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1.
Biomaterials ; 314: 122872, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39383779

RESUMO

Periodontal bone defects represent an irreversible consequence of periodontitis associated with reactive oxygen species (ROS). However, indiscriminate removal of ROS proves to be counterproductive for tissue repair and insufficient for addressing existing bone defects. In the treatment of periodontitis, it is crucial to rationally alleviate local ROS while simultaneously promoting bone regeneration. In this study, Zr-based large-pore hierarchical mesoporous metal-organic framework (MOF) nanoparticles (NPs) HMUiO-66-NH2 were successfully proposed as bifunctional nanomaterials for bone regeneration and ROS scavenging in periodontitis therapy. HMUiO-66-NH2 NPs demonstrated outstanding biocompatibility both in vitro and in vivo. Significantly, these NPs enhanced the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under normal and high ROS conditions, upregulating osteogenic gene expression and mitigating oxidative stress. Furthermore, in vivo imaging revealed a gradual degradation of HMUiO-66-NH2 NPs in periodontal tissues. Local injection of HMUiO-66-NH2 effectively reduced bone defects and ROS levels in periodontitis-induced C57BL/6 mice. RNA sequencing highlighted that differentially expressed genes (DEGs) are predominantly involved in bone tissue development, with notable upregulation in Wnt and TGF-ß signaling pathways. In conclusion, HMUiO-66-NH2 exhibits dual functionality in alleviating oxidative stress and promoting bone repair, positioning it as an effective strategy against bone resorption in oxidative stress-related periodontitis.

2.
Small ; : e2403313, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39377344

RESUMO

Hepatic ischemia-reperfusion injury (IRI) is a severe complication that occurs in the process of liver transplantation, hepatectomy, and other end-stage liver disease surgery, often resulting in the failure of surgery operation and even patient death. Currently, there is no effective way to prevent hepatic IRI clinically. Here, it is reported that the ultra-small copper-based multienzyme-like nanoparticles with catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) catalytic activities significantly scavenge the surge-generated endogenous reactive oxygen species (ROS) and effectively protects hepatic IRI. Density functional theory calculations confirm that the nanoparticles efficiently scavenge ROS through their synergistic effects of the ultra-small copper SOD-like activity and manganese dioxides CAT-like activity. Furthermore, the results show that the biocompatible CMP NPs significantly protected hepatocytes from IRI in vitro and in vivo. Importantly, their therapeutic effect is much stronger than that of N-acetylcysteamine acid (NAC), an FDA-approved antioxidative drug. Finally, it is demonstrated that the protective effects of CMP NPs on hepatic IRI are related to suppressing inflammation and hepatocytic apoptosis and maintaining endothelial functions through scavenging ROS in liver tissues. The study can provide insight into the development of next-generation nanomedicines for scavenging ROS.

3.
Plant J ; 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39378337

RESUMO

Leaf senescence is a complex developmental process influenced by abscisic acid (ABA) and reactive oxygen species (ROS), both of which increase during senescence. Understanding the regulatory mechanisms of leaf senescence can provide insights into enhancing crop yield and stress tolerance. In this study, we aimed to elucidate the role and mechanisms of rice (Oryza sativa) LONG GRAIN 3 (OsLG3), an APETALA2/ETHYLENE RESPONSIVE FACTOR (AP2/ERF) transcription factor, in orchestrating dark-induced leaf senescence. The transcript levels of OsLG3 gradually increased during dark-induced and natural senescence. Transgenic plants overexpressing OsLG3 exhibited delayed senescence, whereas CRISPR/Cas9-mediated oslg3 mutants exhibited accelerated leaf senescence. OsLG3 overexpression suppressed senescence-induced ABA signaling by downregulating OsABF4 (an ABA-signaling-related gene) and reduced ROS accumulation by enhancing catalase activity through upregulation of OsCATC. In vivo and in vitro binding assays demonstrated that OsLG3 downregulated OsABF4 and upregulated OsCATC by binding directly to their promoter regions. These results demonstrate the critical role of OsLG3 in fine-tuning leaf senescence progression by suppressing ABA-mediated signaling while simultaneously activating ROS-scavenging mechanisms. These findings suggest that OsLG3 could be targeted to enhance crop resilience and longevity.

