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Sesquiterpene coumarins from Ferula samarkandica Korovin and their bioactivity.

Phytochemistry 2021 May 3;187:112705. Epub 2021 May 3.

The State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization and Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing South Road 40-1, Urumqi, 830011, China. Electronic address:

Phytochemical study on the ethanolic extract of the dried roots of Ferula samarkandica Korovin led to the isolation of nine undiscribed sesquiterpene coumarins, samarcandicins A-I, along with thirteen known sesquiterpene coumarins. Their structures were characterized by detailed spectroscopic analysis including NMR and HR-ESI-MS. Mogoltacin and nevskin exhibited high inhibitory activity against MV-4-11 cell with IC values of 3. Read More

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pH-tunable nanoparticles composed of copolymers of lactide and allyl-glycidyl ether with various functionalities for the efficient delivery of anti-cancer drugs.

Colloids Surf B Biointerfaces 2021 Apr 29;204:111801. Epub 2021 Apr 29.

Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363, Łódź, Poland. Electronic address:

The designing of biocompatible nanocarriers for the efficient delivery of their cargos to the desired targets remains a challenge. In this regard, the most promising strategy relies on the construction of pH- or thermo-responsive nanoparticles (NPs). However, it is also important to preserve the balance between the responsiveness of the carrier and their stability in physiological conditions. Read More

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Discovery of new inhibitor for the protein arginine deiminase type 4 (PAD4) by rational design of α-enolase-derived peptides.

Comput Biol Chem 2021 Apr 23;92:107487. Epub 2021 Apr 23.

Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400, UPM, Serdang, Malaysia. Electronic address:

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease affecting about 0.24 % of the world population. Protein arginine deiminase type 4 (PAD4) is believed to be responsible for the occurrence of RA by catalyzing citrullination of proteins. Read More

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Design, synthesis, and biological evaluation of novel dual inhibitors targeting lysine specific demethylase 1 (LSD1) and histone deacetylases (HDAC) for treatment of gastric cancer.

Eur J Med Chem 2021 Apr 25;220:113453. Epub 2021 Apr 25.

School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, 453003, China. Electronic address:

LSD1 and HDAC are physical and functional related to each other in various human cancers and simultaneous pharmacological inhibition of LSD1 and HDAC exerts synergistic anti-cancer effects. In this work, a series of novel LSD1/HDAC bifunctional inhibitors with a styrylpyridine skeleton were designed and synthesized based on our previously reported LSD1 inhibitors. The representative compounds 5d and 5m showed potent activity against LSD1 and HDAC at both molecular and cellular level and displayed high selectivity against MAO-A/B. Read More

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Promotion of the anticancer activity of curcumin based on a metal-polyphenol networks delivery system.

Int J Pharm 2021 May 3:120650. Epub 2021 May 3.

College of Food Science, Southwest University, Chongqing, 400715, People's Republic of China; Research Center of Food Storage & Logistics, Southwest University, Chongqing 400715, People's Republic of China. Electronic address:

Curcumin (Cur), a hydrophobic active pharmaceutical ingredient with high anticancer activity, has poor water solubility and low bioavailability. Although many delivery systems have been developed to improve their bioavailability, some limitation such as low drug loading efficiency and poor stability are still remained. The metal-polyphenol networks (MPNs) delivery system designed in this subject solved above problems and effectively improved the anticancer activity of Cur. Read More

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The Cell-impermeable Ru(II) Polypyridyl Complex as a Potent Intracellular Photosensitizer under Visible Light Irradiation via Ion-Pairing with Suitable Lipophilic Counter-Anions.

