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1.
EMBO Rep ; 24(6): e56282, 2023 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-37009826

RESUMEN

Human microproteins encoded by long non-coding RNAs (lncRNA) have been increasingly discovered, however, complete functional characterization of these emerging proteins is scattered. Here, we show that LINC00493-encoded SMIM26, an understudied microprotein localized in mitochondria, is tendentiously downregulated in clear cell renal cell carcinoma (ccRCC) and correlated with poor overall survival. LINC00493 is recognized by RNA-binding protein PABPC4 and transferred to ribosomes for translation of a 95-amino-acid protein SMIM26. SMIM26, but not LINC00493, suppresses ccRCC growth and metastatic lung colonization by interacting with acylglycerol kinase (AGK) and glutathione transport regulator SLC25A11 via its N-terminus. This interaction increases the mitochondrial localization of AGK and subsequently inhibits AGK-mediated AKT phosphorylation. Moreover, the formation of the SMIM26-AGK-SCL25A11 complex maintains mitochondrial glutathione import and respiratory efficiency, which is abrogated by AGK overexpression or SLC25A11 knockdown. This study functionally characterizes the LINC00493-encoded microprotein SMIM26 and establishes its anti-metastatic role in ccRCC, and therefore illuminates the importance of hidden proteins in human cancers.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , ARN Largo no Codificante , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Mitocondrias/metabolismo , Proliferación Celular/genética , Neoplasias Renales/genética , Neoplasias Renales/patología , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/metabolismo , Micropéptidos
2.
Anal Chem ; 96(18): 7101-7110, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38663376

RESUMEN

While DNA amplifier-built nanobiosensors featuring a DNA polymerase-free catalytic hairpin assembly (CHA) reaction have shown promise in fluorescence imaging assays within live biosystems, challenges persist due to unsatisfactory precision stemming from premature activation, insufficient sensitivity arising from low reaction kinetics, and poor biostability caused by endonuclease degradation. In this research, we aim to tackle these issues. One aspect involves inserting an analyte-binding unit with a photoinduced cleavage bond to enable a light-powered notion. By utilizing 808 nm near-infrared (NIR) light-excited upconversion luminescence as the ultraviolet source, we achieve entirely a controllable sensing event during the biodelivery phase. Another aspect refers to confining the CHA reaction within the finite space of a DNA self-assembled nanocage. Besides the accelerated kinetics (up to 10-fold enhancement) resulting from the nucleic acid restriction behavior, the DNA nanocage further provides a 3D rigid skeleton to reinforce enzymatic resistance. After selecting a short noncoding microRNA (miRNA-21) as the modeled low-abundance sensing analyte, we have verified that the innovative NIR light-powered and DNA nanocage-confined CHA nanobiosensor possesses remarkably high sensitivity and specificity. More importantly, our sensing system demonstrates a robust imaging capability for this cancer-related universal biomarker in live cells and tumor-bearing mouse bodies, showcasing its potential applications in disease analysis.


Asunto(s)
Técnicas Biosensibles , ADN , Rayos Infrarrojos , MicroARNs , MicroARNs/análisis , Humanos , Técnicas Biosensibles/métodos , Animales , ADN/química , Ratones , Imagen Óptica , Nanoestructuras/química
3.
Clin Oral Implants Res ; 35(3): 251-257, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38031527

RESUMEN

OBJECTIVE: This study aimed to evaluate the differences in the accuracy of immediate intraoral, immediate extraoral, and delayed dental implant placement with surgical guides (static computer-aided implant surgery) in patients treated with mandibular reconstruction. METHODS: This was a retrospective study. The patients were divided into three groups: immediate intraoral placement (IIO), immediate extraoral placement (IEO), and delayed placement (DEL). Four variables were used to compare the planned and actual implant positions: angular deviation, three-dimensional (3D) deviation at the entry point of the implant, 3D deviation at the apical point of the implant, and depth deviation. RESULTS: The angular deviation was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .05) groups. The 3D deviation at the entry point was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .01) groups. The 3D deviation at the apical point was significantly higher in the IIO group than in the IEO (p < .01) and DEL (p < .01) groups. The depth deviation was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .05) groups. There was no statistical difference between the IEO and DEL group in angular and 3D deviation. CONCLUSION: With surgical guides, among the different approaches for implant placement, delayed implant placement remains the most accurate approach for patients treated with mandibular reconstruction.


