IRE1α protects against osteoarthritis by regulating progranulin-dependent XBP1 splicing and collagen homeostasis

Liang Li,Zhang Fengmei,Feng Naibo,Kuang Biao,Fan Mengtian,Chen Cheng,Pan Yiming,Zhou Pengfei,Geng Nana,Li Xingyue,Xian Menglin,Deng Lin,Li Xiaoli,Kuang Liang,Luo Fengtao,Tan Qiaoyan,Xie Yangli,Guo Fen 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Osteoarthritis (OA) is a full-joint, multifactorial, degenerative and inflammatory disease that seriously affects the quality of life of patients due to its disabling and pain-causing properties. ER stress has been reported to be closely related to the progression of OA. The inositol-requiring enzyme 1α/X-box-binding protein-1 spliced (IRE1α/XBP1s) pathway, which is highly expressed in the chondrocytes of OA patients, promotes the degradation and refolding of abnormal proteins during ER stress and maintains the stability of the ER environment of chondrocytes, but its function and the underlying mechanisms of how it contributes to the progression of OA remain unclear. This study investigates the role of IRE1α/ERN1 in OA. Specific deficiency of ERN1 in chondrocytes spontaneously resulted in OA-like cartilage destruction and accelerated OA progression in a surgically induced arthritis model. Local delivery of AdERN1 relieved degradation of the cartilage matrix and prevented OA development in an ACLT-mediated model. Mechanistically, progranulin (PGRN), an intracellular chaperone, binds to IRE1α, promoting its phosphorylation and splicing of XBP1u to generate XBP1s. XBP1s protects articular cartilage through TNF-α/ERK1/2 signaling and further maintains collagen homeostasis by regulating type II collagen expression. The chondroprotective effect of IRE1α/ERN1 is dependent on PGRN and XBP1s splicing. ERN1 deficiency accelerated cartilage degeneration in OA by reducing PGRN expression and XBP1s splicing, subsequently decreasing collagen II expression and triggering collagen structural abnormalities and an imbalance in collagen homeostasis. This study provides new insights into OA pathogenesis and the UPR and suggests that IRE1α/ERN1 may serve as a potential target for the treatment of joint degenerative diseases, including OA.

Isoindolin-1-ones from the stems of Nicotiana tabacum and their antiviral activities

Guang-Yu Yang,Jia-Meng Dai,Zhen-Jie Li,Jin Wang,Feng-Xian Yang,Xin Liu,Jing Li,Qian Gao,Xue-Mei Li,Yin-Ke Li,Wei-Guang Wang,Min Zhou,Qiu-Fen Hu 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.8

In previous studies, several isoindolin-1-oneanalogs that exhibited signifi cant anti-tobacco mosaic virus(anti-TMV) activities were isolated from Nicotiana tabacum . Since gene-editing mutants provide a new sample for thediscovery of active metabolites, we focused on the stems ofYN-18–23 (a mutant N. tabacum for gene editing with thealkaloid metabolic pathway cultivated by Yunnan TobaccoCompany), which led to the isolation of four new ( 1–4 )and four known ( 5–8 ) isoindolin-1-ones. To the best of ourknowledge, nicindole C ( 3 ) is the fi rst subclass of isoindolin-1-one bearing a pentacyclic ketone, while nicindole D ( 4 )is the fi rst example of isoindolin-1-one bearing a methylpyridin-2-(1 H )-one moiety. Compounds 1–4 were testedfor their anti-TMV activities, and the results revealed thatcompounds 1 , 3 , and 4 exhibited high anti-TMV activities atconcentrations of 20 μM with inhibition rates of 48.6, 42.8,and 71.5%, respectively. These rates are higher than the inhibitionrate of the positive control (33.2%). The mechanisticstudy of compound 4 , which had the highest anti-TMV activityrevealed that increased potentiation of defense-related enzyme activities and downregulation of expression of theNtHsp70 protein may induce resistance in tobacco againstthe viral pathogen TMV. Molecular docking studies alsorevealed that the isoindolin-1-one substructure is fundamentalfor anti-TMV activity. The methyl-pyridin-2-(1 H )-onemoiety in compound 4 and the 2-oxopropyl groups in compounds1 and 3 at the N -2 position may increase inhibitoryactivities. This study of the structure–activity relationshipis helpful for fi nding new anti-TMV activity inhibitors. Tostudy whether the isoindolin-1-ones have broader antiviralactivities, compounds 1–4 were also tested for their antirotavirusactivities. Compound 4 exhibited high anti-rotavirusactivity with a therapeutic index (TI) value of 20.7. This TI value is close to that of the positive control (20.2).

