查找使用阿拉丁产品的科研文献

Dual-thermo-responsive microneedle patch for accelerated diabetic wound healing through on-demand drug release and active temperature management

Xia Dan,Wu Yumeng,Xu Ruodan,Zhou Linxi,Wu Xiaotong,Wang Donghui,Liang Chunyong,Li Ning

Diabetic foot ulcers (DFUs), prone to infection and deterioration without timely intervention, significantly increase risks of amputation and mortality. Elevated local temperature in DFUs further impedes the healing process. Although microneedles (MNs) represent a promising strategy for DFUs treatment, conventional passive drug release systems suffer from slow release kinetics and low utilization efficiency. To address these limitations, we developed a dual-thermo-responsive microneedle patch (DTMN) that actively controls drug delivery through temperature-induced structural transitions. The inner layer consists of sodium alginate-poly (N-isopropylacrylamide) (SA-PNIPAM) loaded with sucrose octasulfate sodium salt (SOS), utilizing the volume phase transition of PNIPAM to accelerate drug expulsion in response to temperature change. The outer layer comprises a polyethylene glycol/polylactic acid-glycolic acid copolymer (PEG-PLGA) loaded with urea, which undergoes gel-sol transition to facilitate controlled urea release and wound cooling. An upper electrospun nanofiber membrane made of poly (ε-caprolactone)/chitosan (PCL/CS) incorporated with tetracycline hydrochloride (TH) and SOS provides enhanced antibacterial efficacy and increased drug loading capacity. The resulting DTMN exhibits efficient drug release (85.23% SOS and 35.44% urea-derived ammonia at 24 h), remarkable antioxidant activities, potent antibacterial performance, excellent biocompatibility, and significantly enhanced wound healing. This multifunctional system offers a novel and effective strategy for the management of DFUs. Graphical A dual-thermo-responsive microneedle patch (DTMN) that actively controls drug delivery through temperature-induced structural transitions for DFUs treatment.

Carrier-free dual-drug nanoplatforms cooperatively remodel macrophage and VSMC fate specifications for treating abdominal aortic aneurysm

Xianru Bi,Yuxuan Xiao,Rongjie Zhang,Wei Sun,Yu Li,Chao Qi,Jiqin Lian,Lu Lu,Yingxue Hao

Abdominal aortic aneurysm (AAA) is a cardiovascular disease with extremely high mortality rate, yet its treatment options are still limited in the clinic. This study presents a carrier-free dual-drug nanoplatform to therapeutically reprogram macrophage fate for improving AAA treatment efficacy. The nanoplatform was synthesized through the self-assembly of naringenin (NGN) and rapamycin (RAP) and modified with DSPE-PEG 2K and DSPE-PEG 2K -cRGD (named RNR NPs) to confer AAA targeting capability. The RNR NPs could efficiently accumulate in AAA site after systemic administration for on-demand delivery of the NGN/RAP drug combination to vascular smooth muscle cells (VSMCs) and residing M1-like macrophages. Here the NGN and RAP components could cooperatively activate the transcription factor EB (TFEB) signaling in the AAA-residing pro-inflammatory M1-like macrophages to reprogram them into an anti-inflammatory M2-like phenotype to reverse local inflammation. Meanwhile, they could also scavenge reactive oxygen species in VSMCs and inhibit apoptosis signaling to inhibit VSMCs apoptosis and calcification. These effects could act in a cooperative manner for effectively ameliorating AAA symptoms in vivo . Overall, the RNR NPs present an approach for the efficient treatment of AAA in the clinic with optimal safety.

Integrating causal human genetics and In vivo transcriptomics to uncover a shared lipid-centric architecture in metabolic and neurocognitive disease

Yi Li,Zhu Ni,Xiao-Yong Xia,Na Cheng,Yu Bo,Junwen He,Yang He,Xiang-Yu Meng,Xu Wang,Xuan Xu

