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1.
Mater Horiz ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38836844

RESUMEN

Expanding the detection information of wearable smart devices in applications has practical implications for their use in daily life and healthcare. Damage and breakage caused by mechanical injuries and continuous use are unavoidable for polymer matrices so self-healing properties are expected to be conferred on flexible sensors to extend their life and durability. In addition, a good linearity of relative resistance change vs. strain (gauge factor, GF) facilitates the streamlined conversion of electrical signals to 3D information of human motion, whereas existing works on sensors neglect the quantitative analysis of signals. This letter reports a self-healable flexible electronic sensor based on hydrogen bonding and electrostatic interaction between maleic acid-grafted natural rubber (MNR), polyaniline (PANI), and phytic acid (PA). MNR is the flexible matrix and the template for aniline (ANI) polymerization, and PA acts as the dopant and crosslinking agent. The MNR-PANI-PA sensor shows easy self-healing at room temperature, enhanced mechanical behaviour (∼2.5 MPa, 1000% strain), and excellent linearity (GF of 13.8 over 250% strain and GF of 32.0 over 250-100% strain). Due to the highly linear relationship between ΔR/R and bending angle, the electrical signals of human limb movement can output relevant information on bending angle and frequency. By constructing a sensing array, changes in the position and magnitude of applied pressure could also be detected in real-time. Based on these advantages, the MNR-PANI-PA composite sensor is expected to have potential applications in health monitoring, body motion detection, and electronic skins.

2.
J Colloid Interface Sci ; 671: 505-515, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38815386

RESUMEN

Dendrite growth and side reactions of zinc metal anode have severely limited the practical application of aqueous zinc ion batteries (AZIBs). Herein, we introduce an artificial buffer layer composed of functional MXene (Ti3CN) for zinc anodes. The synthesized Ti3CN exhibits superior conductivity and features duplex zincophilic sites (N and F). These characteristics facilitate the homogeneous deposition of Zn2+, accelerate the desolvation process of hydrated Zn2+, and reduce the nucleation overpotential. The Ti3CN-protected Zn anode demonstrates significantly enhanced reversibility compared to bare Zn anode during long-term cycling, achieving a cumulative plating capacity of 10,000 mAh cm-2 at 10 mA cm-2. In Ti3CN-Zn||Cu asymmetric cell, it maintains nearly 100 % Coulombic efficiency over 2500 cycles at 2 mA cm-2. Furthermore, the assembled Ti3CN-Zn//δ-K0.51V2O5 (KVO) full cell exhibit a low capacity decay rate of 0.002 % per cycle at 5 A/g. Even at 0 °C, the Ti3CN-Zn symmetric cell maintains steady cycling for 2000 h. This study introduces a novel approach for designing artificial solid electrolyte interlayers for commercial AZIBs.

3.
Animals (Basel) ; 14(10)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38791715

RESUMEN

The gut microbiota plays a crucial role in the host's metabolic processes. Many studies have shown significant changes in the gut microbiota of mammals during hibernation to adapt to the changes in the external environment, but there is limited research on the colonic epithelial tissue and gut microbiota of the wild chipmunks during hibernation. This study analyzed the diversity, composition, and function of the gut microbiota of the wild chipmunk during hibernation using 16S rRNA gene high-throughput sequencing technology, and further conducted histological analysis of the colon. Histological analysis of the colon showed an increase in goblet cells in the hibernation group, which was an adaptive change to long-term fasting during hibernation. The dominant gut microbial phyla were Bacteroidetes, Firmicutes, and Proteobacteria, and the relative abundance of them changed significantly. The analysis of gut microbiota structural differences indicated that the relative abundance of Helicobacter typhlonius and Mucispirillum schaedleri increased significantly, while unclassified Prevotella-9, unclassified Prevotellaceae-UCG-001, unclassified Prevotellaceae-UCG-003 and other species of Prevotella decreased significantly at the species level. Alpha diversity analysis showed that hibernation increased the diversity and richness of the gut microbiota. Beta diversity analysis revealed significant differences in gut microbiota diversity between the hibernation group and the control group. PICRUSt2 functional prediction analysis of the gut microbiota showed that 15 pathways, such as lipid metabolism, xenobiotics biodegradation and metabolism, amino acid metabolism, environmental adaptation, and neurodegenerative diseases, were significantly enriched in the hibernation group, while 12 pathways, including carbohydrate metabolism, replication and repair, translation, and transcription, were significantly enriched in the control group. It can be seen that during hibernation, the gut microbiota of the wild chipmunk changes towards taxa that are beneficial for reducing carbohydrate consumption, increasing fat consumption, and adapting more strongly to environmental changes in order to better provide energy for the body and ensure normal life activities during hibernation.

