P < 0.001) than the 36.90% in BSFL. The relative CF was higher in BSFL (39.14%) compared to that of Drosophila (27.03-30.10%, P < 0.001). Although both insects contained sufficient levels of minerals to meet the dietary requirements of most animals, Drosophila overall possessed a lower content of iron, sodium, and calcium (P < 0.001) with a higher gross energy than the BSFL (P < 0.01). Comparative studies of amino acid (AA) and fatty acid (FA) profiles were further carried out among Drosophila larva (DL), pupa, and BSFL for their economic effectiveness. The AA spectra of insect larvae generally were similar except that the DL was higher in certain AA such as lysine (P < 0.01), which is an essential AA often critical for chicken growth. In contrast, the BSFL included more essential FA such as linoleic (C18:2, ω-6) and linolenic (C18:3, ω-3) acids (P < 0.01). To follow up, a husbandry trial was performed by allotting 120, 1-d-old, weight-matched, Arbor Acres broilers at random into treatment groups consisting of a low-protein diet background that contained ~20% CP supplemented with 4% BSFL and 4% or 8% DL. The average daily growth (ADG) and average daily feed intake (ADFI) of broilers, compared to the control low-protein diet, were significantly improved by feeding DL diets (P < 0.01), with better live and carcass weight and higher muscle pH (P < 0.001), which were positively correlated with the inclusion level of DL (P < 0.001). However, no differences between the control and 4% BSFL diet were observed for the performance parameters mentioned above. Moreover, all birds under our experimental setting exhibited a comparable feed conversion ratio (FCR) and were in a healthy status as indicated by the meat traits and hematological indexes within normal physiological ranges. Collectively, the findings in this study provide a theoretical basis for the further exploitation of Drosophila as potential dietary ingredients for feed production in order to meet the food challenge in the future.


Insects are regarded as one of the most promising protein sources for feed production due to its high nutritional value and low environmental cost. The objectives of this study were to analyze the dynamic nutritional composition of Drosophila (fruit fly) at various developmental phases in parallel with a commercial black soldier fly larvae (BSFL) meal, as well as to determine the effect of diets with their inclusion on broilers. Results showed that Drosophila larvae possessed a higher crude protein and a lower crude fat content when compared to the BSFL product. In the feeding trial, the performance of broilers receiving Drosophila diets was remarkably improved, with no significant influence on bird metabolic status and meat quality, except the pH of breast and thigh muscles in Drosophila diet groups being higher than that of the control group, but still in the normal range. To sum up, Drosophila meal evaluated herein has a good nutritional composition and thereby elicits a beneficial impact on the growth performance and meat production of broilers, making it a potential dietary protein source for poultry.


Asunto(s)
Pollos , Drosophila melanogaster , Animales , Pollos/fisiología , Alimentación Animal/análisis , Proteínas en la Dieta , Dieta/veterinaria , Dieta con Restricción de Proteínas/veterinaria , Larva , Aminoácidos , Minerales
18.
J Oncol ; 2022: 1608936, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35444700

RESUMEN

Background: LINC00922 has been found to promote epithelial-mesenchymal transition (EMT) in a variety of tumors. But its functions in gastric cancer (GC) remain unclear. We attempt to investigate the correlation between LINC00922 and GC via bioinformatics analysis, in vitro and in vivo experiments. Methods: TCGA and GTEx databases were utilized to obtain the RNAseq and clinical data of GC, and then, identified the correlation of LINC00922 with patients' clinicopathological characteristics and prognosis. GSEA and GO/KEGG enrichment analyses were performed to explore the potential functions or signaling pathways that LINC00922 participated in GC. Infiltration levels of immune cells were employed by ssGSEA algorithm, and then Wilcoxon rank sum test was applied to analyze their correlations with LINC00922. Scratch and transwell assays were conducted to detect the invasion and migration abilities of GC cells. Western blot was performed to explore the expression level of EMT-related proteins. Furthermore, we constructed the xenograft tumor model and metastatic tumor model in nude mice to explore the effect of LINC00922 downregulating on metastasis of GC cells in vivo. Results: Compared with normal tissues, LINC00922 was highly expressed in GC tissues and positively correlated with poor prognosis. The correlation existed between LINC00922 and immune infiltration in GC. Downregulation of LINC00922 inhibited the EMT process of GC cells. In addition, both in vitro and in vivo experiments showed that LINC00922 affects the invasion and migration abilities of GC. Conclusions: LINC00922 promotes the migration, invasion, and EMT in GC and has the potential to be used as a prognostic biomarker and therapeutic target for GC.

