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1.
Artigo em Inglês | MEDLINE | ID: mdl-35762276

RESUMO

INTRODUCTION: Evidence has shown that some microRNAs (miRNAs) play a role in tumorigenesis of hepatocellular carcinoma (HCC). Herein, we aimed to evaluate the diagnostic and prognostic values of serum exosomal miR-370-3p and miR-196a-5p in patients with HCC. MATERIAL AND METHODS: Serum exosomes in 90 HCC patients were extracted and identified. Serum exosomal miR-370-3p and miR-196a-5p expression in HCC patients were detected. The diagnostic value of miR-370-3p and miR-196a-5p, relationship between miR-370-3p and miR-196a-5p expression and clinicopathological features and prognosis of patients with HCC were analyzed. Relationship between miR-370-3p and miR-196a-5p expression and liver function indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in HCC patients were analyzed. The effects of miR-370-3p and miR-196a-5p on Huh7 HCC cells' proliferation, invasion and migration were determined. RESULTS: Lower expression of miR-370-3p and higher expression of miR-196a-5p were found in serum exosomes of HCC patients. Serum exosomal miR-370-3p and miR-196a-5p were associated with tumor size, tumor grade and TNM stage as well as prognosis and liver function indices of HCC patients. Overexpressed miR-370-3p or silenced miR-196a-5p suppressed proliferation, invasion and migration of Huh7 HCC cells. CONCLUSIONS: We suggest that miR-370-3p/miR-196a-5p in serum exosomes of HCC patients could be potential biomarkers for the diagnosis and prognosis of HCC.

2.
J Adv Res ; 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35718080

RESUMO

Intro duction Chronic psychological stress is a well-established risk factor for breast cancer development. Si-Ni-San (SNS) is a classical traditional Chinese medicine formula prescribed to psychological disorder patients. However, its action effects, molecular mechanisms, and bioactive phytochemicals against breast cancer are not yet clear. OBJECTIVES: This study aimed to explore the modulatory mechanism and bioactive compound of SNS in regulating estrogen metabolism during breast cancer development induced by chronic psychological stress. METHODS: Mouse breast cancer xenograft was used to determine the effect of SNS on breast cancer growth and metastasis. Metabolomics analysis was conducted to discover the impact of SNS on metabolic profile changes in vivo. Multiple molecular biology experiments and breast cancer xenografts were applied to verify the anti-metastatic potentials of the screened bioactive compound. RESULTS: SNS remarkably inhibited chronic psychological stress-induced breast cancer growth and metastasis in the mouse breast cancer xenograft. Meanwhile, chronic psychological stress increased the level of cholic acid, accompanied by the elevation of estradiol. Mechanistic investigation demonstrated that cholic acid activated farnesoid X receptor (FXR) expression, which inhibited hepatocyte nuclear factor 4α (HNF4α)-mediated estrogen sulfotransferase (EST) transcription in hepatocytes, and finally resulting in estradiol elevation. Notably, SNS inhibited breast cancer growth by suppressing estradiol level via modulating FXR/EST signaling. Furthermore, luciferase-reporting gene assay screened naringenin as the most bioactive compound in SNS for triggering EST activity in hepatocytes. Interestingly, pharmacokinetic study revealed that naringenin had the highest absorption in the liver tissue. Following in vivo and in vitro studies demonstrated that naringenin inhibited stress-induced breast cancer growth and metastasis by promoting estradiol metabolism via FXR/EST signaling. CONCLUSION: This study not only highlights FXR/EST signaling as a crucial target in mediating stress-induced breast cancer development, but also provides naringenin as a potential candidate for breast cancer endocrine therapy via promoting estradiol metabolism.