4.
Adv Mater ; : e2411618, 2024 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-39394880

RESUMO

Traumatic spinal cord injury (SCI) represents a complex neuropathological challenge that significantly impacts the well-being of affected individuals. The quest for efficacious antioxidant and anti-inflammatory therapies is both a compelling necessity and a formidable challenge. Here, in this work, the innovative synthesis of electron-rich Ru clusters on non-stoichiometric copper hydroxide that contain oxygen vacancy defects (Ru/def-Cu(OH)2), which can function as a biocatalytic reactive oxygen species (ROS) scavenger for efficiently suppressing the inflammatory cascade reactions and modulating the endogenous microenvironments in SCI, is introduced. The studies reveal that the unique oxygen vacancies promote electron redistribution and amplify electron accumulation at Ru clusters, thus enhancing the catalytic activity of Ru/def-Cu(OH)2 in multielectron reactions involving oxygen-containing intermediates. These advancements endow the Ru/def-Cu(OH)2 with the capacity to mitigate ROS-mediated neuronal death and to foster a reparative microenvironment by dampening inflammatory macrophage responses, meanwhile concurrently stimulating the activity of neural stem cells, anti-inflammatory macrophages, and oligodendrocytes. Consequently, this results in a robust reparative effect on traumatic SCI. It is posited that the synthesized Ru/def-Cu(OH)2 exhibits unprecedented biocatalytic properties, offering a promising strategy to develop ROS-scavenging and anti-inflammatory materials for the management of traumatic SCI and a spectrum of other diseases associated with oxidative stress.

5.
Biomedicines ; 12(9)2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39335584

RESUMO

Rat H9c2 cardiomyocytes overexpressing the abscisic acid (ABA) hormone receptors LANCL1 and LANCL2 have an increased mitochondrial proton gradient, respiration, and vitality after hypoxia/reoxygenation. Our aim was to investigate the role of the ABA/LANCL1-2 system in ROS turnover in H9c2 cells. H9c2 cells were retrovirally infected to induce the overexpression or silencing of LANCL1 and LANCL2, without or with the concomitant silencing of the transcription factor ERRα. Enzymes involved in radical production or scavenging were studied by qRT-PCR and Western blot. The mitochondrial proton gradient and ROS were measured with specific fluorescent probes. ROS-generating enzymes decreased, ROS-scavenging enzymes increased, and mitochondrial ROS were reduced in LANCL1/2-overexpressing vs. control cells infected with the empty vector, while the opposite occurred in LANCL1/2-silenced cells. The knockdown of ERRα abrogated all beneficial effects on ROS turnover in LANCL1/2 overexpressing cells. Taken together, these results indicate that the ABA/LANCL1-2 system controls ROS turnover in H9c2 via ERRα. The ABA/LANCL system emerges as a promising target to improve cardiomyocyte mitochondrial function and resilience to oxidative stress.

6.
Macromol Rapid Commun ; : e2400495, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39292816

RESUMO

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the degradation of articular cartilage. Recent studies have demonstrated that chondrocyte ferroptosis plays a crucial role in the progression of OA. Consequently, developing nanomedicines that suppress chondrocyte ferroptosis is a promising strategy for OA treatment. However, there are few reports on nanomedicines specifically targeting chondrocyte ferroptosis for OA therapy. In this study, Curcumin-loaded nanoparticles (Cur-NPs) are fabricated to suppress chondrocyte ferroptosis by regulating reactive oxygen species (ROS), ferrous ion (Fe2⁺), and Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) levels of chondrocyte. This is achieved by combining the functions of curcumin and an amphiphilic block copolymer with ROS scavenging and iron-chelating properties. The in vitro anti-ferroptotic effects of Cur-NPs are thoroughly investigated. The findings indicate that Cur-NPs decrease the expression of ferroptosis markers such as ROS, Fe2⁺, and ACSL4, while protecting the mitochondrial membrane potential of chondrocytes. Additionally, Cur-NPs attenuated lipid peroxidation in chondrocytes. Furthermore, Cur-NPs significantly reduced the expression of the catabolic factor Matrix Metallopeptidase 13 (MMP13) and increased the expression of the anabolic factor Collagen type II (Col II) in vitro. This study demonstrates that Cur-NPs exhibit enhanced chondroprotective effects through anti-ferroptotic actions, presenting a promising approach for inhibiting chondrocyte ferroptosis using bioactive nanomaterials in OA treatment.

