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1.
Front Immunol ; 15: 1366260, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38655260

RESUMEN

Resistance to targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC) is a significant challenge in the treatment of this disease. The mechanisms of resistance are multifactorial and include molecular target alterations and activation of alternative pathways, tumor heterogeneity and tumor microenvironment change, immune evasion, and immunosuppression. Promising strategies for overcoming resistance include the development of combination therapies, understanding the resistance mechanisms to better use novel drug targets, the identification of biomarkers, the modulation of the tumor microenvironment and so on. Ongoing research into the mechanisms of resistance and the development of new therapeutic approaches hold great promise for improving outcomes for patients with NSCLC. Here, we summarize diverse mechanisms driving resistance to targeted therapy and immunotherapy in NSCLC and the latest potential and promising strategies to overcome the resistance to help patients who suffer from NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Resistencia a Antineoplásicos , Inmunoterapia , Neoplasias Pulmonares , Terapia Molecular Dirigida , Microambiente Tumoral , Humanos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/inmunología , Inmunoterapia/métodos , Microambiente Tumoral/inmunología , Animales , Biomarcadores de Tumor
2.
Dalton Trans ; 52(41): 14896-14903, 2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37795943

RESUMEN

Transition metal sulfides are widely regarded as the most promising electrode materials for supercapacitors. Herein, we utilized a straightforward electrodeposition method to prepare an iron-cobalt bimetallic sulfide nanosheet-assembled nanosphere on nickel foam (FeCo2S4/NF). The synergistic effect between bimetals and the unique three-dimensional structure significantly improved its capacitive performance. As a result, it demonstrated a remarkable specific capacitance, brilliant long-term stability and acceptable rate capability. Moreover, FeCo2S4/NF and active carbon (AC) were used to assemble an asymmetric supercapacitor (ASC), and FeCo2S4//AC displays a maximum energy density of 29.4 W h kg-1 at 800 W kg-1. Moreover, when adopted as an electrocatalyst for the hydrogen evolution reaction (HER), FeCo2S4/NF exhibited excellent catalytic properties (η10 = 165 mV). Our research provides a valuable insight into the multidisciplinary integration of high-performance energy materials.

3.
Medicine (Baltimore) ; 102(35): e34570, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37657050

RESUMEN

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) has caused a great threat to human health. Metabolic associated fatty liver disease (MAFLD) is a liver disease with a high prevalence rate. Previous studies indicated that MAFLD led to increased mortality and severe case rates of COVID-19 patients, but its mechanism remains unclear. METHODS: This study analyzed the transcriptional profiles of COVID-19 and MAFLD patients and their respective healthy controls from the perspectives of bioinformatics and systems biology to explore the underlying molecular mechanisms between the 2 diseases. Specifically, gene expression profiles of COVID-19 and MAFLD patients were acquired from the gene expression omnibus datasets and screened shared differentially expressed genes (DEGs). Gene ontology and pathway function enrichment analysis were performed for common DEGs to reveal the regulatory relationship between the 2 diseases. Besides, the hub genes were extracted by constructing a protein-protein interaction network of shared DEGs. Based on these hub genes, we conducted regulatory network analysis of microRNA/transcription factors-genes and gene - disease relationship and predicted potential drugs for the treatment of COVID-19 and MAFLD. RESULTS: A total of 3734 and 589 DEGs were screened from the transcriptome data of MAFLD (GSE183229) and COVID-19 (GSE196822), respectively, and 80 common DEGs were identified between COVID-19 and MAFLD. Functional enrichment analysis revealed that the shared DEGs were involved in inflammatory reaction, immune response and metabolic regulation. In addition, 10 hub genes including SERPINE1, IL1RN, THBS1, TNFAIP6, GADD45B, TNFRSF12A, PLA2G7, PTGES, PTX3 and GADD45G were identified. From the interaction network analysis, 41 transcription factors and 151 micro-RNAs were found to be the regulatory signals. Some mental, Inflammatory, liver diseases were found to be most related with the hub genes. Importantly, parthenolide, luteolin, apigenin and MS-275 have shown possibility as therapeutic agents against COVID-19 and MAFLD. CONCLUSION: This study reveals the potential common pathogenesis between MAFLD and COVID-19, providing novel clues for future research and treatment of MAFLD and severe acute respiratory syndrome coronavirus 2 infection.


