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1.
Opt Lett ; 49(9): 2445-2448, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691740

RESUMO

Spatial-temporal optical vortices (STOVs) have recently become the focus of newly structured optical fields. In this paper, their propagation on a 2D curved surface named the constant Gaussian curvature surface (CGCS) is studied. Using the matrix optics approach, we provide the analytical solution of the STOV propagation under the paraxial approximation on the CGCS with positive curvature. One method of creating timers is made possible by the spatiotemporal distribution direction of STOV light intensity, which swings like a pendulum throughout the evolution, in contrast to propagation on a flat surface. This swing, however, stops when the curved surface's curvature radius matches the light's Rayleigh distance. Besides, the transverse orbital angular momentum of STOV is deduced, and we find that the intrinsic and extrinsic OAM periodically exchange, but the total transverse OAM is always zero during the propagation on CGCS. It aids in controlling the transverse extrinsic orbital angular momentum of STOV in nontrivial space.

2.
Int J Gen Med ; 17: 2203-2221, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774724

RESUMO

Purpose: To study the relationship between LARS1 expression and immune infiltration and prognosis in hepatocellular carcinoma (HCC). Patients and Methods: The clinical characteristics together with LARS1 expression levels were obtained from the TCGA database. Immunohistochemistry confirmed LARS1 expression levels in paraneoplastic and tumor tissues. To investigate LARS1-related downstream molecules, a network of protein-protein interactions (PPIs) and the Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) were built. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathways associated with LARS1 expression, whereas Single-sample GSEA (ssGSEA) was applied to perform an association study between immune infiltration and LARS1 gene expression. The TISCH Database and the TISIDB database were used to compare the difference of LARS1 expression in hepatocellular carcinoma and immunomodulators. Results: In comparison to that in normal tissues, the LARS1 expression level was elevated in tumor tissues. LARS1 expression exhibited substantial correlation with AFP, Histologic grade, pathologic stage, Residual tumor, and Vascular invasion in HCC. Higher LARS1 expression in HCC was linked to lower progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). According to the GO/KEGG study, the important biological process (neutral lipid metabolic process), cellular component (triglyceride-rich plasma lipoprotein), molecular functions (lipase inhibitor activity), and KEGG pathway (cholesterol metabolism) could be a probable function mechanism in promoting HCC. Various pathways as per GSEA revealed that they were enriched in samples with elevated LARS1 expression. The expression level of LARS1 in malignant tumor cells after immunotherapy was significantly higher than that before immunotherapy. LARS1 was also remarkably linked to the infiltration level and the immunomodulators. Conclusion: LARS1 can be used as a biomarker of HCC, which is associated to immune infiltration of HCC.

3.
J Cancer Res Clin Oncol ; 150(3): 148, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512513

RESUMO

INTRODUCTION: Accumulating evidence demonstrates that aberrant methylation of enhancers is crucial in gene expression profiles across several cancers. However, the latent effect of differently expressed enhancers between INSS stage 4S and 4 neuroblastoma (NB) remains elusive. METHODS: We utilized the transcriptome and methylation data of stage 4S and 4 NB patients to perform Enhancer Linking by Methylation/Expression Relationships (ELMER) analysis, discovering a differently expressed motif within 67 enhancers between stage 4S and 4 NB. Harnessing the 67 motif genes, we established the INSS stage related signature (ISRS) by amalgamating 12 and 10 distinct machine learning (ML) algorithms across 113 and 101 ML combinations to precisely diagnose stage 4 NB among all NB patients and to predict the prognosis of NB patients. Based on risk scores calculated by prognostic ISRS, patients were categorized into high and low-risk groups according to median risk score. We conducted comprehensive comparisons between two risk groups, in terms of clinical applications, immune microenvironment, somatic mutations, immunotherapy, chemotherapy and single-cell analysis. Ultimately, we empirically validated the differential expressions of two ISRS model genes, CAMTA2 and FOXD1, through immunochemistry staining. RESULTS: Through leave-one-out cross-validation, in both feature selection and model construction, we selected the random forest algorithm to diagnose stage 4 NB, and Enet algorithm to develop prognostic ISRS, due to their highest average C-index across five NB cohorts. After validations, the ISRS demonstrated a stable predictive capability, outperforming the previously published NB signatures and several clinic variables. We stratified NB patients into high and low-risk group based on median risk score, which showed the low-risk group with a superior survival outcome, an abundant immune infiltration, a decreased mutation landscape, and an enhanced sensitivity to immunotherapy. Single-cell analysis between two risk groups reveals biologically cellular variations underlying ISRS. Finally, we verified the significantly higher protein levels of CAMTA2 and FOXD1 in stage 4S NB, as well as their protective prognosis value in NB. CONCLUSION: Based on multi-omics data and ML algorithms, we successfully developed the ISRS to enable accurate diagnosis and prognostic stratification in NB, which shed light on molecular mechanisms of spontaneous regression and clinical utilization of ISRS.