4.
Diagnostics (Basel) ; 13(18)2023 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-37761235

RESUMEN

Mitral valve prolapse (MVP) is a prevalent cardiac disorder that impacts approximately 2% to 3% of the overall population. While most patients experience a benign clinical course, there is evidence suggesting that a subgroup of MVP patients face an increased risk of sudden cardiac death (SCD). Although a conclusive causal link between MVP and SCD remains to be firmly established, various factors have been associated with arrhythmic mitral valve prolapse (AMVP). This study aims to provide a comprehensive review encompassing the historical background, epidemiology, pathology, clinical manifestations, electrocardiogram (ECG) findings, and treatment of AMVP patients. A key focus is on utilizing multimodal imaging techniques to accurately diagnose AMVP and to highlight the role of mitral annular disjunction (MAD) in AMVP.

5.
Int J Mol Sci ; 24(2)2023 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-36675036

RESUMEN

Anthocyanin is a natural antioxidant agent extracted from the fruits of Sambucus canadensis, which has been considered to have potential anti-aging effects. Cell senescence is the primary cause of aging and related diseases. Recently, research on the development of compounds for eliminating senescent cells or damaged organs have shown prospects. The compounds which promote the clearing of senescent cells are called "senolytics". Though anthocyanin is considered to have potential anti-aging effects owing to its anti-inflammatory and antioxidant activities, the mechanism of the elimination of senescent cells remains unclear. In this study, we prepared anthocyanins extracted from the fruits of Sambucus canadensis and evaluated their anti-aging effects in vivo and in vitro. We found that anthocyanin could significantly reduce cell senescence and aging of the lens by inhibiting the activity of the PI3K/AKT/mTOR signaling pathway, consequently promoting the apoptosis of senescent cells, increasing the autophagic and mitophagic flux, and enhancing the renewal of mitochondria and the cell to maintain cellular homeostasis, leading to attenuating aging. Therefore, our study provided a basis for anthocyanin to be used as new "senolytics" in anti-aging.


Asunto(s)
Antocianinas , Sambucus , Antocianinas/farmacología , Antioxidantes/farmacología , Fosfatidilinositol 3-Quinasas , Senescencia Celular , Estrés Oxidativo
6.
Nat Mater ; 22(4): 450-458, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35739274

RESUMEN

Two-dimensional (2D) materials with multiphase, multielement crystals such as transition metal chalcogenides (TMCs) (based on V, Cr, Mn, Fe, Cd, Pt and Pd) and transition metal phosphorous chalcogenides (TMPCs) offer a unique platform to explore novel physical phenomena. However, the synthesis of a single-phase/single-composition crystal of these 2D materials via chemical vapour deposition is still challenging. Here we unravel a competitive-chemical-reaction-based growth mechanism to manipulate the nucleation and growth rate. Based on the growth mechanism, 67 types of TMCs and TMPCs with a defined phase, controllable structure and tunable component can be realized. The ferromagnetism and superconductivity in FeXy can be tuned by the y value, such as superconductivity observed in FeX and ferromagnetism in FeS2 monolayers, demonstrating the high quality of as-grown 2D materials. This work paves the way for the multidisciplinary exploration of 2D TMPCs and TMCs with unique properties.

