Article
Biology
Rossella Delle Donne, Rosa Iannucci, Laura Rinaldi, Luca Roberto, Maria A. Oliva, Emanuela Senatore, Domenica Borzacchiello, Luca Lignitto, Giorgio Giurato, Francesca Rizzo, Assunta Sellitto, Francesco Chiuso, Salvatore Castaldo, Giovanni Scala, Virginia Campani, Valeria Nele, Giuseppe De Rosa, Chiara D'Ambrosio, Corrado Garbi, Andrea Scaloni, Alessandro Weisz, Concetta Ambrosino, Antonella Arcella, Antonio Feliciello
Summary: The study identifies praja2 as an essential regulator of cancer cell metabolism in glioblastoma (GBM) and a potential therapeutic target to suppress GBM growth. Silencing praja2 using siRNA delivered by nanoparticles reduces tumor size in GBM-bearing mice.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Francisco Carranza, Hossein Shenasa, Klemens J. Hertel
Summary: Alternative splicing is a highly combinatorial mechanism that allows higher eukaryotes to increase mRNA diversity. The selection of alternative splice sites is influenced by sequence, cis-regulatory elements, exon and intron length, and RNA secondary structures. The study showed that the mode of splice site recognition, either intron or exon definition, plays a role in alternative splicing decisions.
Article
Biochemistry & Molecular Biology
Luis Coronel, David Haeckes, Katjana Schwab, Konstantin Riege, Steve Hoffmann, Martin Fischer
Summary: Recent studies have shown that p53 regulates cell metabolism through activation of DDIT4 via RFX7, leading to inhibition of mTORC1 and AKT. This suggests a nutrient-dependent model for p53-RFX7-mediated mTORC1 inhibition, highlighting the essential role of RFX7 and DDIT4 as effectors in metabolic control elicited by p53.
Article
Multidisciplinary Sciences
Martin L. Rennie, Connor Arkinson, Viduth K. Chaugule, Helen Walden
Summary: In this study, the enzyme-substrate-inhibitor complex of USP1 and the well-established inhibitor, ML323, was studied using cryo-electron microscopy. A novel binding mode of the inhibitor disrupting part of the hydrophobic core of USP1 was revealed, leading to subtle rearrangements in the active site and elucidating the mechanism of inhibition.
Article
Biochemistry & Molecular Biology
Kinneret Shefer, Ayub Boulos, Valer Gotea, Maram Arafat, Yair Ben Chaim, Aya Muharram, Sara Isaac, Amir Eden, Joseph Sperling, Laura Elnitski, Ruth Sperling
Summary: This study reveals that latent splice sites are highly abundant in human introns, and their activation under stress and in cancer leads to the generation of numerous nonsense mRNAs. The previously proposed mechanism to suppress latent splicing was shown to be independent of protein translation and dependent on initiator-tRNA. The nuclear protein nucleolin (NCL) was identified as directly and specifically interacting with initiator-tRNA in the nucleus, and its association with pre-mRNA was also demonstrated. It was further revealed that nucleolin is essential for the recovery of suppression of latent splicing by initiator-tRNA. Knockdown of nucleolin led to the activation of latent splicing in coding transcripts with important cellular functions. Therefore, nucleolin, as a component of the endogenous spliceosome, is proposed as the first protein of a nuclear quality control mechanism that regulates splice site selection to prevent defective mRNA generation.
Article
Biochemistry & Molecular Biology
Ming Chen, Vemana Gowd, Mingfu Wang, Feng Chen, Ka-Wing Cheng
Summary: Phloretin effectively inhibits breast cancer cell growth, particularly under glucose-limiting conditions, by downregulating mTOR/ULK1 signaling and suppressing autophagy. It also synergistically enhances the growth inhibitory effects of chemotherapeutic agents and restores chemosensitivity in tamoxifen-resistant cell lines.
Article
Oncology
Samuel Cytryn, Virginia Ferreira, Patrick Boland, Abraham Chachoua, Joshua Sabari
Summary: The case suggests that non-metastatic, unresectable NSCLC patients with high PD-L1 expression and concomitant driver mutations may benefit more from targeted tyrosine kinase inhibitors rather than immune checkpoint inhibitor therapy.
Article
Biology
Lauren A. Levesque, Scott Roy, Nicole Salazar
Summary: Through investigating the expression and splicing events of CXCR3 in breast cancer, its association with breast cancer progression and immune infiltration was revealed. The importance of A3SS in regulating CXCR3 was validated, while the splicing events in breast cancer indicated the role of A3SS in the integrated splicing network.