Asunto(s)
Implantes Dentales , Reconstrucción Mandibular , Cirugía Asistida por Computador , Humanos , Implantación Dental Endoósea/métodos , Estudios Retrospectivos , Cirugía Asistida por Computador/métodos , Diseño Asistido por Computadora , Imagenología Tridimensional , Tomografía Computarizada de Haz Cónico
4.
Cancer Sci ; 114(5): 2029-2040, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36747492

RESUMEN

The biological function of many mitochondrial proteins in mechanistic detail has not been well investigated in clear cell renal cell carcinoma (ccRCC). A seven-mitochondrial-gene signature was generated by Lasso regression analysis to improve the prediction of prognosis of patients with ccRCC, using The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium cohort. Among those seven genes, EFHD1 is less studied and its role in the progression of ccRCC remains unknown. The decreased expression of EFHD1 was validated in clinical samples and was correlated with unfavorable outcome. Overexpression of EFHD1 in ccRCC cells resulted in the reduction of mitochondrial Ca2+ , and the inhibition of cell migration and invasion in vitro and tumor metastasis in vivo. Mechanistically, EFHD1 physically bound to the core mitochondrial calcium transporter (mitochondrial calcium uniporter, MCU) through its N-terminal domain. The interaction between EFHD1 and MCU suppressed the uptake of Ca2+ into mitochondria, and deactivated the Hippo/YAP signaling pathway. Further data revealed that the ectopic expression of EFHD1 upregulated STARD13 to enhance the phosphorylation of YAP protein at Ser-127. The knockdown of STARD13 or the overexpression of MCU partly abrogated the EFHD1-mediated induction of phosphorylation of YAP at Ser-127 and suppression of cell migration. Taken together, the newly identified EFHD1-MCU-STARD13 axis participates in the modulation of the Hippo/YAP pathway and serves as a novel regulator in the progression of ccRCC.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/patología , Mitocondrias/metabolismo , Pronóstico , Proteómica
5.
Opt Express ; 31(2): 2373-2385, 2023 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-36785252

RESUMEN

Wide bandwidth THz pulses can be used to record the distinctive spectral fingerprints related to the vibrational or rotational modes of polycrystalline biomolecules, and can be used to resolve the time-dependent dynamics of such systems. Waveguides, owing to their tight spatial confinement of the electromagnetic fields and the longer interaction distance, are promising platforms with which to study small volumes of such systems. The efficient input of sub-ps THz pulses into waveguides is challenging owing to the wide bandwidth of the THz signal. Here, we propose a sensing chip comprised of a pair of back-to-back Vivaldi antennas feeding into, and out from, a 90° bent slotline waveguide to overcome this problem. The effective operating bandwidth of the sensing chip ranges from 0.2 to 1.15 THz, and the free-space to on-chip coupling efficiency is as high as 51% at 0.44 THz. Over the entire band, the THz signal is ∼42 dB above the noise level at room temperature, with a peak of ∼73 dB above the noise. In order to demonstrate the use of the chip, we have measured the characteristic fingerprint of α-lactose monohydrate, and its sharp absorption peak at ∼0.53 THz was successfully observed, demonstrating the promise of our technique. The chip has the merits of efficient in-plane coupling, ultra-wide bandwidth, ease-of-integration, and simple fabrication. It has the potential for large-scale manufacture, and can be a strong candidate for integration into other THz light-matter interaction platforms.

