查找使用阿拉丁产品的科研文献

Phosphorylation of α-CateninS641 Suppresses the NF-κB Pathway in Fibroblasts to Activate Skin Wound Repair

Yingjie Shen,Zhongxin Zhu,Weitao Cong,Mengying Jiang,Jianan Wang,Xixi Chen,Nan Wang,Ying Yu,Yetong Dong,Zhili Liu,Jia Sun,Wenjie Gong,Siyi Zhang,Kwonseop Kim,Litai Jin

Skin wound healing is a complex process involving intricate molecular mechanisms that remain unknown. Restoration of homeostasis after wounding requires the remodeling function of fibroblasts. In this study, we show that phosphorylation of α-catenin S641 was upregulated in fibroblasts during wounding, which accelerated their proliferation and migration to restore the skin barrier. At the wound edge, phosphorylated α-catenin S641 stabilized IκBα and thereby impaired the expression of NF-κB target genes to promote proliferation and migration of fibroblasts. Mechanically, phosphorylated α-catenin S641 blocked K48-linked polyubiquitination and proteasomal degradation of IκBα. Moreover, we also showed that EGF/EGFR/CK2α functioned as key upstream signaling of α-catenin by phosphorylating α-catenin at S641. Wound repair was significantly disrupted in the skin of mice in which α-catenin phosphorylation and CK2α kinase activity were perturbed in fibroblasts. These findings provide insights into the molecular control of fibroblast proliferation and migration in response to wounding and identify potential targets for the treatment of defective wound repair.

Amentoflavone Inhibits Osteoclastogenesis and Wear Debris-Induced Osteolysis via Suppressing NF-κB and MAPKs Signaling Pathways

Zhen Zhang,Shuai Zhao,Xiaolei Li,Xiaoqi Zhuo,Wu Zhang,Qian Nie,Shuguang Wang,Lianqi Yan,Yu Sun

Wear debris-induced osteolysis is one of the major reasons for subsequent aseptic loosening after cementless hip arthroplasty. Increasing evidence suggests that receptor activator of nuclear factor kappa-B (NF-κB) ligand-mediated osteoclastogenesis and osteolysis are responsible for wear debris-induced aseptic loosening. In the present study, we explored the effect of amentoflavone (AMF) on inhibiting osteoclast generation and wear debris-induced osteolysis in vitro and in vivo. Twenty-four male C57BL/J6 mice were randomly divided into four groups: a sham group and groups with titanium wear debris treatment followed by intraperitoneal injection of various concentrations of AMF (0, 20, and 40 mg/kg/day). The micro computed tomography scanning and histological analysis were performed. Bone marrow-derived macrophages were cultured to investigate the effect of AMF on osteoclast generation and function. The results showed that AMF suppressed osteoclastogenesis, F-actin ring formation, and bone absorption without cytotoxicity. AMF prevented titanium wear debris-induced osteolysis in mice. AMF suppressed the relative proteins of NF-κB and mitogen-activated protein kinase (MAPKs) signaling pathways. Thus, the present study suggests that AMF derived from plants could inhibit osteoclastogenesis and titanium wear debris-induced osteolysis via suppressing NF-κB and MAPKs signaling pathways.

Colon-Targeted astragalus polysaccharide nanoparticles prevent NAFLD-Driven hepatocarcinogenesis via microbiota remodeling and NF-κB Inhibition

Liu Dan,Li Runtian,Li Mingzhu,Liang Ying,Wang Zhao,Sun Yang,Ge Pengling

Hepatocellular carcinoma (HCC), often arising from liver fibrosis in nonalcoholic fatty liver disease (NAFLD), remains a leading cause of cancer-related death. Targeting the gut–liver axis offers new therapeutic opportunities to prevent this progression. In this study, colon-targeted chitosan/pectin-based nanoparticles loaded with Astragalus polysaccharide (APs-CS/PT-NPs) were developed to modulate gut microbiota and inhibit liver tumorigenesis. The nanoparticles exhibited robust physicochemical stability and pH-responsive release. In vivo, oral administration of APs-CS/PT-NPs attenuated hepatic steatosis, reduced inflammatory cytokines, and suppressed NAFLD-induced HCC development. 16 S rRNA sequencing revealed restoration of microbial diversity and enhanced production of short-chain fatty acids, especially acetate. Mechanistically, transcriptomic profiling and functional analysis identified acetate as a key mediator, acting via G-protein-coupled receptor 43 (GPR43) to inhibit the NF-κB pathway. These results highlight the therapeutic potential of APs-CS/PT-NPs in modulating the gut–liver axis, rebalancing intestinal microbiota, and suppressing pro-inflammatory signaling. This nanoparticle-based strategy offers a promising food-derived preventive intervention for liver fibrosis–HCC transition. Graphical

