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1.
Crit Rev Immunol ; 44(4): 23-39, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505919

RESUMO

Enhancer of zeste homolog 2 (EZH2)gene has a prognostic role in hepatocellular carcinoma (HCC). This study aimed to identify the role of microRNAs (miRNAs) let-7c-5p by targeting EZH2 in HCC. We downloaded gene and miRNA RNA-seq data from The Cancer Genome Atlas (TCGA) database. Differences in EZH2 expression between different groups were analyzed and the association of EZH2 expression with HCC prognosis was detected using Cox regression analysis. The miRNA-EZH2-pathway network was constructed. Dual-luciferase reporter assay was performed to detect the hsa-let-7c-5p-EZH2. Cell proliferation, migration, invasion, and apoptosis were detected by CCK-8, Wound healing, Transwell, and Flow cytometry, respectively. RT-qPCR and Western blot were used to detect the expression of let-7c-5p and EZH2. EZH2 was upregulated in HCC tumors (P < 0.0001). Cox regression analysis showed that TCGA HCC patients with high EZH2 expression levels showed a short survival time [hazard ratio (HR) = 1.677, 95% confidence interval (CI) 1.316-2.137; P < 0.0001]. Seven miRNAs were negatively correlated with EZH2 expression and were significantly downregulated in HCC tumor samples (P < 0.0001), in which hsa-let-7c-5p was associated with prognosis in HCC (HR = 0.849 95% CI 0.739-0.975; P = 0.021). We identified 14 immune cells that showed significant differences in EZH2 high- and low-expression groups. Additionally, let-7c-5p inhibited HCC cell proliferation, migration, and invasion and reversed the promoted effects of EZH2 on HCC cell malignant characteristics. hsa-let-7c-5p-EZH2 significantly suppressed HCC malignant characteristics, which can be used for HCC prognosis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/farmacologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica
2.
New Phytol ; 243(2): 688-704, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38769723

RESUMO

Potato (Solanum tuberosum) is the fourth largest food crop in the world. Late blight, caused by oomycete Phytophthora infestans, is the most devastating disease threatening potato production. Previous research has shown that StRFP1, a potato Arabidopsis Tóxicos en Levadura (ATL) family protein, positively regulates late blight resistance via its E3 ligase activity. However, the underlying mechanism is unknown. Here, we reveal that StRFP1 is associated with the plasma membrane (PM) and undergoes constitutive endocytic trafficking. Its PM localization is essential for inhibiting P. infestans colonization. Through in vivo and in vitro assays, we investigated that StRFP1 interacts with two sugar transporters StSWEET10c and StSWEET11 at the PM. Overexpression (OE) of StSWEET10c or StSWEET11 enhances P. infestans colonization. Both StSWEET10c and StSWEET11 exhibit sucrose transport ability in yeast, and OE of StSWEET10c leads to an increased sucrose content in the apoplastic fluid of potato leaves. StRFP1 ubiquitinates StSWEET10c and StSWEET11 to promote their degradation. We illustrate a novel mechanism by which a potato ATL protein enhances disease resistance by degrading susceptibility (S) factors, such as Sugars Will Eventually be Exported Transporters (SWEETs). This offers a potential strategy for improving disease resistance by utilizing host positive immune regulators to neutralize S factors.


Assuntos
Resistência à Doença , Phytophthora infestans , Doenças das Plantas , Proteínas de Plantas , Solanum tuberosum , Ubiquitina-Proteína Ligases , Doenças das Plantas/microbiologia , Resistência à Doença/genética , Phytophthora infestans/patogenicidade , Solanum tuberosum/microbiologia , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Membrana Celular/metabolismo , Ubiquitinação , Regulação da Expressão Gênica de Plantas , Sacarose/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/microbiologia , Ligação Proteica , Transporte Proteico
3.
Pharmacol Res ; 197: 106980, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37944835

