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Journal of Inflammation Research · 2025 · IF 4.1

Observation of the Effects of Infrapatellar Fat Pad Excision on the Inflammatory Progression of Knee Osteoarthritis in Mice

Ya Li,Peizhi Lu,Haoyu Yao,Shuo Yang,Bizhi Tu,Lingchao Kong,Rende Ning

Background Knee osteoarthritis (KOA) is a degenerative joint disease characterized by cartilage degradation, synovial inflammation, and joint pain. The infrapatellar fat pad (IFP) has been suggested to play a role in modulating the inflammatory processes in KOA. Excision of the IFP is considered a potential therapeutic approach to reduce inflammation and slow disease progression.Methods A mouse model of KOA was used to evaluate the impact of IFP excision on inflammation. Mice were divided into five groups: sham (control), unexcised IFP, quarter excision, partial excision, and complete excision of the IFP. Knee joints were collected at early, middle, and late stages of KOA. Gait analysis, micro-computed tomography (micro-CT), HE staining, Safranin O-Fast Green staining, and immunohistochemistry (IHC) were performed to assess joint stability, bone changes, and inflammatory markers (MMP-3, IL-6, TNF-α, COL-2). qRT-PCR was conducted for cartilage tissue analysis.Results Partial IFP excision significantly improved joint stability, particularly in the middle and late stages of KOA. Micro-CT analysis showed increased bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) in excised groups, with the most significant effects in the partial and complete excision groups. IHC and qRT-PCR indicated reduced MMP-3, IL-6, and TNF-α levels in excised groups, particularly in the partial and complete excision groups, suggesting reduced inflammation. COL-2 expression was higher in excised groups, particularly in late-stage KOA, indicating cartilage protection. The partial excision group exhibited the most balanced reduction in inflammation and improved cartilage integrity across all disease stages.Conclusion IFP excision, especially partial excision, significantly modulates the inflammatory response in KOA. Partial excision showed the most effective and balanced impact on joint stability, bone integrity, and cartilage protection, offering potential as a therapeutic approach for KOA.

CAS / MDL: 60-00-4 865-49-6 68-04-2
研究领域: 医学 · 病理学 · 骨科 · 分子生物学
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Battery-free antenna sticker for wireless sensing joint rotation

Pengxiang Si,Mingrui Liang,Jihua Zou,Yu Kuang,Juntao Zhang,Qingsha S. Cheng,Yiqian Kong,Yuxin Cai,Guozhi Huang,Yun Wu,Zhu Long,Boxin Zhao,Dan Zhang

Bio-integrated electronic devices are skin-mounted accurate tools for acquiring biological signals. The knee joint is one of the most important joints for human movement, playing a crucial role in functions such as walking, standing, sitting and containing important physiological health information about orthopedic disease diagnosis, prevention, and rehabilitation. However, it is still challenging to precisely and directly monitor joint rotation via skin-mounted bio-integrated electronic devices because joints are hidden inside the skin. In this study, we design a reusable, sustainable, battery-free, wireless, and flexible antenna sticker to adhere to the skin that can directly measure knee joint rotation degree. The antenna sticker is adhered to the lower leg and powered by electromagnetic radiation from a radio frequency identification (RFID) reader. When rotating the knee, the distance between the antenna sticker and the reader changes, leading to an alteration in the received signal strength indicator (RSSI). Meanwhile, the 3D optical motion capture system collects joint rotation data as a “gold standard”. After matching two series of real-time data using the Gaussian method, one RSSI can represent one specific joint rotation degree. The antenna sticker is stable at a variety of humidity and temperatures. The antenna sticker shows great potential to sense joint rotation and human motions. The scientific insights and engineering principles revealed in this antenna sticker will be applicable to a broad range of applications including skin-mounted epidermal electronics and wearable devices.

研究领域: 生物医学工程 · 电子皮肤 · 无线通信
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ADVANCED MATERIALS · 2025 · IF 26.8

Light-Driven Artificial Cell Micromotors for Degenerative Knee Osteoarthritis

Chao Gao,Ye Feng,Suyi Liu,Bin Chen,Miaomiao Ding,Dailing Du,Wenjing Zhang,Daniela A. Wilson,Yingfeng Tu,Fei Peng

