EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Shuai Zhan,Ningjing Zhang,Yijie Lou,Xia Ding,Zhe Chen,Yun Huang,Wanjing Ding
Acute lung injury (ALI), characterized by uncontrolled inflammatory responses, is a critical condition with limited clinical treatment options. Activation of the NLRP3 inflammasome represents a pivotal event in ALI pathogenesis. Although targeting NLRP3 (The NOD-like receptor (NLR) family member containing a pyrin domain 3) inflammasome has been considered to be a potential therapy, the underlying mechanism through which pathway the pulmonary inflammation is modulated remains controversial. Here, we demonstrate that 475A, a highly selective ROCK2 (Rho-associated coiled-coil forming protein kinases 2) inhibitor, effectively attenuates pulmonary inflammation and alleviates lung injury. Mechanistically, 475A promotes NLRP3 protein ubiquitination and subsequent proteasomal degradation by disrupting YAP (Yes-associated protein)-NLRP3 protein interactions, thereby suppressing inflammatory cytokine production in macrophages. This study provides the first evidence linking ROCK2 inhibition to enhanced NLRP3 degradation in ALI treatment, paving the way for developing 475A as a therapeutic agent and establishing the ROCK2/YAP/NLRP3 axis as a novel strategy for treating NLRP3-driven inflammatory diseases.
研究领域:
免疫学
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药理学
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分子生物学
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呼吸医学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Rili Hao,Xing Zhou,Xinyue Zhao,Xiaqing Lv,Xiangyang Zhu,NaNa Gao,Yang Jiang,Maoyu Wu,Dongxiao Sun-Waterhouse,Dapeng Li
Cadmium (Cd), as Group I carcinogen, can induce damage to various organs including the gut. It is of great importance to meet the rising demand for effective therapies against Cd-induced damage and investigate the mechanism. Flammulina velutipes is a popular edible mushroom, despite the well-known health benefits of Flammulina velutipes , little is known about the effect of its polysaccharide (FVP) against CdCl 2 -intestinal injury. In this study, a FVP (uronic acid, 5.10 %; degree of methylation, 41.24 %) was produced via hot water extraction (85 °C) and ethanol precipitation. The FVP contained eight major monosaccharides and exhibited good thermal stability at temperatures lower than 139.73 °C. FVP (100 mg/kg b. w., gavage for 4 weeks) alleviated CdCl 2 (1.5 mg/kg b. w., gavage for 4 weeks)-induced intestinal inflammation and apoptosis, intestinal permeability alteration and intestinal barrier disruption. FVP increased the abundance of Bacteroides , whilst decreasing the abundance of Desulfovibrionales and Clostridium . FVP also restored the levels of short-chain fatty acids (SCFAs), including acetic, propionic, isobutyric, butyric, isovaleric and valeric acids. Correlation analysis indicated the interplays among the FVP, gut microbes, SCFAs, intestinal barrier/cells and gut inflammation. FVP enhances the metabolic functions of gut microbiota via functional pathways analyzed by KEGG database. Furthermore, gut microbial transplantation of FVP + CdCl 2 group mice partially alleviated CdCl 2 caused-gut damage. Thus, FVP may be an effective therapeutic agent against CdCl 2 -induced gut damage via SCFA-mediated regulation of intestinal inflammation and gut microbiota-related energy metabolism. This study may open a new avenue for developing alternative strategies to prevent CdCl 2 -caused injury.