Free Radic Biol Med 2021 May 3. Epub 2021 May 3.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, And University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, 100085, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China; Joint Institute for Environmental Science, Research Center for Eco-Environmental Sciences and Hong Kong Baptist University, Hong Kong PR China. Electronic address:

Developing the cell-impermeable Ru(II) polypyridyl cationic complexes as effective photosensitizers (PS) which have high cellular uptake and photo-toxicity, but low dark toxicity, is quite challenging. Here we found that the highly reactive singlet oxygen (O) can be generated by the irradiation of a typical Ru(II) polypyridyl complex Ru(II)tris(tetramethylphenanthroline) ([Ru(TMP)]) under visible light irradiation by ESR with TEMPO (2,2,6,6-tetramethyl-4-piperidone-N-oxyl) as O probe. Effective cellular and nuclear delivery of cationic [Ru(TMP)] was achieved through our recently developed ion-pairing method, and 2,3,4,5-tetrachlorophenol (2,3,4,5-TeCP) was found to be the most effective among all chlorophenols tested. Read More

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Preparation and in-vitro evaluation of mesoporous biogenic silica nanoparticles obtained from rice and wheat husk as a biocompatible carrier for anti-cancer drug delivery.

Eur J Pharm Sci 2021 May 3:105866. Epub 2021 May 3.

Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.

In this study, mesoporous silica nanocarriers were synthesized from natural sources such as rice and wheat husk for drug delivery application. First, the biogenic silica in cereals husk was extracted by acid leaching and then converted to sodium silicate as a silica precursor. Mesoporous silica nanoparticles were then synthesized by adding sodium silicate to the template mixture by continuous and discrete modes during the sol-gel process. Read More

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Pseudoginsenoside-F11 ameliorates okadiac acid-induced learning and memory impairment in rats via modulating protein phosphatase 2A.

Mech Ageing Dev 2021 May 3:111496. Epub 2021 May 3.

Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address:

We have reported that pseudoginsenoside-F11 (PF11) can significantly improve the cognitive impairments in several Alzheimer's disease (AD) models, but the mechanism has not been fully elucidated. In the present study, the effects of PF11 on AD, in particular the underlying mechanisms related with protein phosphatase 2A (PP2A), were investigated in a rat model induced by okadaic acid (OA), a selective inhibitor of PP2A. The results showed that PF11 treatment dose-dependently improved the learning and memory impairments in OA-induced AD rats. Read More

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Anti-inflammatory Effects of Three Withanolides Isolated from Physalis angulata L. in LPS-activated RAW 264.7 Cells through Blocking NF-κB Signaling Pathway.

J Ethnopharmacol 2021 May 3:114186. Epub 2021 May 3.

Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, Yantai, 264005, PR China. Electronic address:

Ethnopharmacological Relevance: Physalis angulata L. is commonly used in many countries as popular medicine for the treatment of a variety of diseases such as malaria, hepatitis, dermatitis and rheumatism. But the anti-inflammatory active constituents of this medicinal plant and their molecular mechanism are still not elucidated clearly. Read More

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Electrohydrodynamic Atomisation Driven Design and Engineering of Opportunistic Particulate Systems For Applications in Drug Delivery, Therapeutics and Pharmaceutics.

Adv Drug Deliv Rev 2021 May 3. Epub 2021 May 3.

The Leicester School of Pharmacy, De Montfort University, Leicester, UK. Electronic address:

Electrohydrodynamic atomisation (EHDA) technologies have evolved significantly over the past decade; branching into several established and emerging healthcare remits through timely advances in the engineering sciences and tailored conceptual process designs. More specifically for pharmaceutical and drug delivery spheres, electrospraying (ES) has presented itself as a high value technique enabling a plethora of different particulate structures. However, when coupled with novel formulations (e. Read More

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Modulation of Akt vs Stat3 activity by the focal adhesion kinase in non-neoplastic mouse fibroblasts.

Exp Cell Res 2021 May 3:112601. Epub 2021 May 3.

Department of Biomedical and Molecular Sciences and Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada K7L 3N6.

Adhesion of cells to each other and to the extracellular matrix (ECM) are both required for cellular functions. Cell-to-cell adhesion is mediated by cadherins and their engagement triggers the activation of Stat3, which offers a potent survival signal. Adhesion to the ECM on the other hand, activates FAK which attracts and activates Src, as well as receptor tyrosine kinases (RTKs), the PI3k/Akt and Ras/Erk pathways. Read More

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Nitazoxanide impairs mitophagy flux through ROS-mediated mitophagy initiation and lysosomal dysfunction in bladder cancer.

Biochem Pharmacol 2021 May 3:114588. Epub 2021 May 3.