7.
Adv Healthc Mater ; : e2402452, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39235573

RESUMO

The treatment of chronic diabetic wounds is a major challenge due to oxidative stress, persistent hyperglycemia, and susceptibility to bacterial infection. In this study, multifunctional sandwich-structured nanofiber dressings (SNDs) are prepared via electrospinning. The SNDs consisted of an outer layer of hydrophobic polylactic acid (PLA) fibers encapsulating MgB2 nanosheets (MgB2 NSs), a middle layer of PLA and polyvinylpyrrolidone (PVP) fibers encapsulating the MgB2 NSs and metformin hydrochloride complex (MgB2-Met), and an inner layer of water-soluble PVP fibers encapsulating MgB2-Met. Because of their special sandwich structure, SNDs have high photothermal conversion efficiency (24.13%) and photothermal cycle performance. SNDs also exhibit a photothermal effect, bacteria-targeting effect of MgB2, electrostatic attraction ability of metformin hydrochloride (Met), and strong antibacterial activity against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA). SNDs can eliminate intracellular reactive oxygen species (ROS) by regulating the hydrogen release from MgB2. In addition, SNDs have good biocompatibility, can effectively inhibit the inflammatory factor Interleukin-6 (IL-6), and promote granulation tissue formation, collagen deposition, and diabetic wound healing. These findings offer a promising approach for clinical treatment of diabetic wounds.

8.
ACS Appl Mater Interfaces ; 16(39): 52766-52779, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39155443

RESUMO

In pursuit of enhancing the photostability of chlorophyll, a novel organic-inorganic hybrid pigment has been synthesized via a supramolecular intercalation assembly method, incorporating cerium-ion-doped hydrotalcite as the host matrix and chlorophyll as the intercalated guest molecule. This innovative pigment amalgamates the vivid coloration properties of organic dyes with the robust stability characteristic of inorganic substances. Determined from the detailed investigation of the structural evolution of chlorophyll during photodegradation, the dual physicochemical protection mechanism is critical to the advancement of chlorophyll photostability. It leverages the oxygen barrier attributes of the hydrotalcite's laminate structure and the ultraviolet light absorption and scattering capabilities of CeO2 nanoparticles formed in situ. Furthermore, Ce-doping introduces a redox cycle between Ce4+ and Ce3+ ions, which serves as a chemical defense by neutralizing reactive oxygen species that emerge during chlorophyll degradation. This multifaceted approach results in a substantial enhancement of photostability, with the hybrid pigment containing 0.3 Ce doped content, demonstrating a mere 5.90% alteration in reflectance at the 635 nm peak after 250 h of UV-accelerated aging. This breakthrough provides a dual physicochemical protective strategy that not only significantly prolongs the lifespan of chlorophyll pigments but also holds potential for broadening their application scope in various industries, including plastics and coatings, where color fastness and durability are paramount.

9.
Int J Biol Macromol ; 278(Pt 3): 134896, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39168206

RESUMO

Oxidative stress caused by excessive reactive oxygen species (ROS) accumulation significantly hinders wound healing in patients with diabetes. Scavenging ROS and reducing inflammation are crucial for rapid healing. In this work, a multi-responsive sodium hyaluronate (HA)/tannic acid (TA) hydrogel was developed based on boronate ester bonds. Sodium hyaluronate with 3-aminophenyl boronic acid modification (HA-APBA) was mixed and crosslinked with TA to form HA-APBA/TA hydrogels. These hydrogels are injectable, self-healing, and biocompatible. The HA-APBA/TA hydrogels could release free TA through the collapse of the structure at low pH, high H2O2 concentration, and high glucose concentration, thus possessing good ROS scavenging ability. In full-thickness skin wounds of db/db mice, the HA-APBA/TA hydrogels promoted wound healing, collagen deposition, and significant angiogenesis. Furthermore, they have been shown to effectively reduce the levels of inflammatory factors in wounds and lower the expression of CD86, a pro-inflammatory macrophage surface marker. This resulted in a more effective transition of wound healing from the inflammatory phase to the proliferative phase. This study provides an optional strategy for alleviating oxidative stress and controlling excessive inflammation, thereby promoting diabetic wound healing.


