Resveratrol targets PD-L1 glycosylation and dimerization to enhance antitumor T-cell immunity.


:New strategies to block the immune evasion activity of programmed death ligand-1 (PD-L1) are urgently needed. When exploring the PD-L1-targeted effects of mechanistically diverse metabolism-targeting drugs, exposure to the dietary polyphenol resveratrol (RSV) revealed its differential capacity to generate a distinct PD-L1 electrophoretic migration pattern. Using biochemical assays, computer-aided docking/molecular dynamics simulations, and fluorescence microscopy, we found that RSV can operate as a direct inhibitor of glyco-PD-L1-processing enzymes (α-glucosidase/α-mannosidase) that modulate N-linked glycan decoration of PD-L1, thereby promoting the endoplasmic reticulum retention of a mannose-rich, abnormally glycosylated form of PD-L1. RSV was also predicted to interact with the inner surface of PD-L1 involved in the interaction with PD-1, almost perfectly occupying the target space of the small compound BMS-202 that binds to and induces dimerization of PD-L1. The ability of RSV to directly target PD-L1 interferes with its stability and trafficking, ultimately impeding its targeting to the cancer cell plasma membrane. Impedance-based real-time cell analysis (xCELLigence) showed that cytotoxic T-lymphocyte activity was notably exacerbated when cancer cells were previously exposed to RSV. This unforeseen immunomodulating mechanism of RSV might illuminate new approaches to restore T-cell function by targeting the PD-1/PD-L1 immunologic checkpoint with natural polyphenols.


Aging (Albany NY)




Verdura S,Cuyàs E,Cortada E,Brunet J,Lopez-Bonet E,Martin-Castillo B,Bosch-Barrera J,Encinar JA,Menendez JA




Has Abstract


2020-01-04 00:00:00














  • Calreticulin increases growth and progression of natural killer/T-cell lymphoma.

    abstract::In this study, we investigated the role of calreticulin (CALR) in the pathogenesis of natural killer/T-cell lymphoma (NKTCL). CALR expression was significantly higher in the NKTCL tissues than normal control tissues in the GSE80632 dataset. High CALR expression correlated with poorer overall survival of NKTCL patients...


    pub_type: 杂志文章


    authors: Zheng Y,Li C,Xin P,Peng Q,Zhang W,Liu S,Zhu X

    更新日期:2020-11-18 00:00:00

  • White light emitting diode induces autophagy in hippocampal neuron cells through GSK-3-mediated GR and RORα pathways.

    abstract::Autophagy plays an important role in cell survival under diverse stress conditions. Here, we show that white LED light exposure for 24 h significantly activated autophagy-related genes and increased autophagosome formation in hippocampal neural cells (HT-22). Concurrently, the rhythmic pattern of clock-related gene ex...


    pub_type: 杂志文章


    authors: Yang Y,Jia Y,Sun Q,Dong H,Zhao R

    更新日期:2019-03-28 00:00:00

  • DR region specific antibody ameliorated but ouabain worsened renal injury in nephrectomized rats through regulating Na,K-ATPase mediated signaling pathways.

    abstract::Reduced Na+-K+-ATPase function is reported in various renal diseases. This implies that increase of Na+-K+-ATPase function may be a new target in treatment of renal injury. We previously reported that Na+-K+-ATPase was stabilized by DRm217, a specific antibody against DR region of Na+-K+-ATPase. In this study, we comp...


    pub_type: 杂志文章


    authors: Wang J,Ullah SH,Li M,Zhang M,Zhang F,Zheng J,Yan X

    更新日期:2019-02-26 00:00:00

  • Expression and prognosis analysis of DNMT family in acute myeloid leukemia.

    abstract::DNA methyltransferases (DNMTs) by regulating DNA methylation play crucial roles in the progression of hematologic malignancies, especially for acute myeloid leukemia (AML). Accumulating investigations have identified the high incidence of DNMT3A mutation in AML, and it is correlated with poor prognosis. Although a few...


    pub_type: 杂志文章


    authors: Zhang TJ,Zhang LC,Xu ZJ,Zhou JD

    更新日期:2020-06-26 00:00:00

  • Osteoprotegerin as a biomarker of geriatric frailty syndrome.