Institute of Urology, The Third Affiliated Hospital of Shenzhen University (Luohu Hospital Group), Shenzhen 518000, China; Shenzhen Following Precision Medical Research Institute, Luohu Hospital Group, Shenzhen 518000, China; Teaching Center of Shenzhen Luohu Hospital, Shantou University Medical College, Shenzhen 518000, China; Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China. Electronic address:

Bladder cancer is one of the most common malignancy in the urinary tract with high recurrence and drug resistance in clinics. Alternative treatments from existing drugs might be a promising strategy. Nitazoxanide (NTZ), an FDA-approved antiprotozoal drug, has got increasingly noticed because of its favorable safety profile and antitumor potential, yet the effects in bladder cancer and underlying mechanisms remain poorly understood. Read More

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Integration of temporal single cell cellular stress response activity with Logic-ODE modeling reveals activation of ATF4-CHOP axis as a critical predictor of drug-induced liver injury.

Biochem Pharmacol 2021 May 3:114591. Epub 2021 May 3.

Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands. Electronic address:

Drug-induced liver injury (DILI) is the most prevalent adversity encountered in drug development and clinical settings leading to urgent needs to understand the underlying mechanisms. In this study, we have systematically investigated the dynamics of the activation of cellular stress response pathways and cell death outcomes upon exposure of a panel of liver toxicants using live cell imaging of fluorescent reporter cell lines. We established a comprehensive temporal dynamic response profile of a large set of BAC-GFP HepG2 cell lines representing the following components of stress signaling: i) unfolded protein response (UPR) [ATF4, XBP1, BIP and CHOP]; ii) oxidative stress [NRF2, SRXN1, HMOX1]; iii) DNA damage [P53, P21, BTG2, MDM2]; and iv) NF-κB pathway [A20, ICAM1]. Read More

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Evolving cryo-EM structural approaches for GPCR drug discovery.

Structure 2021 May 2. Epub 2021 May 2.

Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, VIC, Australia; ARC Centre for Cryo-Electron Microscopy of Membrane Proteins, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, VIC, Australia. Electronic address:

G protein-coupled receptors (GPCRs) are the largest class of cell surface drug targets. Advances in stabilization of GPCR:transducer complexes, together with improvements in cryoelectron microscopy (cryo-EM) have recently been applied to structure-assisted drug design for GPCR agonists. Nonetheless, limitations in the commercial application of these approaches, including the use of nanobody 35 (Nb35) to aid complex stabilization and the high cost of 300 kV imaging, have restricted broad application of cryo-EM in drug discovery. Read More

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Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications.

Med Res Rev 2021 May 6. Epub 2021 May 6.

Department of Neurology and State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.

Ischemic stroke caused by arterial occlusion is the most common type of stroke, which is among the most frequent causes of disability and death worldwide. Current treatment approaches involve achieving rapid reperfusion either pharmacologically or surgically, both of which are time-sensitive; moreover, blood flow recanalization often causes ischemia/reperfusion injury. However, even though neuroprotective intervention is urgently needed in the event of stroke, the exact mechanisms of neuronal death during ischemic stroke are still unclear, and consequently, the capacity for drug development has remained limited. Read More

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Adverse immunological responses against non-viral nanoparticle (NP) delivery systems in the lung.

J Immunotoxicol 2021 Dec;18(1):61-73

Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.

There is a large, unmet medical need to treat chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis and other respiratory diseases. New modalities are being developed, including gene therapy which treats the disease at the DNA/RNA level. Despite recent innovations in non-viral gene therapy delivery for chronic respiratory diseases, unwanted or adverse interactions with immune cells, particularly macrophages, can limit drug efficacy. Read More

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December 2021

Effect of Pharmaceutical Excipients on Intestinal Absorption of Metformin via Organic Cation-Selective Transporters.

Mol Pharm 2021 May 6. Epub 2021 May 6.

Department of Pharmaceutical Analysis, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.

Growing evidence has shown that some pharmaceutical excipients can act on drug transporters. The present study was aimed at investigating the effects of 13 commonly used excipients on the intestinal absorption of metformin (MTF) and the underlying mechanisms using Caco-2 cells and an mouse non-everted gut sac model. First, the uptake of MTF in Caco-2 cells was markedly inhibited by nonionic excipients including Solutol HS 15, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, and crospovidone. Read More

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Inverse agonism at the Na/K-ATPase receptor reverses EMT in prostate cancer cells.

