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1.
Chemosphere ; 360: 142325, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38754489

RESUMEN

Enhancing the kinetic performance of thick electrodes is essential for improving the efficiency of lithium extraction processes. Biochar, known for its affordability and unique three-dimensional (3D) structure, is utilized across various applications. In this study, we developed a biochar-based, 3D-conductive network thick electrode (∼20 mg cm-2) by in-situ deposition of LiFePO4 (LFP) onto watermelon peel biomass (WB). Utilizing Density Functional Theory (DFT) calculations complemented by experimental data, we confirmed that this The thick electrode exhibits outstanding kinetic properties and a high capacity for lithium intercalation in brines, even in environments where the Magnesia-lithium ratios are significantly high. The electrode showed an impressive intercalation capacity of 30.67 mg g-1 within 10 min in a pure lithium solution. It also maintained high intercalation performance (31.17 mg g-1) in simulated brines with high Magnesia-lithium ratios. Moreover, in actual brine, it demonstrated a significant extraction capacity (23.87 mg g-1), effectively lowering the Magnesia-lithium ratio from 65 to 0.50. This breakthrough in high-conductivity thick electrode design offers new perspectives for lithium extraction technologies.


Asunto(s)
Carbón Orgánico , Electrodos , Litio , Litio/química , Litio/aislamiento & purificación , Carbón Orgánico/química , Lagos/química , Magnesio/química , Citrullus/química , Sales (Química)/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Cinética , Hierro , Fosfatos
2.
Biochem Genet ; 62(2): 1200-1215, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37561335

RESUMEN

Transmembrane (TMEM) proteins are integral membrane proteins that traverse biological membranes. Several members of the TMEM family have been linked to the development and progression of various tumors. However, the specific role and mechanism of TMEM44 in tumor biology remain largely unexplored. In this study, we initially conducted an extensive analysis using the TCGA database to investigate the expression patterns and survival associations of TMEM44 across various human tumors. Subsequently, we focused on KIRC and found a significant correlation between TMEM44 expression and this particular cancer type. To validate our findings, we performed western blot and quantitative polymerase chain reaction (qPCR) assays to confirm the expression levels of TMEM44 in KIRC. Following this, we employed a series of functional assays, including CCK8 viability assay, EDU incorporation assay, wound healing assay, and transwell migration assay, to investigate the biological role of TMEM44 in KIRC. We observed a significant upregulation of TMEM44 expression in KIRC, indicating its potential involvement in the pathogenesis of this cancer. We intervened in the expression of TMEM44 in KIRC cells and found significant inhibitory effects on cell proliferation, migration, and invasion in KIRC cells. Furthermore, our findings indicated that TMEM44 could serve as an independent prognostic factor in KIRC, highlighting its potential clinical significance. Consequently, TMEM44 holds promise as both a prognostic biomarker and a prospective therapeutic target for KIRC.

3.
ACS Nano ; 17(24): 24619-24631, 2023 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-38051592

RESUMEN

The interfacial stability of a Zn battery is dependent on the electrical double layer (EDL) that forms at the interface between the electrolyte and the Zn metal anode. A fundamental understanding of the regulation of the EDL structure and stability on the Zn surface is highly desirable for practical applications of aqueous batteries. Herein, the interfacial chemistry of the EDL is regulated by the adsorption of supramolecular cyclodextrin anions in the inner Helmholtz plane (IHP). The nucleation overpotential and the charge transfer activation energy for Zn2+ to go through the OHP (Ea1) and IHP (Ea2) are increased, leading to slower Zn2+ transfer kinetics. The electric field distribution and Zn2+ flux in the proximity of the Zn metal surface are homogenized, thus suppressing the growth of dendrites. The mechanism is supported with theoretical and experimental analyses. Consequently, a Zn||Zn symmetric cell achieves an ultrahigh cumulative capacity of 10000 and 4250 mAh cm-2 at a respective current density of 10 and 50 mA cm-2, and an average Coulombic efficiency of 99.5% over 1000 cycles under harsh conditions (at a high current density of 10 mA cm-2 with a high capacity of 10 mAh cm-2). This work provides insight into the introduction of supramolecular anions to regulate the electrical double layer EDL structure and improve the interfacial stability.