Combining artificial cellular compartmentalization and intelligent motion benefits of micro/nanomotors, light is used as energy input to construct an artificial cell-based micromotor capable of photosynthetic anabolism and intelligent directional movement. This system is assembled from phospholipids functionalized with F-ATP synthase and molybdenum disulfide (MoS 2 ) nanoparticles (Vesical@MoS 2 -ATPase). The underlying mechanism involves the generation of protons (H + ) through photo-hydrolysis of MoS 2 nanoparticles within vesicles, which generates a local electroosmotic flow inside the vesicles and drives the negatively charged MoS 2 toward light. The established proton gradient across the phospholipid membrane, in turn, drives the ATP synthase to catalyze ATP production. Both in vitro and in vivo models demonstrate that the micromotor can elevate local intracellular ATP levels upon light and improve the metabolism of denatured chondrocytes. This cell mimicry, with capabilities of migration and biosynthesis, emerges as a promising platform for the next generation of functional bio-interface.

研究领域: 生物医学工程 · 纳米医学 · 再生医学
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Materials Today Bio · 2022 · IF 10.761

Arbutin-modified microspheres prevent osteoarthritis progression by mobilizing local anti-inflammatory and antioxidant responses

Jiale Jin,Yang Liu,Chao Jiang,Yifan Shen,Guangyu Chu,Can Liu,Lejian Jiang,Guanrui Huang,Yifang Qin,Yijian Zhang,Chi Zhang,Yue Wang

Osteoarthritis (OA) is a common degenerative joint disease worldwide and currently there is no effective strategy to stop its progression. It is known that oxidative stress and inflammation can promote the development of OA, and therapeutic strategies against these conditions may alleviate OA. Arbutin (ARB), a major ingredient of the Chinese medicinal herb cowberry leaf, exerts good antioxidant and anti-inflammatory activities yet has not been studied in OA. Here we developed ARB-loaded gelatine methacryloyl-Liposome ( [email protected] ) microspheres which showed long-term release of ARB and excellent cartilage-targeting effects. The ARB-loaded microspheres effectively reduced the inflammatory response in interleukin (IL)-1β-treated arthritic chondrocytes. Moreover, the synthesized [email protected] microspheres regulated cartilage extracellular matrix (ECM) homeostasis through anti-inflammation effect via inhibiting NF-κB signaling and anti-oxidative stress effect via activating Nrf2 pathway. Intra-articular use of [email protected] can effectively reduce inflammation and oxidative stress in the articular cartilage and thus, attenuating OA progression in a mouse model. The study proposed a novel ARB-laden functional microsphere, [email protected] , and demonstrated that this compound may be used as an alternative therapeutics for treating OA.

CAS / MDL: 57-88-5 111-86-4
研究领域: 药理学 · 骨科 · 生物医学工程
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Contrast Media & Molecular Imaging · 2019 · IF 1.984

Comparative Evaluation of 68Ga-Citrate PET/CT and 18F-FDG PET/CT in the Diagnosis of Type II Collagen-Induced Arthritis in Rats

Zi Wang,Liang Cai,Tingting Xu,Dan Tang,Lin Liu,Yue Chen

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic, symmetrical, and erosive synovitis. RA is one of the most common disabling diseases in the clinic. The main clinical intervention strategies are early diagnosis and early treatment. This study aims to predict the diagnostic value of 68Ga-citrate and 18F-FDG PET/CT in RA by comparing and analyzing the value of 68Ga-citrate and 18F-FDG PET/CT for diagnosing type II collagen-induced arthritis (CIA) in rats. Some CIA models were established. Normal rats were selected as the control group, and 23 days and 40 days were selected as the early and late time points of arthritis, respectively. The semiquantitative analysis of CIA rats was carried out with 68Ga-citrate PET/CT and 18F-FDG PET/CT, and the ratio of the maximum standardized uptake (SUVmax) values in the regions of interest (ROIs) of the hind foot ankle joint and thigh muscle was calculated and statistically analyzed. The distribution of CIA rats in vivo at the 68Ga-citrate 90 min time point was studied, and the ankle tissues were evaluated with hematoxylin and eosin (HE) staining. 68Ga-citrate PET/CT is obviously superior to 18F-FDG PET/CT for CIA imaging, and the statistical results show that the difference between the two examination methods is statistically significant (). The uptake of these two radiopharmaceuticals showed the same trend in arthritis rats with different scores. The distribution of 68Ga-citrate at 90 min is consistent with the trend shown by 68Ga-citrate PET/CT. 68Ga-citrate PET/CT can reflect the inflammatory activity of affected joints in CIA rats earlier and more sensitively than 18F-FDG PET/CT, and this imaging advantage continues until the later stage of inflammation. Therefore, 68Ga-citrate PET/CT is worthy of further promotion and application in the clinical diagnosis of RA.

