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Luo Rongjin,Li Gaocai,Zhang Weifei,Liang Huaizhen,Lu Saideng,Cheung Jason Pui Yin,Zhang Teng,Tu Ji,Liu Hui,Liao Zhiwei,Ke Wencan,Wang Bingjin,Song Yu,Yang Cao 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. Abnormalities in O-GlcNAcylation and ER-phagy have been documented in a wide variety of human pathologies. However, whether O-GlcNAcylation or ER-phagy is involved in the pathogenesis of intervertebral disc degeneration (IDD) is largely unknown. In this study, we investigated the function of O-GlcNAcylation and ER-phagy and the related underlying mechanisms in IDD. We found that the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) were notably increased in degenerated NP tissues and nutrient-deprived nucleus pulposus (NP) cells. By modulating the O-GlcNAc level through genetic manipulation and specific pharmacological intervention, we revealed that increasing O-GlcNAcylation abundance substantially enhanced cell function and facilitated cell survival under nutrient deprivation (ND) conditions. Moreover, FAM134B-mediated ER-phagy activation was regulated by O-GlcNAcylation, and suppression of ER-phagy by FAM134B knockdown considerably counteracted the protective effects of amplified O-GlcNAcylation. Mechanistically, FAM134B was determined to be a potential target of OGT, and O-GlcNAcylation of FAM134B notably reduced FAM134B ubiquitination-mediated degradation. Correspondingly, the protection conferred by modulating O-GlcNAcylation homeostasis was verified in a rat IDD model. Our data demonstrated that OGT directly associates with and stabilizes FAM134B and subsequently enhances FAM134B-mediated ER-phagy to enhance the adaptive capability of cells in response to nutrient deficiency. These findings may provide a new option for O-GlcNAcylation-based therapeutics in IDD prevention.
Honglin Luo,Yang Zhang,Zhiwei Yang,Guifu Zuo,Quanchao Zhang,Fanglian Yao,Yizao Wan 한국물리학회 2019 Current Applied Physics Vol.19 No.11
In this work, doxorubicin (DOX) was intercalated into layered nanohydroxyapatite (LHAp). The drug loaded LHAp (DOX@LHAp) was then mixed with poly(lactic-co-glycolic acid) (PLGA) and electrospun to yield DOX@ LHAp/PLGA composite scaffolds. As control, needle-like nanohydroxyapatite (nHAp) was also used to make an DOX@nHAp/PLGA composite scaffold and bare DOX was used to fabricate DOX/PLGA scaffold. The morphology, release behavior of DOX, and capability to inhibit cancer cells were assessed. The addition of DOXloaded nHAp to PLGA causes a slight decrease in the average fiber diameter of DOX@LHAp/PLGA as compared to PLGA. The in vitro drug release tests reveal a much faster release of DOX from DOX/PLGA than DOX@LHAp/ PLGA. Moreover, DOX@LHAp/PLGA displays a more sustainable release over DOX@nHAp/PLGA due to the storage of DOX in the gallery of LHAp, which is further proved by their cancer cell inhibition results. We believe that the DOX@LHAp/PLGA scaffold has potential as an implantable drug delivery system.
Yuanyang Nie,Zhiwei Zhou,Jiuqiang Guan,Baixue Xia,Xiaolin Luo,Yang Yang,Yu Fu,Qun Sun 아세아·태평양축산학회 2017 Animal Bioscience Vol.30 No.7
Objective: To understand the dynamic structure, function, and influence on nutrient metabolism in hosts, it was crucial to assess the genetic potential of gut microbial community in yaks of different ages. Methods: The denaturing gradient gel electrophoresis (DGGE) profiles and Illumina-based metagenomic sequencing on colon contents of 15 semi-domestic yaks were investigated. Unweighted pairwise grouping method with mathematical averages (UPGMA) clustering and principal component analysis (PCA) were used to analyze the DGGE fingerprint. The Illumina sequences were assembled, predicted to genes and functionally annotated, and then classified by querying protein sequences of the genes against the Kyoto encyclopedia of genes and genomes (KEGG) database. Results: Metagenomic sequencing showed that more than 85% of ribosomal RNA (rRNA) gene sequences belonged to the phylum Firmicutes and Bacteroidetes, indicating that the family Ruminococcaceae (46.5%), Rikenellaceae (11.3%), Lachnospiraceae (10.0%), and Bacteroidaceae (6.3%) were dominant gut microbes. Over 50% of non-rRNA gene sequences represented the metabolic pathways of amino acids (14.4%), proteins (12.3%), sugars (11.9%), nucleotides (6.8%), lipids (1.7%), xenobiotics (1.4%), coenzymes, and vitamins (3.6%). Gene functional classification showed that most of enzyme-coding genes were related to cellulose digestion and amino acids metabolic pathways. Conclusion: Yaks’ age had a substantial effect on gut microbial composition. Comparative metagenomics of gut microbiota in 0.5-, 1.5-, and 2.5-year-old yaks revealed that the abundance of the class Clostridia, Bacteroidia, and Lentisphaeria, as well as the phylum Firmicutes, Bacteroidetes, Lentisphaerae, Tenericutes, and Cyanobacteria, varied more greatly during yaks’ growth, especially in young animals (0.5 and 1.5 years old). Gut microbes, including Bacteroides, Clostridium, and Lentisphaeria, make a contribution to the energy metabolism and synthesis of amino acid, which are essential to the normal growth of yaks.
Zhang Weifeng,Li Gaocai,Luo Rongjin,Lei Jie,Song Yu,Wang Bingjin,Ma Liang,Liao Zhiwei,Ke Wencan,Liu Hui,Hua Wenbin,Zhao Kangcheng,Feng Xiaobo,Wu Xinghuo,Zhang Yukun,Wang Kun,Yang Cao 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Low back pain (LBP) is a major musculoskeletal disorder and the socioeconomic problem with a high prevalence that mainly involves intervertebral disc (IVD) degeneration, characterized by progressive nucleus pulposus (NP) cell death and the development of an inflammatory microenvironment in NP tissue. Excessively accumulated cytosolic DNA acts as a damage-associated molecular pattern (DAMP) that is monitored by the cGAS-STING axis to trigger the immune response in many degenerative diseases. NLRP3 inflammasome-dependent pyroptosis is a type of inflammatory programmed death that promotes a chronic inflammatory response and tissue degeneration. However, the relationship between the cGAS-STING axis and NLRP3 inflammasome-induced pyroptosis in the pathogenesis of IVD degeneration remains unclear. Here, we used magnetic resonance imaging (MRI) and histopathology to demonstrate that cGAS, STING, and NLRP3 are associated with the degree of IVD degeneration. Oxidative stress induced cGAS-STING axis activation and NLRP3 inflammasome-mediated pyroptosis in a STING-dependent manner in human NP cells. Interestingly, the canonical morphological and functional characteristics of mitochondrial permeability transition pore (mPTP) opening with the cytosolic escape of mitochondrial DNA (mtDNA) were observed in human NP cells under oxidative stress. Furthermore, the administration of a specific pharmacological inhibitor of mPTP and self-mtDNA cytosolic leakage effectively reduced NLRP3 inflammasome-mediated pyroptotic NP cell death and microenvironmental inflammation in vitro and degenerative progression in a rat disc needle puncture model. Collectively, these data highlight the critical roles of the cGAS-STING-NLRP3 axis and pyroptosis in the progression of IVD degeneration and provide promising therapeutic approaches for discogenic LBP.