Assuntos
Aprendizado de Máquina , Neuroblastoma , Humanos , Prognóstico , Fatores de Risco , Neuroblastoma/diagnóstico , Neuroblastoma/genética , Neuroblastoma/metabolismo , DNA , Microambiente Tumoral , Fatores de Transcrição Forkhead/metabolismo , Proteínas de Ligação ao Cálcio , Transativadores/metabolismo
4.
Nanomaterials (Basel) ; 14(4)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38392752

RESUMO

A tunable dual-band terahertz sensor based on graphene is proposed. The sensor consists of a metal bottom layer, a middle dielectric layer, and single-layer graphene patterned with four strips on the top. The numerical simulations results show that the proposed sensor exhibits two significant absorption peaks at 2.58 THz and 6.07 THz. The corresponding absorption rates are as high as nearly 100% and 98%, respectively. The corresponding quality factor (Q) value is 11.8 at 2.58 THz and 29.6 at 6.07 THz. By adjusting the external electric field or chemical doping of graphene, the positions of the dual-frequency resonance peak can be dynamically tuned. The excitation of plasma resonance in graphene can illustrate the mechanism of the sensor. To verify the practical application of the device, the terahertz response of different kinds and different thicknesses of the analyte is investigated and analyzed. A phenomenon of obvious frequency shifts of the two resonance peaks can be observed. Therefore, the proposed sensor has great potential applications in terahertz fields, such as material characterization, medical diagnosis, and environmental monitoring.

5.
Nanomaterials (Basel) ; 13(19)2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37836318

RESUMO

Zirconium-based metallic glass films are promising materials for nanoelectronic and biomedical applications, but their mechanical behavior under different conditions is not well understood. This study investigates the effects of radio frequency (RF) power and test temperature on the nanostructure, morphology, and creep behavior of Zr55Cu30Al10Ni5 metallic glass films prepared by RF magnetron sputtering. The films were characterized by X-ray diffraction and microscopy, and their mechanical properties were measured by a bulge test system. The results show that the films were amorphous and exhibited a transition from noncolumnar to columnar morphology as the RF power increased from 75 W to 125 W. The columnar morphology reduced the creep resistance, Young's modulus, residual stress, and hardness of the films. The creep behavior of the films was also influenced by the test temperature, with higher temperature leading to higher creep strain and lower creep stress. The findings of this study provide insights into the optimization of the sputtering parameters and the design of zirconium-based metallic glass films for various applications.

6.
Appl Opt ; 62(26): 6857-6863, 2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37707022

RESUMO

A multicarrier light source based on a recirculating frequency shift loop (RFSL) driven by a parity-time (PT)-symmetric optoelectronic oscillator (OEO) is proposed and experimentally demonstrated. The impact of the side-mode suppression ratio (SMSR) of the radio frequency (RF) signal on the multicarrier is studied for the first time, to our knowledge. The RFSL driven by PT-symmetric OEO significantly optimizes the phase noise and flatness of the multicarrier, facilitating the system miniaturization. In the experiment, a 10.019 GHz RF signal with a SMSR of 42 dB is generated with -98.63d B c/H z measured phase noise at 10 kHz offset frequency (actual phase noise should be lower than -122.87d B c/H z). Up to 120 subcarriers with 2.32 dB flatness are obtained successfully, covering the overall bandwidth of approximately 1.2 THz.

