Involvement of DJ-1 in the pathogenesis of intervertebral disc degeneration via hexokinase 2-mediated mitophagy

Lin Jialiang,Wang Longjie,Wu Yuhao,Xiang Qian,Zhao Yongzhao,Zheng Xuanqi,Jiang Shuai,Sun Zhuoran,Fan Dongwei,Li Weishi 생화학분자생물학회 2024 Experimental and molecular medicine Vol.56 No.-

Intervertebral disc degeneration (IDD) is an important pathological basis for degenerative spinal diseases and is involved in mitophagy dysfunction. However, the molecular mechanisms underlying mitophagy regulation in IDD remain unclear. This study aimed to clarify the role of DJ-1 in regulating mitophagy during IDD pathogenesis. Here, we showed that the mitochondrial localization of DJ-1 in nucleus pulposus cells (NPCs) first increased and then decreased in response to oxidative stress. Subsequently, loss- and gain-of-function experiments revealed that overexpression of DJ-1 in NPCs inhibited oxidative stress-induced mitochondrial dysfunction and mitochondria-dependent apoptosis, whereas knockdown of DJ-1 had the opposite effect. Mechanistically, mitochondrial translocation of DJ-1 promoted the recruitment of hexokinase 2 (HK2) to damaged mitochondria by activating Akt and subsequently Parkin-dependent mitophagy to inhibit oxidative stress-induced apoptosis in NPCs. However, silencing Parkin, reducing mitochondrial recruitment of HK2, or inhibiting Akt activation suppressed DJ-1-mediated mitophagy. Furthermore, overexpression of DJ-1 ameliorated IDD in rats through HK2-mediated mitophagy. Taken together, these findings indicate that DJ-1 promotes HK2-mediated mitophagy under oxidative stress conditions to inhibit mitochondria-dependent apoptosis in NPCs and could be a therapeutic target for IDD.

A Simplified Synchronous Pulse-Width Modulation Method for Three-level Inverter of High-speed Train

Fei Lin,Qiaona Lian,Jialiang Yuan,Zhongping Yang,Zhiqiang Zhang,Yue Xu,Jinghai Jiao 보안공학연구지원센터 2015 International Journal of Smart Home Vol.9 No.12

The synchronous Pulse-Width Modulation (PWM) is quite complex for three-level neutral point-clamped (NPC) inverter. A simple central 60° synchronous modulation method is presented in this paper for three-level NPC inverter used in the multi-mode PWM strategy. For the fundamental voltage command, the switching angle could be real-time calculated based on this modulation method with different carrier frequency ratios. The switching strategy between these modes is discussed for multi-mode PWM. According to this method, a simulation model of the drive system with three-level inverter and induction motor is built. The simulation results at asynchronous modulation, central 60° synchronous modulation and square wave area, show that the output voltage values can meet the requirements with a good symmetry even in the case of low carrier frequency ratio. The smooth switching among different modes is also accomplished with low impulse current.

Biomimetic Biphasic Electrospun Scaffold for Anterior Cruciate Ligament Tissue Engineering

Tang Ya,Tian Jialiang,Li Long,Huang Lin,Shen Quan,Guo Shanzhu,Jiang Yue 한국조직공학과 재생의학회 2021 조직공학과 재생의학 Vol.18 No.5

