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1.
J Am Chem Soc ; 146(9): 6157-6167, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38393979

RESUMO

Fluorine electron-nuclear double resonance (19F ENDOR) has recently emerged as a valuable tool in structural biology for distance determination between F atoms and a paramagnetic center, either intrinsic or conjugated to a biomolecule via spin labeling. Such measurements allow access to distances too short to be measured by double electron-electron resonance (DEER). To further extend the accessible distance range, we exploit the high-spin properties of Gd(III) and focus on transitions other than the central transition (|-1/2⟩ ↔ |+1/2⟩), that become more populated at high magnetic fields and low temperatures. This increases the spectral resolution up to ca. 7 times, thus raising the long-distance limit of 19F ENDOR almost 2-fold. We first demonstrate this on a model fluorine-containing Gd(III) complex with a well-resolved 19F spectrum in conventional central transition measurements and show quantitative agreement between the experimental spectra and theoretical predictions. We then validate our approach on two proteins labeled with 19F and Gd(III), in which the Gd-F distance is too long to produce a well-resolved 19F ENDOR doublet when measured at the central transition. By focusing on the |-5/2⟩ ↔ |-3/2⟩ and |-7/2⟩ ↔ |-5/2⟩ EPR transitions, a resolution enhancement of 4.5- and 7-fold was obtained, respectively. We also present data analysis strategies to handle contributions of different electron spin manifolds to the ENDOR spectrum. Our new extended 19F ENDOR approach may be applicable to Gd-F distances as large as 20 Å, widening the current ENDOR distance window.


Assuntos
Elétrons , Flúor , Espectroscopia de Ressonância de Spin Eletrônica , Proteínas/química , Marcadores de Spin
2.
Nano Lett ; 23(2): 710-717, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36626837

RESUMO

Charge transfer plays a key role at the interfaces of heterostructures, which can affect electronic structures and ultimately the physical properties of the materials. However, charge transfer is difficult to manipulate externally once the interface is formed. The recently discovered van der Waals ferromagnets with atomically sharp interfaces provided a perfect platform for the electrical control of interfacial charge transfer. Here, we report magnetoresistance experiments revealing electrically tunable charge transfer in Fe3GeTe2/Cr2Ge2Te6/Fe3GeTe2 all-magnetic van der Waals heterostructures, which can be exploited to selectively modify the switching fields of the top or bottom Fe3GeTe2 electrodes. The directional charge transfer from metallic Fe3GeTe2 to semiconducting Cr2Ge2Te6 is revealed by first-principles calculations, which remarkably modifies the magnetic anisotropy energy of Fe3GeTe2, leading to the dramatically suppressed coercivity. The electrically selective control of magnetism demonstrated in this study could stimulate the development of spintronic devices based on van der Waals magnets.

3.
J Am Chem Soc ; 145(8): 4564-4569, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36786809

RESUMO

In structural studies by NMR, pseudocontact shifts (PCSs) provide both angular and distance information. For proteins, incorporation of a di-histidine (diHis) motif, coordinated to Co2+, has emerged as an important tool to measure PCS. Here, we show that using different Co(II)-chelating ligands, such as nitrilotriacetic acid (NTA) and iminodiacetic acid (IDA), resolves the isosurface ambiguity of Co2+-diHis and yields orthogonal PCS data sets with different Δχ-tensors for the same diHis-bearing protein. Importantly, such capping ligands effectively eliminate undesired intermolecular interactions, which can be detrimental to PCS studies. Devising and employing ligand-capping strategies afford versatile and powerful means to obtain multiple orthogonal PCS data sets, significantly extending the use of the diHis motif for structural studies by NMR.

4.
Mol Cancer ; 22(1): 61, 2023 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-36966306

RESUMO

Kidney, bladder, and prostate cancer are the three major tumor types of the urologic system that seriously threaten human health. Circular RNAs (CircRNAs), special non-coding RNAs with a stabile structure and a unique back-splicing loop-forming ability, have received recent scientific attention. CircRNAs are widely distributed within the body, with important biologic functions such as sponges for microRNAs, as RNA binding proteins, and as templates for regulation of transcription and protein translation. The abnormal expression of circRNAs in vivo is significantly associated with the development of urologic tumors. CircRNAs have now emerged as potential biomarkers for the diagnosis and prognosis of urologic tumors, as well as targets for the development of new therapies. Although we have gained a better understanding of circRNA, there are still many questions to be answered. In this review, we summarize the properties of circRNAs and detail their function, focusing on the effects of circRNA on proliferation, metastasis, apoptosis, metabolism, and drug resistance in kidney, bladder, and prostate cancers.


