查找使用阿拉丁产品的科研文献

Hydrogel Microneedles Loaded With a Reactive Oxygen Species (ROS)-Responsive Carbon Monoxide Donor and Finasteride for Synergistic Treatment of Androgenetic Alopecia

Hui Shi,Zhi Wang,Xinbo Zhang,Xiaoyang Hou,Jingxi Zhang,Dacai Chen,Chunsheng Yang,Guan Jiang

Androgenetic alopecia (AGA) is highly prevalent, yet its treatment is limited by systemic side effects and poor patient compliance. This study aims to develop a topical delivery system for synergistic, effective, safe, and highly compliant AGA treatment. A methacrylated hyaluronic acid (HAMA)-based hydrogel microneedle patch (C-F-HMN) co-loaded with a carbon monoxide-releasing molecule (CORM-401) and finasteride (FIN) was prepared. CORM-401 and FIN were formulated into CORM-401@Pluronic F127 (CO@F127) micelles and FIN@hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complexes, respectively. Efficacy, mechanisms, and biocompatibility were evaluated in a testosterone-induced AGA mouse model. C-F-HMN achieved efficient local drug delivery, minimized systemic exposure, and sustained efficacy. FIN reduced dihydrotestosterone (DHT) production by inhibiting 5α-reductase; CORM-401 consumed scalp reactive oxygen species (ROS) and released carbon monoxide (CO) to improve the hair follicle microenvironment. Compared with monotherapy and minoxidil, C-F-HMN showed superior hair regrowth, activated the Wnt/β-catenin pathway, inhibited the transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) pathway, and exhibited good biocompatibility without systemic toxicity. This study establishes a novel, effective, safe, and highly patient-compliant topical combination therapy for AGA, overcoming the limitations of traditional treatments and providing a new strategy for clinical AGA management.

Bisphenol A aggravate selenium deficiency-induced apoptosis via miR-215-3p/Dio1 to activate ROS/PI3K/AKT pathway in chicken arterial

Zhe Li,Tong Xu,Xue Fan,Kai Chen,Chunyan Wan,Xiang Li,Hang Yin,Shu Li

Both bisphenol A (BPA) and selenium (Se) deficiency can affect the expression of microRNAs (miRNAs), which can specifically regulate its target mRNA and induce apoptosis, and play a significant role in cardiovascular injury diseases. To explore the mechanism of apoptosis induced by BPA and Se deficiency in chicken arterial endothelial tissue and the role of miRNAs in this process, the model of BPA exposure/Se deficiency in chicken and PAEC cells have been employed. The targeting relationship between miR-215-3p and iodothyronine deiodinase 1 (Dio1) in PAEC was verified by double luciferase gene report. The level of miR-215-3p was detected by qRT-PCR. The oxidative stress level of arterial endothelial cells was detected by oxidative stress kit and DCFH-DA probe method. The PI3K/AKT pathway, mitochondrial dynamics, and apoptosis-related genes were detected by qRT-PCR and western blot. The mitochondrial ATP level and nitric oxide synthases (NOSs) level were detected with the kit. TUNEL, acridine orange/ethidium bromide, and flow cytometry were used to detect the level of apoptosis. The results showed that BPA exposure and Se deficiency led to overexpression of miR-215-3p, aggravated oxidative stress, inhibited activation of PI3K/AKT pathway, promoted mitochondrial division, increased expression of apoptosis related genes, and finally led to apoptosis of chicken arterial endothelial cells. We also established knockdown/overexpression models of miR-215-3p and Dio1 in vitro, and found that overexpression of miR-215-3p and knockout of Dio1 can induce apoptosis. Interestingly, miR-215-3p-Inhibitor and N-acetyl- l -cysteine (NAC) partially prevented apoptosis caused by BPA exposure and Se deficiency, and LY294002 aggravated apoptosis. These results suggest that BPA exposure aggravates the apoptosis of Se deficient arterial endothelial cells in chickens by regulating the ROS/PI3K/AKT pathway activated by miR-215-3p/Dio1. The miR-215-3p/Dio1 axis provides a new way to understand the toxic mechanism of BPA exposure and Se deficiency, and reveals a new regulatory model of apoptosis damage in vascular diseases.