研究领域:
毒理学
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药理学
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微生物学
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营养学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2023
·Vol. 35
·期 26
·2211432
·
IF 29.4
Xiaojun He,Yuna Qian,Chenglin Wu,Jiayao Feng,Xiaoshuai Sun,Qinxiang Zheng,Xiaokun Li,Jianliang Shen
Bacterial infections, such as bacterial keratitis (BK) and subcutaneous abscess, pose significant challenges to global healthcare. Innovative and new antibacterial agents and antibacterial strategies are in demand to control infections in this era of high drug resistance. Nanotechnology is gradually emerging as an economically feasible and effective anti-infection treatment. High-entropy MXenes (HE MXenes) are used to confer desirable properties with exposed active sites to high-entropy atomic layers, whose potential application in the field of biomedicine remains to be explored. Herein, monolayer HE MXenes are fabricated by implementing transition metals with high entropy and low Gibbs free energy to fill the gap in the biocatalytic performance of non-high-entropy MXenes. HE MXenes are endowed with extremely strong oxidase mimic activity ( K m = 0.227 m m ) and photothermal conversion efficiency (65.8%) in the second near-infrared (NIR-II) biowindow as entropy increases. Subsequently, HE MXenes realize NIR-II-enhanced intrinsic oxidase mimic activity for killing methicillin-resistant Staphylococcus aureus and rapidly removing the biofilm. Furthermore, HE MXenes can effectively treat BK and subcutaneous abscess infection induced by methicillin-resistant Staphylococcus aureus as nanotherapeutic agents with minuscule side effects. Overall, monolayer HE MXenes demonstrate promising clinical application potential in the treatment of drug-resistant bacterial infections and promote the healing of infected tissues.
研究领域:
生物医学工程
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纳米医学
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感染性疾病
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Jiezhou Pan,Haotian Liao,Guidong Gong,Yunxiang He,Qin Wang,Lang Qin,Yaoyao Zhang,Hirotaka Ejima,Blaise L. Tardy,Joseph J. Richardson,Jiaojiao Shang,Orlando J. Rojas,Yong Zeng,Junling Guo
Drug-dependent design of hydrogels is currently required for engineering the controlled release of therapeutics, which is a major contributor to the technical challenges relating to the clinical translation of hydrogel-drug systems. Herein, by integrating supramolecular phenolic-based nanofillers (SPFs) into hydrogel microstructures we developed a facile strategy to endow a range of clinically relevant hydrogels with controlled release properties for diverse therapeutic agents. The assembly of multiscale SPF aggregates leads to tunable mesh size and multiple dynamic interactions between SPF aggregates and drugs, which relaxes the available choices of drugs and hydrogels. This simple approach allowed for the controlled release of 12 representative drugs evaluated with 8 commonly used hydrogels. Moreover, the anesthetic drug lidocaine was loaded into SPF-integrated alginate hydrogel and demonstrated sustained release for 14 days in vivo, validating the potential for long-term anesthesia in patients.
研究领域:
药学
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材料科学
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纳米技术
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Xiaoyue Lei,Qikun Cheng,Zhenyu Yang,Huiqun Hu,Hang Yang,Wenting Zhang,Shuyang Zhang,Ao Sun,Zengwen Zhang,Shuli Deng
Inflammatory bowel disease (IBD) poses significant therapeutic challenges due to its complex pathophysiology, which involves oxidative stress and dysbiosis of the intestinal microbiota. Antioxidant nanozymes offer promising intervention options because of their potent reactive oxygen species (ROS)-scavenging abilities; however, their instability and leakage in the upper gastrointestinal tract remain major challenges. This study introduced a novel oral drug delivery system, SP@CSC, which combines Spirulina platensis (SP), a natural microcarrier, with chitosan-functionalized cerium oxide (CSC) nanogels. The CSC nanogels demonstrated superior antioxidant capabilities compared to CeO 2 nanoparticles. The acid-resistant and intestinal retention properties of SP improved the distribution and prolonged the residence time of CSC nanogels in the gut, thereby facilitating targeted antioxidant actions. SP@CSC effectively protected epithelial cells from oxidative stress-induced damage, restored mitochondrial function, and inhibited apoptosis. Additionally, SP@CSC exhibited immunomodulatory effects by suppressing macrophage infiltration and M1 polarization in IBD-associated microenvironments. In the dextran sulfate sodium–induced mouse colitis models, oral administration of SP@CSC alleviated IBD symptoms through restoring intestinal barrier integrity, modulating the immune-microenvironment, and enhancing the abundance and diversity of gut microbiota. These findings highlighted the potential of SP@CSC as a promising candidate for IBD treatment.
