American Journal of Translational Research
·
2024
·Vol. 16
·期 10
·5385
·
IF 1.7
Hui Huang,Guanhua Wang,Dali Zeng
Objective: To investigate the protective effect of Peimine (PM) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and the underlying mechanisms. Methods: KM mice were randomly divided into five groups: Control, LPS, Peimine low-dose (PM-L, 0.1 mg/kg), medium-dose (PM-M, 1 mg/kg), and high-dose (PM-H, 10 mg/kg) groups. Mice in the PM treatment groups received intraperitoneal injection of Peimine at different doses, while the mice in control and LPS groups received physiological saline. Afterwards, mice in the LPS and PM groups were subjected to intranasal instillation of LPS to establish the model of acute lung injury. The wet-to-dry (W/D) weight ratio of lung tissues was calculated, and H&E staining was performed to observe pathological changes in the lung tissues. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and MDA were measured using ELISA kits. Western blot was employed to assess the expression of NF-κB, IκBα, phospho-IκBα, Nrf2, HO-1, and SOD2 in lung tissues. RT-PCR quantified the mRNA levels of Nrf2 and its downstream genes HO-1 and NQO1. Additionally, RAW264.7 cells were treated with various drug concentrations for 24 hours followed by LPS exposure (100 ng/mL) for another 24 hours. Prior to treatment of RAW264.7 cells with PM and LPS, the ML385+PM group was pre-treated with ML385 (3 μM) for 4 hours. ELISA kits were used to measure TNF-α, IL-6, IL-1β, and MDA in cell supernatants, while ROS levels were determined using a ROS assay kit. Results: Compared with the model group, pretreatment with PM significantly reduced the lung tissue W/D weight ratio, ameliorated lung tissue pathological changes, and inhibited the secretion of TNF-α, IL-6, and IL-1β in bronchoalveolar lavage fluid. PM inhibited the LPS-induced elevation in lung tissue MDA levels, SOD2 consumption, and ROS levels. Furthermore, PM suppressed LPS-induced NF-κB activation and nuclear translocation, while significantly enhancing the protein expression of Nrf2 and HO-1 and increasing the mRNA levels of Nrf2 and its downstream genes, such as HO-1 and NQO1. In RAW264.7 cells, LPS induction led to elevated IL-1β, IL-6, TNF-α, MDA, and ROS levels, which were significantly suppressed by PM treatment. However, the antioxidative and anti-inflammatory effects of PM were effectively blocked by inhibiting the Nrf2 pathway. Conclusion: PM effectively ameliorates LPS-induced lung injury, primarily through inhibition of the NF-κB pathway, and activation of the Nrf2 pathway, alongside a reduction in the release of inflammatory factors.
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Advanced Composites and Hybrid Materials
·
2024
·Vol. 7
·期 6
·1-18
·
IF 23.2
Zhao Kui,Qi Luming,Li Qi,Wang Yin,Qian Cheng,Shi Zhengjun
Biocompatible and mechanically stable porous hydrogels are promising materials for artificial skin in wound healing. The rigid PVA phase was selected to make the scaffold, and a dense and uniform porous phase was formed in both transverse and longitudinal phases by freezing casting technology. The names PVA and PVA + PNS2A were used in in vitro activity tests using polymer solutions that had not been molded before. The crosslinked materials were named Base, CP1 (0.1% PNS2A), and CP2 (0.5% PNS2A). HUVEC and HaCat cell proliferation experiments proved to be safe and non-toxic and significantly promoted proliferation activity after 48 h. The cell model with Raw 264.7 proved anti-inflammatory effect by mixed polymer solution. The scratch test showed that the CP2 promotes the migration of HaCat cells more effectively at 48 h. The cell adhesion experiment showed that the skin-like composite material grew rapidly along the void direction. Animal experiments showed that the multi-layer skin-like CP2 increased the mechanical properties, gelation, and hemostasis (58.8% reduction) and inhibits inflammation through active polysaccharide in the early stage of wound healing. It promoted collagen formation in the late stages of the healing process. Upon contact with the wound, the material undergoes gelation to isolate the wound and completely healed the hurt after 12 days. Stent disintegration and 48-h absorption time provide support for implant material development. Graphical