Galangin protects gastric mucosa from indomethacin induced injury via scavenging ROS and inhibition of PKC, Akt, and NF κB protein expressions

Jingwen Gong,Yu Xie,Yinfen Tan,Hailong Li,Junqing Zhang

Purpose: To investigate the mechanism of action of galangin (GAL) against indomethacin (Indo)-induced gastric injury. Methods: Ten micromolar GAL with 2 mM Indo or 0.5 mM L-NAME or 2 mM propargylglycine were co-administered to human gastric mucosal epithelial cells GES-1 for 24 h. Cell viability assay and reactive oxygen species (ROS) test were conducted with commercial kits. Protein expressions of constitutive and inducible nitric oxide synthase (cNOS and iNOS, respectively), and cystathionine-γ-lyase (CSE) in GSE-1 cells were investigated by western blot. After 100 - 300 mg/kg, GAL was daily administered to rats for 5 days, and 30 mg/kg Indo was administered to induce gastric injury. Protein expressions of endothelial NOS (eNOS), iNOS, CSE, nuclear factor (NF)-κB, PKC, Akt, phospho-eNOS (Ser-1177), and phospho-eNOS (Thr-495) were investigated by western blot. Results: Galangin ameliorated the proliferative inhibitions of Indo, propargylglycine, and L-NAME on GSE-1 cells (p < 0.05), rapidly scavenged ROS, and increased cNOS protein expressions (p < 0.05). Galangin (300 mg/kg) inhibited protein expressions of iNOS (p < 0.01), NF-κB, Akt, and PKC (p < 0.05), inhibited the Ser-1177 and Thr 495 phosphorylation of eNOS, elevated eNOS and CSE protein expressions (p < 0.001). Conclusion: Galangin protects gastric mucosa from Indo by scavenging ROS and inhibiting protein expressions of Akt and PKC. The inhibition leads to Ser-1177 and Thr 495 dephosphorylation of eNOS, thereby prolonging eNOS activity. Besides, GAL inhibits iNOS-produced NO by inhibiting NF-κB to ameliorate the inflammatory reaction induced by Indo.

N-Acetyl-l-cysteine-Derived Carbonized Polymer Dots with ROS Scavenging via Keap1-Nrf2 Pathway Regulate Alveolar Bone Homeostasis in Periodontitis

Xinchan Liu,Yubo Hou,Mingxi Yang,Xirui Xin,Yu Deng,Ruobing Fu,Xingchen Xiang,Niuben Cao,Xiaomeng Liu,Weixian Yu,Bai Yang,Yanmin Zhou

Periodontitis is a type of chronic inflammatory oral disease characterized by the destruction of periodontal connective tissue and progressive alveolar bone resorption. As oxidative stress is the key cause of periodontitis in the early periodontal microenvironment, antioxidative therapy has been considered a viable treatment for periodontitis. However, more stable and effective reactive oxygen species (ROS)-scavenging nanomedicines are still highly needed due to the instability of traditional antioxidants. Herein, a new type of N -acetyl- l -cysteine (NAC)-derived red fluorescent carbonized polymer dots (CPDs) has been synthesized with excellent biocompatibility, which can serve as an extracellular antioxidant to scavenge ROS effectively. Moreover, NAC-CPDs can promote osteogenic differentiation in human periodontal ligament cells (hPDLCs) under H 2 O 2 stimulation. In addition, NAC-CPDs are capable of targeted accumulation in alveolar bone in vivo, reducing the level of alveolar bone resorption in periodontitis mice, as well as performing fluorescence imaging in vitro and in vivo. In terms of mechanism, NAC-CPDs may regulate redox homeostasis and promote bone formation in the periodontitis microenvironment by modulating the kelch-like ECH-associated protein l (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. This study provides a new strategy for the application of CPDs theranostic nanoplatform for periodontitis.

G-/C-rich ssDNA-based Fe and Cu/Fe nanoclusters with peroxidase-like activity for intracellular ROS production and cytotoxicity applications