Asunto(s)
COVID-19 , MicroARNs , Enfermedad del Hígado Graso no Alcohólico , Humanos , COVID-19/genética , Biología Computacional , Genes Reguladores , Factores de Transcripción
4.
Am J Transl Res ; 15(6): 4100-4109, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37434819

RESUMEN

OBJECTIVE: To investigate the relationship of lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and nutritional risk index (NRI) with the prognosis of non-small cell lung cancer (NSCLC). METHODS: The clinical data of 400 NSCLC patients undergoing surgery at Shaoxing Shangyu Hospital of Traditional Chinese Medicine from January 2019 to June 2022 were collected for this retrospective analysis. The optimal cutoff values for NLR, PLR, LMR and NRI were determined using receiver operating characteristic (ROC) curves. The patients were grouped according to the optimal cutoff values, and the clinicopathological characteristics were compared between groups. The Kaplan-Meier survival curve and Cox risk model were used to identify the independent risk factors affecting the prognosis of patients with NSCLC. A nomogram risk prediction model was constructed and its effectiveness was verified. RESULTS: ROC curve analysis revealed that the area under the curve (AUC) values for NLR, PLR, LMR and NRI in predicting overall survival of NSCLC patients were 0.827, 0.753, 0.719 and 0.770, respectively. The optimal cutoff values for NLR, PLR, LMR and NRI were 2.49, 126.32, 3.02 and 89, respectively. Survival analysis found that the survival time was shorter in patients with NLR>2.49, PLR>126.32, LMR>3.02 and NRI≤89. Results from Cox model indicated that TNM staging, NLR>2.49, LMR>3.02, NRI≤89, surgical method, intraoperative blood loss, postoperative complication, and adjuvant chemotherapy were risk factors affecting the prognosis of NSCLC patients. A nomogram was constructed based on the results of multivariate analysis. The AUC of the nomogram was 0.967 (95% CI: 0.943-0.992) and 0.948 (95% CI: 0.874-1) in the training set and the test set, respectively. The C-index was 0.90 and 0.89, respectively. The calibration curve demonstrated good agreement between the predicted values of the nomogram and the actual observed values. CONCLUSION: NLR, LMR and NRI are significant predictors of the prognosis of patients with NSCLC. NLR>2.49, LMR>3.02, and NRI≤89 are risk factors for the prognosis of NSCLC patients.

5.
Small ; 19(47): e2303787, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37438654

RESUMEN

Using three-dimensional current collectors (3DCC) as frameworks for lithium metal anodes (LMAs) is a promising approach to inhibit dendrite growth. However, the intrinsically accumulated current density on the top surface and limited Li-ion transfer in the interior of 3DCC still lead to the formation of lithium dendrites, which can pose safety risks. In this study, it reports that gradient lithiophilic structures can induce uniform lithium deposition within the interior of the 3DCC, greatly suppressing dendrite formation, as confirmed by COMSOL simulations and experimental results. With this concept, a gradient-structured zinc oxide-loaded copper foam (GSZO-CF) is synthesized via an easy solution-combustion method at low cost. The resulting Li@GSZO-CF symmetric cells demonstrate stable cycling performance for over 800 cycles, with an ultra-deep capacity of 10 mAh cm-2 even under an ultra-high current density of 50 mA cm-2 , the top results reported in the literature. Moreover, when combined with a LiFePO4 (LFP) cathode under a low negative/positive (N/P) capacity ratio of 2.9, the Li@GSZO-CF||LFP full cells exhibit stable performance for 200 cycles, with a discharge capacity of 130 mAh g-1 and retention of 85.5% at a charging/discharging rate of 1C. These findings suggest a promising strategy for the development of new-generation LMAs.