RESUMO

The microRNAs (miRNAs) are potent regulators of tumorigenesis in various cancers, especially pancreatic cancer. The abnormal expression of miRNAs can be observed in tumor cells. Noteworthy, miRNAs could be transferred by exosomes as small extracellular vesicles in regulation of carcinogenesis. This research focused on exploring the roles and mechanisms of exosomal miR-484, derived from human bone marrow mesenchymal stem cells (hBMSCs), in the context of molecular interactions and regulation of mitochondrial metabolism. Exosomes were isolated for the examination of miR-484 expression. The impacts of hBMSCs-derived exosomal miR-484 on pancreatic cancer cells were studied using various assays. Evaluation of mitochondrial function and metabolism was performed. Wnt/MAPK pathway-related protein expression was assessed, and an in vivo tumor xenograft model was utilized to examine the functions. Our findings demonstrated a decreased miR-484 expression in pancreatic cancer cells. However, hBMSCs-derived exosomal miR-484 inhibited the proliferation and migration of these cells, while inducing apoptosis. Moreover, miR-484 led to an upsurge in reactive oxygen species production, a decrease in ATP levels, and a disruption in mitochondrial metabolism. In vivo analyses showed that hBMSCs-derived exosomal miR-484 lessened tumor size and weight, while also suppressing the expression of mitochondrial biomarkers. Further, there was a decline in ß-catenin and p-p38 protein levels both in vitro and in vivo. The addition of LiCl restored the disrupted mitochondrial metabolism. Conclusively, our results suggest that hBMSCs-derived exosomal miR-484 mitigates the malignant transformation and mitochondrial metabolism of pancreatic cancer by deactivating the Wnt/MAPK pathway.


Assuntos
MicroRNAs , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , MicroRNAs/genética , Mitocôndrias , Pâncreas , Carcinogênese , Transformação Celular Neoplásica , Neoplasias Pancreáticas
4.
Eur Radiol ; 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37947835

RESUMO

OBJECTIVES: To explore the auxiliary value of combining CT features with existing response evaluation criteria in the prediction of progressive disease (PD) in gastrointestinal stromal tumors (GIST) patients treated with sunitinib. MATERIAL AND METHODS: Eighty-one patients with GISTs who received sunitinib were included in this retrospective multicenter study and divided into training and external validation cohorts. Progression at six months was determined as a reference standard. The predictive performance of the RECIST 1.1 and Choi criteria was compared. CT features at baseline and the first follow-up were analyzed. Logistic regression analyses were used to determine the most significant predictors and develop modified criteria. RESULTS: A total of 216 lesions showed a good response and 107 showed a poor response in 81 patients. The RECIST 1.1 criteria performed better than the Choi criteria in predicting progression (AUC, 0.75 vs. 0.69, p = 0.04). The expanded/intensified high-enhancement area, blurred tumor-tissue interface, and progressive enlarged vessels feeding or draining the mass (EVFDM) differed significantly between lesions with good and poor responses in the training cohort (p = 0.001, 0.003, and 0.000, respectively). Multivariate analysis revealed that the expanded/intensified high-enhancement area (p = 0.001), progressive EVFDM (p = 0.000), and RECIST PD (p = 0.000) were independent predictive factors. Modified RECIST (mRECIST) criteria were developed and showed significantly higher AUCs in the training and external validation cohorts than the RECIST 1.1 criteria (training: 0.81 vs. 0.73, p = 0.002; validation: 0.82 vs. 0.77, p = 0.04). CONCLUSION: The mRECIST criteria, combining CT features with the RECIST 1.1 criteria, demonstrated superior performance in the prediction of early progression in GIST patients receiving sunitinib. CLINICAL RELEVANCE STATEMENT: The mRECIST criteria, which combine CT features with the RECIST 1.1 criteria, may facilitate the early detection of progressive disease in GIST patients treated with sunitinib, thereby potentially guiding the timely switch to late-line medications or combination with surgical excision. KEY POINTS: • The RECIST 1.1 criteria outperformed the Choi criteria in identifying progression of GISTs in patients treated with sunitinib. • GISTs displayed different morphologic features on CT depending on how they responded to sunitinib. • Combining CT morphologic features with the RECIST 1.1 criteria allowed for the prompt and accurate identification of progressing GIST lesions.