Prostate 2021 May 6. Epub 2021 May 6.

Marshall Institute for Interdisciplinary Research (MIIR), Marshall University, Huntington, West Virginia, USA.

The surface expression of Na/K-ATPase α1 (NKA) is significantly reduced in primary prostate tumors and further decreased in bone metastatic lesions. Here, we show that the loss of cell surface expression of NKA induces epithelial-mesenchymal transition (EMT) and promotes metastatic potential and tumor growth of prostate cancer (PCa) by decreasing the expression of E-cadherin and increasing c-Myc expression via the activation of Src/FAK pathways. Mechanistically, reduced surface expression of NKA in PCa is due to increased endocytosis through the activation of NKA/Src receptor complex. Read More

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Intratympanic Lipopolysaccharide Elevates Systemic Fluorescent Gentamicin Uptake in the Cochlea.

Laryngoscope 2021 May 6. Epub 2021 May 6.

Research Service, VA Loma Linda Healthcare System, Loma Linda, California, U.S.A.

Objectives/hypothesis: Lipopolysaccharide (LPS), a key component of bacterial endotoxins, activates macrophages and triggers the release of inflammatory cytokines in mammalian tissues. Recent studies have shown that intratympanic injection of LPS simulates acute otitis media (AOM) and results in morphological and functional changes in the inner ear. Here we established an AOM mouse model with LPS to investigate the uptake of ototoxic gentamicin in the inner ear, and elucidated the underlying mechanism by focusing on cochlear inflammation as a result of AOM. Read More

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Effects of Itraconazole and Micafungin on Aspergillus fumigatus Biofilms.

Mycopathologia 2021 May 6. Epub 2021 May 6.

Institute of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College, 12 Jiangwangmiao Street, Nanjing, 210042, Jiangsu, China.

Aspergillus fumigatus (A. fumigatus) is the most common airborne opportunistic fungal pathogen. Biofilm formation is one of the main pathogenic mechanisms of A. Read More

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Bioactive polyketides from the pathogenic fungus of Epicoccum sorghinum.

Planta 2021 May 6;253(6):116. Epub 2021 May 6.

Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.

Main Conclusion: We discovered and identified a series of characteristic substances, including one new polyketide, epicorepoxydon B, of the important pathogenic fungus, Epicoccum sorghinum, of sorghum. The fungal extract and some isolated polyketides are sensitive to a malignant triple-negative breast cancer cell line, MDA-MB-231. Sorghum (Kaoliang) grain is an important crop with high economic value and several applications. Read More

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Genome-wide Screening of Genes Associated with Momilactone B Sensitivity in the Fission Yeast.

G3 (Bethesda) 2021 May 6. Epub 2021 May 6.

Agro-Biotechnology Research Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.

Momilactone B is a natural product with dual biological activities, including antimicrobial and allelopathic properties, and play a major role in plant chemical defense against competitive plants and pathogens. The pharmacological effects of momilactone B on mammalian cells have also been reported. However, little is known about the molecular and cellular mechanisms underlying its broad bioactivity. Read More

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Nivolumab vs Pembrolizumab for Treatment of US Patients With Platinum-Refractory Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Network Meta-analysis and Cost-effectiveness Analysis.

JAMA Netw Open 2021 May 3;4(5):e218065. Epub 2021 May 3.

Medical Decision and Economic Group, Department of Pharmacy, South Campus, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Importance: Nivolumab and pembrolizumab are approved for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Physicians and patients are uncertain which drug is preferable, rendering a cost-effectiveness comparison between them necessary.

Objective: To evaluate the cost-effectiveness of nivolumab vs pembrolizumab in treating platinum-refractory R/M HNSCC. Read More

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Palladium-catalyzed one-pot phosphorylation of phenols mediated by sulfuryl fluoride.

Chem Commun (Camb) 2021 May;57(37):4588-4591

Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China.