研究领域:
纳米医学
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胃肠病学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Yan Liu,Meiling Zhou,Maochang Xu,Xueqin Wang,Yingying Zhang,Yiping Deng,Zongquan Zhang,Jun Jiang,Xiangyu Zhou,Chunhong Li
Delivering therapeutic agents efficiently to inflamed regions remains an intractable challenge following myocardial ischemia-reperfusion injury (MI/RI) due to the transient nature of the enhanced permeability and retention effect, which disappears after 24 h. Leveraging the inflammation-homing and plasticity properties of circulating monocytes (MN) as hitchhiking carriers and further inducing their polarization into anti-inflammatory phenotype macrophages upon reaching the inflamed sites is beneficial for MI/RI therapy. Herein, DSS/PB@BSP nanoparticles capable of clearing reactive oxygen species and inhibiting inflammation were developed by employing hollow Prussian blue nanoparticles (PB) as carriers to encapsulate betamethasone sodium phosphate (BSP) and further modified with dextran sulfate sodium (DSS), a targeting ligand for the scavenger receptor on MN. This formulation was internalized into MN as living cell drug depots, reprogramming them into anti-inflammation type macrophages to inhibit inflammation. In vitro assessments revealed the successful construction of the nanoparticle. In a murine MI/RI model, circulating MN laden with these nanoparticles significantly enhanced drug delivery and accumulation at the cardiac injury site, exhibiting favorable therapeutic ability and promoting M2-biased differentiation. Our study provides an effective approach with minimally invasion and biosecurity that makes this nanoplatform as a promising candidate for immunotherapy and clinical translation in the treatment of MI/RI.
研究领域:
心脏病学
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纳米技术
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免疫疗法
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Xia Zhang,Lijia Liang,Fengxian Wang,Pedro A. Jose,Ken Chen,Chunyu Zeng
Acute kidney injury (AKI) is the sudden decrease in renal function that can be attributed to dysregulated reactive oxygen species (ROS) production and impaired mitochondrial function. Irisin, a type I membrane protein secreted by skeletal muscles in response to physical activity, has been reported to alleviate kidney damage through regulation of mitochondrial biogenesis and oxidative metabolism. In this study, a macrophage membrane-coated metal-organic framework (MCM@MOF) is developed as a nanocarrier for encapsulating irisin to overcome the inherent characteristics of irisin, including a short circulation time, limited kidney-targeting ability, and low membrane permeability. The engineered irisin-mediated biomimetic nanotherapeutics have extended circulation time and enhanced targeting capability toward injured kidneys due to the preservation of macrophage membrane proteins. The irisin-encapsulated biomimetic nanotherapeutics effectively mitigate acute ischemia-reperfusion injury by protecting mitochondrial function and modulating SOD2 levels in renal tubular epithelial cells. The present study provides novel insights to advance the development of irisin as a potential therapeutic approach for AKI.
研究领域:
纳米技术
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药学
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肾脏生理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2024
·
IF 4.6
Hao Chen,Xilin Xiong,Yuan Huang,Bo Huang,Xinxin Luo,Qi Ke,Pengyu Wu,Suxiao Wang
The global outbreak of the COVID-19 pandemic has indisputably wreaked havoc on societies worldwide, compelling the scientific community to seek urgently needed therapeutic agents with low-cost and low-side effect profiles. Numerous approaches have been investigated in the quest to prevent or treat COVID-19, but many of them exhibit unwelcome side effects, such as dysfunctional viral immune responses and inflammation. Herein, we present the preparation of solid natural human pulmonary alveolar epithelial cell (ATII) membrane-coated PLGA NPs (PLGA NPs@ATII-M), which demonstrate remarkable affinity and competitiveness to neutralize the SARS-CoV-2 S1 protein-coated NPs (SCMMA NPs–S1), which are employed as a surrogate for coronavirus particles. In addition, we first considered the antifouling properties of these types of NPs, and we found that this membrane-coated NP formulation boasts excellent antifouling capabilities, which serve to protect their neutralization properties out of shielding by protein coronas in blood circulation. Moreover, this formulation is easily prepared and stored with a low-cost profile and exhibits good specificity, high targeting efficiency, and potentially side effect avoiding, thus making it a highly promising candidate for COVID-19 treatment.
