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JOURNAL ARTICLE
Ying Han, Siyuan Ling, Shuangqing Hu, Genxiang Shen, Hongchang Zhang, Wei Zhang
Decabromodiphenyl ether (BDE-209) is a common brominated flame retardant in electronic waste, and nano zero-valent iron (nZVI) is a new material in the field of environmental remediation. Little is known about how BDE-209 and nZVI combined exposure influences soil organisms. During the 28 days study, we determined the effects of single and combined exposures to BDE-209 and nZVI on the oxidative stress and metabolic response of earthworms (Eisenia fetida). On day 7, compared to CK, malondialdehyde (MDA) content increased in most combined exposure groups...
March 26, 2024: Science of the Total Environment
#22
JOURNAL ARTICLE
Michaela Serpi, Samule di Ciano, Fabrizio Pertusati
Aryloxy phosphoroamidate triesters, known as ProTides, are a class of prodrugs developed to enhance the physicochemical and pharmacological properties of therapeutic nucleosides. This approach has been extensively investigated in the antiviral and anticancer areas leading to three prodrugs on the market and several others in clinical stage. In this article we have prepared the PS analogues of three ProTides that have reached the clinic as anticancer agents. These novel PS ProTides were tested for their capacity in enzymatic activation and for their cytotoxic properties against a panel of solid and liquid tumor cell lines...
March 25, 2024: Bioorganic & Medicinal Chemistry
#23
REVIEW
Debjit Khan, Paul L Fox
Viruses are obligate, intracellular parasites that co-opt host cell machineries for propagation. Critical among these machineries are those that translate RNA into protein and their mechanisms of control. Most regulatory mechanisms effectuate their activity by targeting sequence or structural features at the RNA termini, i.e., at the 5' or 3' ends, including the untranslated regions (UTRs). Translation of most eukaryotic mRNAs is initiated by 5' cap-dependent scanning. In contrast, many viruses initiate translation at internal RNA regions at internal ribosome entry sites (IRESs)...
March 20, 2024: Viruses
#24
JOURNAL ARTICLE
Yanqing Yang, Jinping Dai, Guozhi Zhang, Deepali Singh, Xiaoxia Zhang, Zhenpu Liang
Baculovirus infection can prevent the pupation of insects. Juvenile hormone (JH) plays a vital role in regulating insect molting and metamorphosis. However, the molecular mechanism of baculovirus preventing the pupation of larvae by regulating the Juvenile hormone (JH) pathway is still unclear. In this study, we found that the Mamestra brassicae multiple nucleopolyhedroviruses (MbMNPV) infection prolonged the larval stage of fourth instar Helicoverpa armigera ( H. armigera ) by 0.52 d and caused an increase in JH titer...
March 18, 2024: Insects
#25
JOURNAL ARTICLE
Jay Z Yin, Alexander F A Keszei, Scott Houliston, Frantisek Filandr, Jonah Beenstock, Salima Daou, Julia Kitaygorodsky, David C Schriemer, Mohammad T Mazhab-Jafari, Anne-Claude Gingras, Frank Sicheri
GCN2 is a stress response kinase that phosphorylates the translation initiation factor eIF2α to inhibit general protein synthesis when activated by uncharged tRNA and stalled ribosomes. The presence of a HisRS-like domain in GCN2, normally associated with tRNA aminoacylation, led to the hypothesis that eIF2α kinase activity is regulated by the direct binding of this domain to uncharged tRNA. Here we solved the structure of the HisRS-like domain in the context of full-length GCN2 by cryoEM. Structure and function analysis shows the HisRS-like domain of GCN2 has lost histidine and ATP binding but retains tRNA binding abilities...
March 22, 2024: Structure
#26
Hsin-Pin Lin, Jennifer D Petersen, Alexandra J Gilsrud, Angelo Madruga, Theresa M D'Silva, Xiaoping Huang, Mario K Shammas, Nicholas P Randolph, Yan Li, Drew R Jones, Michael E Pacold, Derek P Narendra
Mitochondrial dysfunction causes devastating disorders, including mitochondrial myopathy. Here, we identified that diverse mitochondrial myopathy models elicit a protective mitochondrial integrated stress response (mt-ISR), mediated by OMA1-DELE1 signaling. The response was similar following disruptions in mtDNA maintenance, from knockout of Tfam , and mitochondrial protein unfolding, from disease-causing mutations in CHCHD10 (G58R and S59L). The preponderance of the response was directed at upregulating pathways for aminoacyl-tRNA biosynthesis, the intermediates for protein synthesis, and was similar in heart and skeletal muscle but more limited in brown adipose challenged with cold stress...