5.
Int J Colorectal Dis ; 38(1): 31, 2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36757427

RESUMO

AIMS: To evaluate the impact of SARS-CoV-2 vaccine on IBD activity. METHODS: Adult IBD patients from five large IBD centers in China were enrolled and followed up for 6 months. Patients were divided into vaccinated and unvaccinated groups according to vaccination status. Demographic and clinical data were collected. RESULTS: A total of 280 individuals (213 UC and 67 CD patients) were enrolled in the study. The unvaccinated and vaccinated groups of UC patients were comparable for basic characteristics, including age (t = - 0.8, p = 0.425), sex (χ2 = 0.980, p = 0.322), course of disease (z = - 0.513, p = 0.608), surgical conditions (χ2 = 1.042, p = 0.838), disease extent (χ2 = 4.853, p = 0.088), or baseline drug therapy (χ2 = 7.784, p = 0.064). In the subgroup of UC patients, there was no association between vaccination and disease activities, according to the medium disease activity scores for two groups: unvaccinated patients having scores (IQR) 1(2.75), 1(2), 1(2), and 1(2) at baseline, 1, 3, and 6 months, respectively, whereas vaccinated patients having scores (IQR) 1(2), 1(2), 1(2), and 1(2). Similar conclusions were also derived in the subgroup of CD patients. There were also no statistically significant differences in age (t = - 1.48, p = 0.144), sex (χ2 = 0.003, p = 0.957), course of disease (z = - 0.074, p = 0.941), surgical conditions (χ2 = 0.613, p = 0.594), localization (χ2 = 6.261, p = 0.199), or baseline drug therapy (χ2 = 5.881, p = 0.114) between 2 groups of CD patients. The medium disease activity scores (IQR) of the unvaccinated group at baseline, 1, 3, and 6 months were 1(4), 1(3), 1(3), and 1(3), respectively, whereas those of vaccinated group were 2.5(3.75), 2.5(3.75), 3(2), and 2(2), respectively. Overall, very few participants in this study described worsening IBD disease activity requiring a change or addition of medication. CONCLUSIONS: SARS-CoV-2 vaccine has no adverse effect on disease activity in IBD population. IBD patients should be recommended to receive SARS-CoV-2 vaccine in time.


Assuntos
COVID-19 , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Adulto , Chlorocebus aethiops , Animais , Humanos , Doença de Crohn/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Vacinas contra COVID-19/uso terapêutico , Células Vero , COVID-19/prevenção & controle , SARS-CoV-2 , Doenças Inflamatórias Intestinais/tratamento farmacológico , China/epidemiologia
6.
Hepatobiliary Pancreat Dis Int ; 22(5): 504-511, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35909061

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for severe acute pancreatitis (AP). The underlying mechanism remains unclear. We sought to determine how bacterial translocation and cholesterol metabolism in the liver and pancreas affect the severity of AP in NAFLD mice. METHODS: C57BL/6N mice were fed on a high-fat diet (HFD) to generate the NAFLD model, and mice in the control group were provided with a normal diet (ND). After being anesthetized with ketamine/xylazine, mice got a retrograde infusion of taurocholic acid sodium into the pancreatic duct to induce AP, and sham operation (SO) was used as control. Serum amylase and Schmidt's pathological score system were used to evaluate AP severity. Bacterial loads, total cholesterol level, and cholesterol metabolic-associated molecules [low-density lipoprotein receptor (LDLR) and ATP-binding cassette transporter A1 (ABCA1)] were analyzed in the liver and pancreas. RESULTS: Compared with the ND-AP group, mice in the HFD-AP group had severer pancreatitis, manifested with higher serum amylase levels and higher AP pathologic scores, especially the inflammation and hemorrhage scores. Compared with the HFD-SO group and ND-AP group, bacterial loads in the liver and pancreas were significantly higher in the HFD-AP group. Mice in the HFD-AP group showed a decreased LDLR expression and an increased ABCA1 expression in the pancreas, although there was no significant difference in pancreas total cholesterol between the HFD-AP group and the ND-AP group. CONCLUSIONS: NAFLD aggravates AP via increasing bacterial translocation in the liver and pancreas and affecting pancreas cholesterol metabolism in mice.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Pancreatite , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Pancreatite/patologia , Translocação Bacteriana , Doença Aguda , Camundongos Endogâmicos C57BL , Fígado/patologia , Pâncreas/patologia , Colesterol/metabolismo , Dieta Hiperlipídica , Amilases/metabolismo
7.
Int J Med Sci ; 19(5): 842-857, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693733

