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1.
J Cell Mol Med ; 28(1): e18044, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38140764

RESUMO

Breast cancer is the most prevalent cancer worldwide and its incidence increases with age, posing a significant threat to women's health globally. Due to the clinical heterogeneity of breast cancer, the majority of patients develop drug resistance and metastasis following treatment. Ferroptosis, a form of programmed cell death dependent on iron, is characterized by the accumulation of lipid peroxides, elevated levels of iron ions and lipid peroxidation. The underlying mechanisms and signalling pathways associated with ferroptosis are intricate and interconnected, involving various proteins and enzymes such as the cystine/glutamate antiporter, glutathione peroxidase 4, ferroptosis inhibitor 1 and dihydroorotate dehydrogenase. Consequently, emerging research suggests that ferroptosis may offer a novel target for breast cancer treatment; however, the mechanisms of ferroptosis in breast cancer urgently require resolution. Additionally, certain natural compounds have been reported to induce ferroptosis, thereby interfering with breast cancer. Therefore, this review not only discusses the molecular mechanisms of multiple signalling pathways that mediate ferroptosis in breast cancer (including metastasis, invasion and proliferation) but also elaborates on the mechanisms by which natural compounds induce ferroptosis in breast cancer. Furthermore, this review summarizes potential compound types that may serve as ferroptosis inducers in future tumour cells, providing lead compounds for the development of ferroptosis-inducing agents. Last, this review proposes the potential synergy of combining natural compounds with traditional breast cancer drugs in the treatment of breast cancer, thereby suggesting future directions and offering new insights.


Assuntos
Neoplasias da Mama , Ferroptose , Humanos , Feminino , Apoptose , Ácido Glutâmico , Ferro , Peroxidação de Lipídeos
2.
Small ; : e2406485, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39314022

RESUMO

The rational design of S-scheme photocatalysts, achieved by serially integrating two different semiconductors, represents a promising strategy for efficient charge separation and amplified photocatalytic performance, yet it remains a challenge. Herein, ZnIn2S4 (ZIS) and oxygen-doped ZnIn2S4 (O-ZIS) nanosheets are chosen to construct a homojunction catalyst architecture. Theoretical simulations alongside comprehensive in situ and ex situ characterizations confirm that ZIS and O-ZIS with noncentrosymmetric layered structures can generate a polarization-induced bulk-internal electric field (IEF) within the crystal. A robust interface-IEF is also created by the strong interfacial interaction between O-ZIS and ZIS with different work functions. Owing to these features, the O-ZIS/ZIS homojunction adopts an S-scheme directional charge transfer route, wherein photoexcited electrons in ZIS and holes in O-ZIS concurrently migrate to their interface and subsequently recombine. This enables spatial charge separation and provides a high driving force for both reduction and oxidation reactions simultaneously. Consequently, such photocatalyst exhibits an H2 evolution rate up to 142.9 µmol h-1 without any cocatalysts, which is 4.6- and 3.4-fold higher than that of pristine ZIS and O-ZIS, respectively. Benzaldehyde is also produced as a value-added oxidation product with a rate of 146.9 µmol h-1. This work offers a new perspective on the design of S-scheme systems.

3.
Small ; : e2400686, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864439

RESUMO

High-performance energy storage dielectrics capable of low/moderate field operation are vital in advanced electrical and electronic systems. However, in contrast to achievements in enhancing recoverable energy density (Wrec), the active realization of superior Wrec and energy efficiency (η) with giant energy-storage coefficient (Wrec/E) in low/moderate electric field (E) regions is much more challenging for dielectric materials. Herein, lead-free relaxor ferroelectrics are reported with giant Wrec/E designed with polymorphic heterogeneous polar structure. Following the guidance of Landau phenomenological theory and rational composition construction, the conceived (Bi0.5Na0.5)TiO3-based ternary solid solution that delivers giant Wrec/E of ≈0.0168 µC cm-2, high Wrec of ≈4.71 J cm-3 and high η of ≈93% under low E of 280 kV cm-1, accompanied by great stabilities against temperature/frequency/cycling number and excellent charging-discharging properties, which is ahead of most currently reported lead-free energy storage bulk ceramics measured at same E range. Atomistic observations reveal that the correlated coexisting local rhombohedral-tetragonal polar nanoregions embedded in the cubic matrix are constructed, which enables high polarization, minimized hysteresis, and significantly delayed polarization saturation concurrently, endowing giant Wrec/E along with high Wrec and η. These findings advance the superiority and feasibility of polymorphic nanodomains in designing highly efficient capacitors for low/moderate field-region practical applications.

