Identification of a natural inhibitor of methionine adenosyltransferase 2A regulating one-carbon metabolism in keratinocytes.


BACKGROUND:Psoriasis is a common chronic inflammatory skin disease which lacks effective strategies for the treatment. Natural compounds with biological activities are good tools to identify new targets with therapeutic potentials. Acetyl-11-keto-β-boswellic acid (AKBA) is the most bioactive ingredient of boswellic acids, a group of compounds with anti-inflammatory and anti-cancer properties. Target identification of AKBA and metabolomics analysis of psoriasis helped to elucidate the molecular mechanism underlying its effect, and provide new target(s) to treat the disease. METHODS:To explore the targets and molecular mechanism of AKBA, we performed affinity purification, metabolomics analysis of HaCaT cells treated with AKBA, and epidermis of imiquimod (IMQ) induced mouse model of psoriasis and psoriasis patients. FINDINGS:AKBA directly interacts with methionine adenosyltransferase 2A (MAT2A), inhibited its enzyme activity, decreased level of S-adenosylmethionine (SAM) and SAM/SAH ratio, and reprogrammed one‑carbon metabolism in HaCaT cells. Untargeted metabolomics of epidermis showed one‑carbon metabolism was activated in psoriasis patients. Topical use of AKBA improved inflammatory phenotype of IMQ induced psoriasis-like mouse model. Molecular docking and site-directed mutagenesis revealed AKBA bound to an allosteric site at the interface of MAT2A dimer. INTERPRETATION:Our study extends the molecular mechanism of AKBA by revealing a new interacting protein MAT2A. And this leads us to find out the dysregulated one‑carbon metabolism in psoriasis, which indicates the therapeutic potential of AKBA in psoriasis. FUND: The National Natural Science Foundation, the National Program on Key Basic Research Project, the Shanghai Municipal Commission, the Leading Academic Discipline Project of the Shanghai Municipal Education Commission.






Bai J,Gao Y,Chen L,Yin Q,Lou F,Wang Z,Xu Z,Zhou H,Li Q,Cai W,Sun Y,Niu L,Wang H,Wei Z,Lu S,Zhou A,Zhang J,Wang H




Has Abstract


2019-01-01 00:00:00










  • Surgery, neuroinflammation and cognitive impairment.

    abstract::Trauma experienced during surgery can contribute to the development of a systemic inflammatory response that can cause multi-organ dysfunction or even failure. Post-surgical neuroinflammation is a documented phenomenon that results in synaptic impairment, neuronal dysfunction and death, and impaired neurogenesis. Vari...


    pub_type: 杂志文章,评审


    authors: Alam A,Hana Z,Jin Z,Suen KC,Ma D

    更新日期:2018-11-01 00:00:00

  • Intratumor Heterogeneity in Primary Kidney Cancer Revealed by Metabolic Profiling of Multiple Spatially Separated Samples within Tumors.

    abstract::Metabolic alteration constitutes a hallmark of cancer. Glycolysis and antioxidant pathways in kidney cancer are elevated, with frequent mutation of the VHL gene. Intratumor genetic heterogeneity has been recently demonstrated in kidney cancer. However, intratumor metabolic heterogeneity has not been investigated. Here...


    pub_type: 杂志文章


    authors: Okegawa T,Morimoto M,Nishizawa S,Kitazawa S,Honda K,Araki H,Tamura T,Ando A,Satomi Y,Nutahara K,Hara T

    更新日期:2017-05-01 00:00:00

  • OLA-Simple: A software-guided HIV-1 drug resistance test for low-resource laboratories.

    abstract:BACKGROUND:HIV drug resistance (HIVDR) testing can assist clinicians in selecting treatments. However, high complexity and cost of genotyping assays limit routine testing in settings where HIVDR prevalence has reached high levels. METHODS:The oligonucleotide ligation assay (OLA)-Simple kit was developed for detection ...


    pub_type: 杂志文章


    authors: Panpradist N,Beck IA,Vrana J,Higa N,McIntyre D,Ruth PS,So I,Kline EC,Kanthula R,Wong-On-Wing A,Lim J,Ko D,Milne R,Rossouw T,Feucht UD,Chung M,Jourdain G,Ngo-Giang-Huong N,Laomanit L,Soria J,Lai J,Klavins ED,Fr