7.
Int J Cardiovasc Imaging ; 39(4): 697-706, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36460877

RESUMEN

The main objectives of the current study are to investigate valvular involvement in patients with cardiac Behçet's disease (BD) and find out the risk factors of valvular involvement in cardiac BD. We retrospectively assessed the clinical and echocardiographic data in the medical records of 121 patients with BD admitted to Beijing Anzhen Hospital from January 2015 to January 2022. We evaluated the valvular structure and function mainly by echocardiography. A total of 77 BD patients (77/121, 63.64%) had cardiac valvular involvement. Valvular lesions occurred more frequently in males (p = 0.022). Aortic regurgitation (AR) (62/77, 80.52%) was the most common finding and severe AR occupied 80.65% (50/62). The most common manifestations of BD patients with severe AR was aortic valve prolapse (25/50, 50%), followed by echo-free spaces within the aortic annulus (11/50, 22%), vegetation-like lesions (10/50, 20%), and aortic root aneurysm (10/50, 20%). The incidence of paravalvular leaks (PVL) in BD patients was 14.29% (7/49). The diameter of the sinus of Valsalva and proximal ascending aorta, and total cholesterol (TCHO) were the independent risk factors of moderate-severe aortic valvular regurgitation (p < 0.01). Left ventricular end-diastolic dimension (LVEDD), left ventricular ejection fraction (LVEF) and brain natriuretic peptide (BNP) were significantly associated with moderate-severe mitral valvular regurgitation (p < 0.01). The most common valvular abnormality in BD is AR. Echocardiography has great value in the comprehensive evaluation and accurate diagnosis of valvular involvement in BD patients.


Asunto(s)
Insuficiencia de la Válvula Aórtica , Síndrome de Behçet , Insuficiencia de la Válvula Mitral , Masculino , Humanos , Síndrome de Behçet/complicaciones , Síndrome de Behçet/diagnóstico por imagen , Estudios Retrospectivos , Volumen Sistólico , Función Ventricular Izquierda , Valor Predictivo de las Pruebas , Ecocardiografía , Válvulas Cardíacas , Insuficiencia de la Válvula Aórtica/etiología , Insuficiencia de la Válvula Aórtica/complicaciones , Insuficiencia de la Válvula Mitral/complicaciones
8.
Biomimetics (Basel) ; 7(4)2022 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-36546940

RESUMEN

Periodontitis is an inflammatory disease induced by plaque microorganisms. In the clinic, antibiotic assistant periodontal mechanical therapy is the most effective therapy for the treatment of periodontitis. However, the drug resistance of the antibiotics and the repeated coming and diminishing of the disorder of oxidation-reduction balance in the inflammatory tissue could not meet the high requirements for periodontic health control in long periods. Deuterohemin-ala-his-thr-val-glu-lys (DhHP-6) is a biomimetic oxidase-mimicking enzyme that simulates the reactive oxygen radical scavenger function of heme by synthesizing the new molecular material following the key structure and amino acid sequence of heme. In this article, we report the antioxidant and anti-inflammatory properties of DhHP-6 by building a inflammatory model for human gingival fibroblasts (HGFs) stimulated by lipolysaccharide (LPS) and its effects on periodontitis in Wistar rats. DhHP-6 reduced the oxidative stress of HGFs by increasing the amount of the reductase species of glutathione (GSH) and catalase (CAT) while decreasing the amount of oxidase species of malonaldehyde (MDA) and reactive oxygen species (ROS). DhHP-6 had a dose-dependent protective effect on alveolar bone absorption in rats with periodontitis, enhanced antioxidant capacity, and reduced inflammation. As determined by Micro-CT scanning, DhHP-6 reduced alveolar bone loss and improved the bone structure of the left maxillary first molar of rats. There were no obvious morphological and histological differences in the rat organs with or without DhHP-6 treatment. These results suggest that DhHP-6 can be used to treat periodontitis by increasing the expression levels of antioxidant enzymes and antioxidants in systemic and local tissues, thereby reducing levels of oxidation products and cyto-inflammatory factors. The synergistic antioxidant and anti-inflammatory effects of DhHP-6 suggest that there are promising applications of this biomimetic enzyme molecular material for the next generation of agents for periodontitis therapy.

9.
Int J Mol Sci ; 23(24)2022 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-36555672

RESUMEN

The metabolism and apoptosis of tumor cells are important factors that increase their sensitivity to chemotherapeutic drugs. p53 and cisplatin not only induce tumor cell apoptosis, but also regulate the tumor cell metabolism. The TP53-induced glycolysis and apoptosis regulator (TIGAR) can inhibit glycolysis and promote more glucose metabolism in the pentose phosphate pathway. We speculate that the regulation of the TIGAR by the combination therapy of p53 and cisplatin plays an important role in increasing the sensitivity of tumor cells to cisplatin. In this study, we found that the combined treatment of p53 and cisplatin was able to inhibit the mitochondrial function, promote mitochondrial pathway-induced apoptosis, and increase the sensitivity. Furthermore, the expression of the TIGAR was inhibited after a combined p53 and cisplatin treatment, the features of the TIGAR that regulate the pentose phosphate pathway were inhibited, the glucose flux shifted towards glycolysis, and the localization of the complex of the TIGAR and Hexokinase 2 (HK2) on the mitochondria was also reduced. Therefore, the combined treatment of p53 and cisplatin may modulate a glycolytic flux through the TIGAR, altering the cellular metabolic patterns while increasing apoptosis. Taken together, our findings reveal that the TIGAR may serve as a potential therapeutic target to increase the sensitivity of lung cancer A549 cells to cisplatin.