4.
Int J Biol Macromol ; 253(Pt 6): 127243, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37806414

RESUMEN

The SOX family plays a vital role in determining the fate of cells and has garnered attention in the fields of cancer research and regenerative medicine. It also shows promise in the study of wound healing, as it actively participates in the healing processes of various tissues such as skin, fractures, tendons, and the cornea. However, our understanding of the mechanisms behind the SOX family's involvement in wound healing is limited compared to its role in cancer. Gaining insight into its role, distribution, interaction with other factors, and modifications in traumatized tissues could provide valuable new knowledge about wound healing. Based on current research, SOX2, SOX7, and SOX9 are the most promising members of the SOX family for future interventions in wound healing. SOX2 and SOX9 promote the renewal of cells, while SOX7 enhances the microvascular environment. The SOX family holds significant potential for advancing wound healing research. This article provides a comprehensive review of the latest research advancements and therapeutic tools related to the SOX family in wound healing, as well as the potential benefits and challenges of targeting the SOX family for wound treatment.


Asunto(s)
Factores de Transcripción SOX , Cicatrización de Heridas , Factores de Transcripción SOX/genética , Piel , Medicina Regenerativa
5.
Int Immunopharmacol ; 123: 110779, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37582313

RESUMEN

Skin wound healing is a multifaceted and intricate process involving inflammation, tissue proliferation, and scar formation, all of which are accompanied by the continuous application of mechanical forces. Mechanotransduction is the mechanism by which the skin receives and reacts to physical signals from the internal and external environment, converting them into intracellular biochemical signals. This intricate process relies on specialized proteins known as mechanotransducers, with Piezo1 being a critical mechanosensitive ion channel that plays a central role in this process. This article provides an overview of the structural characteristics of Piezo1 and summarizes its effects on corresponding cells or tissues at different stages of skin trauma, including how it regulates skin sensation and skin-related diseases. The aim is to reveal the potential diagnostic and therapeutic value of Piezo1 in skin trauma and skin-related diseases. Piezo1 has been reported to be a vital mediator of mechanosensation and transduction in various organs and tissues. Given its high expression in the skin, Piezo1, as a significant cell membrane ion channel, is essential in activating intracellular signaling cascades that trigger several cellular physiological functions, including cell migration and muscle contraction. These functions contribute to the regulation and improvement of wound healing.


Asunto(s)
Canales Iónicos , Mecanotransducción Celular , Membrana Celular/metabolismo , Movimiento Celular , Mecanotransducción Celular/fisiología , Transducción de Señal , Humanos
6.
Biochem Pharmacol ; 215: 115736, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37549795

RESUMEN

In the past, neuropeptide substance P (SP) was predominantly recognized as a neuroinflammatory factor, while its potent healing activity was overlooked. This paper aims to review the regulatory characteristics of neuropeptide SP in both normal and diabetic wound healing. SP actively in the regulation of wound healing-related cells directly and indirectly, exhibiting robust inflammatory properties, promoting cell proliferation and migration and restoring the activity and paracrine ability of skin cells under diabetic conditions. Furthermore, SP not only regulates healing-related cells but also orchestrates the immune environment, thereby presenting unique and promising application prospects in wound intervention. As new SP-based preparations are being explored, SP-related drugs are poised to become an effective therapeutic intervention for diabetic foot ulcers (DFU).