February 29, 2024: bioRxiv
#27
JOURNAL ARTICLE
Fouzia Nasim, Muppidi Shravan Kumar, Mallika Alvala, Insaf Ahmed Qureshi
Aminoacylation by tRNA synthetase is a crucial part of protein synthesis and is widely recognized as a therapeutic target for drug development. Unlike the arginyl-tRNA synthetases (ArgRSs) reported previously, here, we report an ArgRS of Leishmania donovani (LdArgRS) that can follow the canonical two-step aminoacylation process. Since a previously uncharacterized insertion region is present within its catalytic domain, we implemented the splicing by overlap extension PCR (SOE-PCR) method to create a deletion mutant (ΔIns-LdArgRS) devoid of this region to investigate its function...
March 25, 2024: FEBS Journal
#28
JOURNAL ARTICLE
Suzuka Matsuoka, Keiichi Fujiwara, Yuki Takigawa, Saki Ito, Sho Mitsumune, Keisuke Shiraha, Mayu Goda, Tomoyoshi Inoue, Miho Fujiwara, Eri Nakamura, Hiromi Watanabe, Kenichiro Kudo, Akiko Sato, Ken Sato, Takuo Shibayama
A 70-year-old woman with anti-aminoacyl-tRNA synthetase (ARS) antibody-positive interstitial lung disease (ARS-ILD) received daily medications and regular cyclophosphamide cycles for recurring exacerbations. Approximately four years after immunosuppression initiation, the patient was admitted for progressive dyspnea on exertion. Chest computed tomography (CT) findings were suggestive of acute exacerbation. Despite intensified immunosuppressive treatment, the radiographic findings worsened, and serum Krebs von den Lungen-6 (KL-6) levels increased...
March 25, 2024: Internal Medicine
#29
JOURNAL ARTICLE
Karla N Piedl, Paul J Arcoria, Felicia A Etzkorn
Serine-proline (Ser-Pro) backbone-modified dipeptide analogues are powerful tools to investigate the role of cis-trans isomerization in the regulation of the cell cycle and transcription. These studies have previously been limited to synthetic peptides, whose synthesis is a challenge for larger peptides due to the compounding yield loss incurred in each step. We now introduce a method for the aminoacylation of tRNA with dipeptides and dipeptide analogs to permit the installation of cis- and trans-locked Ser-Pro analogues into full-length proteins...
March 2024: Current protocols
#30
REVIEW
YouJin Kim, Suho Cho, Joo-Chan Kim, Hee-Sung Park
The advancement of genetic code expansion (GCE) technology is attributed to the establishment of specific aminoacyl-tRNA synthetase/tRNA pairs. While earlier improvements mainly focused on aminoacyl-tRNA synthetases, recent studies have highlighted the importance of optimizing tRNA sequences to enhance both unnatural amino acid incorporation efficiency and orthogonality. Given the crucial role of tRNAs in the translation process and their substantial impact on overall GCE efficiency, ongoing efforts are dedicated to the development of tRNA engineering techniques...
2024: Frontiers in Genetics
#31
JOURNAL ARTICLE
Haixia Zang, Yijia Cheng, Mengjia Li, Lin Zhou, Li-Li Hong, Hai Deng, Hou-Wen Lin, Yongjun Zhou
BACKGROUND: Natural tetramates are a family of hybrid polyketides bearing tetramic acid (pyrrolidine-2,4-dione) moiety exhibiting a broad range of bioactivities. Biosynthesis of tetramates in microorganisms is normally directed by hybrid polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) machineries, which form the tetramic acid ring by recruiting trans- or cis-acting thioesterase-like Dieckmann cyclase in bacteria. There are a group of tetramates with unique skeleton of 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione, which remain to be investigated for their biosynthetic logics...