We report a general palladium-catalyzed one-pot procedure for the synthesis of phosphonates, phosphinates and phosphine oxides from phenols mediated by sulfuryl fluoride. It features mild conditions, broad substrate scope, high functionality tolerance and water insensitivity. The utility of this procedure has been well demonstrated by gram-scale synthesis, sequential synthesis of click chemistry building blocks, late-stage decoration of drugs and natural products and on-DNA synthesis of phosphine oxide for a DNA-encoded library (DEL). Read More

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Amino acid-based HS donors: -thiocarboxyanhydrides that release HS with innocuous byproducts.

Chem Commun (Camb) 2021 May 6. Epub 2021 May 6.

Department of Chemistry, Virginia Tech Center for Drug Discovery, and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA 24061, USA.

A library of N-thiocarboxyanhydrides (NTAs) derived from natural amino acids with benign byproducts and controlled H2S-release kinetics is reported. Minimal acute in vitro toxicity was observed in multiple cell lines, while longer-term toxicity in cancer cells was observed, with slow-releasing donors exhibiting the greatest cytotoxic effects. Read More

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HDAC inhibitor, MS-275, increases vascular permeability by suppressing Robo4 expression in endothelial cells.

Tissue Barriers 2021 May 6:1911195. Epub 2021 May 6.

Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.

Roundabout guidance receptor 4 (Robo4) is an endothelial-specific membrane protein that suppresses pathological angiogenesis and vascular hyperpermeability by stabilizing endothelial cells. Robo4 suppresses severe systemic inflammation induced by pathogens and endotoxins and inhibits tumor growth and metastasis, therefore serving as a potential therapeutic target. Although the regulation of Robo4 expression through transcription factors and epigenetic mechanisms has been studied, the role of histone deacetylases (HDACs) has not been explored. Read More

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miR-1/133a and miR-206/133b clusters overcome HGF induced gefitinib resistance in non-small cell lung cancers with EGFR sensitive mutations.

J Drug Target 2021 May 6:1-14. Epub 2021 May 6.

The First Clinical Medical College, Wenzhou Medical University, Wenzhou 325000, China.

It has been reported that clustered miRNAs can be transcribed coordinately and exhibit similar functions by regulating the same targets. miR-1/133a and miR-206/133b are well characterized miRNA clusters. However, the effect of these clusters on EGFR-TKI resistance is not clear. Read More

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Probiotic Supplementation Improved Capecitabine Protective Effect against Gastric Cancer Growth in Male BALB/c Mice.

Nutr Cancer 2020 Oct 14:1-11. Epub 2020 Oct 14.

Department of Pathology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.

The gastric cancer (GC) is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Herein, we studied the effects of probiotics () on subcutaneous implantation of xenograft GC. Moreover, the effect of probiotics () was compared with the capecitabine drug as known used drug against GC. Read More

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October 2020

Photoelectric Bacteria Enhance the Production of Tetrodotoxin for Antitumor Therapy.

Nano Lett 2021 May 6. Epub 2021 May 6.

Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, P.R. China.

Engineered bacteria are promising bioagents to synthesize antitumor drugs at tumor sites with the advantages of avoiding drug leakage and degradation during delivery. Here, we report an optically controlled material-assisted microbial system by biosynthesizing gold nanoparticles (AuNPs) on the surface of K3259 () to obtain Bac@Au. Leveraging the dual directional electron transport mechanism of , the hybrid biosystem enhances synthesis of antineoplastic tetrodotoxin (TTX) for a promising antitumor effect. Read More

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N -methyladenosine Steers RNA Metabolism and Regulation in Cancer.

Cancer Commun (Lond) 2021 May 6. Epub 2021 May 6.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P. R. China.

As one of the most studied ribonucleic acid (RNA) modifications in eukaryotes, N -methyladenosine (m A) has been shown to play a predominant role in controlling gene expression and influence physiological and pathological processes such as oncogenesis and tumor progression. Writer and eraser proteins, acting opposite to deposit and remove m A epigenetic marks, respectively, shape the cellular m A landscape, while reader proteins preferentially recognize m A modifications and mediate fate decision of the methylated RNAs, including RNA synthesis, splicing, exportation, translation, and stability. Therefore, RNA metabolism in cells is greatly influenced by these three classes of m A regulators. Read More

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