PHYTOMEDICINE
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2024
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IF 6.7
Dihao Xie,Simin Zhong,Meixue Luo,Jiahao Xu,Ruoyan Zheng,Jiading Luo,Yiting Wang,Yongxing Guo,Lianxia Guo,Baojian Wu,Danyi Lu
Background Aristolochic acid I (AAI), an emerging biogenic contaminant widely present in Aristolochic plants, has been implicated in the progression of tubulointerstitial disease, known as aristolochic acid nephropathy (AAN). The circadian clock, a vital regulator of organ homeostasis, is susceptible to external chemical cues, including toxins. However, the reciprocal interactions between AAI and the circadian clock remain unexplored. Methods We initially assessed sex- and time-dependent nephropathy and behavioral responses in C57BL/6J mice exposed to AAI. Subsequently, we evaluated changes in the expression of circadian clock genes following treatment with AAI or its bioactive metabolite, aristolactam I, using real-time quantitative PCR and immunoblotting in renal tissues and cells. Additionally, real-time reporter assays were conducted on kidney explants from PER2::Luc knock-in reporter mice and Per2-dLuc / Bmal1-dLuc reporter cell lines. To further elucidate the regulatory role of circadian clocks in AAI-induced nephropathy, mice with global or kidney-specific knockout of Bmal1 , as well as mice subjected to experimental jetlag, were utilized. Results Our findings revealed a sex-dependent nephrotoxicity of AAI, with males exhibiting greater vulnerability. AAI-induced nephropathy was accompanied by impaired spatial cognitive function, disruptions in free-running locomotor activity, altered renal expression of multiple core clock genes, and disturbances in the circadian rhythm of renal PER2::Luc activity. Notably, kidney-specific ablation of the core clock gene Bmal1 significantly exacerbated renal injury and inflammation, whereas disruptions to the central clock, either genetically (through conventional knockout of Bmal1 ) or environmentally (mimicking jetlag), had minimal effects on AAI nephrotoxicity. Furthermore, both AAI and its bioactive metabolite aristolactam I demonstrated the ability to disrupt circadian clocks in human osteosarcoma cells (U2OS) and mouse renal tubular epithelial cells (mRTEC). Conclusion Collectively, these findings highlight the detrimental impact of aristolochic acids on local renal circadian clocks, ultimately exacerbating kidney damage. This study provides novel insights into the molecular mechanisms underlying AAI nephrotoxicity, potentially opening avenues for therapeutic interventions aimed at modulating the renal circadian clock to treat AAN.
研究领域:
肾病学
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药理学
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分子生物学
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时间生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Ting Tai,Yuan-Yuan Shao,Yu-Qi Zheng,Li-Ping Jiang,Hao-Ru Han,Na Yin,Hao-Dong Li,Jin-Zi Ji,Qiong-Yu Mi,Li Yang,Lei Feng,Fu-Yang Duan,Hong-Guang Xie
Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) frequently confers an increased risk of vascular thrombosis; however, the marketed antiplatelet drugs are investigated for the prevention and treatment of MASLD in patients with these coexisting diseases.Methods: To determine whether clopidogrel could ameliorate high-fat diet (HFD)-induced hepatic steatosis in mice and how it works, mice were fed on normal diet or HFD alone or in combination with or without clopidogrel for 14 weeks, and primary mouse hepatocytes were treated with palmitate/oleate alone or in combination with the compounds examined for 24 h. Body weight, liver weight, insulin resistance, triglyceride and total cholesterol content in serum and liver, histological morphology, transcriptomic analysis of mouse liver, and multiple key MASLD-associated genes and proteins were measured, respectively.Results and discussion: Clopidogrel mitigated HFD-induced hepatic steatosis (as measured with oil red O staining and triglyceride kit assay) and reduced elevations in serum aminotransferases, liver weight, and the ratio of liver to body weight. Clopidogrel downregulated the expression of multiple critical lipogenic (Acaca/Acacb, Fasn, Scd1, Elovl6, Mogat1, Pparg, Cd36, and Fabp4), profibrotic (Col1a1, Col1a2, Col3a1, Col4a1, Acta2, and Mmp2), and proinflammatory (Ccl2, Cxcl2, Cxcl10, Il1a, Tlr4, and Nlrp3) genes, and enhanced phosphorylation of AMPK and ACC. However, compound C (an AMPK inhibitor) reversed enhanced phosphorylation of AMPK and ACC in clopidogrel-treated primary mouse hepatocytes and alleviated accumulation of intracellular lipids. We concluded that clopidogrel may prevent and/or reverse HFD-induced hepatic steatosis in mice, suggesting that clopidogrel could be repurposed to fight fatty liver in patients.
