Small molecule natural compound agonist of SIRT3 as a therapeutic target for the treatment of intervertebral disc degeneration

Jianle Wang,Majid Nisar,Chongan Huang,Xiangxiang Pan,Dongdong Lin,Gang Zheng,Haiming Jin,Deheng Chen,Naifeng Tian,Qianyu Huang,Yue Duan,Yingzhao Yan,Ke Wang,Congcong Wu,Jianing Hu,Xiaolei Zhang,Xiangy 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of intervertebral disc degeneration (IVDD). Sirtuin 3 (SIRT3), a sirtuin family protein located in mitochondria, is essential for mitochondrial homeostasis; however, the role of SIRT3 in the process of IVDD has remained elusive. Here, we explored the expression of SIRT3 in IVDD in vivo and in vitro; we also explored the role of SIRT3 in senescence, apoptosis, and mitochondrial homeostasis under oxidative stress. We subsequently activated SIRT3 using honokiol to evaluate its therapeutic potential for IVDD. We assessed SIRT3 expression in degenerative nucleus pulposus (NP) tissues and oxidative stressinduced nucleus pulposus cells (NPCs). SIRT3 was knocked down by lentivirus and activated by honokiol to determine its role in oxidative stress-induced NPCs. The mechanism by which honokiol affected SIRT3 regulation was investigated in vitro, and the therapeutic potential of honokiol was assessed in vitro and in vivo. We found that the expression of SIRT3 decreased with IVDD, and SIRT3 knockdown reduced the tolerance of NPCs to oxidative stress. Honokiol (10 μM) improved the viability of NPCs under oxidative stress and promoted their properties of anti-oxidation, mitochondrial dynamics and mitophagy in a SIRT3-dependent manner. Furthermore, honokiol activated SIRT3 through the AMPKPGC- 1α signaling pathway. Moreover, honokiol treatment ameliorated IVDD in rats. Our study indicated that SIRT3 is involved in IVDD and showed the potential of the SIRT3 agonist honokiol for the treatment of IVDD.

Oxidative stress-induced circKIF18A downregulation impairs MCM7-mediated anti-senescence in intervertebral disc degeneration

Wang Jianle,Xia Dongdong,Lin Yan,Xu Wenbin,Wu Yaosen,Chen Jiaoxiang,Chu Junjie,Shen Panyang,Weng Sheji,Wang Xiangyang,Shen Lifeng,Fan Shunwu,Shen Shuying 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Low back pain, triggered by intervertebral disc degeneration (IVDD), is one of the most common causes of disability and financial expenditure worldwide. However, except for surgical interventions, effective medical treatment to prevent the progression of IVDD is lacking. This study aimed to investigate the effects of circKIF18A, a novel circRNA, on IVDD progression and to explore its underlying mechanism in IVDD. In this study, we found that oxidative stress was positively correlated with nucleus pulposus cell (NPC) senescence in IVDD and that circKIF18A was downregulated in IVDD and attenuated senescent phenotypes such as cell cycle arrest and extracellular matrix degradation in NPCs. Mechanistically, circKIF18A competitively suppressed ubiquitin-mediated proteasomal degradation of MCM7, and the protective effects of circKIF18A on NPCs were partially mediated by MCM7 under oxidative stress. Intradiscal injection of adenoviral circKIF18A ameliorated IVDD in a rat model. This study revealed that circKIF18A regulates NPC degeneration by stabilizing MCM7 and identified a novel signaling pathway, the circKIF18A-MCM7 axis, for anti-senescence molecular therapy in IVDD.

The Positive Association between Subclinical Hypothyroidism and Newly-Diagnosed Hypertension Is More Explicit in Female Individuals Younger than 65

Xichang Wang,Haoyu Wang,Li Yan,Lihui Yang,Yuanming Xue,Jing Yang,Yongli Yao,Xulei Tang,Nanwei Tong,Guixia Wang,Jinan Zhang,Youmin Wang,Jianming Ba,Bing Chen,Jianling Du,Lanjie He,Xiaoyang Lai,Yanbo Li 대한내분비학회 2021 Endocrinology and metabolism Vol.36 No.4

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure(BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosedaccording to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in femalesor subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP)were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely relatedwith SCH in female subjects aged <65 years. Conclusion: The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BPcomponents in females younger than 65 years.