研究领域:
药学
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纳米技术
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病毒学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Yueying Xu,Le Xiao,Jia Chen,Quanxin Wu,Wenhua Yu,Weishen Zeng,Yaxin Shi,Yingnian Lu,Yun Liu
Due to the negligible bacterial resistance , chemodynamic therapy (CDT) is a promising treatment for bacterial infection. However, it is severely impeded by the constant body temperature, shortage of Fe(Ⅱ) ions and insufficient H 2 O 2 level in infected tissue. To enhance the therapeutic efficiency of CDT, improved strategies are urgently needed to tackle these problems. Herein, we exploited an infection microenvironment-responsive nanotherapeutics for near-infrared (NIR)/dihydroartemisinin (DHA) dual-augmented antibacterial CDT. The convenient encapsulation of DHA-loaded α-Fe 2 O 3 nanorods with metal-polyphenol networks (MPN) led to the generation of an antibacterial nanoagent Fe 2 O 3 @ [email protected] (FDM). Afterwards, its photothermal and peroxidase-like activities were intensively studied. Furthermore, the bactericidal efficacy of FDM was evaluated through both in vitro and in vivo antibacterial assays. Firstly, FDM showed both satisfactory photothermal and NIR/DHA dual-augmented peroxidase-like activities. Besides, it exhibited a pH-responsive release behavior of both Fe(Ⅱ) ions and DHA. Moreover, it presented tannic acid-mediated bacterial adhesion effect. In vitro experiments demonstrated that FDM could achieve a satisfactory efficiency against both planktonic bacteria and biofilms . In vivo assays illustrated both the extraordinary synergistic antibacterial effect and efficient anti-inflammatory ability of FDM. The outcomes indicated that the exploited antibacterial agent could offer new insight on developing intelligent nanotherapeutics for clinical use in the future. Statement of significance The antibacterial efficiency of chemodynamic therapy (CDT) is seriously limited by the constant body temperature, shortage of Fe(Ⅱ) ions and insufficient H 2 O 2 level at the mildly acidic inflammatory microenvironment. To address these issues, we have developed a pH-responsive nanoagent (Fe 2 O 3 @ [email protected] ) for near-infrared (NIR)/dihydroartemisinin (DHA) dual-augmented CDT. Through the NIR-induced photothermal effect of exterior Fe(Ⅲ)/tannic acid complex, the increased local temperature led to a photothermal enhanced CDT. Besides, a continuous supply of Fe(Ⅱ) ions could be achieved by tannic acid-mediated Fe(Ⅲ) reduction. Moreover, DHA was adopted as a substitute for H 2 O 2 to initiate DHA-mediated CDT. Both in vitro and in vivo assays demonstrated its outstanding bactericidal efficiency. Therefore, the developed nanotherapeutics could be a promising candidate for clinical trials .
研究领域:
纳米技术
·
药学
·
生物医学工程
·
微生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Zhe Zhao,Yufei Zhang,Yijie Cheng,Jie Li,Wenbo Wang,Siyuan Huang,Xinlong Ma,Xinge Zhang
Chronic osteomyelitis is an inflammatory skeletal disease caused by a bacterial infection that affects the periosteum, bone, and bone marrow. Methicillin-resistant Staphylococcus aureus (MRSA) is the most common causative agent. The bacterial biofilm formed on the necrotic bone is a considerable challenge to treating MRSA-infected osteomyelitis. Here, we developed an all-in-one cationic thermosensitive nanotherapeutic (TLCA) for treating MRSA-infected osteomyelitis. The prepared TLCA particles were positively charged and <230 nm in size, which allowed them to diffuse effectively into the biofilm. The positive charges of the nanotherapeutic accurately targeted the biofilm, and it subsequently regulated the drug release under near-infrared (NIR) light irradiation, thereby efficiently exerting the synergistic effect of NIR light-driven photothermal sterilization and chemotherapy. More than 80% of the antibiotics were abruptly released at 50 °C, which dispersed the biofilm by up to 90%. When applied to MRSA-infected osteomyelitis, with a localized temperature of 50 °C induced by 808 nm laser irradiation, it not only eliminated the bacteria and controlled infection but also inhibited the bone tissue inflammatory response, significantly reducing TNF-α, IL-1β, and IL-6 levels. In conclusion, we constructed an all-in-one antimicrobial treatment modality that provides a new and effective strategy for the topical treatment of chronic osteomyelitis.