    更新日期:2019-12-01 00:00:00

  • Skeletal muscle as potential central link between sarcopenia and immune senescence.

    abstract::As our population grows older, age-related pathologies are becoming more prevalent. Deterioration of skeletal muscle and the immune system manifests as sarcopenia and immune senescence respectively. The disease burden of these pathologies emphasizes the need for a better understanding of the underlying mechanisms. Ske...


    pub_type: 杂志文章,评审


    authors: Nelke C,Dziewas R,Minnerup J,Meuth SG,Ruck T

    更新日期:2019-11-01 00:00:00

  • Correcting a Fundamental Flaw in the Paradigm for Antimicrobial Susceptibility Testing.

    abstract::The emergence and prevalence of antibiotic-resistant bacteria are an increasing cause of death worldwide, resulting in a global 'call to action' to avoid receding into an era lacking effective antibiotics. Despite the urgency, the healthcare industry still relies on a single in vitro bioassay to determine antibiotic e...


    pub_type: 杂志文章


    authors: Ersoy SC,Heithoff DM,Barnes L 5th,Tripp GK,House JK,Marth JD,Smith JW,Mahan MJ

    更新日期:2017-06-01 00:00:00

  • Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging.

    abstract::Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiolog...


    pub_type: 杂志文章


    authors: Lin JB,Sene A,Santeford A,Fujiwara H,Sidhu R,Ligon MM,Shankar VA,Ban N,Mysorekar IU,Ory DS,Apte RS

    更新日期:2018-06-01 00:00:00

  • Human placental mesenchymal stem cells improve stroke outcomes via extracellular vesicles-mediated preservation of cerebral blood flow.

    abstract:BACKGROUND:Besides long-term trans-differentiation into neural cells, benefits of stem cell therapy (SCT) in ischemic stroke may include secretion of protective factors, which partly reflects extracellular vesicle (EVs) released by stem cell. However, the mechanism(s) by which stem cells/EVs limit stroke injury have ye...


    pub_type: 杂志文章


    authors: Barzegar M,Wang Y,Eshaq RS,Yun JW,Boyer CJ,Cananzi SG,White LA,Chernyshev O,Kelley RE,Minagar A,Stokes KY,Lu XH,Alexander JS

    更新日期:2021-01-01 00:00:00

  • The Population Level Cascade of Care for Hepatitis C in British Columbia, Canada: The BC Hepatitis Testers Cohort (BC-HTC).

    abstract:BACKGROUND:Population-level monitoring of hepatitis C virus (HCV) infected people across the cascade of care identifies gaps in access and engagement in care and treatment. We characterized a population-level cascade of care for HCV in British Columbia (BC), Canada and identified factors associated with leakage at each...


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    authors: Janjua NZ,Kuo M,Yu A,Alvarez M,Wong S,Cook D,Wong J,Grebely J,Butt ZA,Samji H,Ramji A,Tyndall M,Krajden M

    更新日期:2016-10-01 00:00:00

  • Splicing modulation as novel therapeutic strategy against diffuse malignant peritoneal mesothelioma.

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    pub_type: 杂志文章


    authors: Sciarrillo R,Wojtuszkiewicz A,El Hassouni B,Funel N,Gandellini P,Lagerweij T,Buonamici S,Blijlevens M,Zeeuw van der Laan EA,Zaffaroni N,Deraco M,Kusamura S,Würdinger T,Peters GJ,Molthoff CFM,Jansen G,Kaspers GJL,Cloos J

    更新日期:2019-01-01 00:00:00

  • Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial.

    abstract:BACKGROUND:In a placebo-controlled trial of the peptide-based therapeutic HIV-1 p24Gag vaccine candidate Vacc-4x, participants on combination antiretroviral therapy (cART) received six immunizations over 18weeks, followed by analytical treatment interruption (ATI) between weeks 28 and 52. Cell-mediated immune responses...


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    authors: Huang Y,Pantaleo G,Tapia G,Sanchez B,Zhang L,Trondsen M,Hovden AO,Pollard R,Rockstroh J,Ökvist M,Sommerfelt MA

    更新日期:2017-10-01 00:00:00

  • Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug.

    abstract::The last major advance in the treatment of glioblastoma multiforme (GBM) was the introduction of temozolomide in 1999. Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone. However, virtually all glioblastoma patients experience disease progression...