RESUMO

Background: Complement component 1 Q subcomponent binding protein (C1QBP) plays a vital role in the progression and metabolism of cancer. Studies have shown that xanthine dehydrogenase (XDH)-derived reactive oxygen species (ROS) accelerates tumor growth, and also induces mutations or produces cytotoxic effects concurrently. However, the role of C1QBP in metabolism, oxidative stress, and apoptosis of renal cell carcinoma (RCC) cells have not yet been explored. Methods: Metabolomics assay was applied to investigate the role of C1QBP in RCC metabolism. C1QBP knockdown and overexpression cells were established via lentiviral infection and subjected to apoptosis and ROS assay in vitro. RNA stability assay was applied to characterize the mechanism of C1QBP regulating XDH transcription. In vivo, orthotopic tumor xenografts assay was performed to investigate the role of C1QBP in RCC progression. Results: Metabolomics investigation revealed that C1QBP dramatically diminished the hypoxanthine content in RCC cells. C1QBP promoted the mRNA and protein expression of hypoxanthine catabolic enzyme XDH. Meanwhile, C1QBP may affect XDH transcription by regulating the mRNA level of XDH transcriptional stimulators IL-6, TNF-α, and IFN-γ. Moreover, the expression of C1QBP and XDH was lower in RCC tumors compared with the tumor-associated normal tissues, and their down-regulation was associated with higher Fuhrman grade. C1QBP significantly increased ROS level, apoptosis, and the expression of apoptotic proteins such as cleaved caspase-3 and bax/bcl2 via regulating XDH. Conclusion: C1QBP promotes the catabolism of hypoxanthine and elevates the apoptosis of RCC cells by modulating XDH-mediated ROS generation.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Apoptose/genética , Carcinoma de Células Renais/patologia , Proteínas de Transporte/metabolismo , Humanos , Hipoxantinas , Neoplasias Renais/patologia , Proteínas Mitocondriais/genética , RNA Mensageiro , Espécies Reativas de Oxigênio/metabolismo , Xantina Desidrogenase/genética , Xantina Desidrogenase/metabolismo
8.
Sensors (Basel) ; 22(13)2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35808548

RESUMO

Accurate segmentation of nasopharyngeal carcinoma is essential to its treatment effect. However, there are several challenges in existing deep learning-based segmentation methods. First, the acquisition of labeled data are challenging. Second, the nasopharyngeal carcinoma is similar to the surrounding tissues. Third, the shape of nasopharyngeal carcinoma is complex. These challenges make the segmentation of nasopharyngeal carcinoma difficult. This paper proposes a novel semi-supervised method named CAFS for automatic segmentation of nasopharyngeal carcinoma. CAFS addresses the above challenges through three mechanisms: the teacher-student cooperative segmentation mechanism, the attention mechanism, and the feedback mechanism. CAFS can use only a small amount of labeled nasopharyngeal carcinoma data to segment the cancer region accurately. The average DSC value of CAFS is 0.8723 on the nasopharyngeal carcinoma segmentation task. Moreover, CAFS has outperformed the state-of-the-art nasopharyngeal carcinoma segmentation methods in the comparison experiment. Among the compared state-of-the-art methods, CAFS achieved the highest values of DSC, Jaccard, and precision. In particular, the DSC value of CAFS is 7.42% higher than the highest DSC value in the state-of-the-art methods.


