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1.
Angew Chem Int Ed Engl ; 63(22): e202402943, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38529715

RESUMEN

Porous aromatic frameworks (PAFs) show promising potential in anionic conduction due to their high stability and customizable functionality. However, the insolubility of most PAFs presents a significant challenge in their processing into membranes and subsequent applications. In this study, continuous PAF membranes with adjustable thickness were successfully created using liquid-solid interfacial polymerization. The rigid backbone and the stable C-C coupling endow PAF membrane with superior chemical and dimensional stabilities over most conventional polymer membranes. Different quaternary ammonium functionalities were anchored to the backbone through flexible alkyl chains with tunable length. The optimal PAF membrane exhibited an OH- conductivity of 356.6 mS ⋅ cm-1 at 80 °C and 98 % relative humidity. Additionally, the PAF membrane exhibited outstanding alkaline stability, retaining 95 % of its OH- conductivity after 1000 hours in 1 M NaOH. To the best of our knowledge, this is the first application of PAF materials in anion exchange membranes, achieving the highest OH- conductivity and exceptional chemical/dimensional stability. This work provides the possibility for the potential of PAF materials in anionic conductive membranes.

2.
Adv Mater ; : e2400099, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38481340

RESUMEN

Multifunctional flexible electronics present tremendous opportunities in the rapidly evolving digital age. One potential avenue to realize this goal is the integration of polyoxometalates (POMs) and ionic liquid-based gels (ILGs), but the challenge of macrophase separation due to poor compatibility, especially caused by repulsion between like-charged units, poses a significant hurdle. Herein, the possibilities of producing diverse and homogenous POMs-containing ionohydrogels by nanoconfining POMs and ionic liquids (ILs) within an elastomer-like polyzwitterionic hydrogel using a simple one-step random copolymerization method, are expanded vastly. The incorporation of polyzwitterions provides a nanoconfined microenvironment and effectively modulates excessive electrostatic interactions in POMs/ILs/H2 O blending system, facilitating a phase transition from macrophase separation to a submillimeter scale worm-like microphase-separation system. Moreover, combining POMs-reinforced ionohydrogels with a developed integrated self-powered sensing system utilizing strain sensors and Zn-ion hybrid supercapacitors has enabled efficient energy storage and detection of external strain changes with high precision. This work not only provides guidelines for manipulating morphology within phase-separation gelation systems, but also paves the way for developing versatile POMs-based ionohydrogels for state-of-the-art smart flexible electronics.

3.
Biochem Genet ; 62(2): 814-830, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37460862

RESUMEN

DTX3L (Deltex E3 ubiquitin ligase 3 L) is an E3 ubiquitin ligase, a member of the deltex family. It is also known as B-lymphoma and BAL-associated protein (BBAP). DTX3L has been proven to play an important role in various tumor development; however, its role in pancreatic cancer remains unknown. So, we analyzed the DTX3L expression in pancreatic cancer based on the TCGA database and verified it in our samples by qRT­PCR and western blot. We identified that DTX3L was highly expressed in pancreatic cancer, and its expression level was significantly negatively correlated with patients' survival. Using CCK8, colony formation, transwell, and wound healing assays, we found that upregulated DTX3L promotes pancreatic cancer cell proliferation, invasion, and migration. Mechanically, DTX3L combined with EGFR (epidermal growth factor receptor) and prevented the ubiquitination degradation of it. Upregulated EGFR activated the FAK/PI3K/Akt pathway and promoted the progression of pancreatic cancer. Moreover, we found that DTX3L can weaken pancreatic cancer cells' sensitivity to chemotherapy using the orthotopic implant tumor model. In conclusion, DTX3L accelerates pancreatic cancer progression by EGFR dependent FAK/PI3K/Akt pathway activation and may become a potential target for pancreatic cancer treatment.