Asunto(s)
Diabetes Mellitus , Pie Diabético , Humanos , Pie Diabético/tratamiento farmacológico , Sustancia P/farmacología , Sustancia P/uso terapéutico , Cicatrización de Heridas , Piel , Proliferación Celular
7.
Sci Adv ; 9(18): eadf4589, 2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37146149

RESUMEN

The design of Faradaic battery electrodes with high rate capability and long cycle life comparable to those of supercapacitors is a grand challenge. Here, we bridge this performance gap by taking advantage of a unique ultrafast proton conduction mechanism in vanadium oxide electrode, developing an aqueous battery with untrahigh rate capability up to 1000 C (400 A g-1) and extremely long life of 0.2 million cycles. The mechanism is elucidated by comprehensive experimental and theoretical results. Instead of slow individual Zn2+ transfer or Grotthuss chain transfer of confined H+, the ultrafast kinetics and excellent cyclic stability are enabled by rapid 3D proton transfer in vanadium oxide via the special pair dance switching between Eigen and Zundel configurations with little constraint and low energy barriers. This work provides insight into developing high-power and long-life electrochemical energy storage devices with nonmetal ion transfer through special pair dance topochemistry dictated by hydrogen bond.

8.
Sci Adv ; 9(17): eade9510, 2023 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-37115923

RESUMEN

The colonization and expansion of plants on land is considered one of the most profound ecological revolutions, yet the precise timing remains controversial. Because land vegetation can enhance weathering intensity and affect terrigenous input to the ocean, changes in terrestrial plant biomass with distinct negative Δ199Hg and Δ200Hg signatures may overwrite the positive Hg isotope signatures commonly found in marine sediments. By investigating secular Hg isotopic variations in the Paleozoic marine sediments from South China and peripheral paleocontinents, we highlight distinct negative excursions in both Δ199Hg and Δ200Hg at Stage level starting in the early Silurian and again in the Carboniferous. These geochemical signatures were driven by increased terrestrial contribution of Hg due to the rapid expansion of vascular plants. These excursions broadly coincide with rising atmospheric oxygen concentrations and global cooling. Therefore, vascular plants were widely distributed on land during the Ordovician-Silurian transition (~444 million years), long before the earliest reported vascular plant fossil, Cooksonia (~430 million years).


Asunto(s)
Monitoreo del Ambiente , Mercurio , Isótopos de Mercurio/análisis , Isótopos , Plantas
9.
Small ; 19(1): e2205071, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36366943

RESUMEN

High-capacity electrochemical energy storage systems are more urgently needed than ever before with the rapid development of electric vehicles and the smart grid. The most efficient way to increase capacity is to develop electrode materials with low molecular weights. The low-cost metal halides are theoretically ideal cathode materials due to their advantages of high capacity and redox potential. However, their cubic structure and large energy barrier for deionization impede their rechargeability. Here, the reversibility of potassium halides, lithium halides, sodium halides, and zinc halides is achieved through decreasing their dimensionality by the strong π-cation interactions between metal cations and reduced graphene oxide (rGO). Especially, the energy densities of KI-, KBr-, and KCl-based materials are 722.2, 635.0, and 739.4 Wh kg-1 , respectively, which are higher than those of other cathode materials for potassium-ion batteries. In addition, the full-cell with 2D KI/rGO as cathode and graphite as anode demonstrates a lifespan of over 150 cycles with a considerable capacity retention of 57.5%. The metal halides-based electrode materials possess promising application prospects and are worthy of more in-depth researches.


Asunto(s)
Grafito , Compuestos Inorgánicos , Metales , Potasio
10.
Front Surg ; 9: 1009949, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36311920

RESUMEN

Situs inversus totalis (SIT) is a rare internal laterality disorder characterized by the mirror arrangement of organs. Multiple gene mutations and maternal environmental factors are thought to cause this variation. It is usually challenging to perform laparoscopic surgery in these cases. Bladder diverticulum is uncommon in children, with an incidence of 1.7%. We report a 14-year-old male patient who was admitted to our department because of lower abdominal pain and frequent urination. A series of examinations confirmed the rare combination of giant bladder diverticulum and SIT. After extensive preoperative discussion, we performed laparoscopic bladder diverticulectomy. The operation was successful. To the best of our knowledge, this is the first report of successful laparoscopic bladder surgery on a case of SIT. This article summarizes the key technical points and the difficulties of performing this kind of operation. In addition, during the process of reviewing the literature, we found that SIT often coexists with some high-risk factors for bladder diverticulum in some rare syndromes. It is helpful to further understand and provide experience in the diagnosis and treatment of the rare combination of bladder diverticulum and SIT in children.