4.
Small ; 20(31): e2400617, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38441279

RESUMO

Photocatalytic lignocellulose reforming for H2 production presents a compelling solution to solve environmental and energy issues. However, achieving scalable conversion under benign conditions faces consistent challenges including insufficient active sites for H2 evolution reaction (HER) and inefficient lignocellulose oxidation directly by photogenerated holes. Herein, it is found that Pt single atom-loaded CdS nanosheet (PtSA-CdS) would be an active photocatalyst for lignocellulose-to-H2 conversion. Theoretical and experimental analyses confirm that the valence band of CdS shifts downward after depositing isolated Pt atoms, and the slope of valence band potential on pH for PtSA-CdS is more positive than Nernstian equation. These characteristics allow PtSA-CdS to generate large amounts of •OH radicals even at pH 14, while the capacity is lacking with CdS alone. The employment of •OH/OH- redox shuttle succeeds in relaying photoexcited holes from the surface of photocatalyst, and the •OH radicals can diffuse away to decompose lignocellulose efficiently. Simultaneously, surface Pt atoms, featured with a thermoneutral Δ G H ∗ $\Delta G_{\mathrm{H}}^{\mathrm{*}}$ , would collect electrons to expedite HER. Consequently, PtSA-CdS performs a H2 evolution rate of 10.14 µmol h-1 in 1 m KOH aqueous solution, showcasing a remarkable 37.1-fold enhancement compared to CdS. This work provides a feasible approach to transform waste biomass into valuable sources.

5.
Nanotechnology ; 35(50)2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39284321

RESUMO

Owing to its higher earth element reserve and similar chemical properties to lithium, potassium ion batteries (PIBs) have been regarded as a potential alternative to lithium-ion batteries. And considering the relatively larger ionic radius of potassium, available electrode materials need to be equipped with enough space for volume expansion during charge-discharge cycles, thus graphitic carbon nanomaterials with adjustable layer spacing gradually come into researcher's version. Here with copper nanowires serving as growth template and organic polyvinyl pyrrolidone (PVP) providing carbon source, freestanding and ultra-light graphitic carbon nanotube (GCNT) aerogels were simply assembled and annealed, which were directly used as anodes of PIBs. Annealing parameters (temperature and atmosphere) were adapted to regulate the lattice order and interlayer spacing of GCNTs, and N, O heteroatoms derived from PVP were directly doped into the carbon lattice during thermal annealing, to optimize and enhance the cycle capacity and rate performance of GCNT anodes. The electrochemical potassium storage mechanism of GCNTs was also quantitatively analyzed. Most of the potassium ions are reversibly stored by squeezing into and escaping from the carbon lattice, and simultaneously oxygen-containing functional groups with different chemical states also offer active redox sites and dedicate partial capacity. Therefore, our assembled GCNTs with large lumen are expected to sandwich-like load with active substances efficiently, further constructing next-generation PIBs with excellent performance.