Assuntos
Ácido Hialurônico , Hidrogéis , Espécies Reativas de Oxigênio , Cicatrização , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Cicatrização/efeitos dos fármacos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Diabetes Mellitus Experimental/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Polifenóis
10.
PeerJ ; 12: e17849, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39131625

RESUMO

The physiological activity facilitated by arbuscular mycorrhizal fungi (AMF) contributes to plants' ability to tolerate drought. Nevertheless, it is unclear if AMF colonization affects the expression of genes in the host plant that encode antioxidant enzymes in the superoxide dismutase (SOD) family, which help alleviate drought stress in plants. Here, we conducted a pot trial to determine whether colonization by the AMF Rhizophagus irregularis improves drought resistance in Bombax ceiba. We comprehensively analyzed the SOD gene family and evaluated genome-wide expression patterns of SODs and SOD activity in AMF-colonized and non-mycorrhizal plants under simulated drought. We identified a total of 13 SODs in the genome of B. ceiba, including three FeSODs (BcFSDs), three MnSODs (BcMSDs), and seven Cu/ZnSODs (BcCSDs). Phylogenetic analysis based on binding domain revealed that SOD genes from B. ceiba and various other plant species can be divided into three separate groups, showing significant bootstrap values. Our examination of gene composition and patterns suggests that most BcSOD genes in these three subgroups are significantly conserved. Additionally, it was noted that hormones and stress-responsive cis-regulatory elements were found in all BcSOD promoters. Expression profiling by qRT-PCR demonstrated that AMF increased relative expression levels of Cu/Zn-SODs in both roots and shoots under drought stress, except for BcCSD3 in roots. Furthermore, AMF colonization increased the relative expression of BcMSD1a and BcMSD1b in roots, augmenting SOD activities and increasing ROS scavenging during drought. In general, this work offers molecular evidence in support of the beneficial effect of AMF colonization on drought tolerance in B. ceiba. It also elucidates the expression patterns of SOD genes, which will support efforts to optimize mycorrhizal seedling cultivation under stressful conditions.


Assuntos
Secas , Regulação da Expressão Gênica de Plantas , Micorrizas , Superóxido Dismutase , Micorrizas/fisiologia , Micorrizas/genética , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Filogenia , Estresse Fisiológico/genética , Raízes de Plantas/microbiologia , Raízes de Plantas/genética , Família Multigênica/genética , Resistência à Seca , Fungos
11.
Int J Biol Macromol ; 278(Pt 3): 134609, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39134197

RESUMO

Bacterial infections, excessive reactive oxygen species (ROS) accumulation and a persistent inflammatory response severely impede the wound healing process. In this study, we developed a novel multifunctional hydrogel dressing (LCPN) based on lipoic acid modified chitosan (LAMC), polypyrrole nanoparticles (PPy NPs) and nicotinamide mononucleotide (NMN) for accelerated healing of infected wounds. The synthesized LCPN hydrogel has several properties. Modification of lipoic acid significantly enhances the water solubility of chitosan making it easier to dissolve and absorb wound secretions. Interestingly, owing to the breaking and restructuring of disulfide bonds, LCPN hydrogel can be quickly bonded under UV light without relying on photoinitiators. In addition, the incorporation of PPy NPs not only enhances the electrical conductivity of LCPN hydrogel, but also confers photothermal antimicrobial capability to LCPN hydrogel. More importantly, the sustained release of NMN in LCPN hydrogel can significantly enhance cell proliferation, migration and antioxidant capacity, which is conducive to accelerated wound healing. In vitro and in vivo experiments have shown that LCPN hydrogel has excellent biocompatibility and the ability to promote wound healing. Therefore, the prepared multifunctional hydrogel is expected to be used as a novel dressing to accelerate wound healing.