Asunto(s)
Proteínas Reguladoras de la Apoptosis , Cisplatino , Neoplasias Pulmonares , Monoéster Fosfórico Hidrolasas , Humanos , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Cisplatino/farmacología , Glucólisis , Neoplasias Pulmonares/tratamiento farmacológico , Monoéster Fosfórico Hidrolasas/metabolismo , Proteína p53 Supresora de Tumor/metabolismo
10.
Animals (Basel) ; 12(19)2022 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-36230279

RESUMEN

Specific pathogen-free (SPF) grade laboratory animals are kept in specific cages for life. The limited space could affect the characterization of colonization and dynamic changes related to gut microorganisms, and affect adipokines, even further affecting the fat synthesis and muscle quality of animals. The objective of this study was to analyze the stocking density on the dynamic distribution of gut microbiota, fat synthesis and muscle quality of SPF grade Kunming mice. Three housing densities were accomplished by raising different mice per cage with the same floor size. Kunming mice were reared at low stocking density (LSD, three mice a group), medium stocking density (MSD, 5 mice a group), and high stocking density (HSD, 10 mice a group) for 12 weeks. The results demonstrated that the stocking density affected intestinal microbial flora composition. We found that compared with the MSD group, the abundance of Lactobacillus in the LSD group and the HSD group decreased, but the abundance of unclassified_Porphyromonadaceae increased. Moreover, fat synthesis and muscle quality were linked to the intestinal microbial flora and stocking density. Compared with the LSD group and the HSD group, the MSD group had a more balanced gut flora, higher fat synthesis and higher muscle quality. Overall, this study demonstrated that stocking density could affect gut microbiota composition, and reasonable stocking density could improve fat synthesis and muscle quality. Our study will provide theoretical support for the suitable stocking density of laboratory animals.

11.
Int J Mol Sci ; 23(19)2022 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-36233059

RESUMEN

Skeletal muscles require muscle satellite cell (MuSC) differentiation to facilitate the replenishment and repair of muscle fibers. A key step in this process is called myogenic differentiation. The differentiation ability of MuSCs decreases with age and can result in sarcopenia. Although mitochondria have been reported to be involved in myogenic differentiation by promoting a bioenergetic remodeling, little is known about the interplay of mitochondrial proteostasis and myogenic differentiation. High-temperature-requirement protein A2 (HtrA2/Omi) is a protease that regulates proteostasis in the mitochondrial intermembrane space (IMS). Mice deficient in HtrA2 protease activity show a distinct phenotype of sarcopenia. To investigate the role of IMS proteostasis during myogenic differentiation, we treated C2C12 myoblasts with UCF101, a specific inhibitor of HtrA2 during differentiation process. A key step in this process is called myogenic differentiation. The differentiation ability of MuSCs decreases with age and can result in sarcopenia. Further, CHOP, p-eIF2α, and other mitochondrial unfolded protein response (UPRmt)-related proteins are upregulated. Therefore, we suggest that imbalance of mitochondrial IMS proteostasis acts via a retrograde signaling pathway to inhibit myogenic differentiation via the UPRmt pathway. These novel mechanistic insights may have implications for the development of new strategies for the treatment of sarcopenia.