6.
BMC Musculoskelet Disord ; 24(1): 418, 2023 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-37231454

RESUMEN

PURPOSE: The purpose of this study was to explore the feasibility and evaluate the clinical outcomes of treatment for phalangeal and metacarpal segmental defects with the induced membrane technique and autologous structural bone grafting. METHODS: Sixteen patients who sustained phalangeal or metacarpal bone segmental defects were treated by the induced membrane technique and autologous structural bone grafting from June 2020 to June 2021 at our center. RESULTS: The average follow-up was 24 weeks (range, 12-40 weeks). Radiography demonstrated union of all bone grafts after an average of 8.6 weeks (range, 8-12 weeks). All incisions at donor and recipient sites demonstrated primary heal without infection complications. The mean visual analog scale score of the donor site was 1.8 (range, 0-5), with a good score in 13 cases and a fair score in 3. The mean total active motion of the fingers was 179.9°. CONCLUSIONS: The feasibility of the induced membrane technique and structural treatment with a cylindrical bone graft for segmental bone defects of the metacarpal or phalanx is demonstrated by follow-up radiography results. The bone graft provided much more stability and structural support in the bone defects, and the bone healing time and bone union rate were ideal.


Asunto(s)
Huesos del Metacarpo , Humanos , Huesos del Metacarpo/diagnóstico por imagen , Huesos del Metacarpo/cirugía , Resultado del Tratamiento , Trasplante Óseo/métodos , Estudios de Factibilidad , Radiografía , Estudios Retrospectivos
7.
Medicine (Baltimore) ; 102(11): e33124, 2023 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-36930079

RESUMEN

In the past few years, immunotherapy of tumors has become an extensive research hotspot, and the value of IKZF family genes in the tumor microenvironment has also been increasingly recognized. However, the expression of the IKAROS family zinc finger 3 (IKZF3) gene in human head and neck squamous cell carcinoma (HNSCC) and its prognostic value were not reported for the main subset until now. In the present study, we analyzed the relationship between IKZF3 gene expression and the survival of HNSCC patients. To evaluate the potential of IKZF3 as a prognostic biomarker for HNSCC comprehensively, multiple online analysis tools, including UALCAN, cBioPortal, GEPIA, WebGestalt, String, Genomic Data Commons, and TIMER databases were utilized in our study. We observed that the HNSCC patients with higher IKZF3 expression tended to exhibit longer overall survival. Univariate and multivariate Cox regression analyses indicated that age and grade were independent prognostic indicators in HNSCC. Moreover, Gene Ontology and KEGG function enrichment analyses showed that several pathways in HNSCC might be pivotal pathways regulated by IKZF3, which revealed that IKZF3 was probably participating in the occurrence and development of HNSCC. Furthermore, the hypomethylation of the IKZF3 gene was closely associated with genes that observed mutation in HNSCC. IKZF3 was significantly correlated with several immune cells in HNSCC (e.g., CD8+ T cell, CD4+ cell, and dendritic cell). We explored the potential prognostic values and roles of the IKZF3 in HNSCC, revealing that IKZF3 was probably a novel and reliable prognostic biomarker for patients with HNSCC.


Asunto(s)
Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/genética , Pronóstico , Biología Computacional , Biomarcadores , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Microambiente Tumoral , Factor de Transcripción Ikaros/genética
8.
World J Microbiol Biotechnol ; 39(1): 26, 2022 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-36422715

RESUMEN

Grain crops are easily contaminated by fungi due to the existence of various microorganisms in the storage process, especially in humid and warm storage conditions. Compared with conventional methods, surface-enhanced Raman scattering (SERS) has paved the way for the detection of fungi in grain crops as it is a rapid, nondestructive, and sensitive analytical method. In this work, Aspergillus niger, Saccharomyces cerevisiae, Fusarium moniliforme and Trichoderma viride in grain crops were detected using colloidal Au nanoparticles and SERS. The results indicated that different fungi showed different Raman phenotypes, which could be easily characterized by SERS. Combined with multivariate statistical analysis, identification of a variety of fungi could be accomplished rapidly and accurately. This research can be applied for the rapid detection of fungi in the food and biomedical industries.