7.
Stem Cells Int ; 2023: 5537610, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37771550

RESUMO

Background: Long-term extensive use of glucocorticoids will lead to hormonal necrosis of the femoral head, and osteoblasts play an important role in the prevention of osteonecrosis. However, there is no complete cure for necrosis of the femoral head. Mesenchymal stem cell- (MSCs-) derived exosomes are widely used for the repair of various tissue lesions. Therefore, the aim of this study was to investigate the mechanism of dexamethasone- (DEX-) induced osteoblast apoptosis and the therapeutic effect of human umbilical cord MSC- (hucMSC-) derived exosome mimetic vesicles (EMVs) on osteoblast-induced apoptosis by DEX. Methods: The viability and apoptosis of primary MC3T3-E1 cells were determined by the Cell Counting Kit-8 (CCK-8), FITC-Annexin V/PI staining and immunoblot. The intracellular levels of reactive oxygen species (ROS) after DEX treatment were measured by 2', 7' -dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In this study, hucMSC-EMVs and N-acetyl-l-cysteine (NAC) were used as therapeutic measures. The expression of B-cell lymphoma 2-associated X, Bcl 2, HO-1, and nuclear factor erythroid-derived 2-like 2 and MAPK- signaling pathway in osteogenic cell MC3T3-E1 cells treated with Dex was analyzed by the immunoblotting. Results: DEX significantly induced osteoblasts MC3T3-E1 apoptosis and ROS accumulation. MAPK-signaling pathway was activated in MC3T3-E1 after DEX treatment. hucMSC-EMVs intervention significantly downregulated DEX-induced MAPK-signaling pathway activation and ROS accumulation. In addition, hucMSC-EMVs can reduce the apoptosis levels in osteoblast MC3T3-E1 cells induced by DEX. Conclusions: Our study confirmed that hucMSC-EMVs regulates MAPK-signaling pathway and ROS levels to inhibit DEX-induced osteoblast apoptosis.

8.
Dalton Trans ; 52(35): 12478-12489, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37602756

RESUMO

Ruthenium(II) polypyridyl complexes have drawn growing attention due to their photophysical properties and anticancer activity. Herein we report four ruthenium(II) polypyridyl complexes [(N^N)2RuII(L)]2+ (1-4, L = 4-anilinoquinazoline derivatives, N^N = bidentate ligands with bis-nitrogen donors) as multi-functional anticancer agents. The epidermal growth factor receptor (EGFR) is overexpressed in a broad range of cancer cells and related to many kinds of malignance. EGFR inhibitors, such as gefitinib and erlotinib, have been approved as clinical anticancer drugs. The EGFR-inhibiting 4-anilinoquinazoline ligands greatly enhanced the in vitro anticancer activity of these ruthenium(II) polypyridyl complexes against a series of human cancer cell lines compared to [Ru(bpy)2(phen)], but interestingly, these complexes were actually not potent EGFR inhibitors. Further mechanism studies revealed that upon irradiation with visible light, complexes 3 and 4 generated a high level of singlet oxygen (1O2), and their in vitro anticancer activities against human non-small-cell lung (A549), cervical (HeLa) and squamous (A431) cancer cells were significantly improved. Specifically, complex 3 displayed potent phototoxicity upon irradiation with blue light, of which the photo-toxicity indexes (PIs) against HeLa and A431 cells were 11 and 8.3, respectively. These complexes exhibited strong fluorescence emission at ca. 600 nm upon excitation at about 450 nm. A subcellular distribution study by fluorescence microscopy imaging and secondary ion mass spectrometry imaging (ToF-SIMS) demonstrated that complex 3 mainly localized at the cytoplasm and complex 4 mainly localized in the nuclei of cells. Competitive binding with ctDNA showed that complex 4 was more favorable to bind to the DNA minor groove than complex 3. These differences support that complex 3 possibly exerts its anticancer activities majorly by photo-induced 1O2 generation and complex 4 by binding to DNA.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Rutênio , Humanos , Ligantes , Luz , Receptores ErbB
9.
Appl Opt ; 62(12): 3100-3104, 2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37133156

RESUMO

In this paper, we propose a novel, to the best of our knowledge, method to our knowledge for generating and accurately measuring Nyquist pulse sequences with an ultra-low duty cycle of only 0.037, which breaks the limitations caused by the noise and bandwidth of the optical sampling oscilloscope (OSO) by using a narrow-bandwidth real-time oscilloscope (OSC) and an electrical spectrum analyzer (ESA). By this method, it is found that the bias point drift of the dual parallel Mach-Zehnder modulator (DPMZM) is the main cause of the distortion of the waveform. In addition, we increase the repetition rate of Nyquist pulse sequences by a factor of 16 by multiplexing the unmodulated Nyquist pulse sequences.