6.
Small ; : e2307386, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38084447

RESUMO

Selective photocatalytic production of high-value acetaldehyde concurrently with H2 from bioethanol is an appealing approach to meet the urgent environment and energy issues. However, the difficult ethanol dehydrogenation and insufficient active sites for proton reduction within the catalysts, and the long spatial distance between these two sites always restrict their catalytic activity. Here, guided by the strong metal-substrate interaction effect, an atomic-level catalyst design strategy to construct Pt-S3 single atom on ZnIn2 S4 nanosheets (PtSA -ZIS) is demonstrated. As active center with optimized H adsorption energy to facilitate H2 evolution reaction, the unique Pt single atom also donates electrons to its neighboring S atoms with electron-enriched sites formed to activate the O─H bond in * CH3 CHOH and promote the desorption of * CH3 CHO. Thus, the synergy between Pt single atom and ZIS together will reduce the energy barrier for the ethanol oxidization to acetaldehyde, and also narrow the spatial distance for proton mass transfer. These features enable PtSA -ZIS photocatalyst to produce acetaldehyde with a selectivity of ≈100%, which will spontaneously transform into 1,1-diethoxyethane via acetalization to avoid volatilization. Meanwhile, a remarkable H2 evolution rate (184.4 µmol h-1 ) is achieved with a high apparent quantum efficiency of 10.50% at 400 nm.

7.
Small ; 19(12): e2206662, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36587975

RESUMO

The development of high-performance lead-free dielectric ceramic capacitors is essential in the field of advanced electronics and electrical power systems. A huge challenge, however, is how to simultaneously realize large recoverable energy density (Wrec ), ultrahigh efficiency (η), and satisfactory temperature stability to effectuate next-generation high/pulsed power capacitors applications. Here, a strategy of utilizing nanoscale polarization heterogeneous regions is demonstrated for high-performance dielectric capacitors, showing comprehensive properties of large Wrec (≈6.39 J cm-3 ) and ultrahigh η (≈94.4%) at 700 kV cm-1 accompanied by excellent thermal endurance (20-160 °C), frequency stability (5-200 Hz), cycling reliability (1-105 cycles) at 500 kV cm-1 , and superior charging-discharging performance (discharge rate t0.9 ≈ 28.4 ns, power density PD ≈161.3 MW cm-3 ). The observations reveal that constructing the polarization heterogeneous regions in a linear dielectric to form novel relaxor ferroelectrics produces favorable microstructural characters, including extremely small polar nanoregions with high dynamics and multiphase coexistence and stable local structure symmetry, which enables large breakdown strength and ultralow polarization switching hysteresis, hence synergistically contributing to high-efficient capacitive energy storage. This study thus opens up a novel strategy to design lead-free dielectrics with comprehensive high-efficient energy storage performance for advanced pulsed power capacitors applications.

8.
Nanotechnology ; 32(26)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33735849

RESUMO

Water pollution is a global environmental problem that has attracted great concern, and functional carbon nanomaterials are widely used in water treatment. Here, to optimize the removal performance of both oil/organic matter and dye molecules, we fabricated porous and hydrophobic core-shell sponges by growing graphene on three-dimensional stacked copper nanowires. The interconnected pores between the one-dimensional nanocore-shells construct the porous channels within the sponge, and the multilayered graphene shells equip the sponge with a water contact angle over 120° even under acidic and alkaline environments, which enables fast and efficient cleanup of oil on or under the water. The core-shell sponge can absorb oil or organic solvents with densities 40-90 times its own, and its oil-sorption capacity is much larger than those of other porous materials like activated carbon and loofah. On the other hand, the adsorption behavior of the core-shell sponge to dyes including methyl orange (MO) and malachite green (MG), also common water pollutants, was also measured. Dynamic adsorption of MG under cyclic compression demonstrated a higher adsorption rate than that in the static state, and an acidic environment was favorable for the adsorption of MO molecules. Finally, the adsorption isotherm for MO molecules was analyzed and fitted with the Langmuir model, and the adsorption kinetics were studied in depth as well.