研究领域: 医学影像学 · 风湿病学
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ACS Applied Materials & Interfaces · 2018 · IF 8.097

Anti-Inflammation and Joint Lubrication Dual Effects of a Novel Hyaluronic Acid/Curcumin Nanomicelle Improve the Efficacy of Rheumatoid Arthritis Therapy

Zengjie Fan,Jie Li,Jianli Liu,Hongjing Jiao,Bin Liu

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, which can cause endless suffering to the patients and severely impact their normal lives. To treat RA, the drugs in use have many serious side effects, high cost, or only focus on their anti-inflammatory mechanisms without taking joint lubrication into consideration. Therefore, in this study, we aim to construct a novel anti-RA drug composed of hyaluronic acid/curcumin (HA/Cur) nanomicelle to resolve these problems. Characterizations show that Cur is bound to HA by ester linkages and self-assembles to form a spherical nanomicelle with a diameter of around 164 nm under the main driving of the hydrophilic and hydrophobic forces. The nanomicelle enjoys excellent biocompatibility that effectively promotes the proliferation of chondrocytes. When injected to the RA rats, the nanomicelle significantly lowers the edema degree of the arthritic rats compared to other groups; more critically, a dramatic decrease in friction between the surfaces of cartilage around the joints has been found, which protects the cartilage from the RA-induced damage. Additionally, systematic mechanism investigation indicates that the nanomicelle diminishes the expression of related cytokines and vascular endothelial growth factor, finally leading to the excellent performance. The newfound nanomicelle has a potential for clinical practice of RA therapy, which will contribute significantly to alleviating the pain of patients and improving the quality of life for them.

研究领域: 药学 · 生物医学工程 · 免疫学
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Frontiers in Pharmacology · 2022 · IF 5.988

Myricitrin inhibits fibroblast-like synoviocyte-mediated rheumatoid synovial inflammation and joint destruction by targeting AIM2.

Chuyu Shen,Meilin Xu,Siqi Xu,Shuoyang Zhang,Wei Lin,Hao Li,Shan Zeng,Qian Qiu,Liuqin Liang,Youjun Xiao,Hanshi Xu

Objective: To explore the effect and underlying mechanism of Myricitrin (Myr) in regulating fibroblast-like synoviocyte (FLS)-mediated synovitis and joint destruction in RA. Methods: FLSs were isolated from synovial tissues from patients with RA. Gene expression was measured using quantitative RT-qPCR. Protein expression was detected by immunohistochemistry or Western blot. Cell apoptosis was performed by an Annexin-PI staining assay. EdU incorporation was used to assess the proliferation of RA FLS. Transwell assay was used to characterize the cell migration and invasion ability of RA FLS. The potential target of Myr was identified by RNA sequencing analysis. The in vivo effect of Myr was assessed in a collagen-induced arthritis (CIA) model. Results: Myr treatment inhibited the lamellipodia formation, migration, and invasion, but not the apoptosis and proliferation, of RA FLSs. Myr also reduced the expression of CCL2, IL-6, IL-8, MMP-1, MMP-3, and MMP-13 induced by TNF-α. The RNA-seq results indicated that AIM2 may be a target gene of Myr in RA FLSs. Furthermore, compared to healthy controls, AIM2 expression showed higher levels in synovial tissues and FLSs from RA patients. AIM2 knockdown also inhibited RA FLS migration, invasion, cytokine, and MMP expression. In addition, either Myr treatment or AIM2 knockdown reduced the phosphorylation of AKT induced by TNF-α stimulation. Importantly, Myr administration relieved arthritis symptoms and inhibited AIM2 expression in the synovium of CIA mice. Conclusion: Our results indicate that Myr exerts an anti-inflammatory and anti-invasion effect in RA FLSs and provide evidence of the therapeutic potential of Myr for RA.