Asunto(s)
Serina Peptidasa A2 que Requiere Temperaturas Altas , Proteínas Mitocondriales , Sarcopenia , Animales , Serina Peptidasa A2 que Requiere Temperaturas Altas/genética , Ratones , Proteínas Mitocondriales/metabolismo , Péptido Hidrolasas
12.
Biomacromolecules ; 23(9): 3752-3765, 2022 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-36001455

RESUMEN

To enhance the efficacy of tumor therapy, the collection of functional components into a targeting system shows advantages over most homogeneous materials in inducing apoptosis of cancer cells. The security and targeting of therapeutic agents also require the effect combination of additional components. However, the construction of multifunctional composites in a simple system with intelligent cooperative responsiveness remains a challenge. Herein, a reduced polyanionic cluster (rP2W18) bearing the absorption at the near infrared (NIR) II region is used as a core carrier to bind the positively charged doxorubicin hydrochloride (DOX) through ionic interaction. To reduce the physiological toxicity, hyaluronic acid grafting ß-cyclodextrin side chains is used to cover the ionic complex through host-guest inclusion to DOX. When the nanocomposite is activated by local laser exposure, the final three-component therapeutic agent is demonstrated to present targeted photothermal conversion capability and chemodynamic activity together with chemotherapy. With the controlled release of DOX under the stimulation of mild acidity in the tumor region and photothermal effect, the exposed rP2W18 is aroused by hydrogen peroxide overexpressed in a tumor microenvironment to produce toxic reactive oxygen species, 1O2. This work presents an opportunity for the development of a nanocomposite in NIR-II photothermal/chemo-therapy and chemodynamic synergistic therapy.


Asunto(s)
Nanopartículas , Neoplasias , Aniones , Línea Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Humanos , Ácido Hialurónico/química , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Fototerapia , Polielectrolitos , Microambiente Tumoral
13.
Int J Mol Sci ; 23(13)2022 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-35805987

RESUMEN

Ultraviolet (UV) radiation is a major cause of photoaging that can induce DNA damage, oxidative stress, and cellular aging. Metformin (MF) can repair DNA damage, scavenge reactive oxygen species (ROS), and protect cells. However, the mechanism by which MF inhibits cell senescence in chronic skin damage induced by UVA is unclear. In this study, human foreskin fibroblasts (HFFs) treated with UVA were used as an in vitro model and UVA-induced skin photoaging in Kunming mice was used as an in vivo model to investigate the potential skin protective mechanism of MF. The results revealed that MF treatment attenuated UVA-induced cell viability, skin aging, and activation of the PI3K/AKT/mTOR signaling pathway. Furthermore, MF treatment alleviated the mitochondrial oxidative stress and decreased mitophagy. Knockdown of Parkin by siRNA increased the clearance of MF in senescent cells. The treatment of Kunming mice with MF at a dose of 10 mg/kg/day significantly reduced UVA-induced skin roughness, epidermal thinning, collagen degradation, and skin aging. In conclusion, our experimental results suggest that MF exerts anti-photoaging effects by inhibiting mitophagy and the PI3K/AKT/mTOR signaling pathway. Therefore, our study improves the current understanding of the protective mechanism of MF against photoaging.


Asunto(s)
Metformina , Envejecimiento de la Piel , Enfermedades de la Piel , Animales , Fibroblastos/metabolismo , Metformina/metabolismo , Metformina/farmacología , Ratones , Mitofagia , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Piel , Enfermedades de la Piel/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Rayos Ultravioleta/efectos adversos
14.
Adv Healthc Mater ; 11(14): e2102352, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35524986

RESUMEN

In the search for materials with enhanced near-infrared (NIR) photothermal properties and capability of providing environment-sensitive therapy, a method that combines isolated components into one nanocomposite is developed. The technique simultaneously involves redox, charge-transfer formation, and ionic complexation. During the polyoxophosphomolybdate (PMo) cluster mixing with biosafe chromogen 3,3',5,5'-tetramethylbenzidine (TMB), the reduced state (rPMo) and the oxidized TMB in the state of charge-transfer complex (cTMB) emerge spontaneously. The two reduced and oxidized components with charges form a stable ionic complex that resists physiology, saline, broad pH, and elevated temperature. Both the rPMo and cTMB contribute to the total sustainable photothermal conversion efficiency of 48.4% in the NIR-II region. The ionic complex exhibits biocompatibility in in vitro cell viability evaluation and is demonstrated to enter tumor cells with sustained photothermal property and complexation stability. Due to the local acidity that triggers further interaction among rPMo clusters, a distinct accumulation of the ionic complex at the tumor position is observed after caudal vein injection. Moreover, a remarkable local NIR-II photothermal image appears. The diminishment of tumor in mice with maintained body weight demonstrates the comprehensive effect of this NIR-II photothermal therapeutic material.