9.
Nanotechnology ; 31(36): 365705, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32454473

RESUMO

Fluorescent anti-counterfeiting technique is generally based on the development of luminescent materials, which generally exhibit single-mode emissions under single-wavelength excitation, thus resulting in a poor anti-fake effect. To improve the anti-forgery performance of fluorescent anti-counterfeiting approaches, dual-mode luminescent nanoparticles with the form of a ß-NaGdF4:Yb/Ho/Ce@ß-NaYF4:Tb/Eu core-shell structure have been skillfully designed and synthesized by a co-precipitation strategy. Through the cross-relaxation process between Ce3+ and Ho3+ ions in the inner core region, the up-conversion luminescence colors of the as-synthesized samples can be turned from green to yellow and finally to red when adjusting the dopant concentration of Ce3+ in the core. By selecting Ce3+ as the sensitizer for harvesting the energy of incident ultraviolet (UV) light and introducing Gd3+ as the ideal intermediate for subsequent energy migration, the down-converting emission colors of the as-obtained samples are also regulated from green to red via a Gd3+-assisted interface energy transfer processes (Ce3+ → Gd3+ → Tb3+, Ce3+ → Gd3+ → Tb3+ → Eu3+). Consequently, dual-mode luminescence with multi-color outputs can be achieved in the pre-designed core-shell nanostructure under the excitation of a 980 nm near-infrared laser and 254 nm UV light. The designed nanoarchitecture with bright dual-mode emissions and tunable colors greatly improves the ability of modern anti-counterfeiting, demonstrating its promising applications in anti-fake and optical multiplexing.

11.
Small ; 14(23): e1800634, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29749012

RESUMO

Cu nanowires (CuNWs) are considered as a promising candidate to develop high performance metal aerogels, yet the construction of robust and stable 3D porous structures remains challenging which severely limits their practical applications. Here, graphene-hybridized CuNW (CuNW@G) core-shell aerogels are fabricated by introducing a conformal polymeric coating and in situ transforming it into multilayered graphene seamlessly wrapped around individual CuNWs through a mild thermal annealing process. The existence of the outer graphene shell reinforces the 3D bulk structure and significantly slows down the oxidation process of CuNWs, resulting in improved mechanical property and highly stable electrical conductivity. When applied in electromagnetic interference shielding, the CuNW@G core-shell aerogels exhibit an average effectiveness of ≈52.5 dB over a wide range (from 8.2 to 18 GHz) with negligible degradation under ambient conditions for 40 d. Mechanism analysis reveals that the graphene shell with functional groups enables dual reflections on the core-shell and a multiple dielectric relaxation process, leading to enhanced dielectric loss and energy dissipation within the core-shell aerogels. The flexible core-shell-structured CuNW@G aerogels, with superior mechanical robustness and electrical stability, have potential applications in many areas such as advanced energy devices and functional composites.

12.
Nanotechnology ; 29(39): 395601, 2018 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-29968569

RESUMO

Recently, semiconducting chalcogenide nanostructures have attracted intense attention due to their excellent properties and broad applications, especially metal chalcogenides in the form of A2(V)B3(VI). Here we synthesized one-dimensional (1D) bismuth sulfide (Bi2S3) nanostructures with a length of more than 100 µm via a one-step hydrothermal method, and found that the reaction temperature and the alkali concentration play vital roles in the morphology of the 1D nanostructures. Since the as-synthesized Bi2S3 nanostructures were disordered in powder form, it is necessary to align them with ordered orientation and uniform distribution before further application. A blown bubble method was specifically applied to align these ultralong 1D nanostructures, and the assembly mechanism was also deeply analyzed, including the drift of nanostructures in the bubble film thickness direction, the relationship between (nanowire) NW spacing and array density, and the angle deviation of aligned arrays assembled from different bubble solutions. Interestingly, the initial straight Bi2S3 NWs could also be converted into buckled nanosprings (NSs) with regular pitches during the assembly process, and different NS formation stages were observed. A possible deformation mechanism or load bearing model of the wavy NS was proposed and verified, and the Young's modulus of an individual NW was figured out for the first time. After annealing under a N2 atmosphere, the aligned Bi2S3 NWs embedded in the bubble film were exposed, and the clean arrays were fabricated into functional optoelectronic devices such as photodetectors with a high performance.