Passive Smoking and Cervical Cancer Risk: A Meta-analysis Based on 3,230 Cases and 2,982 Controls

Zeng, Xian-Tao,Xiong, Ping-An,Wang, Fen,Li, Chun-Yi,Yao, Juan,Guo, Yi Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Objective: Passive smoking has been considered as a risk factor of many cancers. To examine whether it might also pose a risk for cervical cancer, we performed a meta-analysis based on published case-control studies. Methods: We searched the PubMed database and references of included studies up to February 10th, 2012 for relevant studies. After two authors independently assessed the methodological quality and extracted data, a meta-analysis was conducted using CMA v2 software. Publication bias was evaluated by funnel plot, using Egger's and Begg's tests. Results: Finally 11 eligible studies yielded, involving 3,230 cases and 2,982 controls. The results showed that women who never smoke but exposed to smoking experience a 73% increase in risk of cervical cancer compared with non-exposed women (OR = 1.73, 95% CI = 1.35 - 2.21, p<0.001). Subgroup and sensitivity analyses indicated this result to be robust. Moderate publication bias was detected by visualing funnel plot, Egger's and Begg's tests. Conclusion: Based on currently available evidence, the findings of this meta-analysis suggests that passive smoking significantly and independently increases the risk of cervical cancer.

Crocin alleviates neurotoxicity induced by bupivacaine in SH-SY5Y cells with inhibition of PI3K/AKT signaling

Lin Lili,Chen Zhen,Li Jun,Peng Jianye,Wang Jian,Feng Mingjun,Liu Tiancheng,Zhang Mengli,Wu Xian,Ai Fen,Shen Caijie 한국유전학회 2024 Genes & Genomics Vol.46 No.1

Background Bupivacaine, a common local anesthetic, can cause neurotoxicity and permanent neurological disorders. Crocin has been widely reported as a potential neuroprotective agent in neural injury models. Objective The aim of this study was to investigate the role and regulatory mechanism of crocin underlying bupivacaine-induced neurotoxicity. Method Human neuroblastoma SH-SY5Y cells were treated with bupivacaine and/or crocin for 24 h, followed by detecting cell viability using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effect of crocin or bupivacaine on SH-SY5Y cell proliferation was measured by Ki67 immunofluorescence assay. The levels of apoptosis-related proteins and the markers in the PI3K/Akt signaling pathway were examined using western blot analysis. The activities of caspase 3, catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were tested using respective commercial assay kits. Flow cytometry analysis was executed for detecting SH-SY5Y cell apoptosis. Result Crocin attenuated bupivacaine-induced neurotoxicity in SH-SY5Y cells. Meanwhile, crocin inhibited SH-SY5Y cell apoptosis induced by bupivacaine via repressing the activity of caspase-3, reducing Bax expression, and elevating Bcl-2 expression. Moreover, crocin mitigated oxidative stress in SH-SY5Y cells by increasing the content of CAT, SOD, GSH-Px and reducing the content of MDA. Additionally, crocin protected against bupivacaine-induced dephosphorylation of Akt and GSK-3β. The protective effects of crocin against bupivacaine-induced neurotoxicity in SH-SY5Y cells were counteracted by the Akt inhibitor. Conclusion These results suggested that crocin may exert a neuroprotective function by promoting cell proliferation and suppressing apoptosis and oxidative stress in SH-SY5Y cells. Thus, crocin might become a promising drug for the treatment of bupivacaine-induced neurotoxicity. Background Bupivacaine, a common local anesthetic, can cause neurotoxicity and permanent neurological disorders. Crocin has been widely reported as a potential neuroprotective agent in neural injury models. Objective The aim of this study was to investigate the role and regulatory mechanism of crocin underlying bupivacaine-induced neurotoxicity. Method Human neuroblastoma SH-SY5Y cells were treated with bupivacaine and/or crocin for 24 h, followed by detecting cell viability using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effect of crocin or bupivacaine on SH-SY5Y cell proliferation was measured by Ki67 immunofluorescence assay. The levels of apoptosis-related proteins and the markers in the PI3K/Akt signaling pathway were examined using western blot analysis. The activities of caspase 3, catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were tested using respective commercial assay kits. Flow cytometry analysis was executed for detecting SH-SY5Y cell apoptosis. Result Crocin attenuated bupivacaine-induced neurotoxicity in SH-SY5Y cells. Meanwhile, crocin inhibited SH-SY5Y cell apoptosis induced by bupivacaine via repressing the activity of caspase-3, reducing Bax expression, and elevating Bcl-2 expression. Moreover, crocin mitigated oxidative stress in SH-SY5Y cells by increasing the content of CAT, SOD, GSH-Px and reducing the content of MDA. Additionally, crocin protected against bupivacaine-induced dephosphorylation of Akt and GSK-3β. The protective effects of crocin against bupivacaine-induced neurotoxicity in SH-SY5Y cells were counteracted by the Akt inhibitor. Conclusion These results suggested that crocin may exert a neuroprotective function by promoting cell proliferation and suppressing apoptosis and oxidative stress in SH-SY5Y cells. Thus, crocin might become a promising drug for the treatment of bupivacaine-induced neurotoxicity.