Heterointerface engineering of FeNiP-CeO2/NF for efficient and durable oxygen evolution at high current densities

Xinyue Chen,Binjian Chen,Yudong Mao,Min Yan,Zhihao Liu,Yuxuan Jiang,Xianqun Jin

FeNiP-CeO 2 /NF heterostructure is designed for efficient oxygen evolution reaction. • Superior OER activity: 231, 304, 390 mV at 100, 500, 1000 mA·cm −2 . • Performance optimized by heterostructure design and interfacial synergistic effect. • The catalyst exhibits outstanding long-term stability of 200 h at 500 mA·cm −2 . Developing efficient and durable non-noble-metal electrocatalysts for the oxygen evolution reaction under industrially relevant conditions remains a significant challenge. Herein, a heterostructured FeNiP-CeO 2 /NF electrocatalyst was rationally designed and synthesized via a two-step hydrothermal–phosphidation strategy. The resulting catalyst features hierarchically assembled FeNiP nanosheets intimately coupled with oxygen-vacancy-rich CeO 2 nanoparticles, forming abundant heterointerfaces. Benefiting from the synergistic interaction between bimetallic Fe–Ni phosphide active sites and CeO 2 -induced interfacial charge redistribution, FeNiP-CeO 2 /NF exhibits markedly enhanced OER activity in alkaline media, delivering low overpotentials of 231, 304, and 390 mV at current densities of 100, 500, and 1000 mA cm −2 , respectively. In addition, the catalyst demonstrates excellent long-term durability, maintaining stable operation for 200 h at 500 mA cm −2 with a Faradaic efficiency of 99.3%. This work demonstrates that rational heterointerface engineering combined with hierarchical structural design is an effective strategy for constructing highly active and robust OER electrocatalysts, highlighting the promising potential of FeNiP-CeO 2 /NF for industrial water electrolysis applications. Download: Download high-res image (256KB) Download: Download full-size image

Bifunctional Group Synergy in PEI-TMC NF Membrane for Balanced High Permeability and Mg/Li Separation

Ying Cheng,Yanxia Sun,Shengde Dong,Luxiang Ma,Xin He,Qi Xu,Ziyu Wang,Yu Tang,Ping Li,Chunxi Hai,Yuan Zhou

The nanofiltration (NF) membrane, as an emerging lithium resource extraction technology, precisely screens Mg2+ and Li+ through the Donnan effect and steric hindrance. However, most NF membranes still struggle to break through the “trade-off effect”, and how to effectively overcome this effect to achieve a balance between high ion rejection and high permeability remains a great challenge. In this study, sodium alginate (SA) was added to the aqueous phase during the preparation of polyethylenimine-trimesoyl chloride (PEI-TMC) NF membranes. The bifunctional groups of SA can achieve synergistic effects: −COOH can produce electrostatic interaction with PEI to reduce amine sites, while −OH can form a competitive relationship with PEI to reduce the reactivity of amine groups, thereby forming a loose and thin separation layer. The permeability was significantly improved, and its water flux increased from 34.68 L·m–2·h–1 to 92.04 L·m–2·h–1, representing a nearly 3-fold increase compared to the PEI-TMC NF membrane. At the same time, the reduction of amine groups participating in the reaction under the optimal conditions increases the positive charge on the membrane surface, maintaining the original high separation performance SLi+/Mg2+=21.18). Through a three-stage nanofiltration process, the Li+/Mg2+ ratio in real salt-lake brine can be reduced to 0.86, and the improved adsorption-membrane coupled process can further reduce the Li+/Mg2+ ratio to 0.04, significantly reducing the interference of high-concentration Mg2+ in the lithium extraction process. Finally, this study systematically compared the cost and environmental impact of the modifier used in this work with those of other common modifiers. The results show that the proposed modifier is cost-effective and environmentally friendly, with higher feasibility for practical industrial applications. Therefore, this work exhibits promising application prospects in the field of lithium extraction from salt lakes.