19.
Front Surg ; 9: 821600, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35187059

RESUMEN

BACKGROUND: Non-tumor tissue has a significant impact on the prognosis of head and neck squamous cell carcinoma (HNSCC). Previous studies for HNSCC have mainly focused on tumor tissue, greatly neglecting the role of non-tumor tissue. This study aimed to identify HNSCC subtypes and prognostic gene sets based on activity changes of immunologic and hallmark gene sets in tumor and adjacent non-tumor tissues to improve patient prognosis. METHODS: In the study, we used gene set variation analysis (GSVA) to estimate the relative enrichment of gene sets over the sample population, and identified relevant subtypes of HNSCC by Cox regression analysis and the non-negative matrix factorization (NMF) method. The representative gene sets were identified by calculating the differential enrichment score of gene sets between each of the two subgroups, intersecting them, and screening them using univariate Cox regression analysis. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to screen out potential prognostic gene sets and establish a risk model. Finally, genes encompassed in each prognostic gene set were obtained and subjected to enrichment analysis and protein-protein interaction (PPI) in tumor and non-tumor tissues. RESULTS: We identified three subtypes of HNSCC based on gene sets in tumor and non-tumor tissues, and patients with subtype 1 had a higher survival rate than subtypes 2 and 3. The subtypes were related to the survival status, pathological stage, and T stage of HNSCC patients. In total 450 differentially gene sets and 39 representative gene sets were obtained by calculating the differential enrichment score of gene sets between each of the two subgroups, intersecting them, and screening them using univariate Cox regression analysis. The prognostic model was constructed by LASSO regression analysis, including five prognostic gene sets. Kaplan-Meier analysis indicated that different risk groups and the five prognostic gene sets were associated with survival status in the model. Finally, enrichment analysis and PPI indicated that non-tumor and tumor tissues affect the prognosis of HNSCC patients in different ways. CONCLUSION: In conclusion, we provide a novel insight for rational treatment strategies and precise prognostic assessments based on tumor and adjacent non-tumor tissues, suggesting that more emphasis should be placed on changes in adjacent non-tumor and tumor tissues, rather than just the tumor itself.

20.
Sci Rep ; 12(1): 20404, 2022 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-36437265

RESUMEN

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous malignancy with poor prognosis. This article aims to explore the clinical significance of cell differentiation trajectory in HNSCC, identify different molecular subtypes by consensus clustering analysis, and develop a prognostic risk model on the basis of differentiation-related genes (DRGs) for predicting the prognosis of HNSCC patients. Firstly, cell trajectory analysis was performed on single-cell RNA sequencing (scRNA-seq) data, four molecular subtypes were identified from bulk RNA-seq data, and the molecular subtypes were predictive of patient survival, clinical features, immune infiltration status, and expression of immune checkpoint genes (ICGs)s. Secondly, we developed a 10-DRG signature for predicting the prognosis of HNSCC patients by using weighted correlation network analysis (WGCNA), differential expression analysis, univariate Cox regression analysis, and multivariate Cox regression analysis. Then, a nomogram integrating the risk assessment model and clinical features can successfully predict prognosis with favorable predictive performance and superior accuracy. We projected the response to immunotherapy and the sensitivity of commonly used antitumor drugs between the different groups. Finally, we used the quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analysis and western blot to verify the signature. In conclusion, we identified distinct molecular subtypes by cell differentiation trajectory and constructed a novel signature based on differentially expressed prognostic DRGs, which could predict the prognosis and response to immunotherapy for patients and may provide valuable clinical applications in the treatment of HNSCC.


Asunto(s)
Neoplasias de Cabeza y Cuello , Inmunoterapia , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Pronóstico , Factores Inmunológicos , Diferenciación Celular/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/terapia
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