4.
Small ; 20(16): e2308499, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38009797

RESUMEN

Efficient construction of proton transport channels in proton exchange membranes maintaining conductivity under varied humidity is critical for the development of fuel cells. Covalent organic frameworks (COFs) hold great potential in providing precise and fast ion transport channels. However, the preparation of continuous free-standing COF membranes retaining their inherent structural advantages to realize excellent proton conduction performance is a major challenge. Herein, a zwitterionic COF material bearing positive ammonium ions and negative sulphonic acid ions is developed. Free-standing COF membrane with adjustable thickness is constructed via surface-initiated polymerization of COF monomers. The porosity, continuity, and stability of the membranes are demonstrated via the transmission electron microscopy (TEM), atomic force microscopy (AFM), and scanning electron microscopy (SEM) characterization. The rigidity of the COF structure avoids swelling in aqueous solution, which improves the chemical stability of the proton exchange membranes and improves the performance stability. In the higher humidity range (50-90%), the prepared zwitterionic COF membrane exhibits superior capability in retaining the conductivity compared to COF membrane merely bearing sulphonic acid group. The established strategy shows the potential for the application of zwitterionic COF in the proton exchange membrane fuel cells.

5.
Inorg Chem ; 62(49): 20506-20512, 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-37988635

RESUMEN

Materials with high proton conductivity have attracted significant attention for their wide-ranging applications in proton exchange membrane fuel cells. However, the design of new and efficient porous proton-conducting materials remains a challenging task. The structure-controllable and highly stable metal phosphates can be synthesized into layer or frame networks to provide proton transport capabilities. Herein, we have successfully synthesized three isomorphic metal phosphovanadates, namely, H2(C2H10N2)2[MII(H2O)2(VIVO)8(OH)4(PO4)4(HPO4)4] (C2H8N2 = 1,2-ethylenediamine; M = Co, Ni, and Cu), by the hydrothermal method employing ethylenediamine as a template. These pure inorganic open frameworks exhibit a cavity width ranging from 6.4 to 7.5 Å. Remarkably, the proton conductivity of compounds 1-3 can reach 1 × 10-2 S·cm-1 at 85 °C and 97% relative humidity (RH), and they can remain stable at high temperatures as well as long-term stability. This work provides a novel strategy for the development and design of porous proton-conducting materials.

6.
Chem Commun (Camb) ; 59(90): 13446-13449, 2023 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-37877313

RESUMEN

The assembly of [Mo2O2S2]2+ units depends on the configuration of polydentate phosphonic acid templates, leading to novel topologies with enhanced nuclearity and complexity. The variation of the assembled structures also gives rise to distinct proton-conducting properties.

7.
Mol Ther ; 31(9): 2734-2754, 2023 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-37415332

RESUMEN

Gastrin-releasing peptide (GRP) binds to its receptor (GRP receptor [GRPR]) to regulate multiple biological processes, but the function of GRP/GRPR axis in acute kidney injury (AKI) remains unknown. In the present study, GRPR is highly expressed by tubular epithelial cells (TECs) in patients or mice with AKI, while histone deacetylase 8 may lead to the transcriptional activation of GRPR. Functionally, we uncovered that GRPR was pathogenic in AKI, as genetic deletion of GRPR was able to protect mice from cisplatin- and ischemia-induced AKI. This was further confirmed by specifically deleting the GRPR gene from TECs in GRPRFlox/Flox//KspCre mice. Mechanistically, we uncovered that GRPR was able to interact with Toll-like receptor 4 to activate STAT1 that bound the promoter of MLKL and CCL2 to induce TEC necroptosis, necroinflammation, and macrophages recruitment. This was further confirmed by overexpressing STAT1 to restore renal injury in GRPRFlox/Flox/KspCre mice. Concurrently, STAT1 induced GRP synthesis to enforce the GRP/GRPR/STAT1 positive feedback loop. Importantly, targeting GRPR by lentivirus-packaged small hairpin RNA or by treatment with a novel GRPR antagonist RH-1402 was able to inhibit cisplatin-induced AKI. In conclusion, GRPR is pathogenic in AKI and mediates AKI via the STAT1-dependent mechanism. Thus, targeting GRPR may be a novel therapeutic strategy for AKI.