Assuntos
Bandagens , Quitosana , Hidrogéis , Cicatrização , Quitosana/química , Quitosana/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Nanopartículas/química , Infecção dos Ferimentos/tratamento farmacológico , Antioxidantes/farmacologia , Antioxidantes/química , Luz , Proliferação de Células/efeitos dos fármacos , Polímeros/química , Humanos , Antibacterianos/farmacologia , Antibacterianos/química
12.
Small ; : e2403667, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39148219

RESUMO

Achieving the delicate balance required for both emulsion and gel characteristics, while also imparting biological functionality in gelled emulsions, poses a significant challenge. Herein, Pickering emulsion biogels stabilized is reported by novel biological nanofibrils assembled from natural glutathione (GSH) and a tripod cholic acid derivative (TCA) via electrostatic interactions. GSH, composed of tripeptides with carboxyl groups, facilitates the protonation and dissolution of TCA compounds in water and the electrostatic interactions between GSH and TCA trigger nanofibrillar assembly. Fibrous nuclei initially emerge, and the formed mature nanofibrils can generate a stable hydrogel at a low solid concentration. These nanofibrils exhibit efficient emulsifying capability, enabling the preparation of stable Pickering oil-in-water (O/W) emulsion gels with adjustable phase volume ratios. The entangled nanofibrils adsorbed at the oil-water interface restrict droplet movement, imparting viscoelasticity and injectability to the emulsions. Remarkably, the biocompatible nanofibrils and stabilized emulsion gels demonstrate promising scavenging properties against reactive oxygen species (ROS). This strategy may open new scenarios for the design of advanced emulsion gel materials using natural precursors and affordable building blocks for biomedical applications.

13.
Planta ; 260(3): 67, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39088064

RESUMO

MAIN CONCLUSION: Overexpression of VvmybA1 transcription factor in 'Hamlin' citrus enhances cold tolerance by increasing anthocyanin accumulation. This results in improved ROS scavenging, altered gene expression, and stomatal regulation, highlighting anthocyanins' essential role in citrus cold acclimation. Cold stress is a significant threat to citrus cultivation, impacting tree health and productivity. Anthocyanins are known for their role as pigments and have emerged as key mediators of plant defense mechanisms against environmental stressors. This study investigated the potential of anthocyanin overexpression regulated by grape (Vitis vinifera) VvmybA1 transcription factor to enhance cold stress tolerance in citrus trees. Transgenic 'Hamlin' citrus trees overexpressing VvmybA1 were exposed to a 30-day cold stress period at 4 °C along with the control wild-type trees. Our findings reveal that anthocyanin accumulation significantly influences chlorophyll content and their fluorescence parameters, affecting leaf responses to cold stress. Additionally, we recorded enhanced ROS scavenging capacity and distinct expression patterns of key transcription factors and antioxidant-related genes in the transgenic leaves. Furthermore, VvmybA1 overexpression affected stomatal aperture regulation by moderating ABA biosynthesis, resulting in differential responses in a stomatal opening between transgenic and wild-type trees under cold stress. Transgenic trees exhibited reduced hydrogen peroxide levels, enhanced flavonoids, radical scavenging activity, and altered phytohormonal profiles. These findings highlighted the role of VvmybA1-mediated anthocyanin accumulation in enhancing cold tolerance. The current study also underlines the potential of anthocyanin overexpression as a critical regulator of the cold acclimation process by scavenging ROS in plant tissues.


Assuntos
Antocianinas , Citrus sinensis , Resposta ao Choque Frio , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Plantas Geneticamente Modificadas , Antocianinas/metabolismo , Citrus sinensis/genética , Citrus sinensis/metabolismo , Citrus sinensis/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Resposta ao Choque Frio/genética , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Vitis/genética , Vitis/fisiologia , Vitis/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Folhas de Planta/fisiologia , Clorofila/metabolismo , Temperatura Baixa , Estômatos de Plantas/fisiologia , Estômatos de Plantas/genética , Ácido Abscísico/metabolismo , Reguladores de Crescimento de Plantas/metabolismo
14.
ACS Nano ; 18(33): 22055-22070, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39116283

