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JOURNAL ARTICLE
Fikret Aydin, Harshwardhan H Katkar, Alisha Morganthaler, Alyssa J Harker, David R Kovar, Gregory A Voth
Vasodilator-stimulated phosphoprotein (VASP) family proteins play a crucial role in mediating the actin network architecture in the cytoskeleton. The Ena/VASP homology 2 (EVH2) domain in each of the four identical arms of the tetrameric VASP consists of a loading poly-Pro region, a G-actin-binding domain (GAB), and an F-actin-binding domain (FAB). Together, the poly-Pro, GAB, and FAB domains allow VASP to bind to sides of actin filaments in a bundle, and recruit profilin-G-actin to processively elongate the filaments...
April 22, 2024: Cytoskeleton
#2
JOURNAL ARTICLE
Minghan Hu, Yan Wang
Proteomics and phosphoproteomics play crucial roles in elucidating the dynamics of post-transcriptional processes. While experimental methods and workflows have been established in this field, a persistent challenge arises when dealing with small samples containing a limited amount of protein. This limitation can significantly impact the recovery of peptides and phosphopeptides. In response to this challenge, we have developed a comprehensive experimental workflow tailored specifically for small-scale samples, with a special emphasis on neuronal tissues like the trigeminal ganglion...
April 2024: Current protocols
#3
REVIEW
Catalina Argandona Lopez, Amanda M Brown
HIV-infection of microglia and macrophages (MMs) induces neuronal injury and chronic release of inflammatory stimuli through direct and indirect molecular pathways. A large percentage of people with HIV-associated neurologic and psychiatric co-morbidities have high levels of circulating inflammatory molecules. Microglia, given their susceptibility to HIV infection and long-lived nature, are reservoirs for persistent infection. MMs and neurons possess the molecular machinery to detect pathogen nucleic acids and proteins to activate innate immune signals...
2024: Frontiers in Immunology
#4
JOURNAL ARTICLE
Takehiro Tozuka, Rintaro Noro, Keisuke Yoshida, Satoshi Takahashi, Mariko Hirao, Kuniko Matsuda, Yasuhiro Kato, Shinji Nakamichi, Susumu Takeuchi, Masaru Matsumoto, Akihiko Miyanaga, Shinobu Kunugi, Kazufumi Honda, Jun Adachi, Masahiro Seike
INTRODUCTION: Osimertinib is a standard treatment for patients with EGFR -mutant NSCLC. Although some osimertinib resistance mechanisms have been identified, nearly 50% of the mechanisms remain to be elucidated. This study was aimed at identifying non-genetic mechanisms underlying osimertinib resistance. METHODS: We established two osimertinib-resistant cell lines from EGFR mutation-positive PC-9 and HCC827 NSCLC cell lines (PC-9OR and HCC827OR, respectively) using a stepwise method...
April 2024: JTO clinical and research reports
#5
REVIEW
Qing Yao, Chubing Long, Pengcheng Yi, Guangyong Zhang, Wei Wan, Xiuqin Rao, Jun Ying, Weidong Liang, Fuzhou Hua
BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder distinguished by a swift cognitive deterioration accompanied by distinctive pathological hallmarks such as extracellular Aβ (β-amyloid) peptides, neuronal neurofibrillary tangles (NFTs), sustained neuroinflammation, and synaptic degeneration. The elevated frequency of AD cases and its proclivity to manifest at a younger age present a pressing challenge in the quest for novel therapeutic interventions. Numerous investigations have substantiated the involvement of C/EBPβ in the progression of AD pathology, thus indicating its potential as a therapeutic target for AD treatment...
April 2024: CNS Neuroscience & Therapeutics
#6
JOURNAL ARTICLE
Owen Zacarias, Cristina C Clement, Shu-Yuan Cheng, Melissa Rosas, Christina Gonzalez, Marion Peter, Peter Coopman, Elise Champeil
Mitomycin C (MC) is an anti-cancer drug which functions by forming interstrand crosslinks (ICLs) between opposing DNA strands. MC analog, 10-decarbamoyl mitomycin C (DMC), unlike MC, has stronger cytotoxic effects on cancer cells with TP53 mutation. We previously demonstrated that MC/DMC could activate p21WAF1/CIP1 in MCF-7 (TP53-proficient) and K562 (TP53 deficient) cells in a TP53-independent mode. We also found that MC/DMC regulate AKT activation in a TP53-dependent manner and that AKT deactivation is not associated with the activation of p21WAF1/CIP1 in response to MC/DMC treatment...