S,Fe-NiFeOxHy/NF as highly efficient electrocatalyst for oxygen evolution reaction at high current densities

Yuan-Yuan Feng,Hua-Shuai Hu,Jin Liu,Zi-Heng Liu,Dan Zhang,Dong-Xing Tan

● S,Fe-NiFeO x H y /NF shows an ultra-low OER overpotential of 305 mV at 1000 mA cm −2 . ● The catalyst exhibits a promising stability for over 40 h without activity decay. ● The total preparation process of S,Fe-NiFeO x H y /NF electrocatalyst only takes 6 min. ● The high performance stems from electronic interactions among S, Fe and NiFeO x H y . Water electrolysis is considered an ideal route for producing high-purity hydrogen, yet its widespread application remains severely constrained by the anodic sluggish oxygen evolution reaction (OER). Herein, we present a high-performance S,Fe-NiFeO x H y /NF electrocatalyst for OER that markedly reduces the overpotential of OER to 196 mV at the benchmark current density of 10 mA cm −2 . Even at high current densities of 500 and 1000 mA cm −2 , the overpotentials are only 291 and 305 mV, respectively, outperforming most previously reported Ni/Fe-based catalysts. The catalyst also exhibits promising long-term stability, maintaining a high current density of 500 mA cm −2 for over 40 h without activity decay. Notably, the entire catalyst preparation takes just 6 min, and this cost-effective and facile synthetic strategy is key to enabling practical water electrolysis. Our findings open up a new avenue for developing non-noble metal catalysts with both high activity and durability for water electrolysis. Download: Download high-res image (267KB) Download: Download full-size image

Naringin Attenuates Diabetic Neuropathic Pain and Modulates TRPV1-Related Ca2+ Dysregulation and MAPK/NF-ΚB Signaling

Xiaoyi Qiu,Lisha Chen,Ting Han,Hongji Wang,Juping Xing,Jiayi Zheng,Changshui Xu

Background/Objectives:Diabetic neuropathic pain (DNP) is a common complication of diabetes characterized by sensory abnormalities, including mechanical allodynia and thermal hyperalgesia. This study aimed to investigate the effects of naringin on experimental DNP and evaluate its association with dorsal root ganglion (DRG) neuronal injury, TRPV1-related calcium imbalance, and inflammatory signaling.Methods:Primary rat DRG neurons were exposed to high-glucose/high-free-fatty-acid (HGHF) conditions (50 mM glucose and 0.60 mM free fatty acids) and treated with naringin (40 or 80 μM). Cell viability, apoptosis, intracellular Ca2+levels, gene/protein expression, and signaling changes were assessed using CCK-8 assay, Annexin V-FITC/PI flow cytometry, Fluo-4 AM imaging, qRT-PCR, and Western blotting. Male Sprague–Dawley rats were fed a high-fat/high-sucrose diet for 4 weeks, injected with streptozotocin (35 mg kg−1), and treated with naringin (50 mg kg−1day−1) by gavage for 2 weeks.Results:HGHF exposure increased neuronal injury, TRPV1 expression, intracellular Ca2+accumulation, and p38 MAPK/NF-κB signaling activation. Naringin attenuated these changes in vitro, with stronger effects observed at 80 μM. In DNP rats, naringin improved pain-related behaviors, partially alleviated metabolic abnormalities, reduced TRPV1 expression and serum IL-1β/TNF-α levels, and decreased phosphorylation of p38 MAPK, NF-κB p65, and ERK in DRGs.Conclusions:Naringin alleviated experimental DNP-associated behavioral and molecular abnormalities, suggesting potential protective effects involving neuronal injury, calcium regulation, and inflammatory responses.

Apigenin accelerates fracture healing by enhancing endochondral differentiation and inflammation resolution via targeting NF-κB signaling

Haiyu Shen,Guoguo Zhi,Zihao Li,Xueqiao Yan,Zhirui Du,Shaoyang Zhang,Ruichen Yang,Xiuying Ma,Huijuan Liu,Funeng Geng,Baojie Li