Assuntos
MicroRNAs , Neoplasias Urológicas , Humanos , RNA Circular/genética , RNA Circular/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores/metabolismo , Biossíntese de Proteínas , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/genética
5.
Int J Cancer ; 152(1): 66-78, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35579992

RESUMO

In clear cell renal cell carcinoma (ccRCC), glycolysis is enhanced mainly because of the increased expression of key enzymes in glycolysis. Hence, the discovery of new molecular biomarkers for glycolysis may help guide and establish a precise system of diagnosis and treatment for ccRCC. Expression profiles of 1079 tumor samples of ccRCC patients (including 311 patients treated with everolimus or nivolumab) were downloaded from public databases. Proteomic profiles of 232 ccRCC samples were obtained from Fudan University Shanghai Cancer Center (FUSCC). Biological changes, tumor microenvironment and prognostic differences were explored between samples with various glycolysis characteristics. There were significant differences in CD8+ effector T cells, epithelial-to-mesenchymal transition and pan-fibroblast TGFb between the Low and High glyScore groups. The tumor mutation burden of the Low glyScore group was lower than that of the High glyScore group. And higher glyScore was significantly associated with worse overall survival (OS) in 768 ccRCC patients (P < .0001). External validation in FUSCC cohort also indicated that glyScore was of strong ability for predicting OS (P < .05). GlyScore may serve as a biomarker for predicting everolimus response in ccRCC patients due to its significant associations with progression-free survival (PFS). And glyScore may also predict overall survival in patients treated with nivolumab. We calculated the glyScore in ccRCC and the defined glyScore was of strong ability for predicting OS. In addition, glyScore may also serve as a biomarker for predicting PFS in patients treated with everolimus and could predict OS in patients treated with nivolumab.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/diagnóstico , Nivolumabe , Everolimo/uso terapêutico , Proteômica , China , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Glicólise , Microambiente Tumoral
6.
Funct Integr Genomics ; 23(4): 340, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37982895

RESUMO

This study aimed to elucidate the roles of cilia- and flagella-associated protein 61 (CFAP61) in male infertility and its underlying mechanisms. CFAP61 expression levels in the testicular tissues of male patients with infertility were determined using quantitative real-time polymerase chain reaction, immunohistochemical assay, and western blotting. Moreover, the specific roles of CFAP61 in male infertility were evaluated using cell counting kit-8, 5-ethynyl-2'-deoxyuridine, flow cytometry, and enzyme-linked immunosorbent assays. Here, CFAP61 was expressed at low levels in the testicular tissues of male patients with infertility. Functionally, CFAP61 knockdown reduced the Leydig cell viability and testosterone secretion and enhanced apoptosis. A mechanistic study further revealed that silencing CFAP61 promoted the expression levels of mitogen-activated protein kinase (MAPK)/cyclooxygenase-2 (COX-2) signaling pathway-related proteins (p-extracellular signal-regulated kinase (p-ERK), p-c-Jun N-terminal kinase (p-JNK), p-P38, and COX-2). In conclusion, CFAP61 knockdown facilitated male infertility by suppressing Leydig cell viability and testosterone secretion and enhanced cell apoptosis by activating the MAPK/COX-2 pathway. Our data suggest CFAP61 as a potential therapeutic target for male infertility.