April 18, 2024: Chemico-biological Interactions
#7
JOURNAL ARTICLE
Yiyuan Zheng, Lina Zhao, Zhekun Xiong, Chaoyuan Huang, Qiuhong Yong, Dan Fang, Yugang Fu, Simin Gu, Chong Chen, Jiacheng Li, Yingying Zhu, Jing Liu, Fengbin Liu, Yong Li
BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on NAFLD. METHODS: Drug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on NAFLD...
April 16, 2024: Clinical and Molecular Hepatology
#8
JOURNAL ARTICLE
Jian Han, Renchen Ji, Shuo Zheng, Xin Xia, Wenxiao Du, Hongtao He, Chuanchun Han, Wenzhi Zhao, Xiaojie Li, Yuan Wang, Lu Zhang
Homeobox B9 (HOXB9) has been shown to play a critical role in several tumors. However, the precise biological mechanisms and functions of HOXB9 in osteosarcoma remain largely unknown. In this study, we found that HOXB9 was increased upon glucose starvation. Elevated HOXB9 suppressed osteosarcoma cell death and supported cell growth and migration under glucose starvation. Further mechanistic studies demonstrated that HOXB9 directly bound to the promoter of secreted phosphoprotein 1 (SPP1) and transcriptionally upregulated SPP1 expression which then led cell death decrease and cell growth increase under glucose deprivation environment...
April 13, 2024: Biochemical Pharmacology
#9
REVIEW
Dario R Alessi, Suzanne R Pfeffer
Activating mutations in leucine-rich repeat kinase 2 (LRRK2) represent the most common cause of monogenic Parkinson's disease. LRRK2 is a large multidomain protein kinase that phosphorylates a specific subset of the ∼65 human Rab GTPases, which are master regulators of the secretory and endocytic pathways. After phosphorylation by LRRK2, Rabs lose the capacity to bind cognate effector proteins and guanine nucleotide exchange factors. Moreover, the phosphorylated Rabs cannot interact with their cognate prenyl-binding retrieval proteins (also known as guanine nucleotide dissociation inhibitors) and, thus, they become trapped on membrane surfaces...
April 15, 2024: Annual Review of Biochemistry
#10
JOURNAL ARTICLE
Chanjuan Zheng, Hui Yao, Lu Lu, Hongqi Li, Lei Zhou, Xueyan He, Xi Xu, Hongzhuo Xia, Siyu Ding, Yiyuan Yang, Xinyu Wang, Muyao Wu, Lian Xue, Sisi Chen, Xiaojun Peng, Zhongyi Cheng, Yian Wang, Guangchun He, Shujun Fu, Evan T Keller, Suling Liu, Yi-Zhou Jiang, Xiyun Deng
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with limited effective therapeutic options readily available. We have previously demonstrated that lovastatin, an FDA-approved lipid-lowering drug, selectively inhibits the stemness properties of TNBC. However, the intracellular targets of lovastatin in TNBC remain largely unknown. Here, we unexpectedly uncovered ribosome biogenesis as the predominant pathway targeted by lovastatin in TNBC. Lovastatin induced the translocation of ribosome biogenesis-related proteins including nucleophosmin (NPM), nucleolar and coiled-body phosphoprotein 1 (NOLC1), and the ribosomal protein RPL3...
2024: International Journal of Biological Sciences
#11
JOURNAL ARTICLE
Jin Xie, Mohamed Ouizougun-Oubari, Li Wang, Guanglei Zhai, Daitze Wu, Zhaohu Lin, Manfu Wang, Barbara Ludeke, Xiaodong Yan, Tobias Nilsson, Lu Gao, Xinyi Huang, Rachel Fearns, Shuai Chen
The transcription and replication processes of non-segmented, negative-strand RNA viruses (nsNSVs) are catalyzed by a multi-functional polymerase complex composed of the large protein (L) and a cofactor protein, such as phosphoprotein (P). Previous studies have shown that the nsNSV polymerase can adopt a dimeric form, however, the structure of the dimer and its function are poorly understood. Here we determine a 2.7 Å cryo-EM structure of human parainfluenza virus type 3 (hPIV3) L-P complex with the connector domain (CD') of a second L built, while reconstruction of the rest of the second L-P obtains a low-resolution map of the ring-like L core region...