13.
Nano Lett ; 16(8): 4917-24, 2016 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-27414282

RESUMO

We use a blown-bubble method to assemble Cu nanowires and in situ fabricate graphene-based one-dimensional heterostructures, including versatile sausage-like configurations consisting of multilayer graphene nanotubes (GNTs) filled by single or periodically arranged Cu nanoblocks (CuNBs). This is done by first assembling Cu nanowires among a polymer-based blown-bubble film (BBF) and then growing graphene onto the nanowire substrate using the polymer matrix as a solid carbon source by chemical-vapor deposition. The formation of sausage-like GNT@CuNB nanostructures is due to the partial melting and breaking of embedded Cu nanowires during graphene growth, which is uniquely related to our BBF process. We show that the GNT skin significantly slows the oxidation process of CuNBs compared with that of bare Cu nanowires, and the presence of stuffed CuNBs also reduces the linear resistance along the GNTs. The large-scale assembled graphene-based heterostructures achieved by our BBF method may have potential applications in heterojunction electronic devices and high-stability transparent conductive electrodes.

14.
Chemistry ; 21(16): 6157-64, 2015 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-25752493

RESUMO

Mesoporous carbon (m-C) has potential applications as porous electrodes for electrochemical energy storage, but its applications have been severely limited by the inherent fragility and low electrical conductivity. A rational strategy is presented to construct m-C into hierarchical porous structures with high flexibility by using a carbon nanotube (CNT) sponge as a three-dimensional template, and grafting Pt nanoparticles at the m-C surface. This method involves several controllable steps including solution deposition of a mesoporous silica (m-SiO2 ) layer onto CNTs, chemical vapor deposition of acetylene, and etching of m-SiO2 , resulting in a CNT@m-C core-shell or a CNT@m-C@Pt core-shell hybrid structure after Pt adsorption. The underlying CNT network provides a robust yet flexible support and a high electrical conductivity, whereas the m-C provides large surface area, and the Pt nanoparticles improves interfacial electron and ion diffusion. Consequently, specific capacitances of 203 and 311 F g(-1) have been achieved in these CNT@m-C and CNT@m-C@Pt sponges as supercapacitor electrodes, respectively, which can retain 96 % of original capacitance under large degree compression.

15.
Nano Lett ; 13(4): 1776-81, 2013 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-23517083

RESUMO

Carbon nanotube-Si and graphene-Si solar cells have attracted much interest recently owing to their potential in simplifying manufacturing process and lowering cost compared to Si cells. Until now, the power conversion efficiency of graphene-Si cells remains under 10% and well below that of the nanotube-Si counterpart. Here, we involved a colloidal antireflection coating onto a monolayer graphene-Si solar cell and enhanced the cell efficiency to 14.5% under standard illumination (air mass 1.5, 100 mW/cm(2)) with a stable antireflection effect over long time. The antireflection treatment was realized by a simple spin-coating process, which significantly increased the short-circuit current density and the incident photon-to-electron conversion efficiency to about 90% across the visible range. Our results demonstrate a great promise in developing high-efficiency graphene-Si solar cells in parallel to the more extensively studied carbon nanotube-Si structures.


Assuntos
Fontes de Energia Elétrica , Grafite/química , Silício/química , Coloides/química , Nanotubos de Carbono/química , Energia Solar
16.
Cancer Treat Rev ; 130: 102817, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39154410