4.
Mol Cancer Res ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35560224

RESUMO

Cancer-associated fibroblasts (CAFs) constitute a major component of the tumor microenvironment. The effects of CAFs on the progression of colorectal cancer (CRC) remain controversial. In this study, we found the ectopic overexpression of Fibronectin leucine-rich transmembrane protein 3 (FLRT3) inhibited the process of Epithelial-mesenchymal transition (EMT), as well as the proliferation, migration, invasion, and promote apoptosis of CRC cells, whereas silencing FLRT3 expression resulted in the opposite phenomenon. FLRT3 downregulation was associated with a poor prognosis in CRC. Also, FLRT3 expression was significantly related to some clinicopathological factors, including T stage (p=0.037), N stage (p=0.042), and E-cadherin (p=0.002) level. Via univariate and multivariate analyses, M stage (p<0.0001), FLRT3 (p=0.044), and E-cadherin (p=0.003) were associated with overall survival and were independent prognostic factors for it. Mechanistically, CAFs secreted TGF-ß, which downregulated FLRT3 expression by activating SMAD4 to promote aggressive phenotypes in CRC cells. Moreover, FLRT3 repressed tumorigenesis and lung metastasis, which could be reversed by LY2109761, a dual inhibitor of TGF-ß receptor type I and II. Treatment with LY2109761 increased IFN-γ expression in CD8+ T cells and reduced the number of regulatory T cells in the tumor microenvironment. Taken together, we revealed the metastasis-suppressive function of FLRT3, which was attenuated during the CAFs-mediated activation of the TGF-ß/SMAD4 signaling pathway to promote EMT in CRC. LY2109761 that significantly inhibited metastasis could be a new treatment option for advanced CRC. Implications: CAFs enhance CRC aggressiveness by reducing FLRT3 expression through activating TGF-ß/SMAD4 signaling pathway. CAFs-targeted therapy and/or LY2109761 were promising treatments for CRC.

5.
Adv Mater ; : e2201981, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524983

RESUMO

Recent years have witnessed thriving efforts in pursuing high-energy batteries at an unaffordable cost of safety. Herein, a high-energy and safe quasi-solid-state lithium battery is proposed by solid-state redox chemistry of polymer-based molecular Li2 S cathode in a fireproof gel electrolyte. This chemistry fully eliminates not only the negative effect of extremely reactive Li metal and oxygen species on cell safety but also the damage of electrode reversibility by soluble redox intermediates. The molecular Li2 S cathode exhibits an exceptional lifetime of 2000 cycles, 100% Coulombic efficiency, high capacity of 830 mA h g-1 with ultralow capacity loss of 0.005-0.01% per cycle and superior rate capability up to 10 C. Meanwhile, it shows high stability in the carbonate-involving electrolyte for maximizing the compatibility with carbonate-efficient Si anode. The optimized cell chemistry exerts high energy over 750 W h kg-1 for 500 cycles with fast rate response, high-temperature adaptability, and no self-discharge. A fire-retardant composite gel electrolyte is developed to further strengthen the intrinsic safe redox between the Li2 S cathode and the Si anode, which secures remarkable safety against extreme abuse of overheating, short circuits, and mechanical damage in air/water or even when on fire.

6.
Front Oncol ; 12: 881953, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600382

RESUMO

Background: Glycerolipid metabolism is involved in the genesis and progression of colon cancer. The current study aims at exploring the prognostic value and potential molecular mechanism of glycerolipid metabolism-related genes in colon cancer from the perspective of multi-omics. Methods: Clinical information and mRNA expression data of patients with colon cancer were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Single-sample gene set enrichment analysis (ssGSEA) was applied to calculate the glycerolipid metabolism-related gene enrichment score (GLMS). Univariable and multivariable Cox regression analyses were used to study the prognostic value of GLMS in TCGA-COAD and GSE39582 cohorts. The molecular mechanism of the prognostic factor was investigated via immune cell infiltration estimation and correlation analysis of cancer hallmark pathways. Single-cell transcriptomic dataset GSE146771 was used to identify the cell populations which glycerolipid metabolism targeted on. Results: The GLMS was found to be associated with tumor location and consensus molecular types (CMSs) of colon cancer in TCGA-COAD cohort (P < 0.05). Patients in the low-GLMS group exhibited poorer overall survival (OS) in TCGA cohort (P = 0.03; HR, 0.63; 95% CI, 0.42-0.94), which was further validated in the GSE39582 dataset (P < 0.001; HR, 0.57; 95% CI, 0.43-0.76). The association between the GLMS and OS remained significant in the multivariable analysis (TCGA cohort: P = 0.04; HR, 0.64; 95% CI, 0.42-0.98; GSE39582 cohort: P < 0.001; HR, 0.60; 95% CI, 0.45-0.80). The GLMS was positively correlated with cancer hallmark pathways including bile acid metabolism, xenobiotic metabolism, and peroxisome and negatively correlated with pathways such as interferon gamma response, allograft rejection, apoptosis, and inflammatory response (P < 0.05). Increased immune infiltration and upregulated expression of immune checkpoints were observed in patients with lower GLMS (P < 0.05). Single-cell datasets verified the different distribution of GLMS in cell subsets, with significant enrichment of GLMS in malignant cells and Tprolif cells. Conclusion: We demonstrated that GLMS was a potential independent prognostic factor for colon cancer. The GLMS was also correlated with several cancer hallmark pathways, as well as immune microenvironment.