Asunto(s)
Lesión Renal Aguda , Cisplatino , Animales , Ratones , Cisplatino/efectos adversos , Necroptosis , Lesión Renal Aguda/metabolismo , Riñón/metabolismo , Inflamación/metabolismo , Ratones Endogámicos C57BL
8.
Angew Chem Int Ed Engl ; 62(30): e202306193, 2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37269225

RESUMEN

Polyoxometalates (POMs) are considered as promising catalysts with unique redox activity at the molecular level for energy storage. However, eco-friendly iron-oxo clusters with special metal coordination structures have rarely been reported for Li-ion storage. Herein, three novel redox-active tetranuclear iron-oxo clusters have been synthesized using the solvothermal method with different ratios of Fe3+ and SO4 2- . Further, they can serve as anode materials for Li-ion batteries. Among them, cluster H6 [Fe4 O2 (H2 O)2 (SO4 )7 ]⋅H2 O, the stable structure extended by SO4 2- with a unique 1D pore, displays a specific discharge capacity of 1784 mAh g-1 at 0.2 C and good cycle performance (at 0.2 C and 4 C). This is the first instance of inorganic iron-oxo clusters being used for Li-ion storage. Our findings present a new molecular model system with a well-defined structure and offer new design concepts for the practical application of studying the multi-electron redox activity of iron-oxo clusters.

9.
Angew Chem Int Ed Engl ; 62(34): e202304797, 2023 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-37376764

RESUMEN

Electrocatalytic nitrogen reduction reaction (NRR) under ambient conditions provides an intriguing pathway to convert N2 into NH3 . However, significant kinetic barriers of the NRR at low temperatures in desirable aqueous electrolytes remain a grand challenge due to the inert N≡N bond of the N2 molecule. Herein, we propose a unique strategy for in situ oxygen vacancy construction to address the significant trade-off between N2 adsorption and NH3 desorption by building a hollow shell structured Fe3 C/Fe3 O4 heterojunction coated with carbon frameworks (Fe3 C/Fe3 O4 @C). In the heterostructure, the Fe3 C triggers the oxygen vacancies of the Fe3 O4 component, which are likely active sites for the NRR. The design could optimize the adsorption strength of the N2 and Nx Hy intermediates, thus boosting the catalytic activity for the NRR. This work highlights the significance of the interaction between defect and interface engineering for regulating electrocatalytic properties of heterostructured catalysts for the challenging NRR. It could motivate an in-depth exploration to advance N2 reduction to ammonia.

10.
Nat Commun ; 14(1): 2767, 2023 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-37179336

RESUMEN

Inorganic salts usually demonstrate simple phasal behaviors in dilute aqueous solution mainly involving soluble (homogeneous) and insoluble (macrophase separation) scenarios. Herein, we report the discovery of complex phase behavior involving multiple phase transitions of clear solution - macrophase separation - gelation - solution - macrophase separation in the dilute aqueous solutions of a structurally well-defined molecular cluster [Mo7O24]6- macroanions with the continuous addition of Fe3+. No chemical reaction was involved. The transitions are closely related to the strong electrostatic interaction between [Mo7O24]6- and their Fe3+ counterions, the counterion-mediated attraction and the consequent charge inversion, leading to the formation of linear/branched supramolecular structures, as confirmed by experimental results and molecular dynamics simulations. The rich phase behavior demonstrated by the inorganic cluster [Mo7O24]6- expands our understanding of nanoscale ions in solution.