April 11, 2024: Nature Communications
#12
JOURNAL ARTICLE
Luis Ortega-Paz, Wilbert Bor, Francesco Franchi, Wout W A van de Broek, Fabiana Rollini, Salvatore Giordano, Mattia Galli, Latonya Been, Ghussan Ghanem, Awss Shalhoub, Haroutioun Garabedian, Tala Al Saleh, Ekin Uzunoglu, Xuan Zhou, Andrea Rivas, Andres M Pineda, Siva Suryadevara, Daniel Soffer, Madeline K Mahowald, Calvin Y Choi, Martin M Zenni, Fladia Phoenix, Ramzi A Ajjan, Jurrien M Ten Berg, Dominick J Angiolillo
BACKGROUND: Among patients treated with a novel oral anticoagulant (NOAC) undergoing percutaneous coronary intervention (PCI), combination therapy with clopidogrel (i.e., known as dual antithrombotic therapy [DAT]) is the treatment of choice. However, there are concerns for individuals with impaired response to clopidogrel. OBJECTIVES: To assess the pharmacodynamic (PD) effects of clopidogrel vs. low-dose ticagrelor in patients with impaired clopidogrel response assessed by the ABCD-GENE score...
April 1, 2024: JACC. Cardiovascular Interventions
#13
JOURNAL ARTICLE
Selena K Tavener, Matthew I Jackson, Kiran S Panickar
BACKGROUND: Ketogenic foods limit digestible carbohydrates but contain high fat, and have antioxidant and anti-inflammatory effects as well as improving mitochondrial function. β-Hydroxybutyrate (BHB), 1 of the ketone bodies, reduces the proinflammatory NLR family pyrin domain containing 3 inflammasomes, as well as chemokines in cultures. OBJECTIVES: We assessed the immune-modulating effects of 2 low-carbohydrate (LoCHO) foods varying in protein and fat and compared their effects with a food replete with high-carbohydrate (HiCHO) in healthy canines...
April 2024: Current Developments in Nutrition
#14
JOURNAL ARTICLE
David Rombaut, Carine Lefèvre, Tony Rached, Sabrina Bondu, Anne Letessier, Raphael M Mangione, Batoul Farhat, Auriane Lesieur-Pasquier, Daisy Castillo-Guzman, Ismael Boussaid, Chloé Friedrich, Aurore Tourville, Magali De Carvalho, Françoise Levavasseur, Marjorie Leduc, Morgane Le Gall, Sarah Battault, Marie Temple, Alexandre Houy, Didier Bouscary, Lise Willems, Sophie Park, Sophie Raynaud, Thomas Cluzeau, Emmanuelle Clappier, Pierre Fenaux, Lionel Adès, Raphael Margueron, Michel Wassef, Samar Alsafadi, Nicolas Chapuis, Olivier Kosmider, Eric Solary, Angelos Constantinou, Marc-Henri Stern, Nathalie Droin, Benoit Palancade, Benoit Miotto, Frédéric Chédin, Michaela Fontenay
Myelodysplastic syndromes (MDS) with mutated SF3B1 gene present features including a favourable outcome distinct from MDS with mutations in other splicing factor genes SRSF2 or U2AF1. Molecular bases of these divergences are poorly understood. Here we find that SF3B1-mutated MDS show reduced R-loop formation predominating in gene bodies associated with intron retention reduction, not found in U2AF1- or SRSF2-mutated MDS. Compared to erythroblasts from SRSF2- or U2AF1-mutated patients, SF3B1-mutated erythroblasts exhibit augmented DNA synthesis, accelerated replication forks, and single-stranded DNA exposure upon differentiation...