10.
Natl Sci Rev ; 10(6): nwad069, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37181085

RESUMO

With the aid of the newly developed 'Sunway' heterogeneous-architecture supercomputer, which has world-leading HPC (high-performance computer) capability, a series of high-resolution coupled Earth system models (SW-HRESMs) with up to 5 km of atmosphere and 3 km of ocean have been developed. These models can meet the needs of multiscale interaction studies with different computational costs. Here we describe the progress of SW-HRESMs development, with an overview of the major advancements made by the international Earth science community in HR-ESMs. We also show the preliminary results of SW-HRESMs with regard to capturing major weather-climate extremes in the atmosphere and ocean, stressing the importance of permitted clouds and ocean submesoscale eddies in modeling tropical cyclones and eddy-mean flow interactions, and paving the way for further model development to resolve finer scales with even higher resolution and more realistic physics. Finally, in addition to increasing model resolution, the development procedure for a non-hydrostatic cloud and ocean submesoscale resolved ESM is discussed, laying out the major scientific directions of such a huge modeling advancement.

11.
Opt Express ; 31(10): 15409-15422, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37157643

RESUMO

We investigate the role of external magnetic fields and linearly polarized pump light, especially when their directions are parallel or vertical, on the propagation of the fractional vector vortex beams (FVVBs) through a polarized atomic system. Herein, the different configurations of external magnetic fields lead to various optically polarized selective transmissions of FVVBs with different fractional topological charge α caused by the polarized atoms, which is theoretically demonstrated by the atomic density matrix visualization analysis and experimentally explored by Cesium atom vapor. Meanwhile, we find that the FVVBs-atom interaction is a vectorial process due to the different optical vector polarized states. In this interaction process, the atomic optically polarized selection property provides potential for the realization of the magnetic compass based on warm atoms. For the FVVBs, due to the rotational asymmetry of the intensity distribution, we can observe some transmitted light spots with unequal energy. Compared with the integer vector vortex beam, it is possible to obtain a more precise magnetic field direction by fitting the different "petal" spots of the FVVBs.

12.
Eur J Pharmacol ; 951: 175747, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37142086

RESUMO

Malignant rhabdoid tumor of the kidney (MRTK) has an inferior prognosis and is insensitive to radiotherapy and chemotherapy. Search for novel, potent medicinal agents is urgent. Herein, data on the gene expression and clinical characteristics of malignant rhabdoid tumors (MRT) were retrieved from the TARGET database. Prognosis-related genes were identified by differential analysis and one-way cox regression analysis, and prognosis-related signalling pathways were identified by enrichment analysis. The prognosis-related genes were imported into the Connectivity Map database for query, and BKM120 was predicted and screened as a potential therapeutic agent for MRTK. A combination of high-throughput RNA sequencing and Western blot verified that the PI3K/Akt signaling pathway is associated with MRTK prognosis and is overactivated in MRTK. Our results outlined that BKM120 inhibited the proliferation, migration, and invasion ability of G401 cells and induced apoptosis and cell cycle G0/G1 phase arrest. In vivo, BKM120 inhibited tumor growth and had no significant toxic side effects. Western blot and immunofluorescence results confirmed that BKM120 could reduce the expression of PI3K and p-AKT, critical proteins of the PI3K/Akt signaling pathway. BKM120 inhibits MRTK by inhibiting PI3K/Akt signalling pathway to induce apoptosis and cell cycle G0/G1 phase arrest, which is anticipated to give the clinical treatment of MRTK a new direction.


