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Marijne Vandebergh, Eliana Marisa Ramos, Nick Corriveau-Lecavalier, Vijay K Ramanan, John Kornak, Carly Mester, Tyler Kolander, Danielle Brushaber, Adam M Staffaroni, Daniel Geschwind, Amy Wolf, Kejal Kantarci, Tania F Gendron, Leonard Petrucelli, Marleen Van den Broeck, Sarah Wynants, Matthew C Baker, Sergi Borrego-Écija, Brian Appleby, Sami Barmada, Andrea Bozoki, David Clark, R Ryan Darby, Bradford C Dickerson, Kimiko Domoto-Reilly, Julie A Fields, Douglas R Galasko, Nupur Ghoshal, Neill Graff-Radford, Ian M Grant, Lawrence S Honig, Ging-Yuek Robin Hsiung, Edward D Huey, David Irwin, David S Knopman, Justin Y Kwan, Gabriel C Léger, Irene Litvan, Joseph C Masdeu, Mario F Mendez, Chiadi Onyike, Belen Pascual, Peter Pressman, Aaron Ritter, Erik D Roberson, Allison Snyder, Anna Campbell Sullivan, M Carmela Tartaglia, Dylan Wint, Hilary W Heuer, Leah K Forsberg, Adam L Boxer, Howard J Rosen, Bradley F Boeve, Rosa Rademakers
BACKGROUND AND OBJECTIVES: TMEM106B has been proposed as a modifier of disease risk in FTLD-TDP, particularly in GRN mutation carriers. Furthermore, TMEM106B has been investigated as a disease modifier in the context of healthy aging and across multiple neurodegenerative diseases. The objective of this study is to evaluate and compare the effect of TMEM106B on gray matter volume and cognition in each of the common genetic FTD groups and in sporadic FTD patients. METHODS: Participants were enrolled through the ARTFL/LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study, which includes symptomatic and presymptomatic individuals with a pathogenic mutation in C9orf72, GRN, MAPT, VCP, TBK1, TARDBP, symptomatic non-mutation carriers, and non-carrier family controls...
April 5, 2024: medRxiv
#2
JOURNAL ARTICLE
Yao Liang, Yun Liang, Qi Wang, Qianna Li, Yingqi Huang, Rong Li, Xiaoxin Pan, Linmiao Lie, Hui Xu, Zhenyu Han, Honglin Liu, Qian Wen, Chaoying Zhou, Li Ma, Xinying Zhou
OBJECTIVES AND DESIGN: As an interferon-inducible protein, Viperin has broad-spectrum antiviral effects and regulation of host immune responses. We aim to investigate how Viperin regulates interferon-γ (IFN-γ) production in macrophages to control Mycobacterium tuberculosis (Mtb) infection. METHODS: We use Viperin deficient bone-marrow-derived macrophage (BMDM) to investigate the effects and machines of Viperin on Mtb infection. RESULTS: Viperin inhibited IFN-γ production in macrophages and in the lung of mice to promote Mtb survival...
April 16, 2024: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
#3
JOURNAL ARTICLE
Aja Aravamudhan, Paul B Dieffenbach, Kyoung Moo Choi, Patrick A Link, Jeffrey A Meridew, Andrew J Haak, Laura E Fredenburgh, Daniel J Tschumperlin
Pulmonary arterial hypertension (PAH) causes pulmonary vascular remodeling, increasing pulmonary vascular resistance (PVR) and leading to right heart failure and death. Matrix stiffening early in the disease promotes remodeling in pulmonary artery smooth muscle cells (PASMCs), contributing to PAH pathogenesis. Our research identified YAP and TAZ as key drivers of the mechanobiological feedback loop in PASMCs, suggesting targeting them could mitigate remodeling. However, YAP/TAZ are ubiquitously expressed and carry out diverse functions, necessitating a cell-specific approach...
April 2024: Physiological Reports
#4
JOURNAL ARTICLE
Alexis J Haas, Mert Karakus, Ceniz Zihni, Maria S Balda, Karl Matter
Tight junctions are a barrier-forming cell-cell adhesion complex and have been proposed to regulate cell proliferation. However, the underlying mechanisms are not well understood. Here, we used cells deficient in the junction scaffold ZO-1 alone or together with its paralog ZO-2, which disrupts the junctional barrier. We found that ZO-1 knockout increased cell proliferation, induced loss of cell density-dependent proliferation control, and promoted apoptosis and necrosis. These phenotypes were enhanced by double ZO-1/ZO-2 knockout...