Background Metabolic disorders and neurocognitive diseases frequently co-occur, yet the specific mechanisms driving this comorbidity remain elusive. While epidemiological associations are well-documented, the causal links between these conditions are complex and incompletely understood, necessitating a systems-level investigation into their shared biological architecture. Methods This study integrates large-scale human genetics with experimental in vivo transcriptomics and computational chemistry to elucidate these shared pathways. Specifically, an AD-like murine model was used to experimentally prioritize a core network of 13 dysregulated genes within a pathologically relevant context. Results Network-informed Mendelian randomization identified bidirectional causalities, including a 14% elevated dementia risk from type 2 diabetes and protective effects of obesity against parental Alzheimer’s disease (AD). The study identified a signature encompassing key lipid metabolism hubs APOE, CLU , and LDLR . This signature serves as a critical biological filter, anchoring human genetic associations by providing direct evidence of their dysregulation in a neurodegenerative environment. Subsequent chemical enrichment and molecular docking analyses indicated that these experimentally-prioritized targets are engaged by both therapeutic agents (e.g., valproic acid) and environmental toxins (e.g., benzo[a]pyrene). Conclusion This multi-modal investigation provides a robust framework that converges on a high-confidence, 13-gene signature of lipid dysregulation as a central mechanistic interface, offering a powerful set of prioritized targets for future functional validation and therapeutic development at the metabolic-neurocognitive nexus.

From biosensing to herbal discovery: A nanozyme cascade platform for acetylcholinesterase monitoring and inhibitor screening in synthetic and natural sources

Shuang Cai,Bao-Wen Fan,Jia Qin,Cheng-Yang Pu,Ya-Jian Qin,Cong-Ting Wu,Wen Xu,Jing Li

Early diagnosis and therapeutic intervention for Alzheimer's disease (AD) necessitate advanced tools for detecting acetylcholinesterase (AChE) activity and screening AChE inhibitors (AChEIs). This study developed a novel bimetallic MOF nanozyme, Cu–NH 2 –88B(Fe), exhibiting significant peroxidase-like activity. This nanozyme was integrated with AChE to construct a dual-enzyme cascade biosensing platform, which achieved highly sensitive AChE detection, with a detection limit of 0.01 mU/mL, and demonstrated excellent accuracy in fetal bovine serum (spiked recoveries: 92.07–111.09%). Additionally, the platform also enabled quantitative assessment of synthetic AChEIs, determining IC 50 values for donepezil (9.85 nM), neostigmine (1.41 μM), huperzine A (6.21 μM), and galantamine (611.31 μM), all of which exhibited broad linear ranges and high sensitivity. All four compounds exhibited a broad linear range and excellent sensitivity. Innovatively, the platform was applied to screen AChE inhibitory activity in seven traditional Chinese medicines (TCMs). Crucially, when comparing four extraction methods, ultrasound-assisted extraction (UAE) proved most effective in liberating active compounds. The UAE-obtained extract of Poria cocos (Yunnan) showed the strongest inhibition, achieving an AChE inhibition rate of 39.03% at 0.01 mg/mL. Notably, the screening results across different species, origins, and extraction methods (including the superior UAE) showed high consistency with the classical Ellman method, validating the platform's reliability. This study not only provides a low-cost, easy-to-operate, sensitive, and reliable analytical strategy for AChE activity detection and AChE inhibitor development, but more importantly, it successfully applies nanozyme technology to the complex system of TCMs, offering strong technical support for the screening and preliminary identification of potential anti-AD active components from TCM resources.

Ultrasmall self-assembled crystal-modulating amplifier suppresses crystalline nephropathy via dual modulation of mineralization microenvironment and oxidative stress homeostasis

Liu-Qing Gu,Xue-Wu Chen,Jun Long,Guang-Zhao Wang,Yan Wang,Ling-Hong Huang,Jian-Ming Ouyang,Xin-Yuan Sun