BackgroundFractures are common yet lack effective pharmacological treatments. Apigenin, a natural flavone, has anti-inflammatory and pro-osteogenic effects. Here, we examined its impact on fracture healing—a multistep process involving hematoma formation, soft callus formation (endochondral differentiation), hard callus formation (osteogenic differentiation), and bone remodeling—and investigated the underlying mechanisms.MethodsFemoral fracture and calvarial injury models were established to evaluate the effects of apigenin. Local apigenin treatment was initiated at postoperative time points to compare the impact of administration timing. Fracture healing was assessed by radiography, micro-CT, histological analysis, and immunostaining. In vitro cultures were performed to examine the effects of apigenin on mesenchymal stem cell (MSC) differentiation. Quantitative PCR, Western blotting, RNA sequencing, and flow cytometry were used to evaluate inflammatory responses and chondrogenic and osteogenic differentiation. Ikbkb knockdown and BAY 11–7082 treatment were used to examine the involvement of IKKβ/NF-κB signaling. Molecular docking and molecular dynamics simulations were performed to investigate the potential interaction between apigenin and IKKβ, which was examined by cellular thermal shift assay (CETSA).ResultsApigenin significantly improved fracture healing when treatment was initiated on postoperative day 5, whereas treatment initiated on day 1 showed no clear therapeutic effect. Apigenin reduced inflammatory responses in the fracture callus and suppressed NF-κB signaling. BAY 11–7082 produced effects similar to those of apigenin in the femoral fracture model, and combined treatment did not produce a clear additional benefit. In BMSCs, apigenin promoted chondrogenic differentiation and attenuated the suppression of chondrogenic markers under inflammatory conditions, whereas its effects on osteogenic differentiation were less consistent. Ikbkb knockdown also enhanced chondrogenic differentiation, and addition of apigenin after Ikbkb knockdown produced no further clear increase. Molecular docking, molecular dynamics simulations, and CETSA provided supportive evidence for a potential interaction between apigenin and IKKβ.ConclusionsThrough modulation of IKKβ/NF-κB signaling, apigenin acts on both inflammatory responses and MSC differentiation to enhance fracture healing. The therapeutic effect was most evident when treatment was initiated on postoperative day 5, during the transition from inflammation to cartilage formation. These findings suggest that appropriately timed apigenin treatment may represent a potential strategy for improving fracture repair.

Construction of Cu-Ru@NF-AC interface-regulated electrocatalyst for the pH-universal hydrogen evolution reaction

Hanyue Xiao,Shasha Zhao,Kai Peng,Yaoyao Xu,Juan Li,Bodun Xie,Yao Si,Guowei Deng,Min Yang,Wei Li

In 1 M KOH, at 10 mA·cm⁻², the overpotential of HER is as low as 60.6 mV, and the Tafel slope is 90.07 mV·dec⁻¹. • At 100 mA·cm⁻², in 0.5 M H 2 SO 4 , the overpotential of OER is only 247.3 mV. After 300 h, the current density remains at 94.8%, and the voltage for overall water splitting is as low as 1.07 V. • CuRu@NF-AC exhibits excellent water splitting performance over the entire pH range, with the Faraday efficiencies of HER and OER reaching as high as 99.73% and 99.87%, respectively. In response to the energy crisis and environmental issues, to address the shortcomings of traditional electrocatalytic materials such as insufficient activity and poor stability, this study innovatively synthesized CuRu@NF-AC nanomaterials through an interface regulation strategy and systematically investigated their performance in electrocatalytic water splitting (hydrogen evolution reaction (HER) and oxygen evolution reaction (OER)) across the entire pH range. Experimental results demonstrate that this material achieves significant electrocatalytic activity through interface structure optimization. At a current density of 10 mA·cm −2 , the overpotentials for OER and HER in alkaline conditions were as low as 44.4 mV and 60.6 mV, respectively, with Tafel slopes of 30.14 mV·dec⁻¹ and 90.07 mV·dec⁻¹. In acidic conditions, the OER excess potential is only 49 mV and the overall water splitting voltage is as low as 1.07 V. In neutral (1.0 M PBS) electrolyte, the HER overpotential is 302.6 mV at 10 mA·cm −2 with a Tafel slope of 76.25 mV·dec⁻¹, exhibiting superior pH-universal adaptability. In addition, the catalyst exhibits excellent long-term stability, maintaining a stable electrocatalytic performance for >100 h. This study provides a new strategy for designing pH-universal hydrogen evolution electrocatalysts via interface regulation, with important theoretical and practical value. Download: Download high-res image (417KB) Download: Download full-size image

Targeted Dermal Delivery of Phloretin via Thermoresponsive Nanoparticles Potently Suppresses STAT3/NF-κB-Driven Psoriatic Inflammation