Assuntos
Neoplasias Renais , Tumor Rabdoide , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proliferação de Células , Tumor Rabdoide/tratamento farmacológico , Tumor Rabdoide/genética , Linhagem Celular Tumoral , Apoptose , Fase G1
13.
Cancers (Basel) ; 15(7)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37046682

RESUMO

Introduction: Neuroblastoma (NB) is one of the most common extracranial solid malignant tumors in children. The 5-year survival rate of high-risk or refractory NB is less than 50%. Therefore, developing new effective therapeutics for NB remains an urgent challenge. Materials and Methods: Based on the NB dataset TARGET-NBL in the TCGA database, the prognosis-related genes were analyzed using univariate cox regression (p < 0.01). The protein network interaction of prognostic genes was analyzed using STRING to obtain 150 hub genes with HR > 1 and 150 hub genes with HR < 1. The Connectivity Map database was used to predict a therapeutic drug: BI-D1870, a ribosomal S6 kinase inhibitor. The inhibitory effect of BI-D1870 on NB was investigated through in vivo and in vitro experiments, and its inhibitory mechanism was explored. Results: Both the in vivo and in vitro experiments showed that BI-D1870 could inhibit tumor proliferation and induce tumor apoptosis. Furthermore, we proved that BI-D1870 caused G2/M phase arrest and mitosis damage in cells. RNA-seq of cells showed that BI-D1870 may inhibit the growth of NB by inhibiting the PI3K-Akt-mTOR axis. Western blot and immunofluorescence testing showed that BI-D1870 inhibited the PI3K-Akt-mTORC1 signal pathway to regulate the phosphorylation of RPS6 and 4E BP1 proteins, inhibit protein translation, and inhibit microtubule formation, thus preventing mitotic proliferation and inducing apoptosis. Conclusions: This study provides strong support that BI-D1870 may be a potential adjuvant therapy for NB.

14.
Front Oncol ; 13: 1144269, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37056349

RESUMO

Background: Ribonucleotide reductase regulatory subunit M2 (RRM2) has been reported to be an oncogene in some malignant tumors, such as lung adenocarcinoma, oral squamous cell carcinoma, glioblastoma, and breast cancer. However, the clinical significance of RRM2 in hepatocellular carcinoma has been less studied. The aim of this study was to assess the importance of RRM2 in hepatocellular carcinoma (HCC) based on the Cancer Genome Atlas (TCGA) database. Methods: The RRM2 expression levels and clinical features were downloaded from the TCGA database. Immunohistochemistry results between tumor tissues and normal tissues were downloaded from the Proteinatlas database. Meanwhile, the expression levels of RRM2 in tumor and paraneoplastic tissues were further verified by qRT-PCR and Western Blotting. Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein-interactions (PPI) network were constructed to analyze RRM2-related downstream molecules. In addition, RRM2 expression-related pathways performed by gene set enrichment analysis (GSEA). Association analysis of RRM2 gene expression and immune infiltration was performed by single-sample GSEA (ssGSEA). Results: The RRM2 expression level in tumor tissues was higher than normal tissues (P <0.001). The elevated expression of RRM2 in HCC was significantly correlated with T stage (P <0.05), pathologic stage (P <0.05), tumor status (P <0.05), histologic grade (P<0.001), and AFP (P <0.001). HCC with higher RRM2 expression was positively associated with worse OS (overall survival), PFS (progression-free survival), and DSS (disease-specific survival). In the univariate analysis, the expression of RRM2, T stage, M stage, pathologic stage, and tumor status were negatively correlated with OS (P <0.05). Further analysis using multivariate Cox regression showed that tumor status (P<0.01) and RRM2 expression (P<0.05) were independent prognostic factors of OS in HCC. GO/KEGG analysis showed that the critical biological process (chromosome condensation and p53 signaling pathway) might be the possible function mechanism in promoting HCC. Moreover, GSEA showed that several pathways were enriched in RRM2 high-expression samples, including PD-1 signaling, cell cycle, P27 pathway, and T cell receptor signaling pathway. RRM2 was significantly correlated with the infiltration level of CD8 T cells, Cytotoxic cells, DCs, Neutrophils, NK cells, and T helper cells (P <0.05). Conclusion: Over-expression of RRM2 predict adverse prognosis and is correlated with immune infiltrates in HCC. RRM2 may be a significant molecular biomarker for HCC diagnosis and prognosis.