研究领域:
纳米技术
·
药剂学
·
传染病学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-18
·
IF 10.6
Wu Cheng,Yan Jing,Ge Chenglong,Xie Lucheng,He Yunjie,Zhao Ziyin,Deng Yekun,Dong Qirong,Yin Lichen
The fracture healing outcome is largely dependent on the quantities as well as osteogenic differentiation capacities of mesenchymal stem cells (MSCs) at the lesion site. Herein, macrophage membrane (MM)-reversibly cloaked nanocomplexes (NCs) are engineered for the lesion-targeted and hierarchical co-delivery of short stromal derived factor-1α peptide (sSDF-1α) and Ckip-1 small interfering RNA (Ckip-1 siRNA, siCkip-1) to promote bone repair by concurrently fostering recruitment and osteogenic differentiation of endogenous MSCs. To construct the NCs, a membrane-penetrating α-helical polypeptide first assembles with siCkip-1, and the cationic NCs are sequentially coated with catalase and an outer shell of sSDF-1α-anchored MM. Due to MM-assisted inflammation homing, intravenously injected NCs could efficiently accumulate at the fractured femur, where catalase decomposes the local hydrogen peroxide to generate oxygen bubbles that drives the shedding of sSDF-1α-anchored MM in the extracellular compartment. The exposed, cationic inner core thus enables robust trans-membrane delivery into MSCs to induce Ckip-1 silencing. Consequently, sSDF-1α-guided MSCs recruitment cooperates with siCkip-1-mediated osteogenic differentiation to facilitate bone formation and accelerate bone fracture healing. This study provides an enlightened strategy for the hierarchical co-delivery of macromolecular drugs into different cellular compartments, and it also renders a promising modality for the management of fracture healing.
研究领域:
纳米技术
·
再生医学
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生物材料
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干细胞生物学
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药学
✓ 已验证
DOI
PubMed
高影响因子
Theranostics
·
2019
·
IF 8.063
Xiangjun Zhang,Qian Cheng,Lanlan Li,Liqing Shangguan,Chenwen Li,Shengke Li,Feihe Huang,Jianxiang Zhang,Ruibing Wang
Succinylcholine (Sch) is the only depolarizing neuromuscular blocking agent widely used for rapid sequence induction in emergency rooms. Unfortunately, a variety of (sometimes lethal) adverse effects, such as hyperkalemia and cardiac arrest, are associated with its use, and currently there are no specific antidotes to reverse Sch or to treat these side-effects. Methods: The binding behaviors of Sch and several synthetic receptors, including cucurbit[7]uril, sulfo-calix[4]arene and water-soluble carboxylatopillar[6]arene (WP[6]), were first investigated. With a mouse model, a leathal dose of Sch was selected for evaluation of the antidotal effects of these synthetic receptors on Sch induced mortality. The antidotal effects of a selected synthetic receptor, WP[6], on Sch induced cardiac arrhythmias, hyperkalemia, rhabdomyolysis and paralysis were subsequently evaluated with rat and mouse models. The reversal mechanism was also investigated at a cellular level. Results: All of these macrocyclic molecules exhibited relatively high binding affinities with Sch in vitro . In a Sch-overdosed mouse model, immediate injection of these synthetic receptors right after Sch administration increased the overall survival rate, with WP[6] standing out with the most effective antidotal effects. In addition, administration of WP[6] also reversed the paralysis induced by Sch in a mouse model. Moreover, infusion of WP[6] to Sch-overdosed rats reduced the incidence of cardiac arrhythmia, inhibited the otherwise abnormally high serum potassium levels, and relieved the muscular damage. At the cellular level, WP[6] reversed the Sch induced depolarization and reduced the efflux of intracellular potassium. Conclusion: Synthetic receptors, particularly WP[6], exhibited high binding affinities towards Sch, and presented a significant potential as supramolecular therapeutics to treat the various side effects of Sch by specifically sequestering Sch in vivo .
研究领域:
药理学
·
药物化学
·
治疗学
✓ 已验证
DOI
PubMed
高影响因子
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