研究领域: 风湿病学 · 免疫学 · 药理学 · 分子生物学
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BIO-MEDICAL MATERIALS AND ENGINEERING · 2024 ·Vol. 35 ·期 5 ·475-485 · IF 1

Fabrication of injectable alginate hydrogels with sustained release of 4-octyl itaconate for articular anti-inflammatory

Bao Ronghua,Mao Yifan,Zhang Yuliang,Chai Junlei,Zhang Yuanbin,Luo Cheng,Zhang Kailong,Jiang Guohua,He Xiaodan

BACKGROUND:Osteoarthritis (OA) is a chronic and degenerative joint disease that remains a great challenge in treatment due to the lack of effective therapies. 4-octyl itaconate (4-OI) is a novel and potent modulator of inflammation for the treatment of inflammatory disease. However, the clinical usage of 4-OI is limited due to its poor solubility and low bioavailability. As a promising drug delivery strategy, injectable hydrogels offers an effective approach to address these limitations of 4-OI. OBJECTIVE:The aim of the study was to verify that the composite 4-OI/SA hydrogels could achieve a controlled release of 4-OI and reduce damage to articular cartilage in the group of osteoarthritic rats treated with the system. METHODS:In this study, an injectable composite hydrogel containing sodium alginate (SA) and 4-octyl itaconate (4-OI) has been developed for continuous intra-articular administration in the treatment of OA. RESULTS:After intra-articular injection in arthritic rats, the as-prepared 4-OI/SA hydrogel containing of 62.5 μM 4-OI effectively significantly reduced the expression of TNF-α, IL-1β, IL-6 and MMP3 in the ankle fluid. Most importantly, the as-prepared 4-OI/SA hydrogel system restored the morphological parameters of the ankle joints close to normal. CONCLUSION:4-OI/SA hydrogel shows a good anti-inflammatory activity and reverse cartilage disruption, which provide a new strategy for the clinical treatment of OA.

研究领域: 生物材料学 · 药剂学 · 炎症与免疫
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ADVANCED FUNCTIONAL MATERIALS · 2025 · IF 19

Injectable Nanocomposite Hydrogel System for miRNA-Based Cartilage Repair in Knee Osteoarthritis

Dianbo Long,Guping Mao,Hongyi Li,Huaiwen Chen,Rui Huang,Tianyu Zhao,Zhiqi Zhang,Xiaoyi Zhao

Knee osteoarthritis (KOA) is a common joint disorder characterized by progressive cartilage degeneration. MiR-455-3p has been identified as a promising therapeutic candidate to maintain cartilage homeostasis. However, clinical application of free miR-455-3p is limited by rapid degradation, poor targeting efficiency, and off-target effects. To overcome these limitations, an injectable nanocomposite hydrogel-based miRNA delivery system consisting of a cartilage affinity nanocarrier (CANC) encapsulated within a PCL-b-PEG-b-PCL hydrogel is developed. The CANC is formulated using 50% PEGylated G5 PAMAM dendrimers to load miR-455-3p and is further modified with chondrocyte-affinity peptides (CAP) and minimal “self” peptides (MSP) to enhance cartilage targeting and evade macrophage uptake. In vitro studies demonstrated that it exhibited excellent stability, low cytotoxicity, superior cartilage penetration and chondrocyte targeting. Moreover, in vivo experiments in miR-455-3p knockout mice and a destabilization of the medial meniscus (DMM) induced KOA model confirmed that the sustained release and targeted delivery of miR-455-3p effectively rescued cartilage degeneration and prevent KOA progression. Notably, the nanocomposite hydrogel demonstrated high biocompatibility without observed cytotoxicity in major organs. This study highlights the therapeutic potential of the nanocomposite hydrogel miRNA delivery system in promoting cartilage regeneration and presents a promising approach for the development of disease-modifying osteoarthritis drugs.

CAS / MDL: 25322-68-3
研究领域: 医学 · 生物材料学 · 分子生物学
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Current Nanoscience · 2024 ·Vol. 21 ·期 4 ·757-765 · IF 1.4

Therapeutic Effect of Unmodified Gold-platinum Nanoparticles on Gouty Arthritis Via the Nrf2/HO-1 Pathway

Zirui Liu,Dan Li,Baofeng Zhao,Xifan Mei

BackgroundGouty arthritis, characterized by excruciating pain and discomfort, poses a significant burden on patients. While nanomedicines have shown promise in addressing this ailment, their complicated synthesis processes often involve potentially toxic procedures, contributing to adverse side effects in disease management.MethodsIn this study, we introduce a straightforward and elegant solution by utilizing easily prepared gold platinum (AuPt) nanoparticles for the treatment of gouty arthritis. The synthesis of these nanoparticles involves the use of gold and platinum precursors in conjunction with NaBH4, simplifying the manufacturing process. Experimental models of gout were established in both in vivo and in vitro settings through lipopolysaccharide and monosodium urate crystal induction.ResultsOur findings revealed that AuPt nanoparticles exhibited potent anti-inflammatory effects against gout. This effect was attributed to their ability to activate the Nrf2/HO-1 pathway, resulting in pain alleviation and the inhibition of inflammation, ultimately leading to the reduction of joint edema. With their uncomplicated synthesis and promising therapeutic potential, these simply prepared AuPt nanoparticles emerge as a compelling candidate for pharmaceutical intervention in the treatment of gouty arthritis.ConclusionThis approach not only holds the promise of delivering effective relief to patients but also minimizes the risk of unwanted side effects associated with complex nanomedicine synthesis processes.