Asunto(s)
Hipertermia Inducida , Nanopartículas , Neoplasias , Animales , Línea Celular Tumoral , Hipertermia Inducida/métodos , Ratones , Nanopartículas/química , Neoplasias/patología , Fototerapia/métodos , Terapia Fototérmica
16.
Int J Mol Sci ; 23(6)2022 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-35328718

RESUMEN

Chemotherapeutic drug-induced p53-dependent crosstalk among tumor cells affects the sensitivity of tumor cells to chemotherapeutic drugs, contributing to chemoresistance. Therefore, pharmacological targeting of p53 may contribute to overcoming drug resistance. The localization of p53 is closely related to its function. Thus, we assessed the effect of p62 on the coordination of p53 mitochondrial localization under chemotherapeutic drug treatment in ovarian cancer cells. We found that the combined use of the proteasome inhibitor epoxomicin and cisplatin led to the accumulation of p53 and sequestosome1(p62) in the mitochondria, downregulated mitochondrial DNA (mtDNA) transcription, inhibited mitochondrial functions, and ultimately promoted apoptosis by enhancing cisplatin sensitivity in ovarian cancer cells. Moreover, the ubiquitin-associated (UBA) domain of p62 was involved in regulating the mitochondrial localization of p53. Our findings suggest that the interaction between p62 and p53 may be a mechanism that determines the fate of tumor cells. In conclusion, p62 coordinated the mitochondrial localization of p53 through its UBA domain, inhibited mtDNA transcription, downregulated mitochondrial function, and promoted ovarian cancer cell death. Our study demonstrates the important role of p53 localization in tumor cell survival and apoptosis, and provides new insights into understanding the anti-tumor mechanism of targeting the ubiquitin-proteasome system in tumor cells.


Asunto(s)
Antineoplásicos , Neoplasias Ováricas , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Línea Celular Tumoral , Cisplatino/uso terapéutico , ADN Mitocondrial/farmacología , Resistencia a Antineoplásicos/genética , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Ubiquitina/metabolismo
17.
Int J Mol Sci ; 23(3)2022 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-35163244

RESUMEN

Interactions between the mitochondrial inner and outer membranes and between mitochondria and other organelles closely correlates with the sensitivity of ovarian cancer to cisplatin and other chemotherapeutic drugs. However, the underlying mechanism remains unclear. Recently, the mitochondrial protease OMA1, which regulates internal and external signals in mitochondria by cleaving mitochondrial proteins, was shown to be related to tumor progression. Therefore, we evaluated the effect of OMA1 on the response to chemotherapeutics in ovarian cancer cells and the mouse subcutaneous tumor model. We found that OMA1 activation increased ovarian cancer sensitivity to cisplatin in vivo and in vitro. Mechanistically, in ovarian cancer, OMA1 cleaved optic atrophy 1 (OPA1), leading to mitochondrial inner membrane cristae remodeling. Simultaneously, OMA1 induced DELE1 cleavage and its cytoplasmic interaction with EIF2AK1. We also demonstrated that EIF2AK1 cooperated with the ER stress sensor EIF2AK3 to amplify the EIF2S1/ATF4 signal, resulting in the rupture of the mitochondrial outer membrane. Knockdown of OMA1 attenuated these activities and reversed apoptosis. Additionally, we found that OMA1 protease activity was regulated by the prohibitin 2 (PHB2)/stomatin-like protein 2 (STOML2) complex. Collectively, OMA1 coordinates the mitochondrial inner and outer membranes to induce ovarian cancer cell death. Thus, activating OMA1 may be a novel treatment strategy for ovarian cancer.


Asunto(s)
Estrés del Retículo Endoplásmico/fisiología , Metaloendopeptidasas/metabolismo , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Neoplasias Ováricas/metabolismo , Prohibitinas/metabolismo , Transducción de Señal/fisiología , Animales , Apoptosis/fisiología , Línea Celular , Línea Celular Tumoral , Citosol/metabolismo , Retículo Endoplásmico/metabolismo , Femenino , Humanos , Ratones , Membranas Mitocondriales/metabolismo
18.
Adv Mater ; 34(11): e2100537, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34951727