    abstract::The lack of a univocal definition of frailty, a condition frequently found in the elderly population which is correlated with an increased risk of mortality, has prompted the search for clinical and laboratory parameters associated with this condition. Whereas OPG is a protein involved in different pathophysiological ...


    pub_type: 杂志文章


    authors: Valentini A,Cianfarani MA,Tarantino U,Di Daniele N,Bertoli A

    更新日期:2019-07-17 00:00:00

  • In vitro and in vivo efficacy of the novel oral proteasome inhibitor NNU546 in multiple myeloma.

    abstract::Proteasome inhibition demonstrates highly effective impact on multiple myeloma (MM) treatment. Here, we aimed to examine anti-tumor efficiency and underlying mechanisms of a novel well tolerated orally applicable proteasome inhibitor NNU546 and its hydrolyzed pharmacologically active form NNU219. NNU219 showed more se...


    pub_type: 杂志文章


    authors: Zhou H,Lei M,Wang W,Guo M,Wang J,Zhang H,Qiao L,Feng H,Liu Z,Chen L,Hou J,Wang X,Gu C,Zhao B,Izumchenko E,Yang Y,Zhu Y

    更新日期:2020-11-16 00:00:00

  • Reduced production of laminin by hepatic stellate cells contributes to impairment in oval cell response to liver injury in aged mice.

    abstract::Aged liver is usually impaired in response to hepatic injury. Tissue-specific stem cells participate in the repair of tissue injury. However, how oval cells (OCs) respond to injury and how the process is regulated by tissue microenvironment in aged mice have not been fully understood. In this study, taking advantage o...


    pub_type: 杂志文章


    authors: Qian L,Zhang H,Gu Y,Li D,He S,Wang H,Cheng Y,Yang W,Yu H,Zhao X,Cai W,Meng L,Jin M,Wang Y,Zhang Y

    更新日期:2018-12-04 00:00:00

  • Rapamycin treatment benefits glucose metabolism in mouse models of type 2 diabetes.

    abstract::Numerous studies suggest that rapamycin treatment promotes insulin resistance, implying that rapamycin could have negative effects on patients with, or at risk for, type 2 diabetes (T2D). New evidence, however, indicates that rapamycin treatment produces some benefits to energy metabolism, even in the context of T2D. ...


    pub_type: 杂志文章


    authors: Reifsnyder PC,Flurkey K,Te A,Harrison DE

    更新日期:2016-11-30 00:00:00

  • Slower rates of accumulation of DNA damage in leukocytes correlate with longer lifespans across several species of birds and mammals.

    abstract::Although there is previous evidence showing an increase in various types of DNA damage with aging in mice and humans, a comparative study determining accumulation rates of DNA double strand breaks, as determined by presence of phosphorylated histone H2AX (γH2AX), in leukocytes of individuals of different ages from phy...


    pub_type: 杂志文章


    authors: Whittemore K,Martínez-Nevado E,Blasco MA

    更新日期:2019-11-15 00:00:00

  • Effects of age-dependent changes in cell size on endothelial cell proliferation and senescence through YAP1.

    abstract::Angiogenesis - the growth of new blood capillaries- is impaired in aging animals. Biophysical factors such as changes in cell size control endothelial cell (EC) proliferation and differentiation. However, the effects of aging on EC size and the mechanism by which changes in cell size control age-dependent decline in E...


    pub_type: 杂志文章


    authors: Mammoto T,Torisawa YS,Muyleart M,Hendee K,Anugwom C,Gutterman D,Mammoto A

    更新日期:2019-09-05 00:00:00

  • Association between serum levels of Klotho and inflammatory cytokines in cardiovascular disease: a case-control study.

    abstract::Decrease in soluble anti-aging Klotho protein levels is associated to cardiovascular disease (CVD). Diverse studies have shown a bidirectional relationship between Klotho and inflammation, a risk factor for the development of CVD. In this work we aimed to evaluate the association between Klotho and inflammatory cytoki...