Assuntos
Cílios , Infertilidade Masculina , Humanos , Masculino , Ciclo-Oxigenase 2/genética , Células Intersticiais do Testículo , Flagelos , Infertilidade Masculina/genética , Testosterona
7.
Nano Lett ; 22(7): 2618-2626, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35364813

RESUMO

Atmospheric water harvesting (AWH) has received tremendous interest because of population growth, limited freshwater resources, and water pollution. However, key challenges remain in developing efficient, flexible, and lightweight AWH materials with scalability. Here, we demonstrated a radiative cooling fabric for AWH via its hierarchically structured cellulose network and hybrid sorption-dewing mechanisms. With 8.3% solar absorption and ∼0.9 infrared (IR) emissivity, the material can drop up to 7.5 °C below ambient temperature without energy consumption via radiative cooling. Water adsorption onto the hydrophilic functional groups of cellulose is dominated by sorption at low relative humidity (RH) and dewing at high RH. The cellulose network provides desirable mechanical properties with entangled high-aspect-ratio fibers over tens of adsorption-extraction cycles. In the field test, the cellulose sample exhibited water uptake of 1.29 kg/kg at 80% RH during the night. The profusion of radiative cooling fabric features desirable cost effectiveness and allows fast deployment into large-scale AWH applications.


Assuntos
Celulose , Água , Temperatura Baixa , Transição de Fase , Têxteis
8.
Angew Chem Int Ed Engl ; 62(20): e202218780, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-36905181

RESUMO

Studies of protein structure and dynamics are usually carried out in dilute buffer solutions, conditions that differ significantly from the crowded environment in the cell. The double electron-electron resonance (DEER) technique can track proteins' conformations in the cell by providing distance distributions between two attached spin labels. This technique, however, cannot access distances below 1.8 nm. Here, we show that GdIII -19 F Mims electron-nuclear double resonance (ENDOR) measurements can cover part of this short range. Low temperature solution and in-cell ENDOR measurements, complemented with room temperature solution and in-cell GdIII -19 F PRE (paramagnetic relaxation enhancement) NMR measurements, were performed on fluorinated GB1 and ubiquitin (Ub), spin-labeled with rigid GdIII tags. The proteins were delivered into human cells via electroporation. The solution and in-cell derived GdIII -19 F distances were essentially identical and lie in the 1-1.5 nm range revealing that both, GB1 and Ub, retained their overall structure in the GdIII and 19 F regions in the cell.


Assuntos
Elétrons , Gadolínio , Humanos , Espectroscopia de Ressonância de Spin Eletrônica , Gadolínio/química , Proteínas/química , Marcadores de Spin , Ubiquitina , Flúor/química
9.
Anal Chem ; 94(26): 9399-9406, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35715196

RESUMO

Chiral analysis is of significant importance for living organisms since chirality is the fundamental phenomenon in nature. In this work, a bifunctional electrochemiluminescent (ECL) platform is constructed for chiral discrimination and chiral sensing. 3-Mercaptopropionic acid-functionalized CdSe quantum dots (CdSe QDs) are combined with aminated TiO2 nanotubes (NH2-TiNTs) via amidation. The resultant CdSe QDs/TiNTs display significantly enhanced ECL signals due to the synergistic effect between CdSe QDs and TiNTs, which are then used for the chiral discrimination of the isomers of nine chiral amino acids (AAs) in the presence of d-AA oxidase (DAAO). DAAO can selectively catalyze the oxidation of d-AAs to generate H2O2, which acts as the coreaction reagent and triggers the ECL signals of CdSe QDs/TiNTs, and thus, the isomers of the nine chiral AAs can be effectively discriminated. In addition, the as-constructed ECL platform can also be used for the sensitive detection of d-AAs in the presence of DAAO with a wide linear range and a low limit of detection. These findings suggest that the CdSe QDs/TiNTs can work as a bifunctional ECL platform (chiral discrimination and chiral sensing), which might be an advanced ECL platform for biomedical applications.


Assuntos
Compostos de Cádmio , Nanotubos , Pontos Quânticos , Compostos de Selênio , Compostos de Cádmio/química , Peróxido de Hidrogênio , Medições Luminescentes , Pontos Quânticos/química , Compostos de Selênio/química , Titânio
10.
Environ Res ; 211: 112956, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35218711

RESUMO

Human health is being threatened by the ever-increasing water pollution. Sulfate radical (SO4•-)-based advanced oxidation processes (SR-AOPs) are rapidly being developed and gaining considerable attention due to their high oxidation potential and selectivity as a way to purify water by degrading organic contaminants in it. Among the catalytic materials that can activate the precursor to generate SO4•-, metal-organic frameworks (MOFs) are the most promising heterogeneous catalytic material in SR-AOPs because of their various structure possibilities, large surface area, ordered porous structure, and regular activation sites. Herein, an in-depth overview of MOFs and their derivatives for water purification with SR-AOPs is provided. The latest studies on pristine MOFs, MOF composites, and MOF derivatives (metal oxides, metal-carbon hybrids, and carbon materials) are summarized. The mechanisms of decomposition of pollutants in water via radical and non-radical pathways are also discussed. This review suggests future research directions for water purification through MOF-based SR-AOP.