Article
Biochemistry & Molecular Biology
Joana Reis, Christoph Gorgulla, Marta Massari, Sara Marchese, Sergio Valente, Beatrice Noce, Lorenzo Basile, Ricarda Toerner, Huel Cox, Thibault Viennet, Moon Hee Yang, Melissa M. Ronan, Matthew G. Rees, Jennifer A. Roth, Lucia Capasso, Angela Nebbioso, Lucia Altucci, Antonello Mai, Haribabu Arthanari, Andrea Mattevi
Summary: In this study, the authors validate inhibitors for human NOX enzymes using computational and experimental methods, opening avenues for cancer drug development and research in redox biology.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Plant Sciences
Weihua Huang, Liqun Zhang, Yajuan Zhu, Jingli Chen, Yawen Zhu, Fengru Lin, Xiaomei Chen, Jirong Huang
Summary: The usage of cryptic splice sites in plants remains unclear. In this study, two cryptic splicing regulators, RBP45d and PRP39a, were identified as homologs of yeast U1 auxiliary protein Nam8 and Prp39, respectively. It was found that RBP45d and PRP39a interact with each other and also with U1C, a core subunit of U1 snRNP, and promote U1 snRNP to recognize specific 5' splice sites by binding to intronic U-rich elements.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Eliezra Glasser, Debanjana Maji, Giulia Biancon, Anees Mohammed Keedakkatt Puthenpeedikakkal, Chapin E. Cavender, Toma Tebaldi, Jermaine L. Jenkins, David H. Mathews, Stephanie Halene, Clara L. Kielkopf
Summary: This study reveals the flexibility of U2AF2 in recognizing polypyrimidine tracts of nascent transcripts and the tolerance of nucleotide substitutions at the central position of the Py tract. The results highlight the importance of RNA flexibility for protein recognition and provide insights into the relationship between splice site motifs and pre-mRNA splicing efficiencies.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Yujiao Zhang, Marie Vandestienne, Jean-Remi Lavillegrand, Jeremie Joffre, Icia Santos-Zas, Aonghus Lavelle, Xiaodan Zhong, Wilfried Le Goff, Maryse Guerin, Rida Al-Rifai, Ludivine Laurans, Patrick Bruneval, Coralie Guerin, Marc Diedisheim, Melanie Migaud, Anne Puel, Fanny Lanternier, Jean-Laurent Casanova, Clement Cochain, Alma Zernecke, Antoine-Emmanuel Saliba, Michal Mokry, Jean-Sebastien Silvestre, Alain Tedgui, Ziad Mallat, Soraya Taleb, Olivia Lenoir, Cecile Vindis, Stephane M. Camus, Harry Sokol, Hafid Ait-Oufella
Summary: Previous studies have suggested a role for the CARD9 pathway in atherosclerosis, but the underlying mechanisms are still unclear. This study shows that the pro-atherogenic effects of Card9 deficiency are mediated by CD36-dependent defective autophagy, which can be reversed by rapamycin and metformin. Therefore, the CARD9 pathway is an important protective pathway in atherosclerosis.
NATURE COMMUNICATIONS
(2023)
Article
Food Science & Technology
Bong-Geum Jang, Jisun Lee, Boyoung Choi, Young Ho Koh, Min-Ju Kim
Summary: Resveratrol, a drug candidate for Alzheimer's disease, has shown beneficial effects in various models but may paradoxically increase Aβ production. This effect may be mediated by AMPK-proteasome signaling pathway.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Multidisciplinary Sciences
Chanawee Jakkawanpitak, Masashi Inafuku, Hirosuke Oku, Nongporn Hutadilok-Towatana, Ruthaiwan Bunkrongcheap, Natthawan Sermwittayawong, Piyapat Aiemchareon, Decha Sermwittayawong
Summary: Laminarin-coated beads inhibit lipid accumulation and stimulate an inflammatory response in adipocytes by acting on IRAK and SYK pathways, activating AMPK and NF-kappa B complexes. Toll-like receptor 2 and CLEC7A/Dectin-1 may be potential beta-glucan receptors on fat cells.
SCIENTIFIC REPORTS
(2021)
Article
Energy & Fuels
Faling Yin, Yonghai Gao, Ye Chen, Baojiang Sun, Shaoqiang Li, Danshi Zhao
Summary: Gas hydrates-bearing shaly silt reservoirs have high reserves and low permeability. The trial production test in the South China Sea shows that horizontal wells have promising prospects for exploiting these hydrate reservoirs. However, the long-term gas production behavior is still unknown. Based on trial production data, the study investigates the optimization of depressurization schemes and reservoir selection to improve gas production efficiency, as well as the influence of compaction on gas production rate attenuation and reservoir stability.
Article
Medicine, Research & Experimental
Tong Cheng, Zhusheng Chen, Yibin Qin, Xiang Zhu, Hongsheng Chen, Zhongling Xu, Xiaqing Ma
Summary: Morphine is commonly used and effective for pain relief, but its side effect of itching limits its clinical use. This paper discusses the potential of using esketamine to treat morphine-induced itching.
MEDICAL HYPOTHESES
(2024)
Article
Medicine, Research & Experimental
Sung Eun Lee, Eunjung Park, Ji-yun Kim, HyukHoon Kim
Summary: Hyperbaric oxygen therapy (HBOT) is a potential therapeutic modality that has been recognized for its favorable mechanisms in various diseases, including sepsis-associated encephalopathy (SAE). HBOT has neuroprotective effects through its anti-inflammatory and antiapoptotic effects as well as increased tissue oxygenation capacity. However, there are caveats and limitations in applying HBOT in sepsis.
MEDICAL HYPOTHESES
(2024)