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PHYTOMEDICINE
·
2026
·
IF 11.3
Yujuan Li,Jingyi Yang,Xiaotong Shao,Yunhe Tao,Shihui Ling,Xiaomeng Li,Qifeng Ye,Bin Guo,Hongsheng Bi
Despite advancements in treatments such as atropine, the pathological changes in high myopia still lead to vision loss, highlighting the need to identify novel therapeutic targets. Clinically, axial elongation are closely related to reduced choroidal blood flow. This study revealed that the pyroptosis-associated protein Gasdermin D (GSDMD) may play a key role in high myopia. Experiments showed that chemical inhibition of GSDMD significantly reduced axial elongation and choroidal blood flow reduction. Furthermore, by screening pharmacologically active traditional Chinese medicine compounds, we identified that Artemisia argyi (Aiye) and its active ingredient apigenin act as effective GSDMD inhibitors, capable of replicating the protective effects observed with chemical inhibition. In all, this study suggests that GSDMD is a potential target mediating axial elongation and choroidal blood flow changes in high myopia, and apigenin is a potential therapeutic strategy for intervening in high myopia.
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JOURNAL OF CONTROLLED RELEASE
·
2026
·
IF 12.4
Dongjing Wang,Xiaonan Li,Kunpeng Wei,Suyan Wang,Wen Zuo,Ze Xu,Chen Li,Hui Wang,Xueyan Zhou,Yanzhuo Zhang
Acute kidney injury (AKI) is a prevalent clinical syndrome associated with high morbidity, mortality, and a heavy medical burden. Oxidative stress, inflammation, and ferroptosis are key drivers of AKI, yet current pharmacotherapies are limited by suboptimal efficacy and systemic side effects. An efficient and precise kidney-targeted delivery system that co-delivers complementary therapeutics could overcome these challenges. Herein, we report a platelet membrane–coated, reactive oxygen species (ROS)-responsive nanozyme (BAPCs@PM) for synergistic AKI therapy. Ultrasmall CeO 2 nanodots (∼3 nm) were in situ mineralized on the outer layer of polydopamine cores, and hydrophobic baicalein was loaded into the mesoporous interior, yielding a stable and well-dispersed multifunctional composite nanozyme. Platelet membrane cloaking conferred renal targeting, immune evasion, and prolonged circulation. BAPCs@PM enabled ROS-triggered release of CeO 2 nanodots and sustained baicalein delivery at injured sites, amplifying local antioxidant, anti-inflammatory, and anti-ferroptotic activity. In a cisplatin-induced AKI model, BAPCs@PM markedly suppressed kidney injury molecule-1 upregulation, inhibited cleaved caspase-3 activation and apoptosis, enhanced mitochondrial protection, modulated macrophage polarization, reduced proinflammatory cytokine production, regulated iron homeostasis, restored glutathione peroxidase 4 expression, attenuated ferroptosis and lipid peroxidation, and ultimately improved renal function. Owing to their ultrasmall size, the ceria nanodots achieved efficient renal accumulation and rapid clearance with minimal systemic toxicity. This study provides an innovative biomimetic and responsive therapeutic strategy for AKI by combining ultrasmall nanozymes, natural bioactive molecules, and biomimetic membrane engineering.