Assuntos
Fenômenos Biológicos , Neoplasias Nasofaríngeas , Humanos , Processamento de Imagem Assistida por Computador/métodos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico por imagem
9.
BMC Cancer ; 21(1): 455, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33892676

RESUMO

BACKGROUND: Preoperative evaluation of lymph node (LN) state is of pivotal significance for informing therapeutic decisions in gastric cancer (GC) patients. However, there are no non-invasive methods that can be used to preoperatively identify such status. We aimed at developing a genomic biosignature based model to predict the possibility of LN metastasis in GC patients. METHODS: We used the RNA profile retrieving strategy and performed RNA expression profiling in a large GC cohort (GSE62254, n = 300) from Gene Expression Ominus (GEO). In the exploratory stage, 300 GC patients from GSE62254 were involved and the differentially expressed RNAs (DERs) for LN-status were determined using the R software. GC samples in GSE62254 were randomly allocated into a learning set (n = 210) and a verification set (n = 90). By using the Least absolute shrinkage and selection operator (LASSO) regression approach, a set of 23-RNA signatures were established and the signature based nomogram was subsequently built for distinguishing LN condition. The diagnostic efficiency, as well as the clinical performance of this model were assessed using the decision curve analysis (DCA). Metascape was used for bioinformatic analysis of the DERs. RESULTS: Based on the genomic signature, we established a nomogram that robustly distinguished LN status in the learning (AUC = 0.916, 95% CI 0.833-0.999) and verification sets (AUC = 0.775, 95% CI 0.647-0.903). DCA demonstrated the clinical value of this nomogram. Functional enrichment analysis of the DERs was performed using bioinformatics methods which revealed that these DERs were involved in several lymphangiogenesis-correlated cascades. CONCLUSIONS: In this study, we present a genomic signature based nomogram that integrates the 23-RNA biosignature based scores and Lauren classification. This model can be utilized to estimate the probability of LN metastasis with good performance in GC. The functional analysis of the DERs reveals the prospective biogenesis of LN metastasis in GC.


Assuntos
Metástase Linfática/genética , Nomogramas , RNA-Seq/métodos , Neoplasias Gástricas/genética , Idoso , Bases de Dados Genéticas , Técnicas de Apoio para a Decisão , Feminino , Genômica , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Período Pré-Operatório , RNA Neoplásico/análise , Distribuição Aleatória , Análise de Regressão , Fatores de Risco , Neoplasias Gástricas/patologia , Transcriptoma
10.
Rev Esp Enferm Dig ; 113(6): 418-422, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33233904

RESUMO

BACKGROUND AND AIM: Glasgow prognostic score is a systemic inflammatory-based score. The aim of this study was to determine whether the Glasgow prognostic score was a useful predictor of short-term outcomes in patients who undergo total proctocolectomy for ulcerative colitis. METHODS: eighty ulcerative colitis patients who underwent a total proctocolectomy with ileal pouch-anal anastomosis or permanent end ileostomy from June 2014 to March 2020 were retrospectively analyzed. Patients were divided into a lower Glasgow prognostic score group and a higher Glasgow prognostic score group. RESULTS: postoperative infectious complication occurred more frequently in the higher Glasgow prognostic score group (8.3 % vs 29.5 %, p = 0.018). According to the univariate and multivariate analysis, only a higher Glasgow prognostic score was associated with an increased risk of postoperative infectious complication (OR: 5.478, 95 % CI: 1.236-24.279). CONCLUSION: Glasgow prognostic score is a simple and useful indicator of postoperative infectious complications.


Assuntos
Colite Ulcerativa , Bolsas Cólicas , Proctocolectomia Restauradora , Colite Ulcerativa/cirurgia , Humanos , Ileostomia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Proctocolectomia Restauradora/efeitos adversos , Prognóstico , Estudos Retrospectivos
11.
Int J Mol Sci ; 21(3)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028746

RESUMO

Acute kidney injury (AKI) causes over 1 million deaths worldwide every year. AKI is now recognized as a major risk factor in the development and progression of chronic kidney disease (CKD). Diabetes is the main cause of CKD as well. Renal fibrosis and inflammation are hallmarks in kidney diseases. Various cytokines contribute to the progression of renal diseases; thus, many drugs that specifically block cytokine function are designed for disease amelioration. Numerous studies showed IL-20 functions as a pro-inflammatory mediator to regulate cytokine expression in several inflammation-mediated diseases. In this review, we will outline the effects of pro-inflammatory cytokines in the pathogenesis of AKI and CKD. We also discuss the role of IL-20 in kidney diseases and provide a potential therapeutic approach of IL-20 blockade for treating renal diseases.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/patologia , Interleucinas/metabolismo , Terapia de Alvo Molecular , Injúria Renal Aguda/metabolismo , Animais , Humanos , Transdução de Sinais
12.
J Craniofac Surg ; 28(5): 1282-1285, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28437267