Crystalline nephropathy is a dynamic pathological process characterized by a self-amplifying feedback loop, where crystal-induced epithelial injury drives iterative crystal nucleation, growth, and aggregation, transforming the kidney into a persistent mineralization reactor. Current therapeutic approaches primarily rely on surgical intervention, which fails to disrupt this pathological cycle. The glomerular filtration barrier (10 nm threshold) limits the efficacy of conventional nanomedicines in renal delivery. This study constructs a 5.7 nm metal-polyphenol network, salvianolic acid B-Eu@BSA (SAB-Eu@BSA), via self-assembly methods for editing of the intrarenal crystal microenvironment, aiming to cut off the pathological cycle of renal mineralization. The SAB-Eu@BSA nanoplatform integrates a SAB Eu 3+ coordination core for dual-action: specific adsorption to the high-energy ( 1 ¯ 01) crystal faces of monohydrate calcium oxalate (COM) to inhibit its growth and promote phase transition to less toxic dihydrate phase, and broad-spectrum antioxidant activity to mitigate oxidative stress. The nanoplatform demonstrates enhanced crystal modulation efficacy, significantly reduces crystal-induced renal injury, and improves renal function in vivo. RNA sequencing analysis reveals modulation of key pathways, including oxidative stress, cell adhesion, and apoptosis. This multifunctional nanoplatform, combining crystal inhibition, oxidative stress regulation, and renal clearance, offers a promising therapeutic strategy for crystalline nephropathy.

Integrative transcriptomic and metabolomic analyses of puerarin against cholestatic liver fibrosis

Danhua Zhu,Qingmiao Shi,Xiaoxi Ouyang,Yanhong Zhang,Xiaopeng Yu,Long Yang,Kunkai Su,Lanjuan Li

Background Cholestatic liver fibrosis is a common pathological manifestation of various biliary tract diseases. Given the limited efficacy of current pharmacotherapies, there is a clear need to develop novel and effective treatment strategies. This study aims to evaluate the protective effects of puerarin against cholestatic liver fibrosis. Methods The therapeutic efficacy of puerarin was assessed in a bile duct ligation rat model. Collagen deposition was evaluated using picrosirius red staining and Masson’s trichrome staining. Immunohistochemistry for cytokeratin 7 (CK7) and CK19 was performed to assess bile duct proliferation. Hepatic mRNA expression profiles and metabolic profiles were analyzed by transcriptome sequencing and untargeted metabolomics, respectively. In parallel, in vitro experiments were conducted using HepaRG hepatocyte cultures exposed to a bile acid mixture, with cell proliferative capacity assessed via EdU assays. Results Puerarin treatment ameliorated serum biochemical abnormalities, histological injury, and bile duct proliferation in the cholestatic liver fibrosis rat model. Mechanistically, puerarin modulated extracellular matrix deposition and regulated the PI3K-Akt signaling pathway. Furthermore, metabolomic analysis indicated that puerarin altered the hepatic bile acid profile, promoting the conjugation of hydrophobic bile acids. In vitro studies demonstrated that puerarin attenuated bile acid mixture-induced hepatotoxicity in hepatocytes. Conclusion The present study suggests that puerarin may alleviate cholestatic liver fibrosis, potentially by reducing bile duct proliferation, modulating extracellular matrix deposition, and promoting the conjugation of toxic bile acids. These findings indicate that puerarin could be a candidate therapeutic agent for cholestatic liver fibrosis. Further studies are required to fully elucidate its net protective effect on bile acid homeostasis.

The inhibitory effect of cryptotanshinone on liver cancer by regulating the IRAK1/NF-κB signaling pathway

Lan-Ting Li,Yan-Xue Zhu,Dong-Mei Zhao,Jin-Le Zhang,Lin-Guo Xia,Rui-Fang Li

Epicatechin-Diarylboronate Aggregates with Inhibited Auto-oxidation and Stable Antioxidant Activity: Structural Modification and Binding Thermodynamics

Wenqi Zhao,Meihuan Yao,Mengdi Zhang,Xinmiao Du,Binbin Zhang,Yujie Wang,Guangyue Bai