6.
Transpl Int ; 36: 11196, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37383842

RESUMEN

Patients undergoing kidney transplantation have a poor response to vaccination and a higher risk of disease progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effectiveness of vaccine doses and antibody titer tests against the mutant variant in these patients remains unclear. We retrospectively analyzed the risk of SARS-CoV-2 infection in a single medical center according to vaccine doses and immune responses before the outbreak. Among 622 kidney transplant patients, there were 77 patients without vaccination, 26 with one dose, 74 with two doses, 357 with three, and 88 with four doses. The vaccination status and infection rate proportion were similar to the general population. Patients undergoing more than three vaccinations had a lower risk of infection (odds ratio = 0.6527, 95% CI = 0.4324-0.9937) and hospitalization (odds ratio = 0.3161, 95% CI = 0.1311-0.7464). Antibody and cellular responses were measured in 181 patients after vaccination. Anti-spike protein antibody titer of more than 1,689.3 BAU/mL is protective against SARS-CoV-2 infection (odds ratio = 0.4136, 95% CI = 0.1800-0.9043). A cellular response by interferon-γ release assay was not correlated with the disease (odds ratio = 1.001, 95% CI = 0.9995-1.002). In conclusion, despite mutant strain, more than three doses of the first-generation vaccine and high antibody titers provided better protection against the omicron variant for a kidney transplant recipient.


Asunto(s)
COVID-19 , Trasplante de Riñón , Vacunas , Humanos , COVID-19/prevención & control , SARS-CoV-2 , Estudios Retrospectivos
7.
Phys Chem Chem Phys ; 25(25): 16908-16920, 2023 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-37325848

RESUMEN

Freshwater is a scarce and vulnerable resource that has never encountered such an extensive focus on a nearly worldwide scale as it does today. Recently, it has been found that desalination powered by two-dimensional (2D) carbon materials as separation membranes has significantly reduced the operational costs and complexity but presents heavy requirements for the structural stability and separation properties of the membrane materials. Here, we combined carbon materials with promising adsorption properties and zeolites characterized by a regular pore structure to obtain a zeolite-like structured carbon membrane Zeo-C and investigated the suitability of the Zeo-C membrane for seawater desalination based on the computational-simulation-driven approach. The results of molecular dynamics (MD) simulations and density functional theory (DFT) calculations revealed that the periodic pore distribution conferred favorable structural stability and mechanical strength to the Zeo-C desalination membrane. The rejection rate of Na+ and Cl- is ensured at 100% under a pressure of 40-70 MPa, and that of Na+ could reach 97.85% even though the pressure increases to 80 MPa, exhibiting superior desalination properties. The porous nature of the zeolite-like structure and the low free energy potential barrier are conducive for reliable adsorption and homogeneous diffusion of salt ions, which facilitates the acquisition of desirable water molecule permeability and salt ion selectivity. In particular, the interlinked delocalized π-network imparts inherent metallicity to Zeo-C for self-cleaning in response to electrical stimulation, thereby extending the lifetime of the desalination membrane. These studies have greatly encouraged theoretical innovations and serve as a guiding reference for desalination materials.

8.
Phys Chem Chem Phys ; 25(48): 32979-32988, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38031515

RESUMEN

The exploration of high-quality and efficient electrocatalysts is crucial for the advancement of clean energy utilization and the development of energy conversion technologies. Recently, high-entropy alloys (HEA) have been actively explored as viable catalysts for water electrolysis due to their unique performance such as wide scope for compositional adjustments, excellent catalytic activity, and outstanding stability. However, the mechanism of synergistic oxygen evolution by HEA electrocatalysts at multiple sites has not been systematically and clearly demystified. Herein, in this paper, Pt is combined with inexpensive metals Ni, Cu, Fe, and Co to form a stable HEA structure. The synergistic catalytic mechanism of the PtNiFeCoCu HEA in the oxygen evolution reaction (OER) has been investigated, and the structure has been demonstrated to exhibit excellent hydrogen evolution reaction (HER) activity. The results suggest that the PtNiFeCoCu HEA catalyst achieved a lower overpotential of 0.44 V in the acidic OER, demonstrating that the PtNiFeCoCu HEA is a bifunctional electrocatalyst. In addition, oxygen intermediates are synergistically adsorbed on the surface of high-entropy alloys through multimetallic sites, which breaks the limitation of limited active sites. Further calculations indicated that the favorable OER activity of the catalyst originated from the strong associative coupling of the d orbitals of the synergistic metal sites to the 2p orbitals of the oxygen intermediates with enhanced synergistic effects. This work further elucidates the multisite synergistic catalysis of the PtNiFeCoCu HEA, providing a unique perspective to uncover the source of the high catalytic performance of HEA electrocatalysts.