Wei Chunying,Lin Huiqing,Bai Hehe

Five G-/C-rich single-stranded DNA (ssDNA) with different sequences and lengths were templated to prepare the DNA-Cu, DNA-Fe, and bimetallic DNA-Cu/M nanoclusters (NCs). The peroxidase-like activities of these nanomaterials were studied using H 2 O 2 and 3,3′,5,5′'-tetramethylbenzidine (TMB) as the reaction substrates in HAc-NaAc buffer. It was found that T30-G2-Fe NCs and T30-G2-Cu/Fe NCs, with a size of about 2 nm, exhibit similar and the strongest enzyme-like activity under optimal conditions. Both NCs possess a similarly high affinity to substrates, and the Michaelis–Menten constant ( K m ) values to TMB and H 2 O 2 are about 11 and 2–3 times lower than those of natural horseradish peroxidase (HRP), respectively. The activity of both nanozymes decreases to about 70% after being kept for one week in pH 4.0 buffer at 4 °C, which is comparable with HRP. Hydroxyl radicals (•OH) are the main reactive oxygen species (ROS) produced in the catalytic reaction. Moreover, both NCs can facilitate in situ generation of ROS in HeLa cells using endogenous H 2 O 2 . MTT assays indicate that the T30-G2-Cu/Fe NCs exhibit the strong selective cytotoxicity to HeLa cells over HL-7702 cells. The cellular viability is about 70% and 50% after incubating with 0.6 M NCs for 24 h without or with 2 mM H 2 O 2 , respectively. The current study shows that the T30-G2-Cu/Fe NCs have the potential for chemical dynamic treatment (CDT). Graphical abstract

Novel dual CAFs and tumour cell targeting pH and ROS dual sensitive micelles for targeting delivery of paclitaxel to liver cancer

Chunjing Guo,Wei Zhang,Qiaoyun Zhang,Yanguo Su,Xiaoya Hou,Qiang Chen,Huimin Guo,Ming Kong,Daquan Chen

Supramolecular Nano-assembly of Caffeate-Strengthened Phenylboronic Ester with Multi-step Ros Scavenging Ability for Targeted Therapy of Acute Kidney Injury

Fan Jia,Bo Yu,Jian Li,Fanghao Cai,Guosheng Fu,Qiao Jin,Jian Ji

Acute kidney injury (AKI) is a life-threatening complication with a considerable occurrence among patients. AKI is typically accompanied by an elevation in reactive oxidative species (ROS) in renal tissues, which is the main contributor to kidney damage. Herein, a supramolecular nano-assembly (Ser-HPEC) containing an ethyl caffeate-strengthened phenylboronic ester with ROS-triggered antioxidative ability was proposed for AKI-targeted therapy. Nano-assemblies can rapidly accumulate in the ischemia-reperfusion-injured kidney via kidney the injury molecule-1 (Kim-1)-mediated homing ability of L-serine. By consuming pathological levels of ROS, two different antioxidants, ethyl caffeate (EC) and 4-hydroxybenzyl alcohol (HBA), were spontaneously released from a single module to relieve oxidative stress and diminish acute inflammation in injured renal tissue. The multistep ROS scavenging strategy combined with a precise targeting capability endowed the aforementioned nano-assembly with effectiveness in preserving the integrity and functions of the injured kidney, providing new inspiration for the treatment of inflammatory diseases, including AKI. This article is protected by copyright. All rights reserved

Cardamonin protects against iron overload induced arthritis by attenuating ROS production and NLRP3 inflammasome activation via the SIRT1/p38MAPK signaling pathway

Li Shaocong,He Qi,Chen Baihao,Zeng Jiaxu,Dou Xiangyun,Pan Zhaofeng,Xiao Jiacong,Li Miao,Wang Fanchen,Chen Chuyi,Lin Yuewei,Wang Xintian,Wang Haibin,Chen Jianfa

Iron homeostasis plays an essential role in joint health, while iron overload can cause damage and death of cartilage cells. Cardamonin (CAR) is a substance found in the fruit of the chasteberry plant and has anti-inflammatory and anti-tumor activities. We first administered iron dextran (500 mg/kg) intraperitoneally to establish an iron overload mouse model and surgically induced osteoarthritis. The extent of OA and iron deposition were assessed using Micro-ct, Safranin-O/fast green staining, H&E staining, and Prussian Blue 10 weeks later. We administered primary chondrocytes with Ferric Ammonium Citrate (FAC) to evaluate the chondrocyte changes. Chondrocytes were identified in vitro by toluidine blue staining, and chondrocyte viability was evaluated by CCK-8. The rate of apoptosis was determined by Annexin V-FITC/PI assay. The mechanism of action of CAR was verified by adding the SIRT1 inhibitor EX527, and the expression of SIRT1 and MAPK signaling pathways was detected by Western blot. Iron overload also promoted chondrocyte apoptosis, a process that was reversed by CAR. In addition, CAR reduced NLRP3 inflammasome production via the SIRT1-MAPK pathway, and the SIRT1 inhibitor EX527 inhibited the treatment of OA by CAR.CAR inhibited cartilage degeneration induced by iron overload both in vivo and in vitro. Besides, our study showed that iron overload not only inhibited type II collagen expression but also induced MMP expression by catalyzing the generation of NLRP3 inflammasome. Our results suggest that CAR can treat KOA by promoting SIRT1 expression and inhibiting p38MAPK pathway expression to reduce the production of NLRP3 inflammasome vesicles.