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ADVANCED FUNCTIONAL MATERIALS
·
2026
·
IF 19.9
Wenjun Zhao,Moran Wang,Yuan Xue,Yao Song,Mengting Shao,MengYa Sun,Li Yang,Mingfei Pan,Feng Chen,Juan Jin,Ning Gu
A key challenge in stroke therapy is overcoming multiple biological barriers in the brain and coordinating between neurovascular units. Cell membrane–based biomimetic carriers offer an approach for bio-navigated drug delivery; however, the modulation of their structure and function remains challenging. Herein, an engineering strategy for the bidirectional regulation of neutrophil-biomimetic xenon nanobubbles (Xe-EBs) is proposed for the multistage sequential treatment of stroke. By adjusting the proteins/lipids ratio through inflammatory activation (positive) and synthetic phospholipids hybridization (negative), the surface tension of membranes was regulated to obtain Xe-EBs with sizes of 563 ± 31, 263 ± 15, and 172 ± 8 nm. Membrane assembly was further modulated to form protein-enriched domains, which exhibited an enhanced inflammatory response similar to the upregulation of proteins. Activated neutrophil-Trojan Xe-EBs can target the inflamed endothelium and penetrate the blood–brain barrier for acute xenon neuroprotection and real-time recanalization. After uptake by activated microglia, the subacute inflammatory microenvironment is reshaped by reprogramming microglia M1–M2 polarization. In vivo and gene transcriptome analyses confirmed the efficacy and sequential mechanisms of stroke treatment. This study provides a paradigm for the modulation of biomimetic nanocarriers and a proof-of-concept for neutrophil-navigated sequential treatment for stroke.
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NEUROCHEMICAL RESEARCH
·
2026
·Vol. 51
·期 4
·207
·
IF 4.5
Fu Jie,Zhang Shaotao,Chu Yifei,Li Jinglun,Chen Xiu
Microglia-mediated neuroinflammation is closely associated with the pathogenesis of epilepsy. Mammalian sterile-20-like kinase 4 (MST4) has been suggested a regulator of inflammation. However, the effect of MST4 on microglia neuroinflammation in epilepsy remains unclear. A pilocarpine-induced rat epilepsy model was constructed and a lipopolysaccharide (LPS)-stimulated microglia cell model was applied in the current research. Knockdown or overexpression of MST4 was established using lentivirus transfection. Electroencephalograph (EEG) was employed to measure brain activities of rats. The protein and mRNA expressions were detected using western blot and qRT-PCR, respectively. Immunofluorescent staining was conducted to detect the distribution of the proteins. TUNEL staining was performed to evaluate cell apoptosis. The protein interaction was evaluated with Co-IP assay. Our results showed that MST4 and nuclear PKM2 expressions were increased in epileptic rats compared to control and colocalized with microglia. MST4 overexpression inhibited microglia activation, the release of TNF-α and IL-1β, and improved neuronal apoptosis in epileptic rats. Furthermore, MST4 interacted with PKM2 and regulated PKM2 nuclear translocation. Inhibiting PKM2 nuclear translocation by TEPP-46 reversed the promoting effect of MST4 knockdown on microglia neuroinflammation. In summary, our study demonstrated that MST4 alleviated microglia-mediated neuroinflammation in epilepsy, and the mechanism of MST4-mediated anti-neuroinflammatory effects may be associated with the inhibition of PKM2 nuclear translocation.
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CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Lin Huang,Fengxiao He,Tao Wu,Jinghao Fan,Lei Liu,Xiang Zhang,Jiangchen Liu,Shiqian Huang,Decheng Wu,Waruna Lakmal Dissanayaka