9.
Phys Chem Chem Phys ; 25(44): 30296-30307, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37930335

RESUMEN

The shortage of freshwater is a critical concern for contemporary society, and reverse osmosis desalination technology has gathered considerable attention as a potential solution to this problem. It has been recognized that the desalination process involving water flow through angstrom-sized pores has tremendous potential. However, it is challenging to obtain angstrom-sized pore structures with internal mass transfer and surface/interface properties matching the application conditions. Herein, a two-dimensional (2D) zeolite-like carbon structure (Carzeo-ANG) was constructed with unique angstrom-sized pores in the zeolite structure; then, the surface/interfacial transport behavior and percolation effect of the Carzeo-ANG desalination membrane were evaluated by density functional theory (DFT) calculations and classical molecular dynamics. The first-principles calculations in density functional theory were implemented through the Vienna ab initio simulation package (VASP), which is a commercial package for the simulation of carbon-based materials. The results show that Carzeo-ANG is periodically distributed with angstrom-sized pores (effective diameter = 5.4 Å) of dodecacyclic carbon rings, which ensure structural stability while maintaining sufficient mechanical strength. The remarkable salt-ion adsorption properties and mass transfer activity combined with the reasonable density distribution and free energy barrier for water molecules endow the membrane with superior desalination ability. At the pressure of 80 MPa, the rejection efficiency of Cl- and Na+ were 100% and 96.25%, and the membrane could achieve a water flux of 132.71 L cm-2 day-1 MPa-1. Moreover, the interconnected electronic structure of Carzeo-ANG imparts a self-cleaning effect.

10.
Phys Chem Chem Phys ; 25(34): 23249-23261, 2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37608737

RESUMEN

It is estimated that the annual cost of corrosion in most countries accounts for 3-4% of gross domestic product, far exceeding the losses caused by natural disasters, prompting scientists to continuously search for high-performance anti-corrosion materials. Among these high-performance materials, two-dimensional carbon materials represented by graphene have received widespread attention due to their excellent chemical stability and anti-permeability. However, some studies have found that the poor ability of graphene to bind to the interface and the electrical coupling caused by metallicity make it possible to protect copper from corrosion only for a short period of time. To circumvent these issues, through phase behavior research, interface binding property simulation and corrosion mechanism exploration, we propose a more promising anti-corrosive three-dimensional (3D) biphenylene diamond-like carbon membrane (BP-DLC). The kinetic study results show that due to the Gibbs free energy of biphenylene structures below three layers being lower than 0, few-layer biphenylene can spontaneously generate phase transitions of limited size, forming a biphenylene diamond-like membrane and exhibiting superior mechanical properties and a certain degree of flexibility. Mechanical and electronic performance results further show that there is a strong bonding effect between BP-DLC and the metal surface, which further enhances the bistate heterostructure and prolongs the coating life of BP-DLC materials. Compared with pure graphene and Cu substrates, BP-DLC membranes exhibit stronger corrosion resistance by reducing porosity, increasing charge transfer and hindering the diffusion of corrosion ions to the substrate. This study provides a new strategy for constructing corrosion-resistant materials by designing long-term stable and highly corrosion-resistant diamond-like membranes.

11.
Phys Chem Chem Phys ; 25(41): 28326-28335, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37840459

RESUMEN

The development of highly active oxygen evolution reaction (OER) catalysts with fast kinetics is crucial for the advancement of clean energy and fuel conversion to achieve a sustainable energy future. Recently, the synergistic effect of single-atom doping and multicomponent clusters has been demonstrated to significantly improve the catalytic activity of materials. However, such synergistic effects involving multi-electron and proton transfer processes are quite complex and many crucial mechanistic details need be well comprehended. We ingeniously propose a catalyst, (Fed-FeSc)@NiS2 (d stands for doping and c stands for clustering), with Fe and FeS acting synergistically on a NiS2 substrate. Specifically, fully dynamic monitoring of multiple active sites at the (Fed-FeSc)@NiS2 interface using metadynamics is innovatively performed. The results show that the rate determining step value at the overpotential of 1.23 V for the synergistic (Fed-FeSc)@NiS2 is 1.55 V, decreased by 6.67% and 35.29% compared to those of the independently acting single-atom doping and multi-clusters. The unique synergistic structure dramatically increases the d-band centre of the Fe site (-1.45 eV), endowing (Fed-FeSc)@NiS2 with more activity than conventional commercial Ir-C catalysts. This study provides insights into the synergistic effects of single-atom doping and multi-component clusters, leading to exploratory inspiration for the design of highly efficient OER catalysts.