Mesoporous Calcium-Silicate Nanoparticles Loaded with Prussian Blue Promotes Enterococcus Faecalis Ferroptosis-Like Death by Regulating Bacterial Redox Pathway ROS/GSH

Xiao Zhao,Ying Wang,Tingting Zhu,Huili Wu,Diya Leng,Zhiguo Qin,Yan Li,Daming Wu

Background Mesoporous calcium-silicate nanoparticles (MCSNs) are advanced biomaterials that have been used to control drug delivery for many years. Ultrasmall Prussian blue nanoparticles (UPBNPs) showed high peroxidase and catalase-like activities. This study evaluated the antibacterial and antibiofilm properties, mechanism and cytotoxicity of UPBNPs-MCSNs composites synthesized by both as precursors. Methods UPBNPs-MCSNs were prepared and characterized. The antibacterial effect of UPBNPs-MCSNs was evaluated by the MTT assay and CFU counting method, and their biosafety was tested by CCK8. Then explore the antibacterial mechanism, including TEM observation of bacterial morphology, and detection of bacterial ROS, LPO and GSH levels. The antibiofilm activity of UPBNPs-MCSNs was tested by E. faecalis biofilm model in human roots. The roots were pretreated with materials and cultured with E. faecalis , and the survival of E. faecalis on the root canal wall was observed by SEM and CLSM. Results The results showed that UPBNPs-MCSNs had potent antibacterial and antibiofilm activities. They can aggregate on the dentin surface and significantly inhibit E. faecalis adhesion and colonization. Their antibacterial activity is as effective as NaClO and calcium hydroxide (CH), can significantly prolong the time of bacterial colonization than CH, but have lower cytotoxicity to normal cells. We found that UPBNPs-MCSNs trigger a like classic ferroptosis pathway in bacteria. UPBNPs-MCSNs can induce bacteria to produce ROS and LPO, and reduce GSH level. Moreover, we observed that the metal ions chelator and the antioxidant could block their antibacterial activity. Conclusion These results reveal that UPBNPS-MCSNs have high antibacterial and antibiofilm, and can mediate the bacterial redox pathway ROS/GSH like the classical pathway of ferroptosis, providing a theoretical basis for them to develop into a safe and effective novel root canal disinfectant.

A tumor pH-responsive autocatalytic nanoreactor as a H2O2 and O2 self-supplying depot for enhanced ROS-based chemo/photodynamic therapy

Furong Liu,Tao He,Songlin Gong,Meiling Shen,Shuang Ma,Xianzhou Huang,Lu Li,Li Wang,Qinjie Wu,Changyang Gong

Combining the internal force-driven chemodynamic therapy (CDT) and the external energy-triggered photodynamic therapy (PDT) holds great promise to achieve an advanced anticancer effect based on reactive oxygen species (ROS). However, the insufficient oxy-substrates supply in tumor microenvironment, like hydrogen peroxide (H 2 O 2 ) and oxygen (O 2 ), is the Achilles heel that greatly restricts the efficacy of this ROS-based treatment. Herein, the construction of a c opper p e roxide-based tumor pH-re s ponsive a utocatalytic nano r eactor (CESAR), via an albumin-mediated biomimetic mineralization strategy is described. The decoration of human serum albumin endows the nanoreactor good hydrophilicity and biocompatibility, which is highly desired for the metal-based materials. Upon exposure to acidic tumor microenvironment, CESAR presents a pH-triggered disintegration with Cu 2+ , H 2 O 2 and O 2 generated instantly. The generated H 2 O 2 complements the hyperoxide deficiency and initiates a localized Fenton-like reaction with the assistance of Cu 2+ for highly toxic hydroxyl radicals (•OH) production for improving CDT. The evolved O 2 gas enables hypoxia relief for enhanced Ce6-mediated PDT. This H 2 O 2 /O 2 self-supplying strategy significantly amplifies the tumor oxidative damage and gains an optimal treatment outcome, which offers a new paradigm for optimizing the tumor therapeutic options limited by oxide or hyperoxide deficiency, not only for CDT/PDT, but also other oxy-substrates involved strategies. Statement of significance The shortage of oxy-substrates in the tumor microenvironment remains a great challenge for ROS-based cancer therapy. Herein, we introduce human serum albumin as a scaffold to stabilize copper peroxide nanomaterials for constant production of H 2 O 2 and O 2 to enhance chemodynamic/photodynamic therapy. The tumor pH-triggered H 2 O 2 /O 2 production and Cu 2+ release are confirmed, assuring the strategy of a highly precise, effective way to destroy tumor without any side effects. This work lends new and exciting insights into the engineering design of autocatalytic oxy-substrates self-supply nanoreactor for overcoming the bottlenecks, like the oxy-substrates deficiency of CDT/PDT and the poor stability of metal peroxides, to achieve highly effective chemodynamic/photodynamic therapy.