Assuntos
Estruturas Metalorgânicas , Purificação da Água , Carbono , Humanos , Sulfatos
11.
Environ Res ; 205: 112417, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34856164

RESUMO

Sulfate radical (SO4•-)-based advanced oxidation processes (SR-AOPs) have recently attracted much attention due to their potential in degrading organic pollutants. Metal-organic frameworks (MOFs) have been reported as effective materials to generate SO4•-. However, it is challenging to separate and recover the dispersed MOF particles from the reaction solution when MOFs are used alone. We used cellulose nanofibers (CNFs) as a porous filter template to immobilize Zn-based MOF, zeolitic imidazolate framework-8 (ZIF-8), and obtained a catalytic composite membrane having peroxymonosulfate (PMS) activating function to produce SO4•-. The CNF was effective in holding ZIF-8 nanoparticle and making a durable porous filter. The activated PMS-produced •OH and SO4•- radicals from ZIF-8 play an important role in the catalytic reaction. More than 90% of methylene blue and rhodamine B was degraded by ZIF-8/CNFs composite membrane in the PMS environment within 60 min. The ZIF-8/CNFs catalytic filters can be used several times without performance reduction for organic dye degradation. The results show that ZIF-8/CNFs catalytic membrane can be separated from organic pollution system quickly and used for the efficient separation and recovery of MOF particle-based catalytic materials. Therefore, this study provides a new perspective for fabricating the MOFs particles-immobilized catalytic filter by biomass nanocellulose-based materials for water purification. This method can be used for facile fabrication of the cellulose-based porous functional filter and open diverse applications.


Assuntos
Estruturas Metalorgânicas , Purificação da Água , Catálise , Oxirredução , Zinco
12.
Angew Chem Int Ed Engl ; 61(23): e202201097, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35278268

RESUMO

In-cell NMR spectroscopy is a powerful tool to investigate protein behavior in physiologically relevant environments. Although proven valuable for disordered proteins, we show that in commonly used 1 H-15 N HSQC spectra of globular proteins, interactions with cellular components often broaden resonances beyond detection. This contrasts 19 F spectra in mammalian cells, in which signals are readily observed. Using several proteins, we demonstrate that surface charges and interaction with cellular binding partners modulate linewidths and resonance frequencies. Importantly, we establish that 19 F paramagnetic relaxation enhancements using stable, rigid Ln(III) chelate pendants, attached via non-reducible thioether bonds, provide an effective means to obtain accurate distances for assessing protein conformations in the cellular milieu.


Assuntos
Mamíferos , Proteínas , Animais , Espectroscopia de Ressonância Magnética/métodos , Ressonância Magnética Nuclear Biomolecular/métodos , Conformação Proteica , Proteínas/química
13.
J Cell Mol Med ; 25(9): 4326-4339, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33797188

RESUMO

Bladder cancer (BLCA) is one of the most common urological cancer with increasing cases and deaths every year. In the present study, we aim to construct an immune-related prognostic lncRNA signature (IRPLS) in bladder cancer (BLCA) patients and explore its immunogenomic implications in pan-cancers. First, the immune-related differentially expressed lncRNAs (IRDELs) were identified by 'limma' R package and the score of IRPLS in every patient were evaluated by Cox regression. The dysregulation of IRDELs expression between cancer and para-cancer normal tissues was validated through RT-qPCR. Then, we further explore the biological functions of a novel lncRNA from IRPLS, RP11-89 in BLCA using CCK8 assay, Transwell assay and Apoptosis analysis, which indicated that RP11-89 was able to promote cell proliferation and invasive capacity while inhibits cell apoptosis in BLCA. In addition, we performed bioinformatic methods and RIP to investigate and validate the RP11-89/miR-27a-3p/PPARγ pathway in order to explore the mechanism. Next, CIBERSORT and ESTIMATE algorithm were used to evaluate abundance of tumour-infiltrating immune cells and scores of tumour environment elements in BLCA with different level of IRPLS risk scores. Finally, multiple bioinformatic methods were performed to show us the immune landscape of these four lncRNAs for pan-cancers. In conclusion, this study first constructed an immune-related prognostic lncRNA signature, which consists of RP11-89, PSORS1C3, LINC02672 and MIR100HG and might shed lights on novel targets for individualized immunotherapy for BLCA patients.