研究领域:
药理学
·
肝病学
·
代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOCHEMISTRY
·
2024
·
IF 3.2
Xiaojie Fan,Jiaxin Guo,Dongyan Feng,Dahong Li,Huiming Hua
Plants of the Garcinia genus were rich in structurally diverse and naturally bioactive components, while limited studies have been reported for Garcinia pedunculata Roxb. and G. nujiangensis C. Y. Wu & Y. H. Li. Four previously undescribed compounds including three chromones , garpedunchromones A-C ( 1 – 3 ), and one biflavonoid , nujiangbiflavone A ( 14 ), along with fifteen known analogs ( 4 – 13 , 15 – 19 ) were isolated from G. pedunculata and G. nujiangensis . The structures of the isolated compounds were determined based on their HRESIMS data, extensive NMR spectroscopic analyses , and ECD calculations. The chromone derivatives were isolated from Garcinia for the first time. Compound 14 was a rare biflavonoid with C-3─C-6″ linkage. The biological evaluation of these isolates against NO production was conducted in the LPS-induced RAW 264.7 cells, resulting in the identification of a series of potent NO inhibitors, of which garpedunchromone B ( 2 ) was the most active with an IC 50 value of 18.11 ± 0.96 μM. In the network pharmacology studies, the potential targets of compounds and inflammation were obtained from PharmMapper and GeneCards database. GO and KEGG enrichment analysis revealed that the overlapped targets were closely related to the major pathogenic processes linked to inflammation. Garpedunchromone B and proteins binding sites were being predicted.
研究领域:
植物化学
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药理学
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天然产物研究
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Chengdong Zhang,Yachen Fei,Meng Li,Jing Li,Maomao Tang,Guichun Wang,Jiaxin Li,Yuxiao Wang,Yang Ding,Chengjun Peng,Mengjie Li,Shuangying Gui,Jian Guo
Periodontitis is an oral chronic inflammatory disease induced by pathogenic bacteria. Pathogens continuously activate immune cells to express a large number of pro-inflammatory factors and reactive oxygen species, eventually leading to periodontal tissue damage. Poor eradication of pathogenic bacteria, persistent inflammatory response and impaired periodontal tissue regeneration are the main challenges to control the progression of periodontitis. However, current clinical drug treatment fails to comprehensively address these issues. In this paper, a chitosan-P407-PNIPAM scaffold multi-crosslinked hydrogel (A/CQ-ML@Gel) encapsulating AgNPs and lipid complex (CQ-ML) is developed. This hydrogel shows thermo- and pH-sensitive properties, exhibits excellent injectability, high viscosity and reliable post-injection mechanical strength. A/CQ-ML@Gel possesses a significant antibacterial effect to Porphyromonas gingivalis after implantation, and then by virtue of the programmed release of quercetin microemulsion and caffeic acid phenethyl ester in CQ-ML, exerting excellent inflammation regulation and osteogenic differentiation of periodontal ligament stem cells. Notably, A/CQ-ML@Gel could activate mitophagy through PINK1/Parkin in inflammatory macrophages, thereby inhibiting the production of excess reactive oxygen species, ultimately reprogramming M1/M2 macrophages phenotype for inflammation suppression. In summary, we present an innovative insight into periodontal delivery system for trimodal synergistic therapy strategy in periodontitis.
研究领域:
口腔医学
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材料科学
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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
CHEMICAL PHYSICS LETTERS
·
2024
·
IF 2.8
Guozheng Zhao
This study introduces a novel biosensor based on a glassy carbon electrode (GCE) modified with nanogold and glucocorticoid receptors (GR) for the sensitive and selective detection of glucocorticoids. The biosensor employs a sensing methodology that capitalizes on the specific adsorption of glucocorticoid molecules to the GR-modified electrode surface, forming a sandwich complex structure that impedes electron transfer, detectable by differential pulse voltammetry (DPV). Electrochemical characterization through cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) demonstrated enhanced electron transfer rates and the effects of electrode surface modifications on the biosensor’s performance. Optimization studies identified ideal conditions for GR concentration and incubation time, enhancing the biosensor’s immune response and detection efficiency. The biosensor exhibited outstanding detection capabilities for six glucocorticoids, with a detection limit ranging from 0.012 to 0.065 ng⋅mL −1 and a broad linear range of 0.1 to 1000 ng⋅mL −1 . Its performance surpassed conventional detection methods, attributing to the conductivity and nanoscale effects of nanogold. Repeatability and stability assessments confirmed the biosensor’s reliability and potential for practical applications. Analysis of actual skincare samples further validated the biosensor’s effectiveness in real-world scenarios, demonstrating high accuracy and recovery rates. The study underscores the biosensor’s potential as a robust tool for environmental analysis, food safety, clinical diagnosis, and on-site glucocorticoid detection, offering significant advantages in terms of cost-effectiveness, portability, and response time.