Melatonin protects endothelial progenitor L255cells against AGE-induced apoptosis via autophagy flux stimulation and promotes wound healing in diabetic mice

Haiming Jin,Zengjie Zhang,Chengui Wang,Qian Tang,Jianle Wang,Xueqin Bai,Qingqing Wang,Majid Nisar,Naifeng Tian,Quan Wang,Cong Mao,Xiaolei Zhang,Xiangyang Wang 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Wound healing is delayed in diabetic patients. Increased apoptosis and endothelial progenitor cell (EPC) dysfunction are implicated in delayed diabetic wound healing. Melatonin, a major secretory product of the pineal gland, promotes diabetic wound healing; however, its mechanism of action remains unclear. Here, EPCs were isolated from the bone marrow of mice. Treatment of EPCs with melatonin alleviated advanced glycation end product (AGE)-induced apoptosis and cellular dysfunction. We further examined autophagy flux after melatonin treatment and found increased light chain 3 (LC3) and p62 protein levels in AGE-treated EPCs. However, lysosome-associated membrane protein 2 expression was decreased, indicating that autophagy flux was impaired in EPCs treated with AGEs. We then evaluated autophagy flux after melatonin treatment and found that melatonin increased the LC3 levels, but attenuated the accumulation of p62, suggesting a stimulatory effect of melatonin on autophagy flux. Blockage of autophagy flux by chloroquine partially abolished the protective effects of melatonin, indicating that autophagy flux is involved in the protective effects of melatonin. Furthermore, we found that the AMPK/mTOR signaling pathway is involved in autophagy flux stimulation by melatonin. An in vivo study also illustrated that melatonin treatment ameliorated impaired wound healing in a streptozotocin-induced diabetic wound healing model. Thus, our study shows that melatonin protects EPCs against apoptosis and dysfunction via autophagy flux stimulation and ameliorates impaired wound healing in vivo, providing insight into its mechanism of action in diabetic wound healing.

Grey Incidence Analysis of Correlations between Leadership-member Exchange and Automobile After-sales Service Quality

Jianling Wang,Robin Qiu 보안공학연구지원센터 2015 International Journal of u- and e- Service, Scienc Vol.8 No.8

The Chinese automotive industry is the largest in the world. Although after-sales services are known to be associated with profitability, it has not obtained its rightful prominence in the Chinese industry. To investigate how the quality of leader-member exchange can influence after-sales services in the Chinese automobile industry, we collected data from individual employees and customers and analyzed it using grey theory model. Based on the results, we proposed the industry to pay more attentions to tangible after-sales service. While previous studies tended to adopt an either customer or employee perspective, our research contributes to the literature by offering a more comprehensive perspective from both the standpoints of the organization and consumers, and our grey theory analytic approach offers a viable option for researchers who are interested in reducing biases in data due to the data aggregation process.

Topology Optimization of Steel Structure for Waste Incineration Steam Generator Based on DE and PSO

Jianling Chen,Yu-Hang Wang,Xu Zhan 한국강구조학회 2021 International Journal of Steel Structures Vol.21 No.4

The paper presents a topology optimization of steel structure about a waste incinerator steam generator to get economical structural layout. Firstly, the load function is got by analyzing the load distribution of a top girder about a certain type of waste incinerator steam generator. According to the theory of structural mechanics, the axial load function of steel frame is proposed. Secondly, the reasonable section class for members are selected and the functional relationship in the steel amount for steel frame with several variables is established. But it is diffi cult to solve them by ordinary analytic method due to these variables are interrelated. Therefore, intelligent bionics algorithm such as DE-diff erential evolution algorithm and PSO-particle swarm optimization are employed, the two algorithms are compared in the experiment. The simulation results show that the intelligent bionic algorithm can eff ectively deal with the optimization problems of steel structure.