    pub_type: 杂志文章


    authors: Martín-Núñez E,Donate-Correa J,Ferri C,López-Castillo Á,Delgado-Molinos A,Hernández-Carballo C,Pérez-Delgado N,Rodríguez-Ramos S,Cerro-López P,Tagua VG,Mora-Fernández C,Navarro-González JF

    更新日期:2020-01-27 00:00:00

  • Assessment of real-time three-dimensional echocardiography as a tool for evaluating left atrial volume and function in patients with type 2 diabetes mellitus.

    abstract:OBJECTIVE:To assess the value of real-time three-dimensional echocardiography (RT-3DE) in evaluating changes in left atrial volume and function in type 2 diabetes mellitus (DM) and type 2 diabetic nephropathy (DN) patients. METHOD:104 control subjects, 109 DN patients, and 111 DM patients were recruited and underwent ...


    pub_type: 杂志文章


    authors: Li X,Dong Y,Zheng C,Wang P,Xu M,Zou C,Wang L

    更新日期:2020-12-03 00:00:00

  • Co-expression network analysis identified hub genes critical to triglyceride and free fatty acid metabolism as key regulators of age-related vascular dysfunction in mice.

    abstract::Background: Aging has often been linked to age-related vascular disorders. The elucidation of the putative genes and pathways underlying vascular aging likely provides useful insights into vascular diseases at advanced ages. Transcriptional regulatory network analysis is the key to describing genetic interactions betw...


    pub_type: 杂志文章


    authors: Li H,Wang X,Lu X,Zhu H,Li S,Duan S,Zhao X,Zhang F,Alterovitz G,Wang F,Li Q,Tian XL,Xu M

    更新日期:2019-09-12 00:00:00

  • Discovering markers of healthy aging: a prospective study in a Danish male birth cohort.

    abstract::There is a pressing need to identify markers of cognitive and neural decline in healthy late-midlife participants. We explored the relationship between cross-sectional structural brain-imaging derived phenotypes (IDPs) and cognitive ability, demographic, health and lifestyle factors (non-IDPs). Participants were recru...


    pub_type: 杂志文章


    authors: Zarnani K,Nichols TE,Alfaro-Almagro F,Fagerlund B,Lauritzen M,Rostrup E,Smith SM

    更新日期:2019-08-26 00:00:00

  • Overexpression of KLF5 is associated with poor survival and G1/S progression in pancreatic cancer.

    abstract::Despite improvements in surgical procedures and comprehensive therapies, pancreatic cancer remains one of the most aggressive and deadly human malignancies. It is therefore necessary to determine which cellular mediators associate with prognosis in pancreatic cancer so as to improve the treatment of this disease. In t...


    pub_type: 杂志文章


    authors: Li Y,Kong R,Chen H,Zhao Z,Li L,Li J,Hu J,Zhang G,Pan S,Wang Y,Wang G,Chen H,Sun B

    更新日期:2019-07-21 00:00:00

  • S-allyl cysteine reduces osteoarthritis pathology in the tert-butyl hydroperoxide-treated chondrocytes and the destabilization of the medial meniscus model mice via the Nrf2 signaling pathway.

    abstract::In this study, we used murine chondrocytes as an in vitro model and mice exhibiting destabilization of the medial meniscus (DMM) as an in vivo model to investigate the mechanisms through which S-allyl cysteine (SAC) alleviates osteoarthritis (OA). SAC significantly reduced apoptosis and senescence and maintained homeo...


    pub_type: 杂志文章


    authors: Shao Z,Pan Z,Lin J,Zhao Q,Wang Y,Ni L,Feng S,Tian N,Wu Y,Sun L,Gao W,Zhou Y,Zhang X,Wang X

    更新日期:2020-10-07 00:00:00

  • CircRNA CDR1as promotes hepatoblastoma proliferation and stemness by acting as a miR-7-5p sponge to upregulate KLF4 expression.

    abstract::Hepatoblastoma (HB) is a malignant embryonal tumor of the liver that consists of heterogenous populations of stem/progenitor cells. Although circular RNAs (circRNAs) play an essential role in tumor development, the effects of circRNA on the proliferation of HB cells, especially cancer stem cells (CSCs), remain unclear...