Asunto(s)
Nanopartículas del Metal , Espectrometría Raman , Espectrometría Raman/métodos , Oro , Análisis Multivariante , Grano Comestible , Productos Agrícolas , Hongos
9.
Artículo en Inglés | MEDLINE | ID: mdl-35958914

RESUMEN

Hsa-microRNA (has-miR)-133a inactivates the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and suppresses the cell proliferation of myocardial fibroblasts by downregulation of the epidermal growth factor receptor (EGFR) expression. Bioinformatics analysis exhibits extended noncoding RNA HLA complex group 18 (lncRNA-HCG18) binds to hsa-miR-133a. The purpose of the current experiment is to explore whether lncRNA-HCG18 adsorbed hsa-miR-133a through sponging, resulting in decreased inhibition of hsa-miR-133a on EGFR and ultimately promoting the proliferation of myocardial fibroblasts. To verify and study the correlation and mechanism between lncRNA-HCG18, hsa-miR-133a, and their target genes. Firstly, after overexpression/silencing of lncRNA-HCG18 in myocardial fibroblasts, the level of hsa-miR-133a expression was evaluated by quantitative reverse transcription-polymerase chain reaction (RT-qPCR), and the EGFR, ERK1/2, and p-ERK1/2 expression levels were assessed by Western blotting to confirm that upregulation of EGFR and p-ERK1/2 protein levels by overexpression of lncRNA-HCG18, siRNA lncRNA-HCG18 (siHCG18) reduced the EGFR and p-ERK1/2 protein levels. Then, the luciferase reporter gene system was used to verify that lncRNA-HCG18 regulated EGFR expression by inhibiting the function of the hsa-miR-133a regulatory target gene. Then, a RAP assay was used to confirm that lncRNA-HCG18 interacted with hsa-miR-133a. Finally, the analysis of CCK-8 results indicated that the cell proliferation of myocardial fibroblasts was significantly reduced by siHCG18 while reversed by overexpression of lncRNA-HCG18. Thus, lncRNA-HCG18 inhibited cell viability of cardiac fibroblasts via the hsa-miR-133a/EGFR axis, which was regarded as a regulator of cell proliferation of cardiac fibroblasts in cardiovascular diseases.

10.
Molecules ; 27(16)2022 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-36014519

RESUMEN

Aspergillus flavus and Aflatoxins in grain crops give rise to a serious threat to food security and cause huge economic losses. In particular, aflatoxin B1 has been identified as a Class I carcinogen to humans by the International Agency for Research on Cancer (IARC). Compared with conventional methods, Surface-Enhanced Raman Scattering (SERS) has paved the way for the detection of Aspergillus flavus and Aflatoxins in grain crops as it is a rapid, nondestructive, and sensitive analytical method. In this work, the rapid detection of Aspergillus flavus and quantification of Aflatoxin B1 in grain crops were performed by using a portable Raman spectrometer combined with colloidal Au nanoparticles (AuNPs). With the increase of the concentration of Aspergillus flavus spore suspension in the range of 102-108 CFU/mL, the better the combination of Aspergillus flavus spores and AuNPs, the better the enhancement effect of AuNPs solution on the Aspergillus flavus. A series of different concentrations of aflatoxin B1 methanol solution combined with AuNPs were determined based on SERS and their spectra were similar to that of solid powder. Moreover, the characteristic peak increased gradually with the increase of concentration in the range of 0.0005-0.01 mg/L and the determination limit was 0.0005 mg/L, which was verified by HPLC in ppM concentration. This rapid detection method can greatly shorten the detection time from several hours or even tens of hours to a few minutes, which can help to take effective measures to avoid causing large economic losses.


Asunto(s)
Aflatoxinas , Nanopartículas del Metal , Aflatoxina B1 , Aflatoxinas/análisis , Aspergillus flavus , Grano Comestible/química , Oro/farmacología , Humanos
11.
Int J Mol Sci ; 23(13)2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35806345

RESUMEN

This study aims to develop a simple, sensitive, low-cost, environmentally friendly and flexible surface-enhanced Raman scattering (SERS) platform, combined with a portable Raman spectrometer, for the rapid and on-site SERS detection of bacteria. Commercial tobacco packaging paper (TPP) with little background interference was used as a loading medium that effectively adsorbed Au nanoparticles and provided sufficient "hot spots". This Au-tobacco packaging paper (Au-TPP) substrate used as a flexible SERS platform can maximize sample collection by wiping irregular surfaces, and was successfully applied to the on-site and rapid detection of pathogenic bacteria. Raman fingerprints of pathogenic bacteria can be obtained by SERS detection of spiked pork using wipeable Au-TPP, which verifies its value in practical applications. The results collected by SERS were further verified by polymerase chain reaction (PCR) results. It showed several advantages in on-site SERS detection, including accurate discrimination, simple preparation, easy operation, good sensitivity, accuracy and reproducibility. This study indicates that the established flexible SERS platform has good practical applications in pathogenic bacterial identification and other rapid detections.