7.
Front Oncol ; 12: 879563, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35619902

RESUMO

Background: Depression plays a significant role in mediating breast cancer recurrence and metastasis. However, a precise risk model is lacking to evaluate the potential impact of depression on breast cancer prognosis. In this study, we established a depression-related gene (DRG) signature that can predict overall survival (OS) and elucidate its correlation with pathological parameters and sensitivity to therapy in breast cancer. Methods: The model training and validation assays were based on the analyses of 1,096 patients from The Cancer Genome Atlas (TCGA) database and 2,969 patients from GSE96058. A risk signature was established through univariate and multivariate Cox regression analyses. Results: Ten DRGs were determined to construct the risk signature. Multivariate analysis revealed that the signature was an independent prognostic factor for OS. Receiver operating characteristic (ROC) curves indicated good performance of the model in predicting 1-, 3-, and 5-year OS, particularly for patients with triple-negative breast cancer (TNBC). In the high-risk group, the proportion of immunosuppressive cells, including M0 macrophages, M2 macrophages, and neutrophils, was higher than that in the low-risk group. Furthermore, low-risk patients responded better to chemotherapy and endocrine therapy. Finally, a nomogram integrating risk score, age, tumor-node-metastasis (TNM) stage, and molecular subtypes were established, and it showed good agreement between the predicted and observed OS. Conclusion: The 10-gene risk model not only highlights the significance of depression in breast cancer prognosis but also provides a novel gene-testing tool to better prevent the potential adverse impact of depression on breast cancer prognosis.

8.
Biochem Biophys Res Commun ; 615: 136-142, 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35617800

RESUMO

Hyperthyroidism can potentiate arrhythmias and cardiac hypertrophy, whereas Ca2+/calmodulin-dependent kinase II (CaMKII) promotes maladaptive myocardial remodeling. However, it remains unclear whether CaMKII contributes to the progression of hyperthyroid heart disease (HHD). This study demonstrated that CaMKII inhibition can relieve adverse myocardial remodeling and reduce sinus tachycardia, isoproterenol-induced atrial fibrillation, and ventricular arrhythmias in hyperthyroid mice with preserved heart function. Hyperthyroid cardiac hypertrophy was promoted by CaMKII upregulation-induced HDAC4/MEF2a activation. Briefly, CaMKII inhibition benefits HHD management greatly in mice by preventing arrhythmias and maladaptive remodeling.


Assuntos
Fibrilação Atrial , Hipertireoidismo , Animais , Fibrilação Atrial/prevenção & controle , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Cardiomegalia/prevenção & controle , Hipertireoidismo/complicações , Camundongos , Miocárdio , Miócitos Cardíacos
9.
J Healthc Eng ; 2022: 4373404, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35469230

RESUMO

Objective: This study seeks to explore the efficacy and prognosis of stereotactic aspiration for malignant middle cerebral artery infarction (mMCAI). Methods: A total of 50 mMCAI patients who were diagnosed and treated in our hospital from January 2018 to June 2020 were collected and then randomly divided into control group (decompressive craniectomy, n = 24) and study group (stereotactic aspiration, n = 26). After 1 and 6 months of treatment, the scores of the National Institutes of Health Stroke Scale (NIHSS), Glasgow Coma Scale (GCS), Barthel Index, and modified Rankin Scale (mRS) were used to evaluate the therapeutic effect. Additionally, the mortality and survival rates after treatment were recorded to compare the prognostic effect between the two groups. Results: One month after treatment, the GCS scores and Barthel Index score increased in both the control and study groups and were significantly higher in the study group. The follow-up results at 1 and 6 months after treatment showed that in comparison with the control group, stereotactic aspiration led to a higher survival rate and lower mortality rate; the latter had superior NIHSS score and mRS score and better prognosis. Conclusion: In comparison with decompressive craniectomy, stereotactic aspiration shows outstanding clinical efficacy and more advantages in the treatment of mMCAI. Therefore, stereotactic aspiration is more worthy of clinical application.