This study introduces a new bioactive Janus membrane for guided bone regeneration (GBR) to treat periodontal bone defects. • Unlike conventional barrier membranes that lack long-term stability or biological function, our bilayer membrane, composed of poly(ε-caprolactone) (PCL), chitosan (CS), and the natural polyphenol proanthocyanidin (PA), combines mechanical strength with antioxidant, antibacterial, and anti-inflammatory properties. • Its asymmetric design, with in situ biomineralized hydroxyapatite particles (HAp) on a chitosan layer, supports bone growth on one side while preventing bacterial invasion on the PA-incorporated side. • This innovative approach addresses major challenges in periodontal tissue engineering and offers a promising platform for more effective and biologically intelligent therapies in clinical bone regeneration. The achievement of periodontal bone regeneration using a barrier membrane in guided bone regeneration (GBR) technology is often limited by either its inferior mechanical strength or bioactivity. To address this limitation, we developed a novel Janus bi-layer membrane by sequentially electrospinning poly(ε-caprolactone) (PCL) mixed with proanthocyanidin (PCL-PA) and chitosan (CS) in acetic acid, then biomineralized it in simulated body fluid (BSF) to form hydroxyapatite particles (HAp) in situ on a CS nanofiber layer (CS-HAp): PCL-PA/CS-HAp. This bi-layer membrane exhibited superior mechanical performance compared to single-layer membranes, with a peeling strength of 58 J/m 2 and tensile strength exceeding 5.0 MPa under hydrated conditions. In vitro antioxidant assays demonstrated the strong free-radical-scavenging ability of PCL-PA/CS-HAp. In addition, the PA-incorporated membranes exhibited greater than 95% bacterial inhibition against both Gram-negative E. coli and Gram-positive S. aureus . The bilayer membrane also alleviated oxidative stress induced by hydrogen peroxide (H 2 O 2 ), thereby promoting the proliferation of MC3T3-E1 cells, as monitored by cytoskeletal staining. Flow cytometry analysis showed that the PA-incorporated membrane can stabilize immunomodulatory effects by about 10% in lipopolysaccharides (LPS)-stimulated RAW264.7 cells. When used in a rat periodontal bone defect model, significant bone regeneration was observed in the PCL-PA/CS-HAp group, with a bone volume to total volume ratio of 36.2% and a significant reduction in bone defect size after 8 weeks, outperforming other treatment groups ( p < 0.001). The PCL-PA/CS-HAp bi-layer membrane represents a promising strategy for guided bone regeneration, effectively combining mechanical stability and bioactive properties. A bi-layer barrier membrane, PCL-PA/CS-HAp, prepared via electrospinning, was effective for periodontal bone regeneration in a rat model. Download: Download high-res image (192KB) Download: Download full-size image
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FOOD RESEARCH INTERNATIONAL
·
2026
·
IF 8.8
Qianqian Wang,Yue Zhang,Zirui Xu,Yingwu Su,Xinyu Fu,Xiao Guan,Sen Li
Mannose-glycosylated soy peptide nanoparticles were developed for vitexin delivery. • Vitexin was amorphously encapsulated with a high efficiency over 94%. • M-SPAV regulated the polarization of macrophage via targeted delivery. • M-SPAV enhanced the cellular uptake of Vitexin and blocked the TLR4/MyD88/NF-κB signaling axis. • The system provides a novel oral delivery strategy for hydrophobic bioactives. Soy peptide aggregates (SPA) are the hydrolysate products of soy protein isolate, which possess good biocompatibility and self-assembly properties, making them excellent materials for nanocarriers. In this study, a green, food-grade nanocarrier based on mannose-modified soy peptide aggregates (M-SPAV) was developed for the efficient encapsulation and targeted delivery of vitexin, a bioactive polyphenol, which has poor water solubility and low bioavailability. The mannose modification of the soy peptide aggregates was performed via a mild and feasible glycosylation method to achieve macrophage targeting. The results demonstrated that nanoparticles prepared at a mannose-to-soy protein aggregate mass ratio of 1:1 exhibited a minimum particle size of 142 nm and achieved an encapsulation efficiency as high as 93.46%. Notably, M-SPAV displayed excellent stability across a broad pH range (3.0–8.0), under high ionic strength conditions and prolonged storage, while effectively protecting vitexin and maintaining antioxidant capacity throughout simulated gastrointestinal digestion. Furthermore, mannose modification not only improved the physicochemical properties