Assuntos
Biomarcadores Tumorais/genética , RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/patologia , Idoso , Biomarcadores Tumorais/imunologia , Biologia Computacional , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Curva ROC , Fatores de Risco , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/imunologia
14.
Nanotechnology ; 32(39)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34161927

RESUMO

Ferroptosis as an iron-dependent lipid peroxidation process causes sevely oxidative damage of cell, but lack of highly efficient and recycable antioxidant agents. To this end, cerium doped carbon dots (Ce-doped CDs) with radical scavenging activity were synthesized using a simple microwave-assisted hydrothermal carbonization. The resultant Ce-doped CDs exhibited an ultra-small size of only approximately 2.6 nm, excellent dispersion in water as well as optical performance. Taking advantage of inherent ultra-small size, Ce-doped CDs were endowed with high Ce3+/Ce4+ratio, which significantly enhanced their radical scavenging activity. Meanwhile, the Ce-doped CDs with superior biocompatibility could enter cells quickly and then localized in the cytoplasm. As we expected, the Ce-doped CDs strongly protected cells from oxidative damage of erastin-mediated ferroptosis. These findings suggest that the as-prepared Ce-doped CDs have the potential to be antioxidant drugs against for ferroptosis-induced oxidative damage.


Assuntos
Cério , Ferroptose/efeitos dos fármacos , Sequestradores de Radicais Livres , Estresse Oxidativo/efeitos dos fármacos , Pontos Quânticos/química , Animais , Carbono/química , Carbono/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cério/química , Cério/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Humanos , Camundongos , Células NIH 3T3
15.
J Cell Mol Med ; 24(16): 9012-9027, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32567187

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most common and highly malignant pathological type of kidney cancer. We sought to establish a metabolic signature to improve post-operative risk stratification and identify novel targets in the prediction models for ccRCC patients. A total of 58 metabolic differential expressed genes (MDEGs) were identified with significant prognostic value. LASSO regression analysis constructed 20-mRNA signatures models, metabolic prediction models (MPMs), in ccRCC patients from two cohorts. Risk score of MPMs significantly predicts prognosis for ccRCC patients in TCGA (P < 0.001, HR = 3.131, AUC = 0.768) and CPTAC cohorts (P = 0.046, HR = 2.893, AUC = 0.777). In addition, G6PC, a hub gene in PPI network of MPMs, shows significantly prognostic value in 718 ccRCC patients from multiply cohorts. Next, G6Pase was detected high expressed in normal kidney tissues than ccRCC tissues. It suggested that low G6Pase expression significantly correlated with poor prognosis (P < 0.0001, HR = 0.316) and aggressive progression (P < 0.0001, HR = 0.414) in 322 ccRCC patients from FUSCC cohort. Meanwhile, promoter methylation level of G6PC was significantly higher in ccRCC samples with aggressive progression status. G6PC significantly participates in abnormal immune infiltration of ccRCC microenvironment, showing significantly negative association with check-point immune signatures, dendritic cells, Th1 cells, etc. In conclusion, this study first provided the opportunity to comprehensively elucidate the prognostic MDEGs landscape, established novel prognostic model MPMs using large-scale ccRCC transcriptome data and identified G6PC as potential prognostic target in 1,040 ccRCC patients from multiply cohorts. These finding could assist in managing risk assessment and shed valuable insights into treatment strategies of ccRCC.