11.
J Environ Manage ; 331: 117252, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36642052

RESUMEN

This paper discusses the compensation standard for exhaust pollution and devises a compensation mechanism for Macao's tourism-related transport sector based on an integration of chemical exergy and universal exergy, using data on gasoline consumption by automobile sector retrieved from the transportation industry. The results reveal that: (1) the exergy values of air pollutant emissions increased from 1.53 × 1012 kJ in 2010 to 2.03 × 1012 kJ in 2019 (an increase of 1.33 times), and the exergy of CO, NOx, and SO2 emissions accounted for 77.5%, 20.4% and 2.1% of total exhaust emissions in Macao respectively. (2) In 2019, the monetary value of emission exergy, and the environmental costs of air pollution, were 1.7 times greater than in 2010. (3) If Light Rail Transit is compensated for, then the mean interval's values of the upper and lower limits of the compensation standard are 0.55 USD and 0.05 USD, respectively. When gasoline tax is used as a means of compensation it is necessary to raise its rate by about 8% based on the tax rate. A three-stage bargaining game model is used to provide evidence that this compensation standard is practical and acceptable.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Gasolina , Macao , Turismo , Contaminación del Aire/análisis , Emisiones de Vehículos/análisis
12.
J Am Chem Soc ; 145(4): 2243-2251, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36580675

RESUMEN

Smart molecular actuators have become a cutting-edge theme due to their ability to convert chemical energy into mechanical energy under external stimulations. However, realizing actuation at the molecular level and elucidating the mechanisms for actuating still remain challenging. Herein, we design and fabricate a novel nanoscaled polyoxometalate-based humidity-responsive molecular actuator {Bi8Mo48} through the assembly of [Mo2O2S2]2+ units, transition metals, and flexible phosphonic acid ligands. {Bi8Mo48} exhibits a semi-flexible cage-like architecture with oxygen-rich surfaces and highly negative charges 72-. The nanoscaled molecular actuator shows reversible expansion and contraction behavior under humidity variations due to lattice expansion and contraction induced by hydrogen bonding and solvation interactions between {Bi8Mo48} and water molecules. Molecular dynamics simulation was further employed to study these processes, which provides a fundamental understanding for the mechanism of humidity actuation at the molecular level.

13.
Inorg Chem ; 61(51): 21024-21034, 2022 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-36520449

RESUMEN

Spatially confined assembly of semimetallic oxyanions (AsO33- and SbO33-) within a [H7P8W48O184]33- (P8W48) macrocycle has afforded three nanoscale polyanions, [{AsIII5O4(OH)3}2(P8W48O184)]32- (As10), [(SbIIIOH)4(P8W48O184)]32- (Sb4), and [(SbIIIOH)8(P8W48O184)]24- (Sb8), which were crystallized as the hydrated mixed-cation salts (Me2NH2)13K7Na2Li10[{AsIII5O4(OH)3}2(P8W48O184)]·32H2O (DMA-KNaLi-As10), K20Li12[(SbIIIOH)4(P8W48O184)]·52H2O (KLi-Sb4), and (Me2NH2)8K6Na5Li5[(SbIIIOH)8(P8W48O184)]·65H2O (DMA-KNaLi-Sb8), respectively. A multitude of solid- and solution-state physicochemical techniques were employed to systematically characterize the structure and composition of the as-made compounds. The polyanion of As10 represents the first example of a semimetal-oxo cluster-substituted P8W48 and accommodates the largest AsIII-oxo cluster in polyoxometalates (POMs) reported to date. The number of incorporated SbO33- groups in Sb4 and Sb8 could be customized by a simple variation of SbIII-containing precursors. Encapsulation of semimetallic oxyanions inside P8W48 sets out a valid strategy not only for the development of host-guest assemblies in POM chemistry but also for their function expansion in emerging applications such as proton-conducting materials, for which DMA-KNaLi-As10 showcases an outstanding conductivity of 1.2 × 10-2 S cm-1 at 85 °C and 70% RH.