Asunto(s)
Oro , Nanopartículas del Metal , Bacterias , Reproducibilidad de los Resultados , Espectrometría Raman/métodos
12.
J Clin Lab Anal ; 36(6): e24458, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35476874

RESUMEN

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common clinical malignancies of the digestive system, characterized by high mortality but not evident early symptoms. Molecular markers for diagnostic and outcome prediction are urgently needed. Circular RNAs might play essential roles in the progression of ESCC. METHODS: Hsa_circ_0000977 was identified using circRNA microarrays and qRT-PCR. The diagnostic value of hsa_circ_0000977 was calculated. We also examined in vitro cell functions in ECA109 and TE12 ESCC cells to determine the effect of hsa_circ_0000977. A dual-luciferase reporter vector validated the binding of hsa_circ_0000977 to miR-874-3p. RESULTS: The top 10 significantly upregulated circRNAs from microarray assays were hsa_circ_0000977, hsa_circ_0006220, hsa_circ_0043278, hsa_circ_0000691, hsa_circ_0000288, hsa_circ_0000367, hsa_circ_0021647, hsa_circ_0006440, hsa_circRNA_405571 and hsa_circRNA_100790, while the top 10 significantly downregulated circRNAs were hsa_circ_0008389, hsa_circ_0089763, hsa_circ_0089762, hsa_circ_0000102, hsa_circ_0001714, hsa_circ_0089761, hsa_circ_0007326, hsa_circ_0001549, hsa_circ_0005133 and hsa_circRNA_405965. Hsa_circ_0000977 was significantly upregulated in ESCC (p < 0.01) and had diagnostic value in ESCC. The hsa_circ_0000977 expression level was related to the pT stage and numbers of lymph nodes in ESCC patients. Elevated hsa_circ_0000977 promoted cell proliferation, migration and inhibited apoptosis in ESCC cells. Hsa_circ_0000977 might function as a micro-RNA sponge to competitively bind miR-874-3p. CONCLUSION: Disordered hsa_circ_0000977 expression can promote carcinogenesis in ESCC and might serve as a diagnostic biomarker to evaluate the occurrence and development of esophageal cancer.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , MicroARNs , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , Regulación hacia Arriba/genética
13.
Spectrochim Acta A Mol Biomol Spectrosc ; 273: 121070, 2022 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-35231762

RESUMEN

Rapid and quantitative detection of bacterial antibiotic resistance is of great significance for the prevention and treatment of infections and understanding drug-resistant mechanism. In this study, label-free surface-enhanced Raman spectroscopy (SERS) technology was applied to dynamically explore oxacillin/cefazolin-derived resistance in Staphylococcus aureus using a portable Raman spectrometer. The results showed that S. aureus rapidly responded to oxacillin/cefazolin stimulation and gradually developed different degrees of drug resistance during the 21 days of exposure. The molecular changes that accumulated in the drug-resistant strains were sensitively recorded by SERS in a whole-cell manner. Principal components-linear discriminant analysis correctly distinguished various degrees of drug-resistant strains. The typical Raman peak intensities of I734/I867 showed a negative and non-linear correlation with the minimum inhibitory concentration (MIC). The correlation coefficient reached above 0.9. The target sites of oxacillin/cefazolin on S. aureus clearly reflected on SERS profiles. The results collected by SERS were further verified by other biological methods including the antibiotic susceptibility test, MIC determination, and PCR results. This study indicates that SERS technology provides a rapid and flexible alternative to current drug susceptibility testing, laying a foundation for qualitative and quantitative evaluation of drug resistance in clinical detection.