11.
Proc Natl Acad Sci U S A ; 119(19): e2115231119, 2022 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-35500118

RESUMEN

Piecing together the history of carbon (C) perturbation events throughout Earth's history has provided key insights into how the Earth system responds to abrupt warming. Previous studies, however, focused on short-term warming events that were superimposed on longer-term greenhouse climate states. Here, we present an integrated proxy (C and uranium [U] isotopes and paleo CO2) and multicomponent modeling approach to investigate an abrupt C perturbation and global warming event (∼304 Ma) that occurred during a paleo-glacial state. We report pronounced negative C and U isotopic excursions coincident with a doubling of atmospheric CO2 partial pressure and a biodiversity nadir. The isotopic excursions can be linked to an injection of ∼9,000 Gt of organic matter­derived C over ∼300 kyr and to near 20% of areal extent of seafloor anoxia. Earth system modeling indicates that widespread anoxic conditions can be linked to enhanced thermocline stratification and increased nutrient fluxes during this global warming within an icehouse.


Asunto(s)
Calentamiento Global , Agua de Mar , Carbono/análisis , Humanos , Hipoxia , Océanos y Mares
12.
Mater Horiz ; 8(7): 2032-2040, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-34846480

RESUMEN

Responsive chromic materials are highly desirable in the fields of displays, anti-counterfeiting, and camouflage, but their advanced applications are usually limited by the unrealized delicate and independent tunability of their three intrinsic attributes of color. This work achieves the separate, continuous, and reversible modulation of structural color brightness and hue with an aqueous suspension of dual-responsive Fe3O4@polyvinylpyrrolidone (PVP)@poly(N-isopropyl acrylamide) (PNIPAM) flexible photonic nanochains. The underlying modulation mechanism of color brightness was experimentally and numerically deciphered by analyzing the morphological responses to stimuli. When an increasing magnetic field was applied, the random worm-like flexible photonic nanochains gradually orientated along the field direction, due to the dominant magnetic dipole interaction over the thermal motion, lengthening the orientation segment length up to the whole of the nanochains. Consequently, the suspension displays increased color brightness (characterized by diffraction intensity). Meanwhile, the color hue (characterized by diffraction frequency) could be controlled by temperature, due to the volume changes of the interparticle PNIPAM. The achieved diverse color modulation advances the next-generation responsive chromic materials and enriches the basic understanding of the color tuning mechanisms. With versatile and facile color tunability and shape patterning, the developed responsive chromic liquid promises to have attractive potential in full-color displays and in adaptive camouflages.

13.
Adv Sci (Weinh) ; 8(19): e2101584, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34342178

RESUMEN

A disordered phase in Li-deposit nanostructure is greatly attractive, but plagued by the uncontrollable and unstable growth, and the nanoscale characterization in the structure. Here, fully characterized in cryogenic transmission electron microscopy (cryo-TEM), more robust amorphous-Li (ALi) clusters are revealed and effectively regulated on heteroatom-activating electronegative sites and an advanced solid electrolyte interphase (SEI) layer. Heteroatom-activating electronegative sites capably enhance the electrostatic interaction of Li+ and heteroatom-doping graphene-like film (HDGs), meaning lower Li diffusion barrier and larger binding energy that is confirmed by small nucleation overpotentials of 13.9 and 10 mV at 0.1 mA cm-2 in the fluoroethylene carbonate-adding ester-based (FEC-ester) and LiNO3 -adding ether-based (LiNO3 -ether) electrolytes. Orderly multilayer SEI structure comprised of inorganic-rich components enables fast ion transports and durable capabilities to construct highly reversible and long-term plating/stripping cycling. ALi cluster anodes exhibit non-crystalline morphologies and perform ultrastable dendrite-free cycling over 2800 times. Stable ALi clusters are also grown in LiFePO4 (LFP) (LFP-ALi-HDGs-N||LiFePO4 [LFP]) full cells with advantageous capacities up to 165.5 and 164.3 mAh g-1 in these optimized electrolytes at 0.1 C; the remarkable capacity retentions maintain to 93% and 91% after 150 cycles at 0.2 C. Structure viability, electrochemical reversibility, and excellent performance in ALi clusters are effectively regulated.