14.
ACS Appl Mater Interfaces ; 14(47): 52877-52885, 2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-36383757

RESUMEN

Alkaline water splitting is a highly efficient and clean technology for hydrogen energy generation. However, in alkaline solutions, most catalysts suffer from extreme instability. Herein, a cross-nanostructured N, F, and CO32- codoped iron oxyhydroxide composite (N,F-FeO(OH)-CO3-NF) rich in oxygen defects is designed for water splitting in the alkaline solution. X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) calculations show that the introduction of F and CO32- can induce electron redistribution around the active center Fe, accelerate the four-electron transfer process, and optimize the d-band center, thereby improving the efficiency and stability of HER and OER. In a 1 M KOH solution, N,F-FeO(OH)-CO3-NF only needs the overpotential of 248 mV for OER and the overpotential of 199 mV for HER to reach the current density of 10 mA·cm-2. Meanwhile, it can reach 100 mA·cm-2 current density at 1.55 V vs RHE and maintains a current density of 10 mA·cm-2 for 120 h in a two-electrode electrolytic water device. Compared with bulk hydroxides, the heteroatom and anion codoped composite hydroxides are more stable and have dual functions in the electrolyte solution. This is of great significance for designing a new stable water-splitting electrocatalyst.

15.
Kidney Int ; 102(4): 828-844, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35752325

RESUMEN

The novel biomarker, insulin-like growth factor binding protein 7 (IGFBP7), is used clinically to predict different types of acute kidney injury (AKI) and has drawn significant attention as a urinary biomarker. However, as a secreted protein in the circulation of patients with AKI, it is unclear whether IGFBP7 acts as a key regulator in AKI progression, and if mechanisms underlying its upregulation still need to be determined. Here we found that IGFBP7 is highly expressed in the blood and urine of patients and mice with AKI, possibly via a c-Jun-dependent mechanism, and is positively correlated with kidney dysfunction. Global knockout of IGFBP7 ameliorated kidney dysfunction, inflammatory responses, and programmed cell death in murine models of cisplatin-, kidney ischemia/reperfusion-, and lipopolysaccharide-induced AKI. IGFBP7 mainly originated from kidney tubular epithelial cells. Conditional knockout of IGFBP7 from the kidney protected against AKI. By contrast, rescue of IGFBP7 expression in IGFBP7-knockout mice restored kidney damage and inflammation. IGFBP7 function was determined in vitro using recombinant IGFBP7 protein, IGFBP7 knockdown, or overexpression. Additionally, IGFBP7 was found to bind to poly [ADP-ribose] polymerase 1 (PARP1) and inhibit its degradation by antagonizing the E3 ubiquitin ligase ring finger protein 4 (RNF4). Thus, IGFBP7 in circulation acts as a biomarker and key mediator of AKI by inhibiting RNF4/PARP1-mediated tubular injury and inflammation. Hence, over-activation of the IGFBP7/PARP1 axis represents a promising target for AKI treatment.


Asunto(s)
Lesión Renal Aguda , Inhibidor Tisular de Metaloproteinasa-2 , Adenosina Difosfato Ribosa , Animales , Biomarcadores , Cisplatino/toxicidad , Inflamación , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/genética , Lipopolisacáridos , Ratones , Ratones Noqueados , Ubiquitina-Proteína Ligasas/metabolismo
16.
Angew Chem Int Ed Engl ; 61(38): e202202650, 2022 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-35381106

RESUMEN

The oxygen reduction reaction (ORR) is a key energy conversion process, which is critical for the efficient operation of fuel cells and metal-air batteries. Here, we report the significant enhancement of the ORR-performance of commercial platinum-on-carbon electrocatalysts when operated in aqueous electrolyte solutions (pH 5.6), containing the polyoxoanion [Fe28 (µ3 -O)8 (L-(-)-tart)16 (CH3 COO)24 ]20- . Mechanistic studies provide initial insights into the performance-improving role of the iron oxide cluster during ORR. Technological deployment of the system is demonstrated by incorporation into a direct formate microfluidic fuel cell (DFMFC), where major performance increases are observed when compared with reference electrolytes. The study provides the first examples of iron oxide clusters in electrochemical energy conversion and storage.