March 21, 2024: Microbial Cell Factories
#32
JOURNAL ARTICLE
Jing Wenguang, Lin Xiaoyu, L I Chu, Zhao Xiaoliang, Cheng Xianlong, Wang Penglong, Wei Feng, M A Shuangcheng
OBJECTIVE: To explore the anti-inflammatory components and mechanism of the non-volatile ingredients of patchouli. METHODS: High performance liquid chromatography-heated electron spray ionization-high resolution mass spectroscope (HPLC-HESI-HRMS) was used to analyze the chemical constituents of the non-volatile ingredients of patchouli. The anti-inflammatory activity of ingredients was evaluated using lipopolysaccharide (LPS) induced RAW264.7 cell inflammation model, and the anti-inflammatory mechanism was investigated using multivariate statistical analysis of cell metabolomics...
April 2024: Journal of Traditional Chinese Medicine
#33
JOURNAL ARTICLE
Yáskara Veruska Ribeiro Barros, Amanda Onduras de Andrade, Larissa Pereira Dantas da Silva, Lucas Aleixo Leal Pedroza, Iverson Conrado Bezerra, Iago Dillion Lima Cavalcanti, Mariane Cajuba de Britto Lira Nogueira, Kristiana Cerqueira Mousinho, Angelo Roberto Antoniolli, Luiz Carlos Alves, José Luiz de Lima Filho, Alexandre Varão Moura, Álex Aparecido Rosini Silva, Andréia de Melo Porcari, Priscila Gubert
INTRODUCTION: Bee venom has therapeutics and pharmacological properties. Further toxicological studies on animal models are necessary due to the severe allergic reactions caused by this product. METHOD: Here, Caenorhabditis elegans was used as an in vivo toxicity model, while breast cancer cells were used to evaluate the pharmacological benefits. The bee venom utilized in this research was collected from Apis mellifera species found in Northeast Brazil. The cytotoxicity caused by bee venom was measured by MTT assay on MDA-MB-231 and J774 A...
March 15, 2024: Anti-cancer Agents in Medicinal Chemistry
#34
JOURNAL ARTICLE
Danique Beijer, Sheila Marte, Jiaxin C Li, Willem De Ridder, Jessie Z Chen, Abigail L D Tadenev, Kathy E Miers, Tine Deconinck, Richard Macdonell, Wilson Marques, Peter De Jonghe, Samia L Pratt, Rebecca Meyer-Schuman, Stephan Züchner, Anthony Antonellis, Robert W Burgess, Jonathan Baets
Pathogenic variants in six aminoacyl-tRNA synthetase (ARS) genes are implicated in neurological disorders, most notably inherited peripheral neuropathies. ARSs are enzymes that charge tRNA molecules with cognate amino acids. Pathogenic variants in asparaginyl-tRNA synthetase ( NARS1 ) cause a neurological phenotype combining developmental delay, ataxia and demyelinating peripheral neuropathy. NARS1 has not yet been linked to axonal Charcot-Marie-Tooth disease. Exome sequencing of patients with inherited peripheral neuropathies revealed three previously unreported heterozygous NARS1 variants in three families...
2024: Brain communications
#35
JOURNAL ARTICLE
Ying Hao, Bingcheng Wang, Yuan Feng, Xiaodong Xin, Yawei Deng, Mingsong Liu, Chunhua Li, Shiqiao Liu, Qingqing Zhang
To analyze the metabolites (blood, urine and feces) in normal rats after intragastric administration of the decoction of Phellodendri Amurensis Cortex (PAC) and to map the metabolic profile of PAC in vivo of rat; meanwhile, to evaluate the anti-rheumatoid arthritis (RA) effect of PAC by blood metabolomics technique and to explore its mechanism. Performing on UPLC-Q-TOF-MS technology with a Waters ACQUITY UPLC BEH-C18 column (100 mm × 2.1 mm, 1.7 μm), the mobile phase was acetonitrile-0...
February 27, 2024: Journal of Pharmaceutical and Biomedical Analysis
#36
JOURNAL ARTICLE
Tianxian Liu, Mingya Zhang, Yameng Fan, Lei Zhao, Dan Huang, Liuchang Zhao, Minjia Tan, Bang-Ce Ye, Jun-Yu Xu
Lysine acylation has been extensively investigated due to its regulatory role in a diverse range of biological functions across prokaryotic and eukaryotic species. In-depth acylomic profiles have the potential to enhance comprehension of the biological implications of organisms. However, the extent of research on global acylation profiles in microorganisms is limited. Here, four lysine acylomes were conducted in Bacillus thuringiensis by using the LC-MS/MS based proteomics combined with antibody-enrichment strategies, and a total of 3438 acetylated sites, 5797 propionylated sites, 1705 succinylated sites, and 925 malonylated sites were identified...