Assuntos
Carcinoma de Células Renais/genética , Glucose-6-Fosfatase/genética , Neoplasias Renais/genética , Transcriptoma/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Estudos de Coortes , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Rim/patologia , Neoplasias Renais/patologia , Masculino , Prognóstico , Microambiente Tumoral/imunologia
16.
J Cell Biochem ; 121(2): 1552-1562, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31512789

RESUMO

OBJECTIVE: Serine palmitoyltransferase, long chain base subunit 1 (SPTLC1) catalyzes the first step in sphingolipid synthesis and has been implicated in the progression of various cancers. However, its role in clear cell renal cell carcinoma (ccRCC) remains unclear. Here, we investigated the expression and prognostic value of SPTLC1 in ccRCC. METHODS: Three ccRCC patient cohorts were studied. ccRCC and adjacent normal kidney tissue samples were obtained from 183 patients at the Fudan University Shanghai Cancer Center (FUSCC) and subjected to immunohistochemical staining and quantitative reverse-transcription polymerase chain reaction to evaluate SPTLC1 protein and messenger RNA (mRNA) expression. Two validation cohorts consisting of mRNA and clinicopathological data sets from patients with ccRCC were obtained from the Cancer Genome Atlas (TCGA, n = 429) and Oncomine (n = 178) databases. Associations between low and high SPTLC1 mRNA and protein expression and survival were evaluated using the Kaplan-Meier method and log-rank test. Independent prognostic factors were identified using univariate and multivariate Cox regression analysis. RESULTS: SPTLC1 mRNA or protein were expressed at significantly lower levels in ccRCC tissues compared with normal kidney tissues in all three patient cohorts (P < .001). Low SPTLC1 expression was significantly associated with shorter overall survival in the FUSCC (P = .041) and Oncomine (P < .001) cohorts, and was significantly associated with shorter overall survival (P < .0001) and progression-free survival (P < .001) in the TCGA cohort. Bioinformatics analysis identified 10 genes significantly coregulated with SPTLC1 in ccRCC, most of which contributed to sphingomyelin metabolism (SPTLC2, SPTLC3, SPTSSA, SPTSSB, ORMDL1, ORMDL2, ORMDL3, ZDHHC9, GOLGA7B, and KDSR). Functional enrichment analysis predicted that SPTLC1 and its network play significant roles in inflammatory, hypoxia, and interferon gamma responses, and in allograft rejection pathways. CONCLUSION: Low SPTLC1 expression is significantly associated with disease progression and poor survival in patients with ccRCC, suggesting that SPTLC1 may function as a tumor suppressor. Thus, SPTLC1 could be a potential new biomarker and/or therapeutic target for ccRCC.


Assuntos
Carcinoma de Células Renais , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais , Proteínas de Neoplasias/biossíntese , Serina C-Palmitoiltransferase/biossíntese , Carcinoma de Células Renais/enzimologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Bases de Dados de Ácidos Nucleicos , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/enzimologia , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Masculino , Proteínas de Neoplasias/genética , Serina C-Palmitoiltransferase/genética , Taxa de Sobrevida
17.
Prostate ; 80(12): 950-961, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32648618