研究领域:
分析化学
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生物医学工程
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环境科学
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产品关联
DOI
高影响因子
MATERIALS & DESIGN
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2024
·
IF 7.6
Zhining Zhuo,Yuehan Ouyang,Xiyue Zheng,Xiaobang Chen,Zequan Lin,Ruitian Zhu,Lan Lan,Dongyang Qian,Rongrong Li,Jixiang Zhu,Yuanye Dang,Yan Wang,Sida Liao,Xiumei Tian,Fanwen Yang
Airway stenosis, a significant cause of dyspnea, is commonly managed with airway stents. However, conventional stents frequently lead to restenosis. Excessive proliferation of fibroblasts and smooth muscle cells during abnormal repair processes is a key factor in airway restenosis. To address this challenge, a novel drug-loaded airway stent has been designed with personalized tailoring for the patient. This stent features a three-layered structure: an outer layer made from a blend of thermoplastic polyurethane (TPU) and Poloxamer 407 (P407), a drug-loading intermediate layer, and an inner layer made of TPU. This design aims to minimize airway irritation and enable adjustable drug release rates by adjusting the drug carrier and/or the content of P407 in the stent’s outer layer. Drug release profile conforms to the Improved First-Order model. Notably, P407 is released from the stent, serving a dual purpose: it creates micropores to regulate the drug release rate and synergizes with PTX to inhibit the proliferation of fibroblasts. This combination significantly enhances the inhibitory effect on the proliferation of fibroblasts and smooth muscle cells, without adversely affecting airway epithelial cells. This may represent a novel approach to reducing restenosis by addressing a critical complication associated with the use of airway stents.
研究领域:
生物医学工程
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药学
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组织工程
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Journal of Advanced Research
·
2024
·
IF 11.4
Dongwei Guan,Pengju Huang,Xinlei Liu,Qing Li,Xiaoxun Zhang,Nan Liu,Yong Wang,Ying Wan,Jin Chai,Shiying Cai,Rui Chen,Zhijia Ye
Introduction Niemann-Pick C1 (NPC1), a lysosomal cholesterol transport protein, is required for efficient efferocytosis. Patients with Npc1 mutation are frequently accompanied with hepatic symptoms, including hepatomegaly, elevated liver transaminases, or even acute liver failure, but the pathogenic mechanism remains unknown. Objectives Our work aims to characterize the functional role of myeloid NPC1 in liver injury and elucidate its underlying mechanism. Methods Analyses of injured livers from patients with liver diseases and mouse models were conducted to examine NPC1 expression. Myeloid cell-specific Npc1 knockout mice were constructed to determine the functional role of macrophage NPC1 in liver injury. Isolated macrophages were subjected to in vitro mechanistical assays. Results We found that NPC1 is mainly expressed in hepatic macrophages. Its mRNA and protein expression are significantly elevated in injured livers from both patients and mouse models. Tissue-specific deletion of myeloid Npc1 increased liver inflammation, levels of serum liver function enzymes, and liver fibrosis in mouse models of liver injury induced by carbon tetrachloride (CCl 4 ) injection and methionine-and-choline-deficient (MCD) diets. Further analyses indicate that Npc1 deficiency in mouse models of liver injury resulted in increased levels of serum HMGB1 and mitochondrial DNA, promoted hepatic macrophage proinflammatory activation, M1 polarization, led to overproduction of hepatic inflammatory cytokines/chemokines, e.g. CCL2 and STING/NFκB pathway activation. In vitro mechanistical studies reveal that Npc1 -deficient macrophages exhibited inefficient efferocytosis, partly due to impaired cargo degradation. Conclusions These findings indicate that elevated expression of myeloid NPC1 in liver diseases protects liver from injury by promoting macrophage efferocytosis of damaged cells. Dysfunction of NPC1 aggravates liver injury, suggesting that NPC1 may be a potential therapeutic target for treating liver diseases.