17.
Acta Pharmacol Sin ; 43(2): 330-341, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33833407

RESUMEN

Stratifin (SFN) is a member of the 14-3-3 family of highly conserved soluble acidic proteins, which regulates a variety of cellular activities such as cell cycle, cell growth and development, cell survival and death, and gene transcription. Acute kidney injury (AKI) is prevalent disorder characterized by inflammatory response, oxidative stress, and programmed cell death in renal tubular epithelial cells, but there is still a lack of effective therapeutic target for AKI. In this study, we investigated the role of SFN in AKI and the underlying mechanisms. We established ischemic and nephrotoxic AKI mouse models caused by ischemia-reperfusion (I/R) and cisplatin, respectively. We conducted proteomic and immunohistochemical analyses and found that SFN expression levels were significantly increased in AKI patients, cisplatin- or I/R-induced AKI mice. In cisplatin- or hypoxia/reoxygenation (H/R)-treated human proximal tubule epithelial cells (HK2), we showed that knockdown of SFN significantly reduced the expression of kidney injury marker Kim-1, attenuated programmed cell death and inflammatory response. Knockdown of SFN also significantly alleviated the decline of renal function and histological damage in cisplatin-caused AKI mice in vivo. We further revealed that SFN bound to RIPK3, a key signaling modulator in necroptosis, to induce necroptosis and the subsequent inflammation in cisplatin- or H/R-treated HK2 cells. Overexpression of SFN increased Kim-1 protein levels in cisplatin-treated MTEC cells, which was suppressed by RIPK3 knockout. Taken together, our results demonstrate that SFN that enhances cisplatin- or I/R-caused programmed cell death and inflammation via interacting with RIPK3 may serve as a promising therapeutic target for AKI treatment.


Asunto(s)
Proteínas 14-3-3/metabolismo , Lesión Renal Aguda/metabolismo , Isquemia/metabolismo , Enfermedades Renales/metabolismo , Necroptosis , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Animales , Modelos Animales de Enfermedad , Técnicas de Silenciamiento del Gen , Humanos , Túbulos Renales/metabolismo , Ratones , Reacción en Cadena en Tiempo Real de la Polimerasa
18.
Angew Chem Int Ed Engl ; 60(27): 14875-14880, 2021 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-33877733

RESUMEN

As a new class of crystalline porous organic materials, covalent organic frameworks (COFs) have attracted considerable attention for proton conduction owing to their regular channels and tailored functionality. However, most COFs are insoluble and unprocessable, which makes membrane preparation for practical use a challenge. In this study, we used surface-initiated condensation polymerization of a trialdehyde and a phenylenediamine for the synthesis of sulfonic COF (SCOF) coatings. The COF layer thickness could be finely tuned from 10 to 100 nm by controlling the polymerization time. Moreover, free-standing COF membranes were obtained by sacrificing the bridging layer without any decomposition of the COF structure. Benefiting from the abundant sulfonic acid groups in the COF channels, the proton conductivity of the SCOF membrane reached 0.54 S cm-1 at 80 °C in pure water. To our knowledge, this is one of the highest values for a pristine COF membrane in the absence of additional additives.