RESUMO

The selective elimination of cytotoxic ROS while retaining essential ones is pivotal in the management of chronic inflammation. Co-occurring bacterial infection further complicates the conditions, necessitating precision and an efficacious treatment strategy. Herein, the dynamic ROS nanomodulators are rationally constructed through regulating the surface states of herbal carbon dots (CDs) for on-demand inflammation or infection elimination. The phenolic OH containing CDs derived from honeysuckle (HOCD) and dandelion (DACD) demonstrated appropriate redox potentials, ensuring their ability to scavenge cytotoxic ROS such as ·OH and ONOO-, while invalidity toward essential ones such as O2·-, H2O2, and NO. This enables efficient treatment of chronic inflammation without affecting essential ROS signal pathways. The surface C-N/C═N of CDs derived from taxus leaves (TACD) and DACD renders them with suitable band structures, facilitating absorption in the red region and efficient generation of O2·- upon light irradiation for sterilization. Specifically, the facilely prepared DACD demonstrates fascinating dynamic ROS modulating ability, making it highly suitable for addressing concurrent chronic inflammation and infection, such as diabetic wound infection. This dynamic ROS regulation strategy facilitates the realization of the precise and efficient treatment of chronic inflammation and infection with minimal side effects, holding immense potential for clinical practice.


Assuntos
Carbono , Inflamação , Pontos Quânticos , Espécies Reativas de Oxigênio , Carbono/química , Carbono/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Inflamação/tratamento farmacológico , Animais , Camundongos , Pontos Quânticos/química , Humanos , Células RAW 264.7 , Propriedades de Superfície
15.
J Nanobiotechnology ; 22(1): 471, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39118143

RESUMO

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, while there is a lack of pharmaceutical interventions to halt AAA progression presently. To address the multifaceted pathology of AAA, this work develops a novel multifunctional gene delivery system to simultaneously deliver two siRNAs targeting MMP-2 and MMP-9. The system (TPNs-siRNA), formed through the oxidative polymerization and self-assembly of epigallocatechin gallate (EGCG), efficiently encapsulates siRNAs during self-assembly. TPNs-siRNA safeguards siRNAs from biological degradation, facilitates intracellular siRNA transfection, promotes lysosomal escape, and releases siRNAs to silence MMP-2 and MMP-9. Additionally, TPNs, serving as a multi-bioactive material, mitigates oxidative stress and inflammation, fosters M1-to-M2 repolarization of macrophages, and inhibits cell calcification and apoptosis. In experiments with AAA mice, TPNs-siRNA accumulated and persisted in aneurysmal tissue after intravenous delivery, demonstrating that TPNs-siRNA can be significantly distributed in macrophages and VSMCs relevant to AAA pathogenesis. Leveraging the carrier's intrinsic multi-bioactive properties, the targeted siRNA delivery by TPNs exhibits a synergistic effect for enhanced AAA therapy. Furthermore, TPNs-siRNA is gradually metabolized and excreted from the body, resulting in excellent biocompatibility. Consequently, TPNs emerges as a promising multi-bioactive nanotherapy and a targeted delivery nanocarrier for effective AAA therapy.


Assuntos
Aneurisma da Aorta Abdominal , Metaloproteinase 9 da Matriz , Camundongos Endogâmicos C57BL , Nanopartículas , RNA Interferente Pequeno , Aneurisma da Aorta Abdominal/tratamento farmacológico , Animais , Camundongos , Nanopartículas/química , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Polifenóis/química , Polifenóis/farmacologia , Catequina/análogos & derivados , Catequina/química , Catequina/farmacologia , Chá/química , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/genética , Humanos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Técnicas de Transferência de Genes , Estresse Oxidativo/efeitos dos fármacos , Células RAW 264.7 , Apoptose/efeitos dos fármacos
16.
Nanomedicine (Lond) ; 19(24): 2011-2026, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39115910

RESUMO

Aim: To target the reactive oxygen species (ROS) accumulation and renal tubular epithelial cell (rTEC) death in renal ischemia-reperfusion injury (IRI), we constructed a nanoparticle that offers ROS scavenging and rTEC-death inhibition: mesoporous zinc-tannic acid nanozyme (ZnTA).Materials & methods: After successfully constructing ZnTA, we proceeded to examine its effect on ROS accumulation, cellular ferroptosis and apoptosis, as well as injury severity.Results: Malondialdehyde, Fe2+ amounts and 4-HNE staining demonstrated that ZnTA effectively attenuated rTEC ferroptosis. TUNEL staining confirmed that Zn2+ carried by ZnTA could effectively inhibit caspase 3 and caspase 9, mitigating apoptosis. Finally, it reduced renal IRI through the synergistic effect of ROS scavenging and cell-death inhibition.Conclusion: This study is expected to provide a paradigm for a combined therapeutic strategy for renal IRI.