研究领域:
肝病学
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免疫学
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细胞生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Xu Wei,Chang Wan,Xu Peng,Yihao Luo,Mengyue Hu,Can Cheng,Shaoxiong Feng,Xixun Yu
Biomaterials with dual functions of osteoimmunomodulation and bone repair are very promising in the field of orthopedic materials. For this purpose, we prepared a copper-based carbon dots (CuCDs) and doped it into oxychondroitin sulfate / poly-acrylamide hydrogel (OPAM) to obtain a hybrid hydrogel (CuCDs/OPAM). We evaluated its osteoimmunomodulatory and bone repair properties in vitro and in vivo. The obtained CuCDs/OPAM exhibited good rBMSCs-cytocompatibility and anti-inflammatory properties in vitro. It also could effectively promote rBMSCs differentiation and the expression of osteogenic differentiation factor from rBMSCs under an inflammatory environment. Moreover, CuCDs/OPAM could induce macrophage phenotype switching (from M1-type macrophages to M2-type macrophages) in vivo which was beneficial to anti-inflammatory and present a good osteoimmunomodulation capability to induce a bone immune microenvironment to promote the differentiation of rBMSCs. In conclusion, CuCDs/OPAM hydrogel has dual functions of osteoimmunomodulatory and bone repair, and is a promising bone filling and repair material.
研究领域:
生物材料
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骨科
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组织工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2024
·
IF 9.4
Xiaorong Li,Yunhui Si,Jingxian Liang,Mengsha Li,Zhiwei Wang,Yinying Qin,Litao Sun
Mesenchymal stem cell-derived exosomes (MSC-Exos) have emerged as promising candidates for cell-free therapy in tissue regeneration. However, the native osteogenic and angiogenic capacities of MSC-Exos are often insufficient to repair critical-sized bone defects, and the underlying immune mechanisms remain elusive. Furthermore, achieving sustained delivery and stable activity of MSC-Exos at the defect site is essential for optimal therapeutic outcomes. Here, we extracted exosomes from osteogenically pre-differentiated human bone marrow mesenchymal stem cells (hBMSCs) by ultracentrifugation and encapsulated them in gelatin methacryloyl (GelMA) hydrogel to construct a composite scaffold. The resulting exosome-encapsulated hydrogel exhibited excellent mechanical properties and biocompatibility, facilitating sustained delivery of MSC-Exos. Osteogenic pre-differentiation significantly enhanced the osteogenic and angiogenic properties of MSC-Exos, promoting osteogenic differentiation of hBMSCs and angiogenesis of human umbilical vein endothelial cells (HUVECs). Furthermore, MSC-Exos induced polarization of Raw264.7 cells from a pro-inflammatory phenotype to an anti-inflammatory phenotype under simulated inflammatory conditions, thereby creating an immune microenvironment conducive to osteogenesis. RNA sequencing and bioinformatics analysis revealed that MSC-Exos activate the p53 pathway through targeted delivery of internal microRNAs and regulate macrophage polarization by reducing DNA oxidative damage. Our study highlights the potential of osteogenic exosome-encapsulated composite hydrogels for the development of cell-free scaffolds in bone tissue engineering.
研究领域:
组织工程
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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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免疫学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Hui Yan,Lietao Wang,Haoshuang Wu,Yongqi An,Yumei Qin,Zhen Xiang,Huining Wan,Yanfei Tan,Li Yang,Fanjun Zhang,Qing Jiang,Rifang Luo,Yunbing Wang
Unhealthy vascular tissue healing after stenting is primarily triggered by endothelial dysfunction and excessive smooth muscle cell proliferation, which is induced and aggravated by local thrombosis and excessive inflammation. Excessive inflammatory response is closely related to elevated concentrations of reactive oxygen species (ROS). Here, an environment-friendly coating strategy termed “Anti-fouling plus” with inflammatory self-regulation ability was proposed. Upon this, membrane-mimicking copolymer MA(PCLA) served as the antifouling coating, effectively inhibiting coagulation and inflammation during the early stage of implantation. Furthermore, a ROS-responsive prodrug was drawn into the coating to promote tissue healing. A molecular prodrug of thioketal-bearing dexamethasone was engineered to be released in a controlled and responsive manner in response to externally high levels of ROS. The released dexamethasone exhibited highly effective anti-inflammation properties after implantation. The combination of ROS-responsive prodrug and membrane-mimicking antifouling interface strategy intelligently integrated inflammation responsiveness and regulation, which could mediate a gentle vascular microenvironment and thus promote vascular remodeling. In vivo stent implantation studies demonstrated that the proposed “Anti-fouling plus” coating effectively inhibited neointima hyperplasia, modulated the inflammatory response and promoted endothelialization, offering promising surface modification approaches for vascular stents.