Renwei Lu,Ruyi Zhao,Panpan Lian,Gang Chen,Ranran Wang,Junaid Wazir,Bojie Ma,Chaode Gu,Wenyuan Pu,Li Li,Zhiqiang Huang,Zhonglan Su,Da Huo,Hongwei Wang

Background Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and immune dysregulation. Although the natural flavonoid Phloretin (Phl) shows anti-inflammatory potential, its poor bioavailability limits its therapeutic use. Purpose This study aimed to elucidate the antipsoriatic mechanism of Phl and develop a targeted, thermoresponsive nanodelivery system to enhance its efficacy for topical treatment. Methods The therapeutic effects of Phl were assessed in an imiquimod (IMQ)-induced psoriasis mouse model. Network pharmacology, molecular docking, and molecular dynamics simulations were used to predict and verify the binding stability of Phl with its potential targets. Quantitative proteomics was conducted to provide a global view of the proteomic shifts and affected pathways. These results were validated in vivo and in cytokine-stimulated HaCaT keratinocytes using western blotting, RT-qPCR, and immunofluorescence. Phl-loaded thermoresponsive phase-change material nanoparticles (PCM-Phl) were synthesized, characterized, and evaluated both in vitro and in vivo . Results Phl administration significantly ameliorated erythema, scaling, and epidermal hyperplasia in psoriatic mice. This effect was mediated through the concurrent inhibition of the STAT3 and NF-κB signaling pathways, which suppressed keratinocyte hyperproliferation, aberrant differentiation, and proinflammatory cytokine expression. The PCM-Phl formulation prolonged drug retention at the lesion site, triggered by the inherent hyperthermia of psoriatic lesions and near-infrared irradiation, and demonstrated superior therapeutic outcomes compared to free Phl, achieving a more profound and sustained inhibition of the target pathways. Conclusion This study identified dual inhibition of STAT3 and NF-κB as key mechanisms for the antipsoriatic activity of Phl. Furthermore, it presents a promising thermoresponsive nanodelivery strategy that overcomes the biopharmaceutical barriers of Phl, offering a novel approach for topical treatment of psoriasis.

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

Sulfated Pelvetia siliquosa Polysaccharides Attenuate Pyroptosis via NF-κB Pathway Inhibition Against Calcium Oxalate Stone Formation

Xin-Yi Tong,Xue-Wu Chen,Jia-Yi Zhang,Jian-Ming Ouyang

Objective: The formation of calcium oxalate (CaOx) kidney stones is accompanied by the pyroptosis of renal epithelial cells. The risk of kidney stone formation can possibly be reduced through pyroptosis inhibition. Methods: Pyroptosis of HK-2 cells induced by 3 µm CaOx monohydrate (COM-3 µm) was inhibited by Pelvetia siliquosa polysaccharides before and after sulfation (PSP0 and PSP3, with −OSO 3 − contents of 1.04% and 36.12%, respectively). The inhibitory efficiency and mechanism of PSP0 and PSP3 were evaluated via caspase-1/PI double staining and Western blot detection of pathway proteins in pyroptosis cells. The potential anti-stone effect of polysaccharides was evaluated through measurement of the extent of crystal adhesion on the cell surface. Results: The proportion of pyroptosis cells induced by COM-3 µm reached 17.87%. After protection by PSP0 and PSP3, the percentage of pyroptosis cells was reduced to 12.7% and 6.35%. The levels of NLRP3, ASC, gasdermin D, IL-1β, and IL-18 related to pyroptosis were downregulated. In addition, the activation of the NF-κB pathway was considerably inhibited. During inhibition of pyroptosis, reactive oxygen species and lactate dehydrogenase levels were decreased, the integrity of zonula occludens-1 protein was restored, and the expressions of CaOx-specific adhesion proteins (ANXA3 and CD44) were substantially decreased. As a result, the adhesion of COM crystals on the cell surface was reduced. PSP3 exhibited a higher protection energy efficiency than PSP0. Conclusions: PSP0 and PSP3 inhibited the pyroptosis of HK-2 cells through the NLRP3/ASC/caspase-1/IL-1β pathway, which caused the inhibition of cell inflammation and injury, reduced the expressions of adhesion proteins, and reduced the risk of CaOx crystal adhesion and stone formation. The biological activity of PSP0 and PSP3 after sulfation modification increased.