15.
Metabolites ; 13(3)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36984764

RESUMO

Understanding the renal region-specific metabolic alteration in different animal models of diabetic nephropathy (DN) is critical for uncovering the underlying mechanisms and for developing effective treatments. In the present study, spatially resolved metabolomics based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was used to compare the local metabolic changes in the kidneys of HFD/STZ-induced diabetic rats and db/db mice. As a result, a total of 67 and 59 discriminating metabolites were identified and visualized in the kidneys of the HFD/STZ-induced diabetic rats and db/db mice, respectively. The result showed that there were significant region-specific changes in the glycolysis, TCA cycle, lipid metabolism, carnitine metabolism, choline metabolism, and purine metabolism in both DN models. However, the regional levels of the ten metabolites, including glucose, AMP, eicosenoic acid, eicosapentaenoic acid, Phosphatidylserine (36:1), Phosphatidylserine (36:4), Phosphatidylethanolamine (34:1), Phosphatidylethanolamine (36:4), Phosphatidylcholine (34:2), Phosphatidylinositol (38:5) were changed in reversed directions, indicating significant differences in the local metabolic phenotypes of these two commonly used DN animal models. This study provides comprehensive and in-depth analysis of the differences in the tissue and molecular pathological features in diabetic kidney injury in HFD/STZ-induced diabetic rats and db/db mice.

16.
Front Chem ; 11: 1124229, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36923690

RESUMO

Composition analysis in wine is gaining increasing attention because it can provide information about the wine quality, source, and nutrition. In this work, in situ liquid secondary ion mass spectrometry (SIMS) was applied to 14 representative wines, including six wines manufactured by a manufacturer in Washington State, United States, four Cabernet Sauvignon wines, and four Chardonnay wines from other different manufacturers and locations. In situ liquid SIMS has the unique advantage of simultaneously examining both organic and inorganic compositions from liquid samples. Principal component analysis (PCA) of SIMS spectra showed that red and white wines can be clearly differentiated according to their aromatic and oxygen-contained organic species. Furthermore, the identities of different wines, especially the same variety of wines, can be enforced with a combination of both organic and inorganic species. Meanwhile, in situ liquid SIMS is sample-friendly, so liquid samples can be directly analyzed without any prior sample dilution or separation. Taken together, we demonstrate the great potential of in situ liquid SIMS in applications related to the molecular investigation of various liquid samples in food science.

17.
Eur J Pharmacol ; 952: 175523, 2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-36736526

RESUMO

Bladder outlet obstruction (BOO) can cause serious complications including kidney damage; nevertheless, there are currently no animal models for studying BOO-induced kidney damage. Mesenchymal stem cells (MSCs) are widely used in therapeutic studies of renal fibrosis. However, MSC-derived exosomes show improved safety profile and more controllable characteristics compared with those of MSCs. Herein, we established a kidney injury mouse model of partial bladder outlet obstruction (PBOO) and evaluated the effects of human umbilical cord MSC-derived exosomes (hucMSC-Exos) on PBOO-induced reflux kidney injury in this model. Exosomes were isolated from a hucMSC-conditioned medium, purified by ultracentrifugation, and examined. Living image was performed to indicate the distribution of hucMSC-Exos. The PBOO-treated mice interacted with PBS (phosphate-buffered saline) or hucMSC-Exos. Morphologic changes and expression of interstitial-fibrosis-related, cell proliferation and Wnt/ß-catenin signaling-pathway indices were evaluated. At 7 days after induction of PBOO, structural destruction of renal tubules was observed. Expression of the interstitial markers and the cellular-proliferation index increased significantly in the PBOO group compared with the control group. The isolated exosomes were 30-150 nm in diameter, showing a round shape and bilayer membrane structure with CD63, TSG101, Alix expressed, enriched in the kidney of the PBOO group. Administering hucMSC-Exos to post-PBOO mice reversed renal injury and suppressed expression of Wnt/ß-catenin signaling pathway-related proteins. hucMSC-Exos inhibited PBOO-induced kidney injury and cellular proliferation and suppressed the Wnt/ß-catenin signaling pathway. Our findings will spur the development of novel hucMSC-Exo-mediated therapies for treating patients with renal fibrosis.