12.
J Formos Med Assoc ; 122(8): 800-804, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36941177

RESUMEN

Data are limited regarding the long-term durability of sustained virologic response (SVR) in solid organ transplant recipients who achieve SVR12 with direct-acting antivirals (DAAs) for hepatitis C virus (HCV). We reported the virologic outcomes in 42 recipients who received DAAs for acute or chronic HCV infection after heart, liver, and kidney transplantation. After achieving SVR12, all recipients received HCV RNA surveys at SVR24, and biannually until the last visit. If HCV viremia was detected during the follow-up period, direct sequencing and phylogenetic analysis were performed to confirm late relapse or reinfection. Sixteen (38.1%), 11 (26.2%), and 15 (35.7%) patients underwent heart, liver and, kidney transplantation. Thirty-eight (90.5%) received sofosbuvir (SOF)-based DAAs. No recipients had late relapse or reinfection after a median (range) of post-SVR12 follow-up 4.0 (1.0-6.0) years. We demonstrate that the durability of SVR in solid organ transplant recipients is excellent once SVR12 is achieved with DAAs.


Asunto(s)
Hepatitis C Crónica , Hepatitis C , Trasplante de Riñón , Humanos , Antivirales/uso terapéutico , Hepacivirus/genética , Respuesta Virológica Sostenida , Hepatitis C Crónica/tratamiento farmacológico , Reinfección/tratamiento farmacológico , Filogenia , Quimioterapia Combinada , Hepatitis C/tratamiento farmacológico , Resultado del Tratamiento
13.
J Am Chem Soc ; 144(36): 16502-16511, 2022 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-36063395

RESUMEN

Base-pair-driven toehold-mediated strand displacement (BP-TMSD) is a fundamental concept employed for constructing DNA machines and networks with a gamut of applications─from theranostics to computational devices. To broaden the toolbox of dynamic DNA chemistry, herein, we introduce a synthetic surrogate termed host-guest-driven toehold-mediated strand displacement (HG-TMSD) that utilizes bioorthogonal, cucurbit[7]uril (CB[7]) interactions with guest-linked input sequences. Since control of the strand-displacement process is salient, we demonstrate how HG-TMSD can be finely modulated via changes to the structure of the input sequence (including synthetic guest head-group and/or linker length). Further, for a given input sequence, competing small-molecule guests can serve as effective regulators (with fine and coarse control) of HG-TMSD. To show integration into functional devices, we have incorporated HG-TMSD into machines that control enzyme activity and layered reactions that detect specific microRNA.


Asunto(s)
ADN , MicroARNs , ADN/química , MicroARNs/química , Recombinación Genética
14.
Anal Chem ; 94(18): 6909-6917, 2022 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-35481762

RESUMEN

It is necessary to explore labeling probes with worthy optical properties and a noninvasive fluorescence imaging manner for stable long-term in situ measuring a single suspension cell. In response to these goals, we herein make a breakthrough on two fronts. On one hand, a co-sensitizer-induced efficient 808 nm near-infrared light-excited luminescence-confined upconversion nanoparticle with a low thermal effect is fabricated by employing a layer-by-layer seed growing approach to develop a sandwich structure, under which the luminescence domain is vastly restricted into an extremely thin inner shell (∼ 2.77 nm) to finally bring about a high-efficiency luminescent resonance energy transfer (LRET) sensing behavior. On the other hand, a self-made optical tweezers integrated upconversion luminescence confocal scanning instrument is applied to enhance the imaging accuracy, after which the liquid viscous force is sufficiently overcome by the resulting single beam gradient force and the analyzed suspension cell is always immobilized to the focal plane to ensure a constant luminescence excitation condition. By making use of a metal ion-dependent DNAzyme and a hairpin DNA strand to design a corresponding LRET sensing system, our nanoprobe shows satisfactory assay performance for two model biomolecules (Ca2+ and TK1 messenger RNA). Following the optical trapping-assisted imaging, this exceptional measurement method is capable of effectively monitoring the intracellular target changes in different physiological states, endowing a powerful toolbox for single cell analysis.