研究领域: 药理学 · 纳米医学 · 炎症研究
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EUROPEAN POLYMER JOURNAL · 2022 · IF 5.546

Wearable, antibacterial, and self-healable modular sensors for monitoring joints movement ultra-sensitively

Dongyong Sha,Shuaimin Tang,Zeyu Dong,Kai Chen,Nan Wang,Changsheng Liu,Xiaofeng Ling,Hongyan He,Yuan Yuan

Joint disorders seriously affect daily life. Rheumatoid arthritis (RA), a type of chronic autoimmune disorder, causes recession for range of motion (ROM) and joint function loss. Monitoring and recording ROM is regarded as an efficient way for assisting in RA diagnosis at an early stage. Here, a multi-function hydrogel-based sensor was developed to monitor RA motion. With an interpenetrating polymer network (IPN) structure was prepared from self-crosslinked the poly ( N -Hydroxyethyl acrylamide – co - Acrylamido-2-methyl-1-propanesulfonic acid) (PHA) network with conductive polymers PEDOT:PSS and Zinc ions, this conductive hydrogel (PHAC) was able to achieve stretchable, sensitive, adhesive and anti-bacterial properties. The hydrogen bonding and ion interaction present in hydrogel network enable PHAC with high stretchable (∼5000 % strain), strong adhesion to connection (61.4 kPa on copper), high conductivity (208.96 mS•cm −1 ), fast self-healing (recovery to 40 % stretchable properties in10 min) and excellent anti-bacterial behavior. After combining this sensor element with customized printed circuit board (PCB) and detachable battery, the RA monitor system demonstrated the real-time recording, accurate detection of ROM, and long-time stability of signal transmission. This line of research work sheds light on stretchable, sensitive, adhesive, self-healable, anti-bacterial and wireless soft sensors with potential applications in human joint monitoring, personal healthcare diagnosis, and soft robots.

CAS / MDL: 7446-20-0
研究领域: 生物医学工程 · 材料科学 · 医疗诊断
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BIOCHEMICAL PHARMACOLOGY · 2024 · IF 5.3

Discovery of CYP2E1 as a novel target in rheumatoid arthritis and validation by a new specific CYP2E1 inhibitor

Zixinying Han,Chenxu Liu,Mingrui Li,Mengyan Deng,Ying Ding,Yunchao Li,Meidan Huo,Haiwei Xu,Hailing Qiao,Na Gao

Considerable evidence indicates that CYP2E1 is associated with a variety of inflammatory diseases. Here we evaluated CYP2E1 as a potential therapeutic target for rheumatoid arthritis (RA) and established the protective effect of a new CYP2E1 inhibitor. Gene-expression datasets were used to analyze the change in expression of CYP2E1 in RA patients; CYP2E1 activity in collagen-induced arthritis (CIA) rats was determined by HPLC. We further evaluated the protective effects of C yp2e1 knockout and a CYP2E1-specific inhibitor, Q11, synthesized by our group, in CIA and adjuvant-induced arthritis (AIA) rats. The expression of CYP2E1 in synovial tissue was elevated in RA patients and in CIA rats and the activity of CYP2E1 in vivo and in vitro in CIA rats was greater than that of controls. C yp2e1 knockout significantly reduced the incidence of CIA and alleviated the severity of symptoms. Treatment with different doses of Q11 decreased paw thickness, volume and arthritis scores and reduced the serum levels of IL‐6, TNF‐α, IL‐1β and MDA, and increased the level of GSH in CIA rats. A similar inhibitory effect was exhibited for Q11 in the AIA rats. Moreover, Q11 significantly impeded proliferation, migration, and invasion of human rheumatoid arthritis synovial fibroblasts cells. Q11 decreased the release of ROS and enhanced Nrf2 nuclear translocation and HO-1 expression in the cell nucleus. Overall, our results indicated that CYP2E1 may be a new target for RA and Q11 has potential protective effects against RA by reducing oxidative stress and opposing the inflammatory response via the ROS/Nrf2/HO-1 signaling pathway.

CAS / MDL: 169590-42-5
研究领域: 药理学 · 免疫学 · 风湿病学
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