19.
Phytomedicine ; 85: 153541, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33773190

RESUMEN

BACKGROUND: Acute kidney injury (AKI), characterised by excessive inflammatory cell recruitment and programmed cell death, has a high morbidity and mortality; however, effective and specific therapies for AKI are still lacking. OBJECTIVE: This study aimed to evaluate the renoprotective effects of gypenoside XLIX (Gyp XLIX) in AKI. METHODS: The protective effects of Gyp XLIX were tested in two AKI mouse models established using male C57BL/6 mice (aged 6-8 weeks) by a single intraperitoneal injection of cisplatin (20 mg/kg) or renal ischemia-reperfusion for 40 min. Gyp XLIX was administered intraperitoneally before cisplatin administration or renal ischemia-reperfusion. Renal function, tubular injury, renal inflammation and programmed cell death were evaluated. In addition, the renoprotective effects of Gyp XLIX were also evaluated in cisplatin- or hypoxia-treated tubular epithelial cells. The mechanisms underlying these effects were then explored using RNA sequencing. RESULTS: In vivo, Gyp XLIX substantially suppressed the increase in serum creatinine and blood urea nitrogen levels. Moreover, tubular damage was alleviated by Gyp XLIX as shown by periodic acid-Schiff staining, electron microscopy and molecular analysis of KIM-1. Consistently, we found that Gyp XLIX suppressed renal necroptosis though the RIPK1/RIPK3/MLKL pathway. The anti-inflammatory and antinecroptotic effects were further confirmed in vitro. Mechanistically, RNA sequencing showed that Gyp XLIX markedly suppressed the levels of IGF binding protein 7 (IGFBP7). Co-immunoprecipitation and western blot analysis further showed that Gyp XLIX reduced the binding of IGFBP7 to IGF1 receptor (IGF1R). Additionally, picropodophyllin, an inhibitor of IGF1R, abrogated the therapeutic effects of Gyp XLIX on cisplatin-induced renal cell injury; this finding indicated that Gyp XLIX may function by activating IGF1R-mediated downstream signalling Additionally, we also detected the metabolic distribution of Gyp XLIX after injection; Gyp XLIX had a high concentration in the kidney and exhibited a long retention time. These findings may shed light on the application of Gyp XLIX for AKI treatment clinically. CONCLUSION: Gyp XLIX may serve as a potential therapeutic agent for AKI treatment via IGFBP7/ IGF1R-dependent mechanisms.


Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Sustancias Protectoras/farmacología , Receptor IGF Tipo 1/metabolismo , Saponinas/farmacología , Lesión Renal Aguda/inducido químicamente , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Cisplatino , Humanos , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Necroptosis
20.
World J Gastroenterol ; 27(3): 240-254, 2021 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-33519139

RESUMEN

BACKGROUND: Recent studies have demonstrated that circular RNA AKT3 (circAKT3) plays a crucial role in regulating the malignant phenotypes of tumor cells. However, the potential effects of circAKT3 on esophageal cancer have not been investigated. AIM: To illuminate the role of circAKT3 in malignant behaviors of esophageal cancer cells and its underlying mechanism. METHODS: Clinical samples were collected to detect the expression of circAKT3. The role of circAKT3 in proliferation, migration, invasion, and apoptosis of esophageal cancer cells was evaluated using Cell Counting Kit-8, wound healing assays, Transwell assays, and fluorescence analysis, respectively. The target of circAKT3 was screened and identified using an online database and luciferase reporter assay. A xenograft nude mouse model was established to investigate the role of circAKT3 in vivo. RESULTS: In vitro assays showed that proliferative, migratory, and invasive capacities of esophageal cancer cells were significantly enhanced by circAKT3 overexpression. Furthermore, miR-17-5p was screened as the target of circAKT3, and miR-17-5p antagonized the effects of circAKT3 on esophageal cancer cells. Moreover, we identified RHOC and STAT3 as the direct target molecules of miR-17-5p, and circAKT3 facilitated expression of RHOC and STAT3 by inhibiting miR-17-5p. In vivo assays showed circAKT3 knockdown inhibited growth of esophageal cancer. CONCLUSION: CircAKT3 contributed to the malignant behaviors of esophageal cancer in vitro and in vivo by sponging miR-17-5p thus providing a potential target for treatment of esophageal cancer.


Asunto(s)
Neoplasias Esofágicas , MicroARNs , Animales , Línea Celular Tumoral , Proliferación Celular , Neoplasias Esofágicas/genética , Regulación Neoplásica de la Expresión Génica , Ratones , MicroARNs/genética , Proteínas Proto-Oncogénicas c-akt , ARN Circular
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