Asunto(s)
Mycobacterium tuberculosis , Staphylococcus aureus , Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Pruebas de Sensibilidad Microbiana , Espectrometría Raman/métodos
14.
Int J Mol Sci ; 23(3)2022 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-35163280

RESUMEN

The rapid identification of bacterial antibiotic susceptibility is pivotal to the rational administration of antibacterial drugs. In this study, cefotaxime (CTX)-derived resistance in Salmonella typhimurium (abbr. CTXr-S. typhimurium) during 3 months of exposure was rapidly recorded using a portable Raman spectrometer. The molecular changes that occurred in the drug-resistant strains were sensitively monitored in whole cells by label-free surface-enhanced Raman scattering (SERS). Various degrees of resistant strains could be accurately discriminated by applying multivariate statistical analyses to bacterial SERS profiles. Minimum inhibitory concentration (MIC) values showed a positive linear correlation with the relative Raman intensities of I990/I1348, and the R2 reached 0.9962. The SERS results were consistent with the data obtained by MIC assays, mutant prevention concentration (MPC) determinations, and Kirby-Bauer antibiotic susceptibility tests (K-B tests). This preliminary proof-of-concept study indicates the high potential of the SERS method to supplement the time-consuming conventional method and help alleviate the challenges of antibiotic resistance in clinical therapy.


Asunto(s)
Infecciones por Salmonella/inmunología , Salmonella typhimurium/inmunología , Espectrometría Raman/métodos , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Farmacorresistencia Microbiana/efectos de los fármacos , Humanos , Infecciones por Salmonella/diagnóstico , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/patogenicidad
15.
J Clin Lab Anal ; 36(2): e24197, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34952991

RESUMEN

BACKGROUND: Currently, the diagnosis and outcome of rheumatic valvular heart disease (RVHD) are less than ideal, and there are no accurate biomarkers. Circular RNA (circRNA) might participate in the occurrence and development of RVHD. MATERIALS AND METHODS: We use circRNA microarray to filter out the target has_circ_0000437. qRT-PCR was used to measure the expression levels of hsa_circ_0000437 in RVHD plasma samples. We assessed the diagnostic value of hsa_circ_0000437 in RVHD. Cell function in vitro experiment was to explore the effect of has_circ_0000437 on RVHD. RESULTS: Has_circ_0000437 is highly expressed in RVHD (p < 0.001). has_circ_0000437 has the diagnostic value in RVHD. In RVHD, hsa_circ_0000437 can promote cell proliferation and migration but inhibits its apoptosis. This may be due to the combination of has_circ_0000437 and target miRNA in the cytoplasm that affects the progress of RVHD. CONCLUSIONS: Has_circ_0000437 can promote the process of RVHD and may be a potential for the diagnosis and treatment of RVHD.


Asunto(s)
Progresión de la Enfermedad , Enfermedades de las Válvulas Cardíacas/fisiopatología , ARN Circular/metabolismo , Cardiopatía Reumática/fisiopatología , Células Cultivadas , Femenino , Humanos , Masculino , Regulación hacia Arriba
16.
Aging (Albany NY) ; 13(22): 24580-24604, 2021 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-34793329

RESUMEN

Valvular heart disease (VHD) is a common heart disease that affects blood flow. It usually requires heart surgery. Valvular heart disease complicated with pulmonary artery hypertension (VHD-PAH) may be lethal due to heart failure that results from increased heart burden. It is important for these patients to seek early treatment in order to minimize the heart damage. However, there is no reliable diagnosis method in VHD. In this study, we found DNA methylation was increased at the promoter of BMPR2 gene in the VHD patients compared with the healthy controls. This finding was confirmed by an independent cohort study of VHD patients and healthy controls. In addition, BMPR2 mRNA levels were reduced in the plasma of the VHD patients. There is strong correlation between BMPR2 promoter DNA methylation and the severity of VHD. Indeed, we found that both BMPR2 promoter DNA methylation and BMPR2 mRNA levels in the plasma are good biomarkers of VHD by themselves, with the respective AUC value of 0.879 and 0.725, respectively. When they were used in combination, the diagnostic value was even better, with the AUC value of 0.93. Consistent with the results in the VHD patients, we observed decreased BMPR2 and increased fibrosis in the lung of a PAH model mouse. BMPR2 was also decreased in the hearts of the PAH mice, whereas BMP4 was increased. Furthermore, BMPR2 was reduced in the heart valve tissue samples of human VHD patients after valve replacement with moderate/severe PAH compared with those with mild PAH. There was also increased apoptosis in the hearts of the PAH mice. BMPR2 promoter DNA methylation and its expression appear to be good biomarkers for VHD. Our results also suggest that DNA methylation may cause PAH through deregulation of BMP signaling and increased apoptosis.