RESUMO

Triple-negative breast carcinoma (TNBC) remains a formidable clinical hurdle owing to its high aggressiveness and scant therapeutic options. Nonetheless, the evolving landscape of immunotherapeutic strategies opens up promising avenues for tackling this hurdle. This review discusses the advancing immunotherapy for TNBC, accentuating personalized interventions due to tumor microenvironment (TME) diversity. Immune checkpoint inhibitors (ICIs) hold pivotal significance, both as single-agent therapies and when administered alongside cytotoxic agents. Moreover, the concurrent inhibition of multiple immune checkpoints represents a potent approach to augment the efficacy of cancer immunotherapy. Synergistic effects have been observed when ICIs are combined with targeted treatments like PARP inhibitors, anti-angiogenics, and ADCs (antibody-drug conjugates). Emerging tactics include tumor vaccines, cellular immunotherapy, and oncolytic viruses, leveraging the immune system's ability for selective malignant cell destruction. This review offers an in-depth examination of the diverse landscape of immunotherapy development for TNBC, furnishing meticulous insights into various advancements within this field. In addition, immunotherapeutic interventions offer hope for TNBC, needing further research for optimization.

17.
Biomed Pharmacother ; 180: 117404, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39307117

RESUMO

As the global incidence of breast cancer continues to surge, the pursuit of novel, low-toxicity, and highly efficacious therapeutic strategies has emerged as a pivotal research focus. Curcumin (CUR), an active constituent of traditional Chinese medicine (TCM) renowned for its antimicrobial, anti-inflammatory, antioxidant, and antitumor properties, exhibits immense potential in breast cancer therapy. Nevertheless, CUR's poor water solubility, chemical instability, and unfavorable pharmacokinetics have impeded its clinical utilization. To address these challenges, nano-delivery systems have been extensively exploited for CUR administration, enhancing its in vivo stability and bioavailability, and facilitating precise targeting of breast cancer lesions. Therefore, we elaborate on CUR's chemical foundations, drug metabolism, and safety profile, and elucidate its potential mechanisms in breast cancer therapy, encompassing inducing apoptosis and autophagy, blocking cell cycle, inhibiting breast cancer metastasis, regulating tumor microenvironment and reversing chemotherapy resistance. The review primarily emphasizes recent advancements in CUR-based nano-delivery systems for the treatment and diagnosis of breast cancer. Liposomes, nanoparticles (encompassing polymer nanoparticles, solid lipid nanoparticles, mesoporous silica particles, metal/metal oxide nanoparticles, graphene nanomaterials, albumin nanoparticles, etc.), nanogels, and nanomicelles can serve as delivery carriers for CUR, exhibiting promising anti-breast cancer effects in both in vivo and in vitro experiments. Furthermore, nano-CUR can be integrated with fluorescence imaging, magnetic resonance imaging, computed tomography imaging, ultrasound, and other techniques to achieve precise localization and diagnosis of breast cancer masses. While this article has summarized the clinical studies of nano-curcumin, it is noteworthy that the research literature on nano-CUR applied to breast cancer diagnosis and the translation of nano-CUR clinical studies in BC patients remain limited. Therefore, future research should intensify exploration in this direction.

18.
FEBS J ; 291(5): 1008-1026, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38037455

RESUMO

The scaffolding protein programmed cell death protein 10 (Pdcd10) has been demonstrated to play a critical role in renal epithelial cell homeostasis and function by maintaining appropriate water reabsorption in collecting ducts. Both ureter and kidney collecting duct systems are derived from the ureter bud during development. Here, we report that cadherin-16 (Cdh16)-cre drives gene recombination with high specificity in the ureter, but not the bladder, urothelium. The consequences of Pdcd10 deletion on the stratified ureter urothelium were investigated using an integrated approach including messenger RNA (mRNA) expression analysis, immunocytochemistry, and high-resolution confocal and electron microscopy. Loss of Pdcd10 in the ureter urothelium resulted in increased expression of uroplakins (Upks) and keratins (Krts), as well as hypertrophy of the ureter urothelium with an associated increase in the number of proliferation marker protein Ki-67 (Ki67)-expressing cells specifically within the basal urothelium layer. Ultrastructural analysis documented significant modification of the intracellular membrane system, including intracellular vesicle genesis and transport along the basal- to umbrella-cell-layer axis. Additionally, Pdcd10 loss resulted in swelling of Golgi compartments, disruption of mitochondrial cristae structure, and increased lysosomal fusion. Lack of Pdcd10 also resulted in decreased fusiform vesicle formation in umbrella cells, increased secretion of exosome vesicles, and alteration in microvillar structure on apical membranes. Our findings indicate that Pdcd10 expression and its influence on homeostasis is associated with modulation of endomembrane trafficking and organelle biogenesis in the ureter urothelium.