Assuntos
Craniotomia , Infarto da Artéria Cerebral Média , Craniotomia/métodos , Escala de Coma de Glasgow , Humanos , Infarto da Artéria Cerebral Média/cirurgia , Prognóstico , Estudos Retrospectivos , Técnicas Estereotáxicas , Resultado do Tratamento , Estados Unidos
11.
Artigo em Inglês | MEDLINE | ID: mdl-35484308

RESUMO

MicroRNA-365 (miR-365) has been revealed to be a vital regulator in tumorigenesis of multiple cancers, while there is a large gap in the knowledge about miR-365 expression and gastric cancer (GC). This research focused on the effects of miR-365 and paired box 6 (PAX6) on GC development. Levels of miR-365 and PAX6 in GC tissues and cell lines were determined, followed by the screening of the AGS and NCI-N87 cells. Gain- or loss-of-function assays were used to analyze the effect of miR-365, PAX6 on AGS and NCI-N87 cell behaviors. The effects of altered miR-365 and PAX6 on animal models were observed. Moreover, to assess the interaction between miR-365 and PAX6, we implemented the bioinformatic method and dual luciferase reporter gene assay. MiR-365 was decreased while PAX6 was increased in GC tissues and cell lines. There existed a negative association between miR-365 and PAX6. The promoted miR-365 could repress oncogenicity in vivo and malignant transformation in vitro of GC. PAX6 was the target gene of miR-365. Overexpression of PAX6 reversed the inhibitory effect of up-regulated miR-365 on malignant behavior of gastric cancer cells. Our research displays that the amplification of miR-365 could suppress the malignant behaviors of GC cells via inhibiting PAX6, which may be helpful for GC treatment.

14.
Angew Chem Int Ed Engl ; : e202203929, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35452186

RESUMO

Energy-saving hydrogen production can be achieved by using renewables or decoupling the sluggish oxygen evolution reaction from overall water splitting, which still needs electricity input. We have realized hydrogen production and water desalination with on-demand electricity output via an electrochemical neutralization chemistry strategy that couples acidic hydrogen evolution and alkaline hydrazine oxidation with ionic exchange. The electrochemical neutralization cells allow efficient use of chemical energy and low-grade heat from the surroundings to output 0.81 kWh electricity per m3 of hydrogen. Cell function can be rapidly switched to electricity output with a high peak power density up to 85.5 mW cm-2 or spontaneous hydrogen production at a high rate up to 70.1 mol h-1 m-2 without breaking cell operation or changing cell configuration. Fast water desalination is simultaneously achieved at a high salt removal rate of 56.1 mol h-1 m-2 without an external electricity supply.

15.
Exp Biol Med (Maywood) ; 247(9): 797-804, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35473318

RESUMO

Hypertensive renal damage is a common secondary kidney disease caused by poor control of blood pressure. Recent evidence has revealed abnormal activation of the complement alternative pathway (AP) in hypertensive patients and animal models and that this phenomenon is related to hypertensive renal damage. Conditions in the setting of hypertension, including high renin concentration, reduced binding of factor H to the glomerular basement membrane, and abnormal local synthesis of complement proteins, potentially promote the AP activation in the kidney. The products of the AP activation promote the phenotypic transition of mesangial cells and tubular cells, attack endothelial cells and recruit immunocytes to worsen hypertensive renal damage. The effects of complement inhibition on hypertensive renal damage are contradictory. Although clinical data support the use of C5 monoclonal antibody in malignant hypertension, pharmacological inhibition in hypertensive animals provides little benefit to kidney function. Therefore, the role of the complement AP in the pathogenesis of hypertensive renal damage and the value of complement inhibition in hypertensive renal damage treatment must be further explored.


Assuntos
Hipertensão , Nefropatias , Animais , Ativação do Complemento , Células Endoteliais/patologia , Humanos , Hipertensão/patologia , Rim/patologia , Nefropatias/patologia
16.
Opt Express ; 30(5): 6700-6712, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35299449

RESUMO

Magneto-optical (MO) properties of the bilayed Au/BIG and trilayered Au/BIG/Au magneto-plasmonic crystals (MPCs) were analyzed by the finite-difference time-domain method. In contrast to the low deflection angle and transmission of the smooth thin film, all the heterostructures with perforated holes in the top Au film displayed a similar trend with two strong resonant bands in Faraday rotation and transmittance in the near infrared wavelength range. The bands and electric distribution relative to the component and hole structure were revealed. The MPC with plasmonic hexagonal holes was found to own superior Faraday effects with distinctive anisotropy. The evolution of the resonant bands with the size and period of hexagonal holes, the thickness of different layers, and the incident light polarization was illustrated. The Faraday rotation of the optimized bilayed and trilayered hexagonal MPCs was improved 15.3 and 17.5 times, and the transmittance was enhanced 12.1 and 11.1 folds respectively at the resonant wavelength in comparison to the continuous Au/BIG film, indicating that the systems might find potential application in MO devices.