研究领域:
生物材料
·
组织工程
·
血管生物学
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药物递送系统
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Yaou Peng,Shuaiyue Pang,Yanlin Zeng,Jiayi Wei,Jinda Lu,Yangfan Ruan,Xinyu Hong,Xiuhui He,Xiaoying Chu,Yishun Guo,Hanwen Guo,Siyuan Qian,Zipei Jiang,Zhengxuan Jiang,Bailiang Wang
Clinical guidelines for infectious keratitis treatment require that anti-inflammatory drugs can only be used after infection elimination, which causes irreversible inflammatory damage to the cornea. In this work, photodynamic metal organic frameworks (PCN-224) were used as drug carrier to load Pt NPs with catalase-like activity and anti-inflammatory drug (Dexamethasone, DXMS) for endogenous oxygen generation and reduced corneal damage, respectively. The photodynamic therapy (PDT) effect was greatly enhanced in bacteria elimination and bacterial biofilms removal through catalysis of overexpressed hydrogen peroxide (H 2 O 2 , ∼8.0 and 31.0 μM in bacterial solution and biofilms, respectively) into oxygen by Pt NPs. More importantly, the cationic liposome modified PCN-224@Pt@DXMS@Liposomes (PPDL NPs) greatly enhanced the adhesion to negatively charged ocular surface and penetration into corneal barrier and bacterial biofilms. Both in vitro cell viability test and in vivo eye irritation tests proved good biocompatibility of PPDL NPs under 660 nm laser irradiation. Furthermore, PDT of PPDL NPs in rapid bacteria killing was verified through infectious keratitis animal model. The superior bactericidal effect of antibacterial materials could largely replace the bactericidal effect of the immune system. It is worth mentioning that this simultaneous sterilization and anti-inflammation treatment mode is a new exploration against the clinical treatment guidelines.
研究领域:
眼科学
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药学
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纳米技术
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传染病学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials
·
2025
·Vol. 18
·期 6
·1351
·
IF 3.2
Ming Liu,Zhicun Liu,Xiangkai Qiao,Cheng Chen,Hongtu Guo,Hao Gu,Junbo Li,Tiedong Sun
Nanomotors driven by endogenous enzymes are favored in biology and pharmacy due to their spontaneous driving and efficient biocatalytic activity, and have potential applications in the treatment of clinical diseases that are highly dependent on targeted effects. For diseases such as muscle atrophy, using energy molecules such as ATP to improve cellular metabolism is a relatively efficient treatment method. However, traditional adenosine triphosphate (ATP) therapies for muscle atrophy face limitations due to instability under physiological conditions and poor targeting efficiency. To address these challenges, we developed an endogenous proton-gradient-driven ATP transport motor (ATM), a nanomotor integrating chloroplast-derived FoF1-ATPase with a biocompatible flask-shaped organic shell (FOS). The ATM is synthesized by vacuum-injecting phospholipid-embedded FoF1-ATPase nanothylakoids into ribose-based FOS, enabling autonomous propulsion in acidic microenvironments through proton-driven negative chemotaxis (directional movement away from regions of higher proton concentration). This nanomotor converts proton gradients into ATP synthesis, directly replenishing cellular energy deficits in atrophic tissues. In vitro studies demonstrated high biocompatibility (>90% cell viability at 150 μg/mL) and pH-responsive motility, achieving speeds up to 4.32 μm/s under physiological gradients (ΔpH = 3). In vivo experiments using dexamethasone-induced muscle atrophy mice revealed that ATM treatment accelerated weight recovery and restored normal muscle morphology, with treated mice exhibiting cell sizes comparable to healthy controls (30–40 μm vs. 15–25 μm in untreated). These results highlight the ATM’s potential as a precision therapeutic platform for metabolic disorders, leveraging the natural enzyme functionality and synthetic material design to enhance efficacy while minimizing systemic toxicity.
研究领域:
生物医学工程
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药理学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）