14.
ACS Appl Mater Interfaces ; 13(25): 29746-29754, 2021 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-34128657

RESUMEN

Aqueous zinc (Zn)-ion batteries are considered very promising in grid-scale energy storage systems. However, the dendrite, corrosion, and H2 evolution issues of Zn anode have restricted their further applications. Herein, to solve these issues, a hydrophilic layer, consisting of a covalent organic polymer (COP) and carboxylmethyl cellulose (CMC), is designed to in situ construct a multifunctional quasi-gel (COP-CMC/QG) interface between Zn metal and the electrolyte. The COP-CMC/QG interface can significantly improve the rechargeability of the Zn anode through enhancing Zn2+ transport kinetics, guiding uniform nucleation, and suppressing Zn corrosion and H2 evolution. As a result, the COP-CMC-Zn anode exhibits a reduced overpotential (12 mV at 0.25 mA cm-2), prolonged cycle life (over 4000 h at 0.25 mA cm-2 and 2000 h at 5 mA cm-2 in symmetrical cells), and elevated full-cell (Zn/MnO2) performance. This work provides an efficient approach to achieve long-life Zn metal anodes and paves the way toward high-performance Zn-based and other metal-ion batteries.

15.
Biosci Rep ; 40(6)2020 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-32436952

RESUMEN

BACKGROUND: Heat stroke (HS) is a physically dysfunctional illness caused by hyperthermia. Lung, as the important place for gas-exchange and heat-dissipation organ, is often first to be injured. Lung injury caused by HS impairs the ventilation function of lung, which will subsequently cause damage to other tissues and organs. Nevertheless, the specific mechanism of lung injury in heat stroke is still unknown. METHODS: Rat lung tissues from controls or HS models were harvested. The gene expression profile was identified by high-throughput sequencing. DEGs were calculated using R and validated by qRT-PCR. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and cell-enrichment were performed using differential expression genes (DEGs). Finally, lung histopathology was accessed by H&E staining. RESULTS: About 471 genes were identified to be DEGs, of which 257 genes were up-regulated, and 214 genes were down-regulated. The most up-regulated and down-regulated DEGs were validated by qRT-PCR, which confirmed the tendency of expression. GO, KEGG, and protein-protein interaction (PPI)-network analyses disclosed DEGs were significantly enriched in leukocyte migration, response to lipopolysaccharide, NIK/NF-kappaB signaling, response to reactive oxygen species, response to heat, and the hub genes were Tnf, Il1b, Cxcl2, Ccl2, Mmp9, Timp1, Hmox1, Serpine1, Mmp8 and Csf1, most of which were closely related to inflammagenesis and oxidative stress. Finally, cell-enrichment analysis and histopathologic analysis showed Monocytes, Megakaryotyes, and Macrophages were enriched in response to heat stress. CONCLUSIONS: The present study identified key genes, signal pathways and infiltrated-cell types in lung after heat stress, which will deepen our understanding of transcriptional response to heat stress, and might provide new ideas for the treatment of HS.