RESUMO

BACKGROUND: Prostate cancer is characterized by aberrant lipid metabolism, including elevated fatty acid oxidation. Carnitine palmitoyltransferase 1B (CPT1B) catalyzes the rate-limiting step of fatty acid oxidation. This study aimed to determine if CPT1B has a critical role in prostate cancer progression and to identify its regulatory mechanism. METHODS: CPT1B expression data from The Cancer Genome Atlas and Gene Expression Omnibus databases was compared with patient survival data. A tissue microarray was constructed with 60 samples of prostate cancer and immunohistochemically stained for CPT1B. Castration-resistant prostate cancer (CRPC) cell lines 22RV1 and C4-2 in which CPT1B expression had been stably knocked down were established; and cell proliferation, cell cycle distribution, and invasion were investigated by Cell Counting Kit-8 (CCK-8) and colony formation assays, flow cytometry, and Transwell assays, respectively. To examine the impact of androgen receptor (AR) inhibition on CPT1B expression, JASPAR CORE was searched to identify AR-binding sites in CPT1B. Dual luciferase and ChIP assays were performed to confirm CPT1B activity and AR binding, respectively. Differentially expressed genes (DEGs) in prostate cancer underwent gene set enrichment analysis (GSEA). Enzalutamide-resistant C4-2 cells were generated and the mechanism of enzalutamide resistance and downstream signaling pathway changes of CPT1B to C4-2 was explored through CCK-8 test. RESULTS: CPT1B expression was upregulated in human prostate cancer compared with normal prostate tissue and was associated with poor disease-free survival and overall survival. Silencing of CPT1B resulted in downregulated cell proliferation, reduced S-phase distribution, and lower invasive ability, whereas the opposite was observed in CRPC cells overexpressing CPTB1. DEGS in prostate cancer were correlated with G-protein-coupled receptor signaling, molecular transducer activity, and calcium ion binding. AR may regulate CPT1B expression and activity via specific binding sites, as confirmed by dual luciferase and ChIP assays. The CCK-8 experiment demonstrated that CPT1B overexpression in C4-2 cells did not significantly increase the ability of enzalutamide resistance. However, overexpression of CPT1B in C4-2R cells significantly increased the enzalutamide resistance. Upregulation of CPT1B expression increased AKT expression and phosphorylation. CONCLUSIONS: CPT1B is upregulated in prostate cancer and is correlated with poor prognosis, indicating its potential as a biomarker. AR inhibits the transcription of CPT1B. In the CRPC cell line, overexpression of CPT1B alone cannot promote enzalutamide resistance, but in the drug-resistant line C4-2R, overexpression of CPT1B can promote the resistance of C4-2R to enzalutamide.


Assuntos
Carnitina O-Palmitoiltransferase/antagonistas & inibidores , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/enzimologia , Benzamidas , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Estudos de Casos e Controles , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Terapia de Alvo Molecular , Nitrilas , Feniltioidantoína/farmacologia , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Androgênicos/biossíntese , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Transdução de Sinais
18.
Environ Res ; 191: 110228, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32950517

RESUMO

Membrane fouling has become the one of main obstacles for the widespread application of membrane technology in water treatment processes. Coagulation as pretreatment is proven to be effective for the alleviation of membrane fouling. In this study, the influence of humic acid (HA)/sodium alginate (SA) fractions in the structure and resistance of cake layer on the membrane surface was investigated. The presence of SA at an appropriate fraction could facilitate the formation of large and loosely branched flocs and thereby form a more permeable cake layer on the membrane surface due to good bridging and charge neutralization abilities of SA molecules. The particle image velocimetry (PIV) technique was employed for monitoring the dynamic formation process of cake layer under different HA/SA fractions. The cake layer with a higher thickness was observed to be rapidly formed on the membrane surface at the presence of SA in water. According to the theoretical analysis, the membrane fouling in coagulation-ultrafiltration (UF) combined system demonstrated to be highly dependent on the size and intra-porosity of flocs. The fractal dimension of flocs might have an impact on the resistance of cake layer through affecting the porosity of aggregated flocs. The SA molecules could be used as the coagulant aid for effective alleviation of membrane fouling and the improvement of filtration performance in a coagulation-UF combined system.


Assuntos
Ultrafiltração , Purificação da Água , Alginatos , Substâncias Húmicas/análise , Membranas Artificiais
20.
Small Methods ; : e2400236, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38697925

RESUMO

The chemical/physical properties and reliable performance of nanoporous materials are strongly influenced by the particle size and corresponding distribution. Among many types of MOFs, ZIF-8, is still widely used and many studies have been conducted to control the particle size and uniformity of ZIF-8 using surfactants and organic solvents. However, the use of surfactants and organic solvents process is expensive and may cause environmental pollution. For the first time, in this paper, a surfactant-free, size-controllable, and scalable green synthesis method of ZIF-8 particles is reported using four reaction parameters (temperature, concentration, pouring time, and reactant ratio) that affect the formation of nuclei and growth of ZIF-8 crystals. The as-synthesized ZIF-8 nanoparticles show great uniformity and controllable particle sizes in the wide range of 147-915 nm. In addition, a 2 L large-scale synthesis of ZIF-8 with narrow size distribution is developed by finely tuned particle size in water without any additives. To demonstrate the efficient utilization of nanopores according to the particle size and size distribution, an adsorption test is conducted on the ZIF-8 nanoparticles. This study will support the synthesis of size-controlled ZIF-8 with narrow size distribution and their composites for achieving high performance in the emerging applications.

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