Asunto(s)
Luminiscencia , Nanopartículas , Transferencia Resonante de Energía de Fluorescencia , Nanopartículas/química , Imagen Óptica , Pinzas Ópticas , Suspensiones
15.
Anal Chem ; 94(13): 5450-5459, 2022 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-35324151

RESUMEN

In light of the worthy design flexibility and the good signal amplification capacity, the recently developed DNA motor (especially the DNA walker)-based fluorescent biosensors can offer an admirable choice for realizing bioimaging. However, this attractive biosensing strategy not only has the disadvantage of uncontrollable initiation but also usually demands the supplement of exogenous driving forces. To handle the above obstacles, some rewarding solutions are proposed here. First, on the surface of an 808 nm near-infrared light-excited low-heat upconversion nanoparticle, a special ultraviolet upconversion luminescence-initiated three-dimensional (3D) walking behavior is performed by embedding a photocleavage linker into the sensing elements, and such light-controlled target recognition can perfectly overcome the pre-triggering of the biosensor during the biological delivery to significantly boost the sensing precision. After that, a peculiar self-driven walking pattern is constructed by employing MnO2 nanosheets as an additional nanovector to physically absorb the sensing frame, for which the reduction of the widespread glutathione in the biological medium can bring about sufficient self-supplied Mn2+ to guarantee the walking efficiency. By selecting an underlying next-generation broad-spectrum cancer biomarker (survivin messenger RNA) as the model target, we obtain that the newly formed autonomous 3D DNA motor shows a commendable sensitivity (where the limit of detection is down to 0.51 pM) and even an outstanding specificity for distinguishing single-base mismatching. Beyond this sound assay performance, our sensing approach is capable of working as a powerful imaging platform for accurately operating in various living specimens such as cells and bodies, showing a favorable diagnostic ability for cancer care.


Asunto(s)
Técnicas Biosensibles , Nanopartículas , ADN/genética , Glutatión , Luminiscencia , Compuestos de Manganeso , Óxidos
16.
Eur J Immunol ; 51(4): 978-988, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33354776

RESUMEN

Icaritin, a small molecule currently being investigated in phase III clinical trials in China (NCT03236636 and NCT03236649) for treatment of advanced hepatocellular carcinoma (HCC), is a prenylflavonoid derivative obtained from the Epimedium genus. Previously, it was found that Icaritin decreased the expression of PD-L1, but its direct molecular targets and the underlying mechanisms have not been identified. In this study, we report the identification of IKK-α as the protein target of Icaritin by biotin-based affinity binding assay. The further mutagenesis assay has provided evidence that C46 and C178 in IKK-α were essential amino acids for Icaritin binding to IKK-α, revealing the binding sites of Icaritin to IKK-α for the first time. Functionally, Icaritin inhibited the NF-κB signalling pathway by blocking IKK complex formation, which led to decreased nuclear translocation of NF-κB p65, and subsequent downregulation of PD-L1 expression in a dose-dependent manner. More importantly, PD-L1-positive patients exhibited longer overall survival upon Icaritin therapy. Finally, Icaritin in combination with checkpoints antibodies, such as α-PD-1, has demonstrated much better efficacy than any single therapy in animal models. This is the first report that anticancer effects of Icaritin are mediated, at least in part, by impairing functions of IKK-α.