Asunto(s)
Citocinas/genética , Golpe de Calor/genética , Pulmón/metabolismo , Estrés Oxidativo/genética , Neumonía/genética , Transcriptoma , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Golpe de Calor/metabolismo , Golpe de Calor/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Mediadores de Inflamación/metabolismo , Pulmón/patología , Masculino , Neumonía/metabolismo , Neumonía/patología , Mapas de Interacción de Proteínas , Ratas Wistar , Transducción de Señal
16.
ACS Appl Mater Interfaces ; 12(18): 20423-20428, 2020 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-32275385

RESUMEN

The room-temperature liquid anode is a feasible method for building dendrite-free alkali-metal-based batteries. The Na-K phase diagram shows a eutectic point as low as 260.53 K with a long liquid range below 298 K with the molar fraction of potassium ranging from 30.48 to 84.99%. However, the NaK alloy exhibits a very high surface tension preventing it from wetting the current collector surface. Herein, a novel homogeneous dual solid-liquid composite in which the liquid alloy is fixed by the solid Na15Sn4 phase and perfectly stuffed into the grid of the mesh has been designed and fabricated. Based on the liquid range of the NaK alloy, the Na-K-Sn mixture possesses a theoretical specific capacity of 768 mAh g-1. The symmetric cells of the Na-K-Sn@mesh electrodes cycled at 2.0 mA cm-2 with 1.0 mAh cm-2 showed little fluctuations with the stable overpotential of ∼200 mV for 550 h, and the full cell coupled with Na3V2(PO4)3 showed an initial discharge capacity of 103 mAh g-1 at 2 C with a retention of 90% after 800 cycles. When the high-loading Na3V2(PO4)3 electrode is applied in the full cell, a stable cycling life is still maintained with a good capacity retention of 86% over 190 cycles (2.7 mAh cm-2) and 91% over 60 cycles (5.2 mAh cm-2).

17.
Adv Mater ; 32(16): e2000074, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32130746

RESUMEN

Aqueous energy-storage systems have attracted wide attention due to their advantages such as high security, low cost, and environmental friendliness. However, the specific chemical properties of water induce the problems of narrow electrochemical stability window, low stability of water-electrode interface reactions, and dissolution of electrode materials and intermediate products. Therefore, new low-cost aqueous electrolytes with different water chemistry are required. The nature of water depends largely on its hydroxyl-based hydrogen bonding structure. Therefore, the super-concentrated hydroxyl-rich sugar solutions are designed to change the original hydrogen bonding structure of water. The super-concentrated sugars can reduce the free water molecules and destroy the tetrahedral structure, thus lowering the binding degree of water molecules by breaking the hydrogen bonds. The ionic electrolytes based on super-concentrated sugars have the expanded electrochemical stability window (up to 2.812 V), wide temperature adaptability (-50 to 80 °C), and fair ionic conductivity (8.536 mS cm-1 ). Aqueous lithium-, sodium-, potassium-ion batteries and supercapacitors using super-concentrated sugar-based electrolytes demonstrate an excellent electrochemical performance. The advantages of ultralow cost and high universality enable a great practical application potential of the super-concentrated sugar-based aqueous electrolytes, which can also provide great experimental and theoretical assistance for further research in water chemistry.

18.
ACS Appl Mater Interfaces ; 12(8): 9347-9354, 2020 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-31994863

RESUMEN

Aqueous zinc-ion batteries (AZIBs) are one of the promising choices for the future large-scale grid energy storage, in which Mn-based cathode materials have the advantages of low cost and environmental friendliness. However, their capacity delivery and cycling stability are limited by the large bulk-induced incomplete zincation and structure pulverization. Here, we develop a strategy of epitaxial polymerization in the liquid phase to fabricate two-dimensional (2D) MnOx/polypyrrole nanosheets to enhance the zinc-ion storage by realizing the efficient utilization of active materials and improving the structural stability via a polymerized framework. An ultrahigh capacity of 408 mAh g-1 is demonstrated at 1C rate, and an excellent capacity retention of 78% is realized after 2800 cycles at 5C rate for the AZIB. Electrochemical and morphological characterizations reveal that the unique 2D structure contributes to both the electron/ion conductivity and structural stability. The epitaxial polymerization of the conducting polymer in the liquid phase provides a new perspective to the synthesis of high-performance electrode materials and 2D conducting polymers.