    pub_type: 杂志文章


    authors: Chen L,Shi J,Wu Y,Qiu R,Zeng L,Lou L,Su J,Liao M,Deng X

    更新日期:2020-10-14 00:00:00

  • LUCS: a high-resolution nucleic acid sequencing tool for accurate long-read analysis of individual DNA molecules.

    abstract::Nucleic acid sequence analyses are fundamental to all aspects of biological research, spanning aging, mitochondrial DNA (mtDNA) and cancer, as well as microbial and viral evolution. Over the past several years, significant improvements in DNA sequencing, including consensus sequence analysis, have proven invaluable fo...


    pub_type: 杂志文章


    authors: Annis S,Fleischmann Z,Logan R,Mullin-Bernstein Z,Franco M,Saürich J,Tilly JL,Woods DC,Khrapko K

    更新日期:2020-04-28 00:00:00

  • Acetate attenuates perioperative neurocognitive disorders in aged mice.

    abstract::Perioperative neurocognitive disorders are common in elderly patients who have undergone surgical procedures. Neuroinflammation induced by microglial activation is a hallmark of these neurological disorders. Acetate can suppress inflammation in the context of inflammatory diseases. We employed an exploratory laparotom...


    pub_type: 杂志文章


    authors: Wen C,Xie T,Pan K,Deng Y,Zhao Z,Li N,Bian J,Deng X,Zha Y

    更新日期:2020-02-26 00:00:00

  • NEAT1/miR-200b-3p/SMAD2 axis promotes progression of melanoma.

    abstract::Melanoma is a skin malignancy with a high mutation frequency of genetic alterations. MicroRNA (miR)-200b-3p is involved in various cancers, while in melanoma its bio-function remains unknown. In this study, we found that miR-200b-3p was down-regulated in melanoma tissues and cell lines compared to benign nevus cells. ...


    pub_type: 杂志文章


    authors: Zhou WJ,Wang HY,Zhang J,Dai HY,Yao ZX,Zheng Z,Meng-Yan S,Wu K

    更新日期:2020-11-16 00:00:00

  • Age-related hearing loss accelerates cerebrospinal fluid tau levels and brain atrophy: a longitudinal study.

    abstract::Age-related hearing loss (ARHL) has been considered as a promising modifiable risk factor for cognitive impairment and dementia. Nonetheless, it is still unclear whether age-related hearing loss associates with neurodegenerative biomarkers of Alzheimer's disease (AD). Participants with ARHL were selected from the esta...


    pub_type: 杂志文章


    authors: Xu W,Zhang C,Li JQ,Tan CC,Cao XP,Tan L,Yu JT,Alzheimer’s Disease Neuroimaging Initiative.

    更新日期:2019-05-22 00:00:00

  • The association of circulating kynurenine, a tryptophan metabolite, with frailty in older adults.

    abstract::Despite the accumulating evidence from in vitro and animal experiments supporting the role of kynurenine (a tryptophan metabolite) in a number of degenerative age-related changes, the relationship between kynurenine and frailty in older adults is not well understood. We collected blood samples from 73 participants who...


    pub_type: 杂志文章


    authors: Jang IY,Park JH,Kim JH,Lee S,Lee E,Lee JY,Park SJ,Kim DA,Hamrick MW,Kim BJ

    更新日期:2020-11-13 00:00:00

  • RasGrf1: genomic imprinting, VSELs, and aging.

    abstract::Increase in life span in RasGrf1-deficient mice revealed that RasGrf1 deficiency promotes longevity. Interestingly, RasGrf1 is one of parentally imprinted genes transcribed from paternally-derived chromosome. Erasure of its imprinting results in RasGrf1 downregulation and has been demonstrated in a population of pluri...


    pub_type: 杂志文章


    authors: Ratajczak MZ,Kucia M,Liu R,Shin DM,Bryndza E,Masternak MM,Tarnowski M,Ratajczak J,Bartke A

    更新日期:2011-07-01 00:00:00

  • Atorvastatin reduces cerebral vasospasm and infarction after aneurysmal subarachnoid hemorrhage in elderly Chinese adults.