Asunto(s)
Antígeno B7-H1/genética , Flavonoides/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Quinasa I-kappa B/antagonistas & inhibidores , Animales , Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Epimedium/química , Femenino , Flavonoides/química , Células HEK293 , Humanos , Quinasa I-kappa B/genética , Quinasa I-kappa B/metabolismo , Células Jurkat , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Ratones Endogámicos C57BL , Estructura Molecular , Neoplasias Experimentales/genética , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Células THP-1 , Carga Tumoral/efectos de los fármacos
17.
Cancer Immunol Immunother ; 71(3): 705-718, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34374812

RESUMEN

BACKGROUND: A major feature of the microenvironment in pancreatic ductal adenocarcinoma (PDAC) is the significant amount of extracellular matrix produced by pancreatic stellate cells (PSCs), which have been reported to enhance the invasiveness of pancreatic cancer cells and negatively impact the prognosis. METHODS: We analyzed the data from two publicly available microarray datasets deposited in the Gene Expression Omnibus and found candidate genes that were differentially expressed in PDAC cells with metastatic potential and PDAC cells cocultured with PSCs. We studied the interaction between PDAC cells and PSCs in vitro and verified our finding with the survival data of patients with PDAC from the website of The Human Protein Atlas. RESULTS: We found that PSCs stimulated PDAC cells to secrete S100A9, which attracted circulatory monocytes into cancer tissue and enhanced the expression of programmed death-ligand 1 (PD-L1) on macrophages. When analyzing the correlation of S100A9 and PD-L1 expression with the clinical outcomes of patients with PDAC, we ascertained that high expression of S100A9 and PD-L1 was associated with poor survival in patients with PDAC. CONCLUSIONS: PSCs stimulated PDAC cells to secrete S100A9, which acts as a chemoattractant to attract circulatory monocytes into cancer microenvironment and induces expression of PD-L1 on macrophages. High expression of S100A9 and PD-L1 was associated with worse overall survival in a cohort of patients with PDAC.


Asunto(s)
Calgranulina B/genética , Carcinoma Ductal Pancreático/etiología , Carcinoma Ductal Pancreático/metabolismo , Comunicación Celular , Neoplasias Pancreáticas/etiología , Neoplasias Pancreáticas/metabolismo , Células del Estroma/metabolismo , Biomarcadores , Calgranulina B/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Comunicación Celular/genética , Comunicación Celular/inmunología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Técnicas de Cocultivo , Medios de Cultivo Condicionados/farmacología , Susceptibilidad a Enfermedades , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Humanos , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Células Estrelladas Pancreáticas/metabolismo , Células Estrelladas Pancreáticas/patología , Pronóstico , Interferencia de ARN , Células del Estroma/patología , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología
18.
J Oral Maxillofac Surg ; 80(11): 1858-1865, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36007546

RESUMEN

PURPOSE: The current standard for mandibular reconstruction is a contour-based approach using a fibular flap offering good cosmetic results but challenging to reconstruct using dental implants. An iliac flap is more amenable to implant placement and better suited for occlusion-driven reconstruction. We aimed to describe an occlusion-driven workflow that involves the use of digital surgical guides to perform mandibular reconstruction using an iliac flap; we also aimed to compare our results to those we achieved with conventional contour-based reconstruction. METHODS: This was a retrospective cohort study. All patients who underwent mandibular reconstruction with an iliac flap at our university hospital between September 2017 and December 2019 were considered eligible for the study. The inclusion criteria included mandibular defects after tumor ablation and stable preoperative occlusal relationship. The exclusion criteria were as follows: defects involving the condyle and ramus, temporomandibular joint disease, and obvious preoperative nontumor-related facial asymmetry. To evaluate surgical outcomes, patients were assigned to 2 groups based on the implemented surgical workflow: the occlusion-driven and traditional contour-driven groups. The intermaxillary distance, intermaxillary angle, surface deviation, and implantation rates were compared between the 2 groups. The operating time, length, and number of iliac bone segments were recorded. Intergroup differences were investigated using an independent samples t test and Fisher exact test. RESULTS: Overall, 24 patients were included (13 in the occlusion-driven group and 11 in the contour-driven group). Implantation rate was higher in the occlusion-driven group (61.5%) compared with the contour-driven group (18.2%; P = .047). The average acceptable intermaxillary distance was greater in the occlusion-driven group (92.3 ± 27.7%) than in the contour-driven group (47.0 ± 47.6%; P = .01). The average intermaxillary angle was 88.2 ± 8.4° in the occlusion-driven group and 76.4 ± 10.3° in the contour-driven group (P < .01). CONCLUSIONS: Digital surgical guides can precisely transfer virtual surgical planning to real-world mandibular surgery. An occlusion-driven workflow might provide a better intermaxillary jaw relationship than traditional contour-driven surgical procedures, resulting in improved mastication.