RESUMEN

Amorphization is an efficient strategy to activate intrinsically inert catalysts. However, the low crystallinity of amorphous catalysts often causes high solubility and poor electrochemical stability in aqueous solution. Here, a different mechanism is developed to simultaneously stabilize and activate the water-soluble amorphous MoSx Oy via a charge-balancing strategy, which is induced by different electronegativity between the co-dopants Rh (2.28) and Sn (1.96). The electron-rich Sn prefers to stabilize the unstable apical O sites in MoSx Oy through charge transfer, which can prevent the H from attacking. Meanwhile, the Rh, as the charge regulator, shifts the main active sites on the basal plane from inert Sn to active apical Rh sites. As a result, the amorphous RhSn-MoSx Oy exhibits drastic enhancement in electrochemical stability (η10 increases only by 12 mV) after 1000 cycles and a distinct activity (η10 : 26 mV and Tafel: 30.8 mV dec-1 ) for the hydrogen evolution reaction in acidic solution. This work paves a route for turning impracticably water-soluble catalysts into treasure and inspires new ideas to design high-performance amorphous electrocatalysts.

19.
J Biochem Mol Toxicol ; 35(10): e22887, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34392578

RESUMEN

Diabetic cardiomyopathy (DCM), a diabetes complication, accounts for diabetes-associated morbidity, mortality, and heart failure. Biflavonoids have been demonstrated to possess extensive pharmacological properties, such as antidiabetic and antioxidant activities. Our study aimed to explore the effects of sciadopitysin, a type of biflavonoid, on DCM and the mechanism involved. An experimental cell model was established in AC16 cardiomyocytes by exposure to high glucose (HG). Cell injury was estimated by detecting cell viability and lactate dehydrogenase (LDH) release. Oxidative stress was determined by measuring malondialdehyde (MDA) level and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT). Apoptosis was assessed by flow cytometry analysis, caspase-3/7 activity assay, and Western blot analysis of cytochrome C (Cyt C) expression. Alternation of the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (PKB)/glycogen synthase kinase-3ß (GSK-3ß) pathway was detected by Western blot. Results showed that HG exposure reduced viability and increased LDH release in AC16 cells, which was abolished by sciadopitysin treatment. Sciadopitysin inhibited HG-induced oxidative stress, as evidenced by the reduced MDA content, and the increased activities of SOD, CAT, and GSH-Px. Sciadopitysin suppressed HG-induced apoptosis, an increase of caspase-3/7 activity, and Cyt C expression in AC16 cells. Mechanistically, sciadopitysin activated the PI3K/PKB/GSK-3ß pathway under HG stimulation in AC16 cells. Inhibition of PI3K/PKB/GSK-3ß pathway by LY294002 blocked the effects of sciadopitysin on HG-induced injury, oxidative stress, and apoptosis in AC16 cells. Summarily, sciadopitysin alleviated HG-caused oxidative stress and apoptosis in cardiomyocytes by activating the PI3K/PKB/GSK-3ß pathway.


Asunto(s)
Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Biflavonoides/farmacología , Glucosa/efectos adversos , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Miocitos Cardíacos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cromonas/farmacología , Cardiomiopatías Diabéticas/metabolismo , Glucosa/metabolismo , Humanos , Morfolinas/farmacología , Miocitos Cardíacos/efectos de los fármacos , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología
20.
J Colloid Interface Sci ; 604: 429-440, 2021 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-34271494

RESUMEN

Generally, preparing high-efficiency heterojunction photocatalysts via a facile room-temperature route is attractive from the perspective of energy and labor saving. Herein, by using dried and glacial acetic acid (HAc)-adsorbed bismuth nitrate, instead of Bi(NO3)3·5H2O, as a Bi source, a ß-Bi2O3/Bi5O7I heterojunction with well dispersed flowery hierarchical architecture was synthesized, which endows it with high surface area, open channels and good light harvest. More importantly, the change of the precursor achieved a successful transformation for both of phase and heterojunction type, i.e. from type-Ⅰ BiOI/[Bi6O5(OH)3](NO3)5·3H2O (labeled as BiOI/BBN) to Z-scheme ß-Bi2O3/Bi5O7I heterojunction. Since both ß-Bi2O3 and Bi5O7I are visible light responsive, ß-Bi2O3/Bi5O7I exhibited improved visible-light photocatalytic activity for the degradation of tetracycline (TC) and malachite green (MG) with apparent reactant rate (kapp) values about 10 and 11 times higher than those of BiOI/BBN. Besides, the presence of more oxygen vacancies also contributed to the enhancement in photocatalytic performance.


Asunto(s)
Luz , Tetraciclina , Antibacterianos , Catálisis
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