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    authors: Sharpe MA,Livingston AD,Gist TL,Ghosh P,Han J,Baskin DS

    更新日期:2015-08-08 00:00:00

  • Molecular subtyping of cancer and nomination of kinase candidates for inhibition with phosphoproteomics: Reanalysis of CPTAC ovarian cancer.

    abstract:BACKGROUND:Molecular subtyping of cancer aimed to predict patient overall survival (OS) and nominate drug targets for patient treatments is central to precision oncology. Owing to the rapid development of phosphoproteomics, we can now measure thousands of phosphoproteins in human cancer tissues. However, limited studie...


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    authors: Tong M,Yu C,Zhan D,Zhang M,Zhen B,Zhu W,Wang Y,Wu C,He F,Qin J,Li T

    更新日期:2019-02-01 00:00:00

  • A prognostic gene expression signature for oropharyngeal squamous cell carcinoma.

    abstract:BACKGROUND:Robust prognostic stratification of patients with oropharyngeal squamous cell carcinoma (OPSCC) is important for developing individualized treatment plans. This study was conducted to develop and validate a clinically feasible prognostic classifier based on transcriptome-wide gene expression profiles. METHO...


    pub_type: 杂志文章


    authors: Liu X,Liu P,Chernock RD,Kuhs KAL,Lewis JS Jr,Luo J,Gay HA,Thorstad WL,Wang X

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  • Neurobiological Correlates and Predictors of Two Distinct Personality Trait Pathways to Escalated Alcohol Use.

    abstract:BACKGROUND:The delineation of the behavioral neurobiological mechanisms underlying the heterogeneous pathways for alcohol use disorders (AUDs) is ostensibly imperative for the development of more cost-effective treatments predicated on better understanding of this complex psychopathology. METHODS:1) Forty-eight high a...


    pub_type: 杂志文章


    authors: Shakra MA,Leyton M,Moghnieh H,Pruessner J,Dagher A,Pihl R

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  • Anthropogenic Carbon Nanotubes Found in the Airways of Parisian Children.

    abstract::Compelling evidence shows that fine particulate matters (PMs) from air pollution penetrate lower airways and are associated with adverse health effects even within concentrations below those recommended by the WHO. A paper reported a dose-dependent link between carbon content in alveolar macrophages (assessed only by ...


    pub_type: 杂志文章


    authors: Kolosnjaj-Tabi J,Just J,Hartman KB,Laoudi Y,Boudjemaa S,Alloyeau D,Szwarc H,Wilson LJ,Moussa F

    更新日期:2015-10-09 00:00:00

  • A Broadly Reactive Human Anti-hemagglutinin Stem Monoclonal Antibody That Inhibits Influenza A Virus Particle Release.

    abstract::Many broadly reactive human monoclonal antibodies against the hemagglutinin (HA) stem of influenza A virus have been developed for therapeutic applications. These antibodies typically inhibit viral entry steps, especially the HA conformational change that is required for membrane fusion. To better understand the mecha...


    pub_type: 杂志文章


    authors: Yamayoshi S,Uraki R,Ito M,Kiso M,Nakatsu S,Yasuhara A,Oishi K,Sasaki T,Ikuta K,Kawaoka Y

    更新日期:2017-03-01 00:00:00

  • Exosome Derived From Human Umbilical Cord Mesenchymal Stem Cell Mediates MiR-181c Attenuating Burn-induced Excessive Inflammation.

    abstract::Mesenchymal stem cell (MSC)-derived exosomes have diverse functions in regulating wound healing and inflammation; however, the molecular mechanism of human umbilical cord MSC (hUCMSC)-derived exosomes in regulating burn-induced inflammation is not well understood. We found that burn injury significantly increased the ...


    pub_type: 杂志文章


    authors: Li X,Liu L,Yang J,Yu Y,Chai J,Wang L,Ma L,Yin H

    更新日期:2016-06-01 00:00:00

  • Gut microbiota from colorectal cancer patients enhances the progression of intestinal adenoma in Apcmin/+ mice.

    abstract:BACKGROUND:Accumulating evidence points to a close relationship between gut dysbiosis and colorectal cancer (CRC). As >90% of CRC develop from adenoma, we aimed to investigate the crucial role of imbalanced gut microbiota on the progression of intestinal adenoma. METHODS:The Apcmin/+ mice gavage with phosphate-buffere...