April 5, 2024: Cells
#5
JOURNAL ARTICLE
Yajuan Jiao, Pengwei Zhao, Ling-Dong Xu, Jia-Qi Yu, Hou-Li Cai, Chong Zhang, Chao Tong, Yong-Le Yang, Pinglong Xu, Qiming Sun, Ning Chen, Bin Wang, Yao-Wei Huang
Non-structural protein 2 (nsp2) exists in all coronaviruses (CoVs), while its primary function in viral pathogenicity, is largely unclear. One such enteric CoV, porcine epidemic diarrhea virus (PEDV), causes high mortality in neonatal piglets worldwide. To determine the biological role of nsp2, we generated a PEDV mutant containing a complete nsp2 deletion (rPEDV-Δnsp2) from a highly pathogenic strain by reverse genetics, showing that nsp2 was dispensable for PEDV infection, while its deficiency reduced viral replication in vitro ...
April 10, 2024: Autophagy
#6
JOURNAL ARTICLE
Feng Xu, Ya Qin, Changxiu Guan
Molecular docking screening identified ochnaflavone, madreselvin B and hydnocarpin as key components for treating COVID-19 with diabetes in honeysuckle using 3 C-like protease (Mpro), angiotensin-converting enzyme 2 (ACE2), and dipeptidyl peptidase 4 (DPP4) as molecular docking targets, ACE2, DPP4, IL2, NFKB1, PLG, TBK1, TLR4 and TNF were the core targets, and multiple antiviral and anti-inflammatory signalling pathways were involved. Further, the levels of IL-1β and DPP4 in cell supernatant that had been activated by LPS was decreased by hypnocarpin, and ACE2 protein and DPP4 mRNA in cells were down-regulated...
April 9, 2024: Natural Product Research
#7
JOURNAL ARTICLE
Chunhui Zhong, Gaoli She, Yukun Zhao, Yufang Liu, Jingmin Li, Xiaona Wei, Zexin Chen, Keyu Zhao, Zhiqing Zhao, Zhichao Xu, Hao Zhang, Yongchang Cao, Chunyi Xue
Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine enteric coronavirus that causes acute watery diarrhea, vomiting, and dehydration in newborn piglets. The type III interferon (IFN-λ) response serves as the primary defense against viruses that replicate in intestinal epithelial cells. However, there is currently no information available on how SADS-CoV modulates the production of IFN-λ. In this study, we utilized IPI-FX cells (a cell line of porcine ileum epithelium) as an in vitro model to investigate the potential immune evasion strategies employed by SADS-CoV against the IFN-λ response...
April 8, 2024: Veterinary Research
#8
JOURNAL ARTICLE
Jiyu Zhang, Hongyan Shi, Liaoyuan Zhang, Tingshuai Feng, Jianfei Chen, Xin Zhang, Zhaoyang Ji, Zhaoyang Jing, Xiaoyuan Zhu, Dakai Liu, Xiaoman Yang, Miaomiao Zeng, Da Shi, Li Feng
Swine acute diarrhea syndrome coronavirus (SADS-CoV), an emerging Alpha-coronavirus, brings huge economic loss in swine industry. Interferons (IFNs) participate in a frontline antiviral defense mechanism triggering the activation of numerous downstream antiviral genes. Here, we demonstrated that TRIM25 overexpression significantly inhibited SADS-CoV replication, whereas TRIM25 deficiency markedly increased viral yield. We found that SADS-CoV N protein suppressed interferon-beta (IFN-β) production induced by Sendai virus (SeV) or poly(I:C)...
April 8, 2024: Veterinary Research
#9
JOURNAL ARTICLE
Chuanqin Shi, Shihua Zhao, Liyan Mi, Deying Niu, Fanwen Hu, Wenwei Han, Bing Li
Fucoidan, a sulfated polysaccharide of marine origin found in brown algae and sea cucumbers, has been identified as a neuroprotective compound. In this study, a novel fucoidan MF4 was extracted from Fucus vesiculosus and isolated using Q-Sepharose fast-flow ion-exchange chromatography. The physicochemical properties of MF4 were characterized. MF4 is primarily composed of fucose, xylose, galactose, glucose, and mannose in a molar ratio of 12.3: 4.9: 1.1: 1.0: 1.1, with an average molecular weight of 67.7 kDa...
April 5, 2024: International Journal of Biological Macromolecules
#10
JOURNAL ARTICLE
Fenghao Geng, Li Zhong, Tingyi Yang, Jianhui Chen, Ping Yang, Fengdi Jiang, Tao Yan, Bin Song, Zuxiang Yu, Daojiang Yu, Jie Zhang, Jianping Cao, Shuyu Zhang
The extensive application of nuclear technology has increased the potential of uncontrolled radiation exposure to the public. Since skin is the largest organ, radiation-induced skin injury remains a serious medical concern. Organisms evolutionally develop distinct strategies to protect against environment insults and the related research may bring novel insights into therapeutics development. Here, 26 increased peptides are identified in skin tissues of frogs (Pelophylax nigromaculatus) exposed to electron beams, among which four promoted the wound healing of irradiated skin in rats...
April 6, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
#11
REVