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Deubiquitination and Stabilization of PD-L1 by CSN5
Lim, Seung-Oe,Li, Chia-Wei,Xia, Weiya,Cha, Jong-Ho,Chan, Li-Chuan,Wu, Yun,Chang, Shih-Shin,Lin, Wan-Chi,Hsu, Jung-Mao,Hsu, Yi-Hsin,Kim, Taewan,Chang, Wei-Chao,Hsu, Jennifer L.,Yamaguchi, Hirohito,Ding Elsevier 2016 Cancer cell Vol.30 No.6
<P><B>Summary</B></P> <P>Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TNF-α stabilizes cancer cell PD-L1 in response to chronic inflammation </LI> <LI> Activation of NF-κB by TNF-α induces CSN5 expression leading to PD-L1 stabilization </LI> <LI> CSN5 enzyme activity controls T cell suppression via PD-L1 deubiquitination </LI> <LI> Destabilization of PD-L1 by CSN5 inhibitor curcumin benefits anti-CTLA4 therapy </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
Li, Hong-Li,Huang, Ding-Zhi,Deng, Ting,Zhou, Li-Kun,Wang, Xia,Bai, Ming,Ba, Yi Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4
Cyclin L2 is a novel member of the cyclin family, recently implicated in the regulation of cell cycle progression and/or transcriptional regulation. The present study was undertaken to investigate the effects of overexpression on tumor cell growth and chemosensitivity in human gastric cells in vitro. Cyclin L2 was transfected into human gastric cancer cell line BCG823 and expressed with a mammalian expression vector pcDNA3.1. The effects and mechanisms of cyclin L2 on cell growth, cell cycling and apoptosis were studied. Compared to control vectors, overexpression of cyclin L2 inhibited the growth of BCG823 cells and enhance their chemosensitivity to fluorouracil, docetaxel and cisplatin. The anti-proliferative effects of cyclin L2 could be due to G0/G1 arrest and apoptosis. Cyclin L2 induced G0/G1 arrest and apoptosis involved upregulation of caspase-3 and down regulation Bcl-2 and survivin. The results indicated that overexpression of cyclin L2 protein may promote efficient growth inhibition and enhance chemosensitivity to chemotherapeutic agents in human gastric cancer cells by inducing G0/G1 cell cycle arrest and apoptosis.
Effects of the silencing of CmMET1 by RNA interference in chrysanthemum (Chrysanthemum morifolium)
Shuailei Li,Mangmang Li,Zhongai Li,Yi Zhu,Hongxu Ding,Xiaoxuan Fan,Fei Li,Zicheng Wang 한국식물생명공학회 2019 Plant biotechnology reports Vol.13 No.1
DNA methylation is an epigenetic modification involving many biological processes. It is known that epigenetic mechanisms such as cytosine methylation play a pivotal role in regulating plant development. In this current study, a conservative domainspliced hairpin RNA (ihpRNA) plant expression vector aimed at gene of DNA METHYLTRANSFERASE1 (CmMET1) has been constructed. Transgenic chrysanthemum materials (Zijingling) were obtained by Agrobacterium-mediated transformation with expression vectors. Transgenic plants were used as rootstock, grafted onto non-transgenic the scions [Guoqinghong (GQH) and Huanshuijinqiu (HSJQ)], which silencing CmMET1 gene, and exhibited the early flower phenotypes. A highperformance liquid chromatography analysis indicated that the decrease of CmMET1 expression decreased the methylation level of genomic DNA. Similarly, a quantitative real-time polymerase chain reaction analysis revealed that CmMET1 expression levels decreased in transgenic chrysanthemum plants and in the scions grafted onto transgenic plants. This decrease of CmMET1 expression upregulated the expression of the methyltransferase gene, METHYLTRANSFERASE2 (CmDRM2), but downregulated the expression of the demethylating enzyme gene, DEMETER (CmDME), while the CHROMOMETHYLASEA (CmCMT3) expression level remained low and could be almost undetectable. Among the CmFT-likes genes that affect flowering time, CmFTL1 expression was downregulated, as well as CmFTL2 and CmFTL3 expression levels which were upregulated. Our data indicated that silencing CmMET1 could decrease plant height, change the phenotype of chrysanthemum, and promote earlier flowering. The transgenic plants bloomed 8 days earlier. GQH and HSJQ scions grafted onto transgenic plants were 12 and 9 days earlier than the scions grafted onto non-transgenic plants, respectively. Overall, the results have some meanings for promoting the flowering of chrysanthemum scion varieties using genetic modified rootstock.
Chengnan Li,Yingying Gan,Zongshao Li,Mengjing Fu,Yuzhen Li,Xinran Peng,Yongqiang Yang,Guo‑bao Tian,Yi Yan Yang,Peiyan Yuan,Xin Ding 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00
Background P. aeruginosa, a highly virulent Gram-negative bacterium, can cause severe nosocomial infections, and it has developed resistance against most antibiotics. New therapeutic strategies are urgently needed to treat such bacterial infection and reduce its toxicity caused by endotoxin (lipopolysaccharide, LPS). Neutrophils have been proven to be able to target inflammation site and neutrophil membrane receptors such as Toll-like receptor-4 (TLR4) and CD14, and exhibit specific affinity to LPS. However, antibacterial delivery system based on the unique properties of neutrophils has not been reported. Methods A neutrophil-inspired antibacterial delivery system for targeted photothermal treatment, stimuli-responsive antibiotic release and endotoxin neutralization is reported in this study. Specifically, the photothermal reagent indocyanine green (ICG) and antibiotic rifampicin (RIF) are co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP-ICG/RIF), followed by coating with neutrophil membrane to obtain antibacterial delivery system (NM-NP-ICG/RIF). The inflammation targeting properties, synergistic antibacterial activity of photothermal therapy and antibiotic treatment, and endotoxin neutralization have been studied in vitro. A P. aeruginosa-induced murine skin abscess infection model has been used to evaluate the therapeutic efficacy of the NM-NP-ICG/RIF. Results Once irradiated by near-infrared lasers, the heat generated by NP-ICG/RIF triggers the release of RIF and ICG, resulting in a synergistic chemo-photothermal antibacterial effect against P. aeruginosa (~ 99.99% killing efficiency in 5 min). After coating with neutrophil-like cell membrane vesicles (NMVs), the nanoparticles (NM-NP-ICG/RIF) specifically bind to inflammatory vascular endothelial cells in infectious site, endowing the nanoparticles with an infection microenvironment targeting function to enhance retention time. Importantly, it is discovered for the first time that NMVs-coated nanoparticles are able to neutralize endotoxins. The P. aeruginosa murine skin abscess infection model further demonstrates the in vivo therapeutic efficacy of NM-NP-ICG/RIF. Conclusion The neutrophil-inspired antibacterial delivery system (NM-NP-ICG/RIF) is capable of targeting infection microenvironment, neutralizing endotoxin, and eradicating bacteria through a synergistic effect of photothermal therapy and antibiotic treatment. This drug delivery system made from FDA-approved compounds provides a promising approach to fighting against hard-to-treat bacterial infections.
Li, Qiong,Yin, Jun,Wang, Xu,Wang, Li-Ming,Shi, Yi-Jun,Zheng, Liang,Tang, Wei-Feng,Ding, Guo-Wen,Liu, Chao,Liu, Rui-Ping,Gu, Hai-Yong,Sun, Jia-Ming,Chen, Suo-Cheng Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7
Aim: Apoptosis has been considered as a fundamental component in cancer pathogenesis, and related genetic factors might play an important role in gastric cardiac adenocarcinoma (GCA) genesis. Methods: We conducted a hospital based case.control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): BCL2 rs17757541 C>G, BCL2 rs12454712 T>C, FAS rs2234767 G>A, FASL/FASLG rs763110 C>T, ERBB2 rs1136201 A>G and VEGFR2/KDR rs11941492 C>T on the development of GCA. A total of 243 GCA cases and 476 controls were recruited for the study and genotypes were determined using a custom-by-design 48-Plex SNPscan$^{TM}$ Kit. Results: The BCL2 rs17757541 C>G polymorphism was associated with increased risk of GCA. However, there was no significant associations with the other five SNPs. Stratified analyses indicated a significantly increased risk of GCA associated with the BCL2 rs17757541 C>G polymorphism among males, older patients and those with a history of smoking or drinking. Conclusion: These findings indicated that the functional polymorphism BCL2 rs17757541 C>G might contribute to GCA susceptibility. However, our results were limited by small sample size. Future larger studies are required to confirm our current findings.
Li, Jiaolong,Hou, Yongqing,Yi, Dan,Zhang, Jun,Wang, Lei,Qiu, Hongyi,Ding, Binying,Gong, Joshua Asian Australasian Association of Animal Productio 2015 Animal Bioscience Vol.28 No.12
This study was carried out to investigate the effects of tributyrin (TB) on the growth performance, pro-inflammatory cytokines, intestinal morphology, energy status, disaccharidase activity, and antioxidative capacity of broilers challenged with lipopolysaccharide (LPS). A total of 160 one-day-old Cobb broilers were allocated to 1 of 4 treatments, with 4 replicated pens per treatment and 10 birds per pen. The experiment consisted of a $2{\times}2$ factorial arrangements of treatments with TB supplementation (0 or 500 mg/kg) and LPS challenge (0 or $500{\mu}g/kg$ body weight [BW]). On days 22, 24, and 26 of the trial, broilers received an intraperitoneal administration of $500{\mu}g/kg$ BW LPS or saline. Dietary TB showed no effect on growth performance. However, LPS challenge decreased the average daily gain of broilers from day 22 to day 26 of the trial. Dietary TB supplementation inhibited the increase of interleukin-$1{\beta}$ (in the jejunum and ileum), interleukin-6 (in the duodenum and jejunum), and prostaglandin $E_2$ (in the duodenum) of LPS-challenged broilers. Similar inhibitory effects of TB in the activities of total nitric oxide synthase (in the ileum) and inducible nitric oxide synthase (in the jejunum) were also observed in birds challenged with LPS. Additionally, TB supplementation mitigated the decrease of ileal adenosine triphosphate, adenosine diphosphate and total adenine nucleotide and the reduction of jejunal catalase activity induced by LPS. Taken together, these results suggest that the TB supplementation was able to reduce the release of pro-inflammatory cytokines and improve the energy status and anti-oxidative capacity in the small intestine of LPS-challenged broilers.
Li Tao,Qin Sheng,Sun Xia,Zhang Kai-xiang,Ding Xin-yi,Wang Xue-yang,Li Muwang 한국응용곤충학회 2022 Journal of Asia-Pacific Entomology Vol.25 No.3
Baculoviruses are enveloped rod-shaped viruses that with circular double-stranded and large DNA genome. Baculoviruses successfully invade by using the host factors, especially at the process of establishing early infection. In this study, we investigated the different resistant strains of silkworm in response to AcMNPV early infection by RNA-sequencing. Our data revealed that the genes involved in innate immunity and ribosomal proteins were suppressed and cytoskeleton were induced in susceptible strain p50, thus facilitating the viral replication. However, in resistant strain C108, the genes participated in endocytosis and RNA transport were down-regulated, while up-regulation of ribosomal proteins and energy metabolic to inhibit the infection of the virus. These data provide a new sight of the initial host transcriptional responses to viral infection in silkworm.
Ding, Yi,Zhang, Bo,Ren, Qifang,Zhang, Qicai,Zha, Weiwei,Li, Xin,Chen, Shaohua,Oh, Won-Chun The Korean Ceramic Society 2017 한국세라믹학회지 Vol.54 No.2
In this article, pure $m-LaVO_4:Eu^{3+}$ and $t-LaVO_4:Eu^{3+}$ nanocrystals were prepared by an EG-assisted hydrothermal method with regular shapes. A series of controlled experiments showed that the pH value of a mixed solution, the volume ratio of $EG/H_2O$ and the dosage of the doped $Eu^{3+}$ all had an important effect on the sizes and shapes of the final products. Furthermore, the constitutional unit of the products changed from 0D to 2D with an increase in the EG dosage. The PL results showed that $t-LaVO_4$ doped with $Eu^{3+}$ ions had better luminescence properties than $m-LaVO_4$ due to its special structure. All of these results not only expand our understanding of the luminescence properties of lanthanide orthovanadates, but they also elucidate the principles of the crystal growth.