April 8, 2024: Nature Communications
#15
JOURNAL ARTICLE
Sol Beccari, Esraa Mohamed, Viva Voong, Stephanie Hilz, Marisa Lafontaine, Anny Shai, Yunita Lim, Jerry Martinez, Benjamin Switzman, Ryon L Yu, Janine M Lupo, Eddie F Chang, Shawn L Hervey-Jumper, Mitchel S Berger, Joseph F Costello, Joanna J Phillips
Biomarker-driven therapeutic clinical trials require implementation of standardized, evidence-based practices for sample collection. In diffuse glioma, phosphatidylinositol 3 (PI3)-kinase/AKT/mTOR (PI3/AKT/mTOR) signaling is an attractive therapeutic target for which window of opportunity clinical trials could facilitate identification of promising new agents. Yet, the relevant preanalytic variables and optimal tumor sampling methods necessary to measure pathway activity are unknown. To address this, we used a murine model for IDH-wildtype glioblastoma (GBM) and human tumor tissue, including IDH-wildtype GBM and IDH-mutant diffuse glioma...
April 6, 2024: Modern Pathology
#16
JOURNAL ARTICLE
Zhuqing Wan, Xiaoqiang Bai, Xin Wang, Xiaodong Guo, Xu Wang, Mo Zhai, Yang Fu, Yunsong Liu, Ping Zhang, Xiao Zhang, Ruili Yang, Yan Liu, Longwei Lv, Yongsheng Zhou
Activating autologous stem cells after the implantation of biomaterials is an important process to initiate bone regeneration. Although several studies have demonstrated the mechanism of biomaterial-mediated bone regeneration, a comprehensive single-cell level transcriptomic map revealing the influence of biomaterials on regulating the temporal and spatial expression patterns of mesenchymal stem cells (MSCs) is still lacking. Herein, the osteoimmune microenvironment is depicted around the classical collagen/nanohydroxyapatite-based bone repair materials via combining analysis of single-cell RNA sequencing and spatial transcriptomics...
April 8, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
#17
JOURNAL ARTICLE
Kyung-Hwak Yoon, Hyosub Chu, Hyeonji Kim, Sunghyun Huh, Eun-Kyu Kim, Un-Beom Kang, Hee-Chul Shin
PURPOSE: Breast cancer is known to be influenced by genetic and environmental factors, and several susceptibility genes have been discovered. Still, the majority of genetic contributors remain unknown. We aimed to analyze the plasma proteome of breast cancer patients in comparison to healthy individuals to identify differences in protein expression profiles and discover novel biomarkers. METHODS: This pilot study was conducted using bioresources from Seoul National University Bundang Hospital's Human Bioresource Center...
April 2024: Annals of Surgical Treatment and Research
#18
JOURNAL ARTICLE
Jiaojiao Liu, Yanchao Liu, Qi Zhao
Colorectal cancer (CRC) is the third most common tumor, with an increasing number of deaths worldwide each year. Tremendous advances in the diagnosis and treatment of CRC have significantly improved the outcomes for CRC patients. Additionally, accumulating evidence has hinted the relationship between acidic nuclear phosphoprotein 32 family member E (ANP32E) and cancer progression. But the role of ANP32E in CRC remains unclear. In our study, through TCGA database, it was demonstrated that the expression of ANP32E was enhanced in COAD tissues ( n = 286)...
2024: Open Life Sciences
#19
JOURNAL ARTICLE
Charlotte Muret, David Crettaz, Lorenzo Alberio, Michel Prudent
BACKGROUND: Pathogen inactivation treatment (PIT) has been shown to alter platelet function, phenotype, morphology and to induce a faster aging of platelet concentrates (PCs). Key pieces of information are still missing to understand the impacts of PITs at the cellular level. OBJECTIVES: This study investigated the impact of amotosalen/UVA on PCs, from a post-translational modifications (PTM) point of view. Phosphoproteomic analyses were conducted on resting platelets, right after the amotosalen/UVA treatment and compared with untreated PCs...
April 2024: Transfusion Medicine and Hemotherapy
#20
JOURNAL ARTICLE
Julia Zeller-Hahn, Anna Kobsar, Marius Bittl, Angela Koessler, Katja Weber, Markus Boeck, Juergen Koessler
INTRODUCTION: Refrigeration of platelets is considered to provide advantages in therapy of acute hemorrhage due to increased platelet responsiveness. The alleviation of inhibitory signaling caused by cold temperature (CT) has been identified as an important mechanism contributing to enhanced platelet reactivity, detectable in freshly prepared platelets within 1 h of cold storage. The aim of this study was to confirm the effects of short-term refrigeration in platelets from apheresis-derived platelet concentrates (APC)...
April 2024: Transfusion Medicine and Hemotherapy
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