    pub_type: 杂志文章


    authors: Li L,Li X,Zhong W,Yang M,Xu M,Sun Y,Ma J,Liu T,Song X,Dong W,Liu X,Chen Y,Liu Y,Abla Z,Liu W,Wang B,Jiang K,Cao H

    更新日期:2019-10-01 00:00:00

  • Visual Restoration after Cataract Surgery Promotes Functional and Structural Brain Recovery.

    abstract:BACKGROUND:Visual function and brain function decline concurrently with aging. Notably, cataract patients often present with accelerated age-related decreases in brain function, but the underlying mechanisms are still unclear. Optical structures of the anterior segment of the eyes, such as the lens and cornea, can be r...


    pub_type: 杂志文章


    authors: Lin H,Zhang L,Lin D,Chen W,Zhu Y,Chen C,Chan KC,Liu Y,Chen W

    更新日期:2018-04-01 00:00:00

  • Pathophysiologic Response to Burns in the Elderly.

    abstract::Over the last decades advancements have improved survival and outcomes of severely burned patients except one population, elderly. The Lethal Dose 50 (LD50) burn size in elderly has remained the same over the past three decades, and so has morbidity and mortality, despite the increased demand for elderly burn care. Th...


    pub_type: 杂志文章


    authors: Jeschke MG,Patsouris D,Stanojcic M,Abdullahi A,Rehou S,Pinto R,Chen P,Burnett M,Amini-Nik S

    更新日期:2015-07-31 00:00:00

  • Anti-Depressant Fluoxetine Reveals its Therapeutic Effect Via Astrocytes.

    abstract::Although psychotropic drugs act on neurons and glial cells, how glia respond, and whether glial responses are involved in therapeutic effects are poorly understood. Here, we show that fluoxetine (FLX), an anti-depressant, mediates its anti-depressive effect by increasing the gliotransmission of ATP. FLX increased ATP ...


    pub_type: 杂志文章


    authors: Kinoshita M,Hirayama Y,Fujishita K,Shibata K,Shinozaki Y,Shigetomi E,Takeda A,Le HPN,Hayashi H,Hiasa M,Moriyama Y,Ikenaka K,Tanaka KF,Koizumi S

    更新日期:2018-06-01 00:00:00

  • HIV Transmission Networks in the San Diego-Tijuana Border Region.

    abstract:BACKGROUND:HIV sequence data can be used to reconstruct local transmission networks. Along international borders, like the San Diego-Tijuana region, understanding the dynamics of HIV transmission across reported risks, racial/ethnic groups, and geography can help direct effective prevention efforts on both sides of the...


    pub_type: 杂志文章


    authors: Mehta SR,Wertheim JO,Brouwer KC,Wagner KD,Chaillon A,Strathdee S,Patterson TL,Rangel MG,Vargas M,Murrell B,Garfein R,Little SJ,Smith DM

    更新日期:2015-07-18 00:00:00

  • Genetic Variation in the Dopamine System Influences Intervention Outcome in Children with Cerebral Palsy.

    abstract:BACKGROUND:There is large variation in treatment responses in children with cerebral palsy. Experimental and clinical results suggest that dopamine neurotransmission and brain-derived neurotrophic factor (BDNF) signalling are involved in motor learning and plasticity, which are key factors in modern habilitation succes...


    pub_type: 临床试验,杂志文章


    authors: Diaz Heijtz R,Almeida R,Eliasson AC,Forssberg H

    更新日期:2018-02-01 00:00:00

  • The neuropeptide calcitonin gene-related peptide alpha is essential for bone healing.

    abstract:BACKGROUND:Impaired fracture healing represents an ongoing clinical challenge, as treatment options remain limited. Calcitonin gene-related peptide (CGRP), a neuropeptide targeted by emerging anti-migraine drugs, is also expressed in sensory nerve fibres innervating bone tissue. METHOD:Bone healing following a femoral...


    pub_type: 杂志文章


    authors: Appelt J,Baranowsky A,Jahn D,Yorgan T,Köhli P,Otto E,Farahani SK,Graef F,Fuchs M,Herrera A,Amling M,Schinke T,Frosch KH,Duda GN,Tsitsilonis S,Keller J