RESUMO

Dog bite injuries are common and the head and neck is most frequently involved in pediatric patients. In severe cases, the combination of crushing, tearing, and puncturing can result in scalp avulsion. Currently, microsurgical replantation of the avulsed scalp remains the gold standard but may not always be possible. The authors present their treatment algorithm with 2 patient examples. In Patient 1, the scalp was deemed unsuitable for replantation due to extensive soft tissue injury; in Patient 2, the scalp was not available on presentation. Both patients underwent debridement and early wound coverage followed by multistage secondary revision through serial tissue expansion and excision. At 3-years follow-up, both patients have achieved satisfactory aesthetic outcomes following the initial loss of 70% and 40% of hair-bearing scalp. There were no infective complications or wound dehiscence and the areas of scar alopecia are much improved with preservation of the hairline. Pediatric scalp avulsion injuries resulting from dog bites are uncommon and involve a unique injury mechanism. Coupled with the diminutive size of vessels in this patient population, replantation may be precluded altogether. A delayed and staged approach to reconstruction can restore a hair-bearing scalp for satisfactory outcomes.


Assuntos
Mordeduras e Picadas/cirurgia , Avulsões Cutâneas/cirurgia , Cães , Couro Cabeludo/cirurgia , Adolescente , Algoritmos , Animais , Pré-Escolar , Feminino , Humanos , Masculino , Couro Cabeludo/lesões , Retalhos Cirúrgicos , Expansão de Tecido
13.
Cancer Biomark ; 40(2): 205-223, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38905034

RESUMO

BACKGROUND: Kidney Renal Clear Cell Carcinoma (KIRC) is a malignant tumor that seriously threatens human health. Rho GTPase-activating protein 4 (ARHGAP4) plays an important role in the occurrence and development of tumors. OBJECTIVE: The purpose of this study was to explore the role of ARHGAP4 in the progression of KIRC and its diagnostic and prognostic value. METHODS: Multiple analytical methods and in vitro cell assays were used to explore the expression of ARHGAP4 and its value in the progression, diagnosis and prognosis of KIRC. The biological function of ARHGAP4 was studied by GO analysis and KEGG pathway analysis, and then the relationship between ARHGAP4 and immune infiltration was analyzed. RESULTS: The expression of ARHGAP4 was significantly up-regulated in KIRC. We found that the high expression of ARHGAP4 was related to the progression of KIRC and suggested a poor prognosis. Compared with normal tissues, ARHGAP4 had a better diagnostic value in KIRC. The biological function of ARHGAP4 was related to immunity, and its expression was also closely related to tumor immune infiltration and immune checkpoints. CONCLUSIONS: Our study demonstrated that ARHGAP4 may be a biomarker, which is related to the progression, diagnosis and prognosis of KIRC. Its biological functions are related to tumor immune infiltration.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais , Proteínas Ativadoras de GTPase , Neoplasias Renais , Humanos , Prognóstico , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/genética , Proteínas Ativadoras de GTPase/metabolismo , Proteínas Ativadoras de GTPase/genética , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/imunologia , Neoplasias Renais/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Masculino , Feminino , Regulação para Cima , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-Idade , Linhagem Celular Tumoral
14.
Int J Biol Sci ; 20(2): 516-536, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38169635