    abstract::We explored whether acute atorvastatin treatment would improve clinical outcomes and reduce the incidence of cerebral vasospasm after aneurysmal subarachnoid hemorrhage in elderly Chinese adults. Patients (60 to 90 years old) were admitted to intensive care units after surgery to clip or embolize their aneurysms. We a...


    pub_type: 杂志文章,随机对照试验


    authors: Chen J,Li M,Zhu X,Chen L,Yang S,Zhang C,Wu T,Feng X,Wang Y,Chen Q

    更新日期:2020-02-07 00:00:00

  • A systematic review and network meta-analysis of single nucleotide polymorphisms associated with pancreatic cancer risk.

    abstract::In this meta-analysis, we systematically investigated the correlation between single nucleotide polymorphisms (SNPs) and pancreatic cancer (PC) risk. We searched PubMed, Network Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Periodical Database (VIP), an...


    pub_type: 杂志文章


    authors: Ye ZM,Li LJ,Luo MB,Qing HY,Zheng JH,Zhang C,Lu YX,Tang YM

    更新日期:2020-11-20 00:00:00

  • RWR-algorithm-based dissection of microRNA-506-3p and microRNA-140-5p as radiosensitive biomarkers in colorectal cancer.

    abstract::Radiotherapy resistance is one of the main causes for treatment failure in colorectal cancer (CRC), and it is associated with the deregulation of certain microRNAs. In this study, we constructed the microRNA-mRNA network consisting of 2275 microRNAs and 7045 target genes, collected the known microRNAs related to CRC-r...


    pub_type: 杂志文章


    authors: Liao F,Chen X,Peng P,Dong W

    更新日期:2020-10-08 00:00:00

  • Leukocyte telomere length is inversely associated with arterial wave reflection in 566 normotensive and never-treated hypertensive subjects.

    abstract::Telomeres are short segments in chromosome ends, the length of which is reduced during cell lifecycles. We examined the association of mean leukocyte telomere length (LTL) and short telomere proportion (STP) with hemodynamic variables in normotensive and never-treated hypertensive volunteers (n=566, 19-72 years). STP ...


    pub_type: 杂志文章


    authors: Honkonen M,Vääräniemi K,Saijonmaa O,Nyman A,Tikkakoski AJ,Koskela J,Lehtimäki T,Kähönen M,Mustonen J,Fyhrquist F,Pörsti I

    更新日期:2020-06-23 00:00:00

  • A single-nucleotide polymorphism (rs1805087) in the methionine synthase (METH) gene increases the risk of prostate cancer.

    abstract::Methionine synthase (METH, i.e., MTR) is a key enzyme in the folate pathway, which plays a critical role in the synthesis, repair, and methylation of DNA. The association between METH gene polymorphisms and prostate cancer susceptibility remains ambiguous. Thus, we performed an updated meta-analysis of METH single-nuc...


    pub_type: 杂志文章,meta分析,评审


    authors: Zhang X,Tang J,Shen N,Ren K

    更新日期:2018-10-18 00:00:00

  • Exosomal miR-183-5p promotes angiogenesis in colorectal cancer by regulation of FOXO1.

    abstract::Exosomes play important roles in proliferation and microenvironment modulation of many types of cancers, including colorectal cancer (CRC). However, the inhibitory effect of CRC cells-derived exosomes in angiogenesis has not been fully discussed. In this study, the roles of microRNA-183-5p (miR-183-5p) in abundant in ...


    pub_type: 杂志文章


    authors: Shang A,Wang X,Gu C,Liu W,Sun J,Zeng B,Chen C,Ji P,Wu J,Quan W,Yao Y,Wang W,Sun Z,Li D

    更新日期:2020-05-03 00:00:00

  • Longitudinal plasma metabolomics of aging and sex.

    abstract::Understanding how metabolites are longitudinally influenced by age and sex could facilitate the identification of metabolomic profiles and trajectories that indicate disease risk. We investigated the metabolomics of age and sex using longitudinal plasma samples from the Wisconsin Registry for Alzheimer's Prevention (W...


    pub_type: 杂志文章


    authors: Darst BF,Koscik RL,Hogan KJ,Johnson SC,Engelman CD

    更新日期:2019-02-24 00:00:00