Asunto(s)
Receptores de Proteínas Morfogenéticas Óseas de Tipo II , Metilación de ADN/genética , Enfermedades de las Válvulas Cardíacas , Regiones Promotoras Genéticas/genética , Hipertensión Arterial Pulmonar , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/genética , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Adulto Joven
18.
Science ; 372(6538): 201-205, 2021 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-33833125

RESUMEN

Cardiac regeneration requires dedifferentiation and proliferation of mature cardiomyocytes, but the mechanisms underlying this plasticity remain unclear. Here, we identify a potent cardiomyogenic role for Krüppel-like factor 1 (Klf1/Eklf), which is induced in adult zebrafish myocardium upon injury. Myocardial inhibition of Klf1 function does not affect heart development, but it severely impairs regeneration. Transient Klf1 activation is sufficient to expand mature myocardium in uninjured hearts. Klf1 directs epigenetic reprogramming of the cardiac transcription factor network, permitting coordinated cardiomyocyte dedifferentiation and proliferation. Myocardial expansion is supported by Klf1-induced rewiring of mitochondrial metabolism from oxidative respiration to anabolic pathways. Our findings establish Klf1 as a core transcriptional regulator of cardiomyocyte renewal in adult zebrafish hearts.


Asunto(s)
Reprogramación Celular , Corazón/fisiología , Factores de Transcripción de Tipo Kruppel/metabolismo , Miocitos Cardíacos/fisiología , Regeneración , Proteínas de Pez Cebra/metabolismo , Animales , Cardiomegalia Inducida por el Ejercicio , Desdiferenciación Celular , Diferenciación Celular , Proliferación Celular , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Glucólisis , Corazón/embriología , Ventrículos Cardíacos/citología , Factores de Transcripción de Tipo Kruppel/genética , Desarrollo de Músculos , Miocardio/metabolismo , Miocitos Cardíacos/citología , Vía de Pentosa Fosfato , Pez Cebra , Proteínas de Pez Cebra/genética
20.
Indian J Pathol Microbiol ; 64(2): 362-368, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33851636

RESUMEN

There were rare clinical reports on clear cell tumor of the lung (CCTL). The clinical characteristics and underlying genetic mutation status of CCTL are poorly understood. From 2012 to 2017, patients pathologically diagnosed with CCTL in our hospital were investigated and analyzed based on clinical manifestations, pathological characteristics, prognosis and full gene mutation status through next generation sequencing (NGS) technology. During a 6-year period, four eligible patients were diagnosed with CCTL through surgical resection and were included in this study. All patients showed solitary nodules or lumps located in the left lung. The average maximum diameter of lesions was 2.5 ± 1.1 cm. Computed tomography (CT) imaging characteristics of these nodules/lumps demonstrated the features of benign tumors. The hematoxylin-eosin (HE) morphology and immunohistochemistry were consistent with the histopathological features of benign CCTL. Subsequent NGS analysis showed frame shift mutations of F2421/E2419, K1466E mutation, and p. 1450_1456 deletion mutation in mTOR gene in two of four patient samples and amplifications of MCL1 were observed in three of four samples. CCTL is a rare type of primary pulmonary mesenchymal tumor with good prognosis. Preliminary diagnosis on CT is usually sclerosing pneumocytoma. It is still unclear whether the occurrence and development of the disease are related to specific gene mutation. In this study, the genomic findings of frame shift mutation of mTOR genes and amplification of MCL1 gene in CCTL suggest that these mutations might play a role in proliferation of CCTL.


Asunto(s)
Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/genética , Serina-Treonina Quinasas TOR/genética , Adenocarcinoma de Células Claras/diagnóstico , Femenino , Mutación del Sistema de Lectura/genética , Amplificación de Genes/genética , Glucógeno/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Persona de Mediana Edad , Pronóstico , Tomografía Computarizada por Rayos X
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