Assuntos
Ureter , Humanos , Urotélio , Mitocôndrias/genética , Complexo de Golgi , Hipertrofia
19.
Clin Chim Acta ; 554: 117785, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38228224

RESUMO

BACKGROUND: The study aimed to investigate the diagnostic value of lupus-related pattern recognition receptors (PRRs) genes in peripheral blood mononuclear cells (PBMCs) and monocytes (MONs) for lupus nephritis (LN). METHODS: PBMCs were isolated from a cohort with 37 LN patients and 39 healthy controls (HCs), and MONs were derived from another cohort with 70 LN patients and 66 HCs. Q-PCR was used to measure the mRNA levels of CGAS, IFNB1, AIM2, IL1Β, NLRC4, NLRP3, NLRP12 and ZBP1 in the PBMCs and MONs. The Mann-Whitney U test was used to compare the data in LN patients and HCs. Eleven GEO datasets of SLE/LN were used to perform differentially expressed genes (DEGs) analysis to these PRR genes. Receiver operating characteristic (ROC) curve analysis was employed to assess the performance of individual genes or the disease prediction model established by combining multiple genes in LN diagnosis. Spearman correlation method was done to analyze the correlation between these PRRs and other clinical characteristics. RESULTS: The mRNA levels of five genes (AIM2, NLRC4, IL1B, NLRP12 and ZBP1) in PBMCs, and seven genes (CGAS, IFNB1, AIM2, IL1B, NLRP3, NLRP12 and ZBP1) in MONs of LN patients were significantly higher than those of HCs (P < 0.05). DEGs analysis based on the GEO datasets showed that ZBP1, AIM2 and IL1B were significantly increased in several datasets. The ROC curve analysis indicated that the area under curve (AUC) of the LN prediction models derived from PBMCs or MONs were 0.82 or 0.91 respectively. In addition, the expression levels of these PRRs were correlated with other clinical features in LN patients, including Anti-Sm, ESR, serum Cr, and C3. CONCLUSION: Our study suggests that these lupus-related PRRs might be served as potential biomarkers of LN.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/genética , Nefrite Lúpica/metabolismo , Leucócitos Mononucleares/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Monócitos/metabolismo , Biomarcadores , RNA Mensageiro/genética , Nucleotidiltransferases , Curva ROC
20.
JACC Basic Transl Sci ; 9(2): 203-219, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38510716

RESUMO

The epicardium provides epicardial-derived cells and molecular signals to support cardiac development and regeneration. Zebrafish and mouse studies have shown that ccm2, a cerebral cavernous malformation disease gene, is essential for cardiac development. Endocardial cell-specific deletion of Ccm2 in mice has previously established that Ccm2 is essential for maintenance of the cardiac jelly for cardiac development during early gestation. The current study aimed to explore the function of Ccm2 in epicardial cells for heart development and regeneration. Through genetic deletion of Ccm2 in epicardial cells, our in vivo and ex vivo experiments revealed that Ccm2 is required by epicardial cells to support heart development. Ccm2 regulates epicardial cell adhesion, cell polarity, cell spreading, and migration. Importantly, the loss of Ccm2 in epicardial cells delays cardiac function recovery and aggravates cardiac fibrosis following myocardial infarction. Molecularly, Ccm2 targets the production of cytoskeletal and matrix proteins to maintain epicardial cell function and behaviors. Epicardial Ccm2 plays a critical role in heart development and regeneration via its regulation of cytoskeleton reorganization.

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