The interaction of ZnO nanoparticles, Cr(VI), and microorganisms triggers a novel ROS scavenging strategy to inhibit microbial Cr(VI) reduction

Zhiyan Yan,Chenrui Liu,Yun Liu,Xiaoqian Tan,Xinyue Li,Yan Shi,Chunlian Ding

Cr(VI) contaminated water usually contains other contaminants like engineered nanomaterials (ENMs). During the process of microbial treatment , the inevitable interaction of Cr(VI), ENMs, and microorganisms probably determines the efficiency of Cr(VI) biotransformation , however, the corresponding information remains elusive. This study investigated the interaction of ZnO nanoparticles (NPs), Cr(VI), and Pannonibacter phragmitetu s BB (hereafter BB), which changed the process of microbial Cr(VI) reduction. ZnO NPs inhibited Cr(VI) reduction, but had no effect on bacterial viability. In particular, Cr(VI) induced BB to produce organic acids and to drive Zn 2+ dissolution from ZnO NPs inside and outside of cells. The dissolved Zn 2+ not only promoted Cr(VI) reduction to Cr(V)/Cr(IV) by strengthening sugar metabolism and inducing increase in NAD(P)H production, but also hindered Cr(V)/Cr(IV) transformation to Cr(III) through down-regulating Cr(VI) reductase genes. A novel bacterial driven ROS scavenging mechanism leading to the inhibition of Cr(VI) reduction was elucidated. Specifically, the accumulated Cr(VI) and Cr(V)/Cr(IV) formed a redox dynamic equilibrium, which triggered the disproportionation of superoxide radicals mimicking superoxide dismutase through the flip-flop of Cr(VI) and Cr(V)/Cr(IV) in bacterial cells. This study provided a realistic insight into design the applicability of biological remediation technology for Cr(VI) contaminant and evaluating environmental risks of ENMs.

Nicotinamide mononucleotide ameliorates DNFB-induced atopic dermatitis-like symptoms in mice by blocking activation of ROS-mediated JAK2/STAT5 signaling pathway

Jie-Fang Gao,Liu Tang,Fei Luo,Yi-Yuan Zhang,Lu Chen,Hong Ding,Zu-Dong Meng

Background and purpose Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by pruritus and impaired skin barrier function. The pathology of AD involves in immune dysfunction and epidermal barrier disruption. Reactive oxygen species (ROS) are found to be associated with AD, and play a role in the immunological abnormalities and dysfunctional skin barrier. Nicotinamide mononucleotide (NMN) plays an important role in oxidative stress related diseases, but its role in AD is unclear. Methods KM mice were treated with DNFB to induce AD-like lesion and typical applied with NMN for two weeks. The dermatitis score, the degree of itching and TEWL were evaluated during modeling. Epidermal thickness of skin lesions and histopathological changes were detected. Further, inflammatory factors, epidermal differentiation-related genes, oxidative stress indicators and JAK2/STAT5 signaling pathway were evaluated. NHEK cells were stimulated by TNF-α/IFN-γ after pre-treatment with NMN, then ROS levels, inflammatory factors and JAK2/STAT5 signaling pathway were detected. Results NMN exhibited potent anti-atopic activities, shown by alleviated AD-like symptoms, inhibited the increased expression of inflammatory cytokines and restored proteins and mRNA level of skin barrier genes. In addition, NMN inhibited TNF-α/IFN-γ-stimulated elevation of inflammatory chemokines, which was associated with blocking the activation of ROS-mediated JAK2/STAT5 pathway. Conclusion NMN may have a positive effect on relieving symptoms of AD.