[Box: see text].


Assuntos
Ferroptose , Espécies Reativas de Oxigênio , Traumatismo por Reperfusão , Zinco , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Animais , Espécies Reativas de Oxigênio/metabolismo , Zinco/química , Zinco/farmacologia , Ferroptose/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Nanopartículas/química , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Masculino , Porosidade , Camundongos , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Túbulos Renais/efeitos dos fármacos , Linhagem Celular
17.
ACS Appl Mater Interfaces ; 16(31): 40739-40752, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39047081

RESUMO

Oxidative stress (OS) is a major mediator of secondary brain injury following intracerebral hemorrhage (ICH). Thus, antioxidant therapy is emerging as an attractive strategy to combat ICH. To achieve both reactive oxygen species (ROS) scavenging ability and on-demand drug release ability, we constructed a novel polydopamine (PDA)-coated diselenide-bridged mesoporous silica nanoparticle (DSeMSN) drug delivery system (PDA-DSeMSN). Edaravone (Eda) was blocked in the pores of DSeMSN by covering the pores with PDA as a gatekeeper. The drug maintained nearly "zero release" before reaching the lesion site, while in the ROS-enriched circumstances, the PDA shell went through degradation and the doped diselenide bonds broke up, triggering the disintegration of nanoparticles and leading to Eda release. Interestingly, the ROS-degradable property of the PDA shell and diselenide bond endowed the system with enhanced ROS-eliminating capacity. The synergistic effect of ROS-responsive drug delivery and ROS-scavenging PDA-DSeMSN showed efficient antioxidative and mitochondria protective performance without apparent toxicity in vitro. Importantly, PDA-DSeMSN@Eda through intravenous administration specifically accumulated in perihematomal sites and demonstrated robust neuroprotection in an ICH mouse model through antioxidative and antiapoptotic effects with high biological safety. Thus, the PDA-DSeMSN platform holds tremendous potential as an excellent carrier for on-demand delivery of drugs and provides a new and effective strategy for the clinical treatment of ICH.


Assuntos
Hemorragia Cerebral , Edaravone , Indóis , Nanopartículas , Espécies Reativas de Oxigênio , Dióxido de Silício , Animais , Dióxido de Silício/química , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/patologia , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Nanopartículas/química , Edaravone/química , Edaravone/farmacologia , Indóis/química , Indóis/farmacologia , Porosidade , Polímeros/química , Polímeros/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Masculino , Antioxidantes/química , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos
18.
J Biomed Mater Res B Appl Biomater ; 112(8): e35456, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39031923

RESUMO

Tissue engineered scaffolds aimed at the repair of critical-sized bone defects lack adequate consideration for our aging society. Establishing an effective aged in vitro model that translates to animals is a significant unmet challenge. The in vivo aged environment is complex and highly nuanced, making it difficult to model in the context of bone repair. In this work, 3D nanofibrous scaffolds generated by the thermally-induced self-agglomeration (TISA) technique were functionalized with polydopamine nanoparticles (PD NPs) as a tool to improve drug binding capacity and scavenge reactive oxygen species (ROS), an excessive build-up that dampens the healing process in aged tissues. PD NPs were reduced by ascorbic acid (rPD) to further improve hydrogen peroxide (H2O2) scavenging capabilities, where we hypothesized that these functionalized scaffolds could rescue ROS-affected osteoblastic differentiation in vitro and improve new bone formation in an aged mouse model. rPDs demonstrated improved H2O2 scavenging activity compared to neat PD NPs, although both NP groups rescued the alkaline phosphatase activity (ALP) of MC3T3-E1 cells in presence of H2O2. Additionally, BMP2-induced osteogenic differentiation, both ALP and mineralization, was significantly improved in the presence of PD or rPD NPs on TISA scaffolds. While in vitro data showed favorable results aimed at improving osteogenic differentiation by PD or rPD NPs, in vivo studies did not note similar improvements in ectopic bone formation an aged model, suggesting that further nuance in material design is required to effectively translate to improved in vivo results in aged animal models.