of the soy protein aggregates but also endowed the nanoparticles with specific macrophage-targeting capability through receptor recognition. This nanoparticle system substantially enhanced the cellular uptake efficiency of vitexin. Consequently, M-SPAV significantly reduced intracellular reactive oxygen species (ROS) levels in LPS-stimulated macrophages compared to free vitexin, and anti-inflammatory activity by inhibiting the TLR4 / MyD88 / NF-κB signaling axis and regulating macrophage polarization. In summary, M-SPAV provides a promising food-grade nanoplatform for precision immunomodulatory intervention in macrophage-associated inflammatory diseases. Download: Download high-res image (194KB) Download: Download full-size image
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CELL DEATH AND DIFFERENTIATION
·
2026
·
IF 13.6
Sun Ya-Zhou,Li Xin-Yan,Wang Jia,Zeng Meng-Liu,Qu Wei-Yi,Cheng Xu,Luo Lei,Wang Wei,Yang Juan,Zhang Jun,Tian Han,Zhang Peng,She Zhi-Gang,Li Hongliang,Zhang Xiao-Jing
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe conditions lacking specific pharmacological treatments. Endoplasmic reticulum (ER) stress plays a pivotal role in their pathophysiology, yet the precise regulatory mechanisms remain elusive. In this study, we identify the E3 ubiquitin ligase ring finger protein 5 (RNF5) as a critical driver of ALI/ARDS. RNF5 is markedly upregulated in response to ALI and significantly exacerbates lung injury by stabilizing HSPA5 (heat shock protein family A member 5), a master regulator of the unfolded protein response (UPR). Notably, in vivo Rnf5 ablation effectively attenuated pulmonary edema, inflammatory cell infiltration, and apoptosis, whereas lung-specific Rnf5 overexpression worsened inflammation and cell death in mice. Mechanistically, RNF5 interacts with HSPA5 and competitively blocks its binding to PERK, facilitating PERK release. Furthermore, RNF5 promotes the retro-translocation of HSPA5 from the ER lumen to the cytosol. In the cytosol, RNF5 mediates the K6- and K63-linked polyubiquitination of HSPA5, enhancing its thermal stability and preventing its re-entry into the ER. This spatial sequestration sustains the persistent dissociation of the PERK-HSPA5 complex, leading to the hyperactivation of the pro-apoptotic and pro-inflammatory PERK-eIF2α-CHOP signaling cascade. The ability of RNF5 to promote ALI is strictly dependent on its E3 ligase activity. In conclusion, our findings uncover a compartment-specific regulatory mechanism of HSPA5, suggesting that the RNF5-HSPA5-PERK axis represents a promising therapeutic target for ALI/ARDS.
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ACS Nano
·
2026
·
IF 17.3
Chuang Liu,Wenqi Xie,Zheng Cao,Yicheng Lv,Xiaoling Fu
Mesenchymal stromal cell-derived nanovesicles (MSC-NVs) prepared via a conventional top-down engineered approach hold great promise as alternatives to traditional cell therapy for cardiovascular diseases. However, these nanovesicles often suffer from substantial loss of cellular components, poor stability, and limited delivery efficiency. To overcome these limitations, we developed a hybrid gelled nanovesicle, Hy-gNVs@chol, through chitosan (CS)-based protein enrichment and functional membrane replacement, enabling efficient concentration of MSC components to form gel nanoparticles (gNPs) while conferring inflammation-targeting capability. Compared to nonenriched nanovesicles (Hy-NVs) prepared by conventional methods, Hy-gNVs@chol exhibited more than a 5-fold increase in protein cargo. Surface coating of gNPs with cholesterol-modified macrophage membrane further promoted cellular uptake and lysosomal escape. In vitro, Hy-gNVs@Chol effectively protected cardiomyocytes from ROS-induced injury, facilitated M2 macrophage repolarization, and enhanced HUVECs’ function. In vivo studies further validated the therapeutic efficacy of Hy-gNVs@chol in treating myocardial infarction. Our study introduces a biomimetic design approach for engineered MSC-derived nanovesicles and highlights their potential for therapeutic cardiac repair following myocardial infarction and other cardiovascular conditions.