Improving the stability of catechins against autoxidation and simultaneously exerting their biological activity to scavenge reactive oxygen species (ROS) are essential for achieving their efficient utilization in healthcare and drug therapy. Focusing on this important objective, a feasible strategy for modifying catechins with arylboronic acid has been proposed as they have good biocompatibility and also controllable release at specific sites. We developed three catechin-diarylboronate (DiarylBA) ester self-assembly carriers, in which DiarylBA serves as the receptor molecules of catechins, including a coupled benzyl ammonium boronic acid (BTEAB) or two coupled pyridinium boronic acids (PyBBA and PyPBA) linked by a spacer, and (−)-epicatechin (EC) is taken as the representative catechin molecule. Specifically, the inhibition of the auto-oxidation and the antioxidant activities for both EC and EC-DiarylBA esters were characterized sufficiently by combining spectroscopies (UV–vis, NMR), and ROS scavenging assessment. The relevant binding thermodynamics and interaction mechanism, as well as their aggregation behavior, were also studied by ITC, NMR, and light scattering. The thermodynamic and spectroscopic results all confirm the generation of EC-DiarylBA esters in a range from a weak acid of pH 6.5 to an alkaline one of pH 8.5. It was found that the esterification of EC with DiarylBA can effectively inhibit the auto-oxidation of EC even at pH 8.5 and still retain the excellent antioxidant activity of the original EC. Furthermore, the EC-BTEAB ester exhibits a favorable H2O2 responsiveness in the H2O2-overexpressed site, while EC-PyBBA and EC-PyPBA esters need to first release the EC component to effectively eliminate H2O2. Therefore, the comprehensive results of stability and antioxidant activity indicate that the EC-DiarylBA ester would be a promising candidate for enhancing EC’s medicinal and health care effects.

Optimization of extraction, structural modification, and bioactivity of polysaccharides from Euphorbia trigona Mill. and their derivatives

Xiaoliang Zhao,Yuanyuan Ma,Haidong Wen,Lixia Xiong,Cunjin Wang,Jing Zhang,Pengcheng Shao,Yuhui Zhao,Ji Zhang,Weijie Zhang

The optimal hot water extraction process for a polysaccharide from Euphorbia trigona Mill. was established using single-factor and orthogonal experiments, yielding the best conditions of a 1:30 (g/mL) solid-to-liquid ratio at 90 °C for 3.5 h, with a polysaccharide yield of 5.89%. Sulfated (ETM-S) and phosphorylated (ETM-P) derivatives were successfully prepared, with degree of substitution of 0.32 and 0.48, respectively. Structural analysis confirmed the polysaccharides were acidic with complex monosaccharide compositions. Bioactivity assessments revealed that both modifications markedly improved functional properties. ETM-P exhibited significantly enhanced antioxidant activity, with IC50 values of 2.16, 1.57, and 1.79 mg/mL against DPPH, ·OH, and O2·–, respectively. Sulfation boosted inhibitory effects on α-amylase and α-glucosidase, suggesting hypoglycemic potential, and also increased pancreatic lipase inhibition, indicating a synergistic role in regulating glucose and lipid metabolism. Furthermore, ETM-S showed the strongest in vitro cytotoxicity against HepG2 cells, achieving an inhibition rate of 45.00% at 800 μg/mL, outperforming ETM-P (33.37% at 400 μg/mL) and the native polysaccharide (27.92% at 800 μg/mL). Both modified polysaccharides promoted RAW264.7 macrophage proliferation, enhanced phagocytosis, and stimulated NO release, demonstrating immunomodulatory capacity. In summary, chemical modification, especially sulfation, effectively enhances the bioactivities of polysaccharides, showing promise for regulating glycolipid metabolism and immune modulation.

Inverted V-shaped albumin binding and CES1/CES2 cascade conversion in aliphatic alcohol-modified CPT prodrug albumin nanoparticles

Dian Jiao,Tao Wang,Yinghou Wang,Zhengdi Ma,Mingjia Sun,Chen Meng,Weihua Chen,Yaqi Wang,Yanxin Li,Yaru Song,Xinnan Hou,Zhong Wen,Jingdong Xiao,Zhonggui He,Tianhong Zhang,Jin Sun,Zhenbao Li,Qikun Jiang

Albumin-based drug-delivery systems garner attention due to their inherent biocompatibility and tumor-targeting potential. However, they are limited by weak human serum albumin (HSA) affinity for drugs like camptothecin (CPT). To address this, we synthesize five CPT prodrug derivatives (CPT-SA-C6–C14) with tunable aliphatic alcohol chains as HSA-binding motifs and a succinic acid linker for carboxylesterase (CES1/CES2)-mediated cascade activation. CPT-SA-C10, C12, and C14 achieve ultrahigh drug loading (>30%) in albumin nanoparticles (ANPs) via enhanced HSA affinity. Aliphatic chain length shows an inverted V-shaped correlation with both HSA-binding affinity and CES1-catalyzed hydrolysis. The resulting intermediate is hydrolyzed by CES2 to release CPT. CPT-SA-C12 ANPs exhibit the highest albumin affinity and fastest enzymatic conversion, yielding superior therapeutic efficacy and favorable tolerability. This work elucidates the structure-activity relationship of albumin-bound prodrugs and advances the design of CES-responsive nanomedicines.