Assuntos
Regeneração Óssea , Indóis , Nanopartículas , Osteogênese , Polímeros , Espécies Reativas de Oxigênio , Alicerces Teciduais , Animais , Camundongos , Indóis/química , Indóis/farmacologia , Osteogênese/efeitos dos fármacos , Polímeros/química , Polímeros/farmacologia , Alicerces Teciduais/química , Regeneração Óssea/efeitos dos fármacos , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Nanofibras/química , Peróxido de Hidrogênio/química , Envelhecimento/metabolismo , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Osteoblastos/metabolismo
19.
Plants (Basel) ; 13(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38999675

RESUMO

The bHLH transcription factor family plays crucial roles in plant growth and development and their responses to adversity. In this study, a highly salt-induced bHLH gene, PagbHLH35 (Potri.018G141600), was identified from Populus alba × P. glandullosa (84K poplar). PagbHLH35 contains a highly conserved bHLH domain within the region of 52-114 amino acids. A subcellular localization result confirmed its nuclear localization. A yeast two-hybrid assay indicated PagbHLH35 lacks transcriptional activation activity, while a yeast one-hybrid assay indicated it could specifically bind to G-box and E-box elements. The expression of PagbHLH35 reached its peak at 12 h and 36 h time points under salt stress in the leaves and roots, respectively. A total of three positive transgenic poplar lines overexpressing PagbHLH35 were generated via Agrobacterium-mediated leaf disk transformation. Under NaCl stress, the transgenic poplars exhibited significantly enhanced morphological and physiological advantages such as higher POD activity, SOD activity, chlorophyll content, and proline content, and lower dehydration rate, MDA content and hydrogen peroxide (H2O2) content, compared to wild-type (WT) plants. In addition, histological staining showed that there was lower ROS accumulation in the transgenic poplars under salt stress. Moreover, the relative expression levels of several antioxidant genes in the transgenic poplars were significantly higher than those in the WT. All the results indicate that PagbHLH35 can improve salt tolerance by enhancing ROS scavenging in transgenic poplars.

20.
J Nanobiotechnology ; 22(1): 446, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075467

RESUMO

Bacterial diseases are one of the most common issues that result in crop loss worldwide, and the increasing usage of chemical pesticides has caused the occurrence of resistance in pathogenic bacteria and environmental pollution problems. Nanomaterial mediated gene silencing is starting to display powerful efficiency and environmental friendliness for improving plant disease resistance. However, the internalization of nanomaterials and the physiological mechanisms behind nano-improved plant disease resistance are still rarely understood. We engineered the polyethyleneimine (PEI) functionalized gold nanoparticles (PEI-AuNPs) with fluorescent properties and ROS scavenging activity to act as siRNA delivery platforms. Besides the loading, protection, and delivery of nucleic acid molecules in plant mature leaf cells by PEI-AuNPs, its fluorescent property further enables the traceability of the distribution of the loaded nucleic acid molecules in cells. Additionally, the PEI-AuNPs-based RNAi delivery system successfully mediated the silencing of defense-regulated gene AtWRKY1. Compared to control plants, the silenced plants performed better resistance to Pseudomonas syringae, showing a reduced bacterial number, decreased ROS content, increased antioxidant enzyme activities, and improved chlorophyll fluorescence performance. Our results showed the advantages of AuNP-based RNAi technology in improving plant disease resistance, as well as the potential of plant nanobiotechnology to protect agricultural production.


Assuntos
Resistência à Doença , Ouro , Nanopartículas Metálicas , Doenças das Plantas , Pseudomonas syringae , RNA Interferente Pequeno , Espécies Reativas de Oxigênio , Ouro/química , Nanopartículas Metálicas/química , Espécies Reativas de Oxigênio/metabolismo , Doenças das Plantas/microbiologia , Polietilenoimina/química , Inativação Gênica , Arabidopsis/genética
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