Background: Replacing damaged anterior cruciate ligaments (ACLs) with tissue-engineered artificial ligaments is challenging because ligament scaffolds must have a multiregional structure that can guide stem cell differentiation. Here, we designed a biphasic scaffold and evaluated its effect on human marrow mesenchymal stem cells (MSCs) under dynamic culture conditions as well as rat ACL reconstruction model in vivo. Methods: We designed a novel dual-phase electrospinning strategy wherein the scaffolds comprised randomly arranged phases at the two ends and an aligned phase in the middle. The morphological, mechanical properties and scaffold degradation were investigated. MSCs proliferation, adhesion, morphology and fibroblast markers were evaluated under dynamic culturing. This scaffold were tested if they could induce ligament formation using a rodent model in vivo. Results: Compared with other materials, poly(D,L-lactide-co-glycolide)/poly(ε-caprolactone) (PLGA/PCL) with mass ratio of 1:5 showed appropriate mechanical properties and biodegradability that matched ACLs. After 28 days of dynamic culturing, MSCs were fusiform oriented in the aligned phase and randomly arranged in a paving-stone-like morphology in the random phase. The increased expression of fibroblastic markers demonstrated that only the alignment of nanofibers worked with mechanical stimulation to promote effective fibroblast differentiation. This scaffold was a dense collagenous structure, and there was minimal difference in collagen direction in the orientation phase. Conclusion: Dual-phase electrospun scaffolds had mechanical properties and degradability similar to those of ACLs. They promoted differences in the morphology of MSCs and induced fibroblast differentiation under dynamic culture conditions. Animal experiments showed that ligamentous tissue regenerated well and supported joint stability. Background: Replacing damaged anterior cruciate ligaments (ACLs) with tissue-engineered artificial ligaments is challenging because ligament scaffolds must have a multiregional structure that can guide stem cell differentiation. Here, we designed a biphasic scaffold and evaluated its effect on human marrow mesenchymal stem cells (MSCs) under dynamic culture conditions as well as rat ACL reconstruction model in vivo. Methods: We designed a novel dual-phase electrospinning strategy wherein the scaffolds comprised randomly arranged phases at the two ends and an aligned phase in the middle. The morphological, mechanical properties and scaffold degradation were investigated. MSCs proliferation, adhesion, morphology and fibroblast markers were evaluated under dynamic culturing. This scaffold were tested if they could induce ligament formation using a rodent model in vivo. Results: Compared with other materials, poly(D,L-lactide-co-glycolide)/poly(ε-caprolactone) (PLGA/PCL) with mass ratio of 1:5 showed appropriate mechanical properties and biodegradability that matched ACLs. After 28 days of dynamic culturing, MSCs were fusiform oriented in the aligned phase and randomly arranged in a paving-stone-like morphology in the random phase. The increased expression of fibroblastic markers demonstrated that only the alignment of nanofibers worked with mechanical stimulation to promote effective fibroblast differentiation. This scaffold was a dense collagenous structure, and there was minimal difference in collagen direction in the orientation phase. Conclusion: Dual-phase electrospun scaffolds had mechanical properties and degradability similar to those of ACLs. They promoted differences in the morphology of MSCs and induced fibroblast differentiation under dynamic culture conditions. Animal experiments showed that ligamentous tissue regenerated well and supported joint stability.

Production of corrugating medium paper with secondary fibers from digested deinking sludge

Dexing Yin,Yunqin Lin,Zhihuan Chen,Jialiang Qiao,Min Xiao,Dehan Wang 한국공업화학회 2016 Journal of Industrial and Engineering Chemistry Vol.37 No.-

This work focused on developing an approach to reusing digested deinking sludge for corrugatingmedium paper manufacture by recycling secondary fibers. The fiber content in the digested deinkingsludge (DDS) was around 41.87%, and the main proportion of fibers (87.6%) was subject to secondaryfines with lengths less than 0.2 mm. The qualified corrugating medium paper was obtained when thesecondary fiber load from DDS was equal or less than 30%. Corrugating medium paper manufactured byadding DDS could maximize reuse and recycling of deinking sludge via methane and papermakingmaterial production, and reduce the environmental pollution as well.

The Nrf2 antioxidant defense system in intervertebral disc degeneration: Molecular insights

Xiang Qian,Zhao Yongzhao,Lin Jialiang,Jiang Shuai,Li Weishi 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Intervertebral disc degeneration (IDD) is a common degenerative musculoskeletal disorder and is recognized as a major contributor to discogenic lower back pain. However, the molecular mechanisms underlying IDD remain unclear, and therapeutic strategies for IDD are currently limited. Oxidative stress plays pivotal roles in the pathogenesis and progression of many age-related diseases in humans, including IDD. Nuclear factor E2-related factor 2 (Nrf2) is a master antioxidant transcription factor that protects cells against oxidative stress damage. Nrf2 is negatively modulated by Kelch-like ECH-associated protein 1 (Keap1) and exerts important effects on IDD progression. Accumulating evidence has revealed that Nrf2 can facilitate the transcription of downstream antioxidant genes in disc cells by binding to antioxidant response elements (AREs) in promoter regions, including heme oxygenase-1 (HO-1), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and NADPH quinone dehydrogenase 1 (NQO1). The Nrf2 antioxidant defense system regulates cell apoptosis, senescence, extracellular matrix (ECM) metabolism, the inflammatory response of the nucleus pulposus (NP), and calcification of the cartilaginous endplates (EP) in IDD. In this review, we aim to discuss the current knowledge on the roles of Nrf2 in IDD systematically.