Assuntos
Exossomos , Obstrução do Colo da Bexiga Urinária , Humanos , Camundongos , Animais , Via de Sinalização Wnt , beta Catenina/metabolismo , Exossomos/metabolismo , Fibrose , Túbulos Renais/metabolismo , Proliferação de Células
18.
Opt Express ; 31(3): 5113-5121, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36785462

RESUMO

In this paper, we present an analysis of the amplitude variations of the opto-magnetic resonance absorption signals obtained in a single-beam magnetometer driven by radially or azimuthally polarized light (RPL/APL). It is shown that optically polarized atoms driven by cylindrical vector beams obtained only the alignment of atomic multipole moments but not the orientation, which is in good agreement with our simulation and experimental results. In comparison with the plane polarized pump light fields, cylindrical vector beams with much more complete electric vector polarization distribution in the transverse plane, make it unlikely to create the "emptying state " (no-atom populated) among the ground-state Zeeman sublevels for any possible orientation of the applied static magnetic field. These characteristics of the RPL/APL lead to generally smaller atomic population difference and lower response intensity of the transmitted signal. The tensor decomposition of atomic polarized states and the evolution of atomic multipole moments with the sweeping radio frequency (RF) field offer the way to show the magnetic orientation sensitivity of the radially or azimuthally polarized probe light, which possess similar profiles as that of the linearly polarized light, only with a constant phase lag of about π/2 and obvious amplitude differences.

19.
Arch Biochem Biophys ; 734: 109497, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36574914

RESUMO

NFIC is a potent transcriptional factor involved in many physiological and pathological processes, including tumorigenesis. However, the role of NFIC1, the longest isoform of NFIC, in the progression of triple negative breast cancer (TNBC) remains elusive. Our study demonstrates that overexpression of NFIC1 inhibits the migration and invasion of TNBC MDA-MB-231 cells. NFIC1 regulates the expression of S100A2, and knockdown of S100A2 reverses the inhibitive effects of NFIC1 on the migration and invasion of MDA-MB-231 cells. Furthermore, knockdown of S100A2 activates the MEK/ERK signaling transduction pathway that is inhibited by NFIC1 overexperssion. Treatment with MEK/ERK pathway inhibitor, U0126, abolishes the effects of S100A2 knockdown. In addition, overexpression of NFIC1 in MDA-MB-231 cells increases the expression of epithelial markers and decreases the expression of mesenchymal markers, and these effects could also be reversed by knockdown of S100A2. Collectively, these results demonstrate that NFIC1 inhibits the Epithelial-mesenchymal transition (EMT) of MDA-MB-231 cells by regulating S100A2 expression, which suppress the activation of MEK/ERK pathway. Therefore, our study confirms the role of NFIC1 as a tumor repressor in TNBC, and reveals the molecular mechanism through which NFIC1 inhibits the migration and invasion of MDA-MB-231 cells.


Assuntos
Sistema de Sinalização das MAP Quinases , Neoplasias de Mama Triplo Negativas , Humanos , Células MDA-MB-231 , Proliferação de Células , Movimento Celular , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/farmacologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Fatores Quimiotáticos/metabolismo , Fatores Quimiotáticos/farmacologia , Proteínas S100/metabolismo , Proteínas S100/farmacologia
20.
J Proteome Res ; 22(1): 36-46, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36564034

RESUMO

Fatty aldehydes (FALs) are involved in various biological processes, and their abnormal metabolism is related to the occurrence and development of neurological diseases. Because of their low ionization efficiency, methods for in situ detection and mass spectrometry imaging (MSI) analysis of FALs remain underreported. On-tissue chemical tagging of hardly ionizable target analytes with easily ionized moieties can improve ionization efficiency and detection sensitivity in MSI experiments. In this study, an on-tissue chemical derivatization-air-flow-assisted desorption electrospray ionization-MSI method was developed to visualize FALs in the rat brain. The method showed high sensitivity and specificity, allowing the use of in situ high-resolution MS3 to identify FALs. The methodology was applied to investigate the region-specific distribution of FALs in the brains of control and diabetic encephalopathy (DE) rats. In DE rats, FALs were found to be significantly enriched in various brain regions, especially in the cerebral cortex, hippocampus, and amygdala. Thus, increased FAL levels and oxidative stress occurred in a region-dependent manner, which may contribute to cognitive function deficits in DE. In summary, we provide a novel method for the in situ detection of FALs in biological tissues as well as new insights into the potential pathogenesis of DE.


Assuntos
Diabetes Mellitus , Espectrometria de Massas por Ionização por Electrospray , Ratos , Animais , Espectrometria de Massas por Ionização por Electrospray/métodos , Aldeídos , Encéfalo/diagnóstico por imagem , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
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