RESUMO

A key player in mitochondrial respiration, p32, often referred to as C1QBP, is mostly found in the mitochondrial matrix. Previously, we showed that p32 interacts with DLAT in the mitochondria. Here, we found that p32 expression was reduced in ccRCC and suppressed progression and metastasis in ccRCC animal models. We observed that increasing p32 expression led to an increase in oxidative phosphorylation by interacting with DLAT, thus, regulating the activation of the pyruvate dehydrogenase complex (PDHc). Mechanistically, reduced p32 expression, in concert with DLAT, suppresses PDHc activity and the TCA cycle. Furthermore, our research discovered that p32 has a direct binding affinity for copper, facilitating the copper-induced oligomerization of lipo-DLAT specifically in ccRCC cells. This finding reveals an innovative function of the p32/DLAT/copper complex in regulating glycometabolism and the TCA cycle in ccRCC. Importantly, our research provides important new understandings of the underlying molecular processes causing the abnormal mitochondrial metabolism linked to this cancer.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Animais , Carcinoma de Células Renais/metabolismo , Cobre , Lipoilação , Fosforilação Oxidativa , Neoplasias Renais/metabolismo
15.
Front Oncol ; 13: 1215729, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37519796

RESUMO

Background: Artificial intelligence (AI) is widely applied in cancer field nowadays. The aim of this study is to explore the hotspots and trends of AI in cancer research. Methods: The retrieval term includes four topic words ("tumor," "cancer," "carcinoma," and "artificial intelligence"), which were searched in the database of Web of Science from January 1983 to December 2022. Then, we documented and processed all data, including the country, continent, Journal Impact Factor, and so on using the bibliometric software. Results: A total of 6,920 papers were collected and analyzed. We presented the annual publications and citations, most productive countries/regions, most influential scholars, the collaborations of journals and institutions, and research focus and hotspots in AI-based cancer research. Conclusion: This study systematically summarizes the current research overview of AI in cancer research so as to lay the foundation for future research.

16.
Microorganisms ; 11(5)2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37317214

RESUMO

The microbiota is present in many parts of the human body and plays essential roles. The most typical case is the occurrence and development of cancer. Pancreatic cancer (PC), one of the most aggressive and lethal types of cancer, has recently attracted the attention of researchers. Recent research has revealed that the microbiota regulates PC carcinogenesis via an altered immune response. Specifically, the microbiota, in several sites, including the oral cavity, gastrointestinal tract, and pancreatic tissue, along with the numerous small molecules and metabolites it produces, influences cancer progression and treatment by activating oncogenic signaling, enhancing oncogenic metabolic pathways, altering cancer cell proliferation, and triggering chronic inflammation that suppresses tumor immunity. Diagnostics and treatments based on or in combination with the microbiota offer novel insights to improve efficiency compared with existing therapies.

17.
ACS Appl Mater Interfaces ; 15(24): 29297-29307, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37293713

RESUMO

Lead halide perovskite nanocrystals (NCs) have been the star material in lighting and displays owing to their excellent photoelectrical properties, but they have not simultaneously realized high photoluminescence quantum yield (PLQY) and high stability. To solve this problem, we propose a perovskite/linear low-density polyethylene (perovskite/LLDPE) core/shell NC by the synergistic role of the pressure effect and steric effect. Green CsPbBr3/LLDPE core/shell NCs with near-unity PLQY and nonblinking behavior were synthesized through an in situ hot-injection process. The mechanism of the improved photoluminescence (PL) properties is the enhanced pressure effect resulting in increased radiative recombination and interaction between the ligand and perovskite crystals, as confirmed by the PL spectra and finite element calculations. Meanwhile, the NCs show high stability under ambient conditions (with a PLQY of 92.5% after 166 days) and against 365 nm UV light (maintaining 61.74% of the initial PL intensity after continuous radiation for 1000 min). This strategy also works well in the blue and red perovskite/LLDPE NCs and red InP/ZnSeS/ZnS/LLDPE NCs. Finally, white-emitting Mini-LEDs were fabricated by combining the green CsPbBr3/LLDPE and red CsPbBr1.2I1.8/LLDPE core/shell NCs with blue Mini-LED chips. The white-emitting Mini-LEDs exhibit super wide color gamut (∼129% of the National Television Standards Committee or 97% of the Rec. 2020 standards).