New Compounds from Euphorbia helioscopia and Absolute Configuration Determination by Computational Methods

Jiangbo He,Hua-Jie Zhu,Gui-Fen Luo,Guang-Ming Liu,Yan Li,Hao Chen,Shaopeng Chen,Xin Lu,Guochun Zhou,Yong-Xian Cheng 대한화학회 2010 Bulletin of the Korean Chemical Society Vol.31 No.8

The whole plant of Euphorbia helioscopia is an important traditional Chinese medicine. Fom its BuOH soluble extract,one new lactam (1), three new terpenoids (2-4) including a new naturally occurring compound, and three known compounds were isolated. Their structures were identified by spectroscopic evidences. In particular, the absolute configurations of side chain of compounds 1 and 2 were determined using computational methods.

Flavones from the Bark of Lindera caudata and Their Anti-Tobacco Mosaic Virus Activity

Yu-Chun Yang,Ying Qin,Xian-Xue Wu,Cong-Fang Xia,Yan-Lin Meng,Bin Zhou,Yan-Qing Ye,Xue-Mei Gao,Yin-Ke Li,Qiu-Fen Hu 대한화학회 2015 Bulletin of the Korean Chemical Society Vol.36 No.4

Two new flavones, 5-hydroxy-8-hydroxymethyl-7,4′-dimethoxy-flavone (1) and 6-hydroxy-8-hydroxymethyl-7,4′-dimethoxy-flavone (2), together with six known flavones (3–8), were isolated from the bark of Lindera caudata. The structures of 1–8 were elucidated by spectroscopic methods including extensive 1D and 2D NMR techniques. Compounds 1–8 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activity. The results showed that Compounds 1 and 2 showed high anti-TMV activity with inhibition rates of 31.2 and 28.8%, respectively. These values are close to those of positive control.

Influence of a Liquid Structural Change on the Solidification of the Alloy CuSn30

Jie Chen,Fang Qiu Zu,Xian Fen Li,Guo Hua Ding,Hon Sheng Chen,Li Zou 대한금속재료학회 2008 METALS AND MATERIALS International Vol.14 No.5

New Compounds from Euphorbia helioscopia and Absolute Configuration Determination by Computational Methods

He, Jiang-Bo,Zhu, Hua-Jie,Luo, Gui-Fen,Liu, Guang-Ming,Chen, Hao,Li, Yan,Chen, Shaopeng,Lu, Xin,Zhou, Guochun,Cheng, Yong-Xian Korean Chemical Society 2010 Bulletin of the Korean Chemical Society Vol.31 No.8

The whole plant of Euphorbia helioscopia is an important traditional Chinese medicine. Fom its BuOH soluble extract, one new lactam (1), three new terpenoids (2-4) including a new naturally occurring compound, and three known compounds were isolated. Their structures were identified by spectroscopic evidences. In particular, the absolute configurations of side chain of compounds 1 and 2 were determined using computational methods.

Molecular characterization of novel haplotypes of eIF4E family in Chinese cabbage (Brassica rapa L. ssp. pekinensis)

Shuan-Tao Liu,Zhi-Gang Zhang,Qiao-Yun Li,Shu-Fen Wang,Zhi-Zhong Zhao,Jin-Dong Lu,Wen-Ling Xu,Xian-Xian Liu,Wei-Min Fu 한국유전학회 2013 Genes & Genomics Vol.35 No.6

Two genes coding for eukaryotic translation initiation factors, eIF4E.a and eIF4E.c, were isolated from twelve accessions of Chinese cabbage (Brassica rapa L. ssp. pekinensis). Polymorphism analysis revealed that 94and 142 polymorphic sites were characterized from allele of BraeIF4E.a and BraeIF4E.c which produced complex haplotype structures. Six novel haplotypes were characterized from the two alleles respectively. Among the six novel haplotypes of BraeIF4E.a, three loss-of-function mutations were identified in which a conserved single nucleotide deletion mutation cause the early termination of BraeIF4E.a coding product; while for six new BraeIF4E.c haplotypes, their coding product show amino acid substitution mutations on non-conservative amino acid residues which might affect TuMV infection in Chinese cabbage.