19.
Artigo em Inglês | MEDLINE | ID: mdl-35231606

RESUMO

An AMP-activated kinase (AMPK) signaling pathway is activated during myocardial ischemia and promotes cardiac fatty acid (FA) uptake and oxidation. Similarly, the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is also triggered by myocardial ischemia, but its function in FA metabolism remains unclear. Here, we explored the role of CaMKII in FA metabolism during myocardial ischemia by investigating the effects of cardiac CaMKII on AMPK-acetyl-CoA carboxylase (ACC), malonyl CoA decarboxylase (MCD), and FA translocase cluster of differentiation 36 (FAT/CD36), as well as cardiac FA uptake and oxidation. Moreover, we tested whether CaMKII and AMPK are binding partners. We demonstrated that diseased hearts from patients with terminal ischemic heart disease displayed increased phosphorylation of CaMKII, AMPK, and ACC and increased expression of MCD and FAT/CD36. AC3-I mice, which have a genetic myocardial inhibition of CaMKII, had reduced gene expression of cardiac AMPK. In post-MI (myocardial infarction) AC3-I hearts, AMPK-ACC phosphorylation, MCD and FAT/CD36 levels, cardiac FA uptake, and FA oxidation were significantly decreased. Notably, we demonstrated that CaMKII interacted with AMPK α1 and α2 subunits in the heart. Additionally, AC3-I mice displayed significantly less cardiac hypertrophy and apoptosis 2 weeks post-MI. Overall, these findings reveal a unique role for CaMKII inhibition in repressing FA metabolism by interacting with AMPK signaling pathways, which may represent a novel mechanism in ischemic heart disease.


Assuntos
Infarto do Miocárdio , Isquemia Miocárdica , Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Animais , Antígenos CD36/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Ácidos Graxos/metabolismo , Humanos , Camundongos
20.
Thorac Cancer ; 13(8): 1176-1183, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35261166

RESUMO

BACKGROUND: The lobar and segmental anatomy are the basis for anatomical pulmonary segmentectomy. METHODS: From October 2017 to June 2021, 136 patients with small pulmonary nodules scheduled for anatomical pulmonary segmentectomy at our institution underwent three-dimensional (3D) lung reconstruction. The anatomy of the left upper lobe (LUL) was statistically analyzed and graphically mapped using the reconstructed models, and the role of this reconstruction method in performing pulmonary segmentectomy was explored. RESULTS: Through the analysis of the reconstructed models, the upper stem (S1 + 2 + 3) bronchus was classified as having two (94/136 cases) or three branches (42/136 cases). The upper stem artery had two branches in 24/136 patients, three in 60/136 cases, four in 44/136 cases, and five in 8/136 cases. A total of 103/136 upper stem veins had two branches, 26/136 had three branches, and 7/136 had four branches. The lingual stem (S4 + 5) bronchus was two-branched in 116/136 cases and three-branched in 20/136 cases, while the lingual artery was single-branched in 61/136 cases, two-branched in 70/136 cases, and three-branched in rare cases (5/136 cases). The lingual stem vein was unbranched in 119/136 cases and two-branched in 17/136 cases. Additionally, six unusual variants (<5%) were identified: one in the bronchus, with four cases; three in the pulmonary artery, with six cases; and two in the pulmonary vein, with two cases. CONCLUSIONS: 3D reconstruction can yield results similar to specimens for lung segment studies. The reconstruction strategy and the data presented in this article will be valuable references for thoracic surgeons performing anatomic resections.


Assuntos
Imageamento Tridimensional , Veias Pulmonares , Humanos , Imageamento Tridimensional/métodos , Pulmão/irrigação sanguínea , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Artéria Pulmonar/cirurgia , Tomografia Computadorizada por Raios X/métodos
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