Asunto(s)
Colgajos Tisulares Libres , Reconstrucción Mandibular , Procedimientos de Cirugía Plástica , Humanos , Trasplante Óseo , Colgajos Tisulares Libres/cirugía , Ilion/cirugía , Mandíbula/cirugía , Reconstrucción Mandibular/métodos , Estudios Retrospectivos , Flujo de Trabajo , Oclusión Dental
19.
J Formos Med Assoc ; 121(11): 2300-2307, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35803885

RESUMEN

BACKGROUND: Living donor kidney transplantation (LDKT) is an important organ resource, especially in countries with low deceased donation rates. Strategies for expanding access to transplantation should be developed by identifying the modifiable factors. In this study, we evaluated these factors in the relatives of patients from both medical centers and dialysis clinics using questionnaires. METHODS: The questionnaires were anonymous and confidential. We collected questionnaires from previous donors, relatives of patients on the waitlist in the medical center, and relatives of dialysis patients in three nephrology clinics. The study groups were divided into three categories: donor group (n = 68), willing group (n = 43), and non-donor group (n = 65). RESULTS: Respondents in the clinics had lower cognition and willingness towards LDKT than those in the medical center. More knowledge of LDKT, better relationship with patients, more familial support, and female gender were positively related to donation. The non-donor group tended to want to maintain an intact body for the afterlife. There was no significant difference in age, educational degree, average monthly income, and medical compliance among the three groups. CONCLUSION: More efforts need to be made in dialysis clinics, where general nephrologists are important for the outreach of information. In addition, dealing with religious ambivalence and reestablishing cultural mindsets with health education programs are important issues in a non-Christian country.


Asunto(s)
Trasplante de Riñón , Donadores Vivos , Femenino , Humanos , Riñón , Diálisis Renal , Encuestas y Cuestionarios
20.
J Formos Med Assoc ; 121(5): 958-968, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34294497

RESUMEN

BACKGROUND/PURPOSE: Hepatitis B surface antigen (HBsAg)-positive renal transplantation recipients must take lifelong immunosuppressants and nucleotide analogues (NAs). We investigated the cellular immune responses of HBsAg-positive renal transplantation recipients taking immunosuppressants and NAs. METHODS: Blood samples were collected from HBsAg-positive individuals with end-stage renal disease on the transplant waiting list (Group 1) and renal transplantation recipients taking immunosuppressants and NAs (Group 2) or immunosuppressants without NAs (Group 3). Hepatitis B virus (HBV)-specific pentamers were used to quantify circulating HBV-specific CD8+ T cells. RESULTS: Groups 2 and 3 had higher cellular immune responses, as indicated by significantly lower regulatory T (Treg)/CD8+ T cell ratios than Group 1. With undetectable viral loads under both immunosuppressant and NAs, the CD8+ T cell and HBV-specific CD8+ T cell frequencies were similar in Group 2 and Group 1. Patients in Group 3 did not use NAs and had an elevated viral load and higher HBV-specific CD8+ T cell and IFN-γ-producing HBV-specific CD8+ T cell frequencies, but lower a frequency of programmed death-1 (PD-1)+ HBV-specific CD8+ T cells than the other groups. Increased viral replication in Group 3 resulted in significantly higher CD8+ T cell and IFN-γ-producing CD8+ T cell frequencies than Group 1. CONCLUSION: Immunosuppressant therapy increases viral replication in HBsAg-positive renal transplant recipients due to disabling or dysregulation of virus-specific CD8+ T cells. The higher cellular immune responses due to lower Treg/CD8+ T cell ratios in HBsAg-positive renal transplant recipients may be one of the reasons to induce liver pathology because of uncontrolled viral replication.


Asunto(s)
Hepatitis B Crónica , Hepatitis B , Trasplante de Riñón , Aloinjertos , Linfocitos T CD8-positivos , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Humanos , Inmunidad Celular , Inmunosupresores/uso terapéutico
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