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Drug Design Development and Therapy
·
2026
·
IF 6.1
Chao Song,Xiaofei Wu,Chaoqi Chen,Baoxin Shen,Yuheng He,Fei Liu,Feng Chen,Zhijiang Fu,Zongchao Liu
Background: Intervertebral disc degeneration (IVDD), characterized by inflammation, cell death, and matrix dysregulation, involves ferroptosis and autophagy interactions, though the role of ferritinophagy remains unclear.Methods: This study integrated bioinformatics analysis of clinical transcriptomes, single-cell sequencing, and experimental models to identify molecular targets linking ferritinophagy to IVDD progression.Results: Multi-omics analysis revealed 10 ferroptosis-related hub genes (eg, NCOA4, TP53, SLC7A11) enriched in hypoxia, autophagy, and ferroptosis pathways. Single-cell profiling demonstrated dynamic shifts in nucleus pulposus cell (NPCs) phenotypes during degeneration, with increased pro-inflammatory monocyte/macrophage infiltration. Clinical and experimental validation showed elevated NCOA4 and ACSL4 (ferroptosis drivers) alongside reduced GPX4 and FSP1 (anti-ferroptotic factors) in degenerated discs. Mechanistically, NCOA4-mediated ferritinophagy promoted iron overload and lipid peroxidation by degrading ferritin, exacerbating oxidative damage. Resveratrol, a natural anti-inflammatory compound, mitigated IVDD in rat models by restoring disc height, suppressing IL1β, TNF-α, and IL6, and reversing ferroptosis/autophagy imbalance via NCOA4 downregulation. Cellular studies confirmed that resveratrol attenuated LPS-induced NPCs degeneration by blocking NCOA4-dependent ferritinophagy, reducing lipid peroxidation and cell death.Conclusion: This work identifies NCOA4 as a critical nexus coordinating ferroptosis-autophagy crosstalk in IVDD and establishes ferritinophagy as a novel pathological mechanism. Resveratrol’s therapeutic efficacy, mediated through multi-target modulation of inflammatory and iron homeostasis pathways, provides a promising strategy for IVDD treatment. The findings advance precision medicine approaches by elucidating ferritinophagy’s role and proposing resveratrol as a targeted intervention to disrupt this self-amplifying cycle of oxidative damage in disc degeneration.
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Biomaterials Research
·
2026
·
IF 9.8
Kai Dong,Zelin Guan,Danyang Wang,Jinyao Sun,Ying Zhang,Cuiyu You,Yuanming Xing
In the pathogenesis of ulcerative colitis (UC), inflammatory responses, mucosal injury, and gutdysbiosis form a mutually reinforcing network that perpetuates disease progression. Current clinicalinterventions can rarely modulate these pathological modules simultaneously, underscoring theurgent need for more effective therapeutic strategies. Here, we report a dual-functional nano-therapythat couples aryl-hydrocarbon-receptor (AhR) activation with on-site reactive oxygen species (ROS)scavenging. An amphiphilic copolymer, HA-TK-LA (HTL), was synthesized by grafting lipoic acid(LA) to hyaluronic acid (HA) via a ROS-cleavable thioketal (TK) linker. The copolymer self-assembles into ~130 nm nanoparticles that encapsulate the natural AhR ligand indole-3-acetic acid(IAA) with a high loading efficiency of 73%. The resulting IAA@HTL nanoparticles exhibitROS/glutathione (GSH)-triggered drug release, and are actively taken up by inflamed intestinalepithelial cells and M1 macrophages through CD44-mediated endocytosis, leading to suppressedepithelial apoptosis and macrophage repolarization toward an anti-inflammatory phenotype. Indextran sulfate sodium (DSS)-induced murine colitis, IAA@HTL specifically accumulates in theinflamed colon and markedly alleviates disease activity. Mechanistically, IAA and LA releasedfrom the nanoparticles synergistically activate AhR/CYP1A1 and Nrf2/HO-1 signaling, skewmacrophages toward an anti-inflammatory state, dampen pro-inflammatory cytokine release, andreinforce the mucosal barrier by up-regulating tight-junction proteins and IL-22 secretion. Asinflammation subsides and mucosal integrity is restored, the gut microbiota gradually returns tohomeostasis. Collectively, this study establishes a ROS-scavenging and AhR-activating nano-delivery system that achieves a “one-stone-three-birds” outcome—attenuating inflammation,repairing mucosa, and rebalancing microbiota—providing new experimental evidence andtheoretical support for UC therapy.Keywords: ulcerative colitis, AhR receptor, reactive oxygen species, active targeting, macrophages
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