18.
Artigo em Inglês | MEDLINE | ID: mdl-38082781

RESUMO

Mental state monitoring is a hot topic especially in neurorehabilitation, skill training, etc, for which the functional near-infrared spectroscopy (fNIRS) has been suggested to be used, and fewer detection channels and cross-subject performance are usually required for real-world application. To this goal, we propose a transformer-based method for cross-subject mental workload classification using fewer channels of fNIRS. Firstly, the input fNIRS signals in a window are divided into patches in the temporal order and transformed into embeddings, to which a classification token and learnable position embeddings are added. Then, a transformer encoder is used to learn the long-range dependencies among the embeddings, of which the output classification token is sent to a multilayer perceptron (MLP) head. Mental workload classification results can be represented by the outputs of the MLP head. Finally, comparison experiments were conducted on the open-access fNIRS2MW dataset. The results show that, the proposed method can outperform previous methods in cross-subject classification accuracy, and relatively efficient computation can be obtained.


Assuntos
Espectroscopia de Luz Próxima ao Infravermelho , Carga de Trabalho , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Redes Neurais de Computação , Aprendizagem , Motivação
19.
Biomed Phys Eng Express ; 8(6)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36327448

RESUMO

Granzymes-based immunotherapy for the treatment of solid tumors has gained great success and played more and more important effect in clinical studies. However, the antitumor effect of Granzymes still requires improvements owing to the cell evasion and metastasis of cancer. To overcome these limitations, synergistic combinatorial anti-tumor effect of Granzyme B (GrB) and miR-21 inhibitor (miR-21i) for breast cancer therapy through a new co-delivery system was investigated in present study. GrB was covalently bonded with miR-21i by disulfide bond and encapsulated in a nanocapsule formed byin situpolymerization of N -(3-aminopropyl) methacrylamide (APM), ethylene glycol dimethacrylate (EGDMA) and 2-Methacryloyloxyethyl phosphorylcholine (MPC). The nanocapsules possessed spherical and uniform diameter size as well as pH responsiveness in various environments. MTT and flow cytometry analysis showed that a synergistic anti-proliferation and promoting apoptosis effect was achieved when the nanocapsules were added into breast cancer cell lines. More importantly, the cell evasion ability was markedly inhibited using the nanocapusles detected through transwell invasion assay. Also thein vivoanti-tumor therapeutic efficacy of GrB-miR-21i nanocapusles was evaluated in a mouse tumor model. In conclusion, the nanocapsules for simultaneously delivery of GrB and miR-21i produce a synergistic effect in human breast cancer therapy.


Assuntos
Neoplasias da Mama , MicroRNAs , Nanocápsulas , Humanos , Camundongos , Animais , Feminino , Granzimas/genética , Granzimas/metabolismo , Granzimas/farmacologia , MicroRNAs/genética , Linhagem Celular Tumoral , Neoplasias da Mama/terapia
20.
Front Surg ; 9: 1006020, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211276

RESUMO

In obstructing left-sided colonic or rectal cancer, endoscopic stent placement with the purpose of decompression and bridge to elective colon resection has been widely utilized and accepted. However, in malignant right-sided colonic obstruction, stent placement prior to colectomy is still highly controversial, due to lower clinical success and high anastomotic leak. We report a case of malignant right-sided colonic obstruction based on the radiological findings of irregular thickening of ascending colon wall and dilation of proximal large bowel on enhanced computed tomography scan. The 72-year-old woman presented with obvious abdominal distension. Due to concerning cardiovascular complications as intermittent chest pain and a long history of type 2 diabetes, a three-step therapeutic plan was instigated. Initially, a self-expandable metallic stent was placed palliatively to relieve the bowel obstruction. Consecutively, coronary angiography was performed, and two coronary stents were implanted to alleviate more than 80% stenosis of two main coronary arteries. One month later, laparoscopic radical resection of right colon and lymphadenectomy were successfully performed, with a blood loss less than 50 millimeters and a harvest of 29 lymph nodes, 1 being positive. The patient was discharged one week postoperatively with no complications, and received adjuvant chemotherapy one month later. During a follow-up of more than one year, the patient was in complete remission with no recurrence and cardiovascular events. In patients presenting with malignant right-sided colonic obstruction and peril of high cardiovascular risks, we propose colonic and coronary stent-first strategy to emergency surgery as a potential approach so as to ensure sufficient cardiovascular preparation improving perioperative safety. Moreover, the anatomical location of the tumor would be significantly achievable thus granting high-quality radical colon resection and lymphadenectomy.

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