March 15, 2024: Proteomics
#37
JOURNAL ARTICLE
Shuaichen Liu, Lan Hong, Song Zhang, Yuxin Tian, Yuchen Wang, Duanduan Zhao, Jingheng Lv, Jingjing Zhuang, Hongyan Xu, Guangjun Xia
This study investigated the regulatory effects of Sporisorium reilianum polysaccharides (SRPS) on metabolism and the intestinal barrier in mice with colitis induced by dextran sulfate sodium (DSS). SRPS were resistant to the digestion of saliva, gastric juices, and intestinal fluid. SRPS significantly reduced the disease activity index and inhibited DSS-induced colon shortening. The expression of proinflammatory cytokines in the colon was normal (P < 0.05). Acetic acid, propionic acid, butyric acid, isobutyric acid, and isovaleric acid contents increased...
March 13, 2024: International Journal of Biological Macromolecules
#38
JOURNAL ARTICLE
Tsuneo Sasai, Yuki Ishikawa, Ran Nakashima, Takuya Isayama, Kiminobu Tanizawa, Tomohiro Handa, Mirei Shirakashi, Ryosuke Hiwa, Hideaki Tsuji, Koji Kitagori, Shuji Akizuki, Hajime Yoshifuji, Tsuneyo Mimori, Akio Morinobu
Anti-aminoacyl-tRNA synthetase (ARS) antibodies are myositis-specific antibodies associated with anti-synthetase syndrome (ASSD). Some patients are positive for anti-ARS antibodies on enzyme-linked immunosorbent assay (ELISA) but negative on RNA-immunoprecipitation (RNA-IP) (the gold standard method). Whether these patients should be considered truly positive for anti-ARS antibodies remains unclear. Therefore, we investigated the clinical characteristics of these patients and verified the authenticity of their anti-ARS positivity...
March 15, 2024: Immunological Medicine
#39
JOURNAL ARTICLE
Anna-Lena Feldberg, Florian Mayerthaler, Jennifer Rüschenbaum, Jonas Kröger, Henning D Mootz
In multi-domain nonribosomal peptide synthetases (NRPSs) the order of domains and their catalytic specificities dictate the structure of the peptide product. Peptidyl-carrier proteins (PCPs) bind activated amino acids and channel elongating peptidyl intermediates along the protein template. To this end, fine-tuned interactions with the catalytic domains and large-scale PCP translocations are necessary. Despite crystal structure snapshots of several PCP-domain interactions, the conformational dynamics under catalytic conditions in solution remain poorly understood...
March 15, 2024: Angewandte Chemie
#40
MULTICENTER STUDY
Aravinthan Loganathan, Giovanni Zanframundo, Akira Yoshida, Sara Faghihi-Kashani, Iazsmin Bauer Ventura, Eduardo Dourado, Francisca Bozan, Gianluca Sambataro, Yasuhiko Yamano, Sharon Sangmee Bae, Darosa Lim, Angela Ceribelli, Natasa Isailovic, Carlo Selmi, Noreen Fertig, Elena Bravi, Yuko Kaneko, André Pinto Saraiva, Vega Jovani, Javier Bachiller-Corral, Jose Cifrian, Antonio Mera-Varela, Siamak Moghadam-Kia, Veronica Wolff, Julien Campagne, Alain Meyer, Margherita Giannini, Konstantinos Triantafyllias, Johannes Knitza, Latika Gupta, Yair Molad, Florenzo Iannone, Ilaria Cavazzana, Matteo Piga, Giacomo De Luca, Sarah Tansley, Emanuele Bozzalla-Cassione, Francesco Bonella, Tamera J Corte, Tracy J Doyle, David Fiorentino, Miguel Angel Gonzalez-Gay, Marie Hudson, Masataka Kuwana, Ingrid E Lundberg, Andrew L Mammen, Neil John McHugh, Fredrick W Miller, Carlomaurizio Montecucco, Chester V Oddis, Jorge Rojas-Serrano, Jens Schmidt, Carlo Alberto Scirè, Albert Selva-O'Callaghan, Victoria P Werth, Claudia Alpini, Sara Bozzini, Lorenzo Cavagna, Rohit Aggarwal
OBJECTIVES: The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis...
February 2024: Clinical and Experimental Rheumatology
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