19.
Life Sci ; 239: 116966, 2019 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-31626790

RESUMEN

AIMS: Enhanced aerobic glycolysis is an essential hallmark of malignant cancer. Blocking the glycolytic pathway has been suggested as a therapeutic strategy to impair the proliferation of tumor cells. Metformin, a widely used anti-diabetes drug, exhibits anti-tumor properties. However, the underlying molecular mechanism of its action linking glucose metabolism with the suppression of proliferation has not been fully clarified. MAIN METHODS: Stable isotope tracing technology and gas chromatography-mass spectrometry method were utilized to analyze the effect of metformin on glycolytic flux in HCC cells. Western blot and immunohistochemistry were utilized to analyze the expression of phosphofructokinase-1 (PFK1) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in HCC cells or xenograft tumor tissues. Lactate measurement and glucose uptake assay were used to analyze the level of lactate and glucose in the presence of frucose-2,6-diphosphate (F2,6BP) in HCC cells treated with metformin. KEY FINDINGS: We found that metformin significantly impaired hepatoma cell proliferation by inhibiting the glycolytic flux via PFK1 blockade. Interestingly, activation of PFK1 by F2,6BP reverses the inhibitory effect of metformin on hepatoma cell proliferation and glycolysis. Mechanistically, PFKFB3,a potent allosteric activator of PFK1, was markedly suppressed through inhibiting hypoxia-induced factor 1 (HIF-1α) accumulation mediated by metformin. SIGNIFICANCE: Taken together these data indicate that HIF-1α/PFKFB3/PFK1 regulatory axis is a vital determinant of glucose metabolic reprogramming in hepatocellular carcinoma, which gives new insights into the action of metformin in combatting liver cancer.


Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Glucólisis/efectos de los fármacos , Metformina/farmacología , Animales , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclo del Ácido Cítrico , Glucosa/metabolismo , Células Hep G2 , Humanos , Hipoglucemiantes , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Masculino , Metformina/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fosfofructoquinasa-1/metabolismo , Fosfofructoquinasa-2/metabolismo , Fosforilación , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
20.
Comput Methods Programs Biomed ; 175: 1-7, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31104698

RESUMEN

BACKGROUND AND OBJECTIVE: Periodically rotated overlapping parallel lines with enhanced reconstruction-echo planar imaging (PROPELLER-EPI) is a promising technique for non-sedated functional imaging due to its unique advantage of motion correction. However, its multiple-blades sampling blood-oxygen-level dependent (BOLD) signal leads to low sampling rate and aliasing of higher frequency physiological signal components such as the cardiac pulsation. METHODS: In this study, we use near infrared spectroscopy (NIRS) synchronized with pulse sequences of PROPELLER-EPI, utilizing the fact that the optical sensing speed is inherently high. NIRS measures changes of oxyhemoglobin and deoxyhemoglobin to identify the transient states of on-BOLD and off-BOLD, and then labels each blade by temporal co-registration. The labeled blades from multiple epochs of a functional experiment are then used for the k-space data combination and subsequent image reconstruction. An eigenfunction model is proposed for temporal co-registration and to quantify the temporal resolution of the hemodynamic response. RESULT: The experiment of NIRS labeled PROPELLER-EPI was carried out with the optical sampling rate of 10 Hz and the magnetic pulses repetition time of 1000 ms, and the temporal resolution is 20 times better than that of the state-of-the-art sliding-window PROPELLER-EPI. We compared the functional imaging results against the conventional magnetic resonance echo planar imaging-measured activity and achieved an accuracy of 0.9. CONCLUSIONS: Using the synchronization of NIRS, the proposed imaging scheme provides an effective way to implement PROPELLER-EPI, which features motion free, high SNR, and enhanced spatial-temporal resolution.


Asunto(s)
Imagen Eco-Planar , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética , Espectroscopía Infrarroja Corta , Artefactos , Hemodinámica , Hemoglobinas/análisis , Humanos , Modelos Estadísticos , Movimiento (Física) , Oxígeno/sangre , Oxihemoglobinas/análisis , Reproducibilidad de los Resultados , Relación Señal-Ruido
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