Engineering a Gram-Negative Bactericidal Hydrogel: CuxTe Nanozyme Functions as a Specific Killer by Hijacking LPS and Flagella Biosynthesis

Jianguo Niu,Yuhao Xue,Wenqi Wang,Wei Zhang,Min Wang,Jiaqi Qin,Dongliang Yang,Xianwen Wang

The treatment of gram-negative bacterial infections remains a formidable challenge due to their resilient outer membrane and adaptive evasion mechanisms. Herein, we present a multifunctional nanozyme hydrogel, copper telluride@cationic guar gum (Cu x Te@CG), which acts as a gram-negative-specific bactericidal platform. This hydrogel integrates the unique enzymatic and physical properties of urchin-like Cu x Te nanozymes with the biocompatible and adhesive cationic guar gum (CG) matrix. The Cu x Te@CG hydrogel exhibits synergistic oxidase- and glutathione peroxidase-like activities, catalyzing the generation of reactive oxygen species (ROS) while depleting bacterial glutathione, thereby inducing lethal oxidative stress. Crucially, transcriptome sequencing revealed that the platform specifically targets Pseudomonas aeruginosa by down-regulating key genes involved in lipopolysaccharide (LPS) biosynthesis and flagellar assembly, compromising their primary defense and motility structures. This targeted interference with LPS and flagella amplifies the ROS-mediated attack, leading to enhanced and specific killing of gram-negative pathogens ( Escherichia coli , P. aeruginosa , and Klebsiella pneumoniae ), effective biofilm disruption, and inhibition. In a P. aeruginosa -infected burn wound model, the Cu x Te@CG hydrogel markedly accelerated healing by eliminating bacteria, promoting angiogenesis, and modulating inflammation, all while demonstrating excellent biosafety. This work establishes the Cu x Te@CG hydrogel as a robust and targeted therapeutic strategy for combating stubborn gram-negative infections.

Sodium Alendronate-Modified PLGA-mPEG Nanomicelles Loaded with Rifapentine for Targeted Delivery to Bone Tissue

Weilin Wang,Xin Cui,Hengfa Wei,Jingjing Wang,Yesbolat Ahehati,Cuiping Jiang,Fei Li,Shasha Li

Background/Objectives:The limited targeting efficiency and systemic toxicity of conventional medicine present significant challenges in the treatment of skeletal disorders, such as bone tuberculosis. To address these limitations, we developed a bone-targeting nanomicelle delivery system functionalized with alendronate (ALN), designated ALN-PLGA-mPEG@RPT, to improve the targeted delivery and therapeutic efficacy of rifapentine (RPT) in bone tissue.Methods:The ALN-PLGA-mPEG blank micelles, prepared in accordance with our research group’s optimized protocol, were loaded with RPT and subjected to systematic formulation optimization. The resulting nanomicellar system was comprehensively characterized in terms of its physicochemical properties, including particle size and polydispersity index (PDI). Additionally, drug-loading capacity, encapsulation efficiency, and in vitro release curve were evaluated. Bone-targeting efficacy was assessed using in vivo imaging techniques, while biodistribution and safety profiles were determined through in vivo distribution studies and histopathological examination.Results:The optimized ALN-PLGA-mPEG@RPT nanomicelles exhibited a mean particle size of 101.90 ± 4.17 nm, and a PDI of 0.242 ± 0.021. The formulation achieved a drug loading of 16.74 ± 0.51% with an encapsulation efficiency of 50.27 ± 1.91%. In vitro release studies confirmed a sustained-release profile, with only 25% of RPT released within 12 h. In vivo imaging revealed significantly enhanced bone-targeting capability in the ALN-modified group, showing a 1.93-fold higher drug accumulation in bone tissue compared to blood. Histopathological analysis indicated no observable pathological alterations in major organs.Conclusions:The ALN-PLGA-mPEG@RPT nanomicelle system exhibits favorable bone-targeting efficiency, sustained-release properties, and biocompatibility, representing a promising strategy for the precise treatment of bone tuberculosis and other skeletal diseases.