    更新日期:2020-09-01 00:00:00

  • Downregulation of circRNA DMNT3B contributes to diabetic retinal vascular dysfunction through targeting miR-20b-5p and BAMBI.

    abstract:BACKGROUND:Diabetic retinopathy, a vascular complication of diabetes mellitus, is the leading cause of visual impairment and blindness. circRNAs act as competing endogenous RNA, sponging target miRNA and thus influencing mRNA expression in vascular diseases. We investigated whether and how circDNMT3B is involved in ret...


    pub_type: 杂志文章


    authors: Zhu K,Hu X,Chen H,Li F,Yin N,Liu AL,Shan K,Qin YW,Huang X,Chang Q,Xu GZ,Wang Z

    更新日期:2019-11-01 00:00:00

  • Gene signatures of quiescent glioblastoma cells reveal mesenchymal shift and interactions with niche microenvironment.

    abstract:BACKGROUND:Glioblastoma (GBM), a highly malignant brain tumor, invariably recurs after therapy. Quiescent GBM cells represent a potential source of tumor recurrence, but little is known about their molecular underpinnings. METHODS:Patient-derived GBM cells were engineered by CRISPR/Cas9-assisted knock-in of an inducib...


    pub_type: 杂志文章


    authors: Tejero R,Huang Y,Katsyv I,Kluge M,Lin JY,Tome-Garcia J,Daviaud N,Wang Y,Zhang B,Tsankova NM,Friedel CC,Zou H,Friedel RH

    更新日期:2019-04-01 00:00:00

  • Crowdsourcing the General Public for Large Scale Molecular Pathology Studies in Cancer.

    abstract:BACKGROUND:Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public...


    pub_type: 杂志文章


    authors: Candido Dos Reis FJ,Lynn S,Ali HR,Eccles D,Hanby A,Provenzano E,Caldas C,Howat WJ,McDuffus LA,Liu B,Daley F,Coulson P,Vyas RJ,Harris LM,Owens JM,Carton AF,McQuillan JP,Paterson AM,Hirji Z,Christie SK,Holmes AR,S

    更新日期:2015-05-09 00:00:00

  • Safety, Tolerability, and Preliminary Efficacy of the Anti-Fibrotic Small Molecule PRI-724, a CBP/β-Catenin Inhibitor, in Patients with Hepatitis C Virus-related Cirrhosis: A Single-Center, Open-Label, Dose Escalation Phase 1 Trial.

    abstract:BACKGROUND:There is currently no anti-fibrotic drug therapy available to treat hepatitis C virus (HCV) cirrhosis. The aim of this study was to assess the safety, tolerability, and anti-fibrotic effect of PRI-724, a small-molecule modulator of Wnt signaling, in patients with HCV cirrhosis. METHODS:In this single-center...


    pub_type: 杂志文章


    authors: Kimura K,Ikoma A,Shibakawa M,Shimoda S,Harada K,Saio M,Imamura J,Osawa Y,Kimura M,Nishikawa K,Okusaka T,Morita S,Inoue K,Kanto T,Todaka K,Nakanishi Y,Kohara M,Mizokami M

    更新日期:2017-09-01 00:00:00

  • Urinary Metabolomics Identifies a Molecular Correlate of Interstitial Cystitis/Bladder Pain Syndrome in a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Cohort.

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    pub_type: 杂志文章


    authors: Parker KS,Crowley JR,Stephens-Shields AJ,van Bokhoven A,Lucia MS,Lai HH,Andriole GL,Hooton TM,Mullins C,Henderson JP

    更新日期:2016-05-01 00:00:00

  • Two years of treatment with the recombinant grass pollen allergy vaccine BM32 induces a continuously increasing allergen-specific IgG4 response.

    abstract:BACKGROUND:BM32, a grass pollen allergy vaccine containing four recombinant fusion proteins consisting of hepatitis B-derived PreS and hypoallergenic peptides from the major timothy grass pollen allergens adsorbed on aluminium hydroxide has been shown to be safe and to improve clinical symptoms of grass pollen allergy ...


    pub_type: 杂志文章


    authors: Eckl-Dorna J,Weber M,Stanek V,Linhart B,Ristl R,Waltl EE,Villazala-Merino S,Hummel A,Focke-Tejkl M,Froeschel R,Neubauer A,Henning R,Perkmann T,Valenta R,Niederberger V

    更新日期:2019-12-01 00:00:00