Growth and Electrochemical Behavior of Poly[Ni(saldMp)] on Carbon Nanotubes as Potential Supercapacitor Materials

Yakun Zhang,Jianling Li,Feiyu Kang,Xindong Wang,Feng Ye,Jun Yang 대한화학회 2012 Bulletin of the Korean Chemical Society Vol.33 No.6

The polymer of (2,2-dimethyl-1,3-propanediaminebis(salicylideneaminato))-nickel(II), Ni(saldMp), was deposited on multi-walled carbon nanotubes (MWCNTs) substrate by the route of potential linear sweep. The nano structures of poly[Ni(saldMp)] have been obtained by adjusting the monomer concentration of 0.1, 0.2, 0.5, 1.0 and 1.5 mmol L−1. The poly[Ni(saldMp)] prepared in acetonitrile solution with monomer concentration of 1.0 mmol L−1 shows the fastest growth rate. The effects of potential window on charge-discharge efficiency and electrodeposition scan number on capacitance performance were discussed. Poly[Ni(saldMp)] prepared with less electrodeposition scans exhibits higher capacitance, but this goes against the improvement of the whole electrode capacitance. Sample with 8 deposition scans is the best compromise with the geometric specific capacitance 3.53 times as high as that of pure MWCNTs, and 1.24 times for the gravimetric specific capacitance under the test potential window 0.0-1.0 V.

Growth and Electrochemical Behavior of Poly[Ni(saldMp)] on Carbon Nanotubes as Potential Supercapacitor Materials

Zhang, Yakun,Li, Jianling,Kang, Feiyu,Wang, Xindong,Ye, Feng,Yang, Jun Korean Chemical Society 2012 Bulletin of the Korean Chemical Society Vol.33 No.6

The polymer of (2,2-dimethyl-1,3-propanediaminebis(salicylideneaminato))-nickel(II), Ni(saldMp), was deposited on multi-walled carbon nanotubes (MWCNTs) substrate by the route of potential linear sweep. The nano structures of poly[Ni(saldMp)] have been obtained by adjusting the monomer concentration of 0.1, 0.2, 0.5, 1.0 and 1.5 mmol $L^{-1}$. The poly[Ni(saldMp)] prepared in acetonitrile solution with monomer concentration of 1.0 mmol $L^{-1}$ shows the fastest growth rate. The effects of potential window on charge-discharge efficiency and electrodeposition scan number on capacitance performance were discussed. Poly[Ni(saldMp)] prepared with less electrodeposition scans exhibits higher capacitance, but this goes against the improvement of the whole electrode capacitance. Sample with 8 deposition scans is the best compromise with the geometric specific capacitance 3.53 times as high as that of pure MWCNTs, and 1.24 times for the gravimetric specific capacitance under the test potential window 0.0-1.0 V.

Infrared Semiconducting Transition-Metal Dichalcogenide Lasing with a Silicon Nanocavity

Hongji Li,Hanlin Fang,Jianling Xiao,Juntao Li,Yue Wang 한국물리학회 2018 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.73 No.3

The remaining challenge for silicon photonics is creating a light-emitter on chip. Recently, a special group of two-dimensional materials, semiconducting transition-metal dichalcogenides, have been developed. These materials demonstrate unique electronic properties and excellent optoelectronic performance, opening up new possibilities to finally overcome this challenge. In this letter, we report a novel nano-scale silicon laser source, which was achieved by combining a far-field optimized silicon photonic crystal cavity and a two-dimensional gain material, tri-layer molybdenum ditelluride. When an optical continuous-wave pump was employed, the maximum lasing output power obtained was at a wavelength of 1080 nm. Such output power shows that this novel source has great potential for use in on-chip optical communication.

circSPG21 protects against intervertebral disc disease by targeting miR-1197/ATP1B3

Huang Yizhen,Zhang Zhenlei,Wang Jianle,Shen Shuying,Yao Teng,Xu Yining,Chen Zizheng,Fang Bin,Ma Jianjun 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

The abnormal expression of circular RNAs (circRNAs) is associated with numerous human diseases. This study investigated the mechanism by which circRNA acts as competitive endogenous RNA in the regulation of degenerative intervertebral disc disease (IVDD). Decreased expression of circSPG21 was detected in degenerated nucleus pulposus cells (NPCs), the function of circSPG21 in NPCs was explored and verified, and the downstream target of circSPG21 was investigated. The interaction between circSPG21 and miR-1197 and its target gene ( ATP1B3 ) was studied by online database prediction and molecular biological verification. Finally, the circSPG21/miR-1197/ATP1B3 axis was verified in the mouse tail-looping model. The expression of circSPG21 in the nucleus pulposus in IVDD was directly related to an imbalance of anabolic and catabolic factors, which affected cell senescence. circSPG21 was found to play a role in human NPCs by acting as a sponge of miR-1197 and thereby affecting ATP1B3 . The regulation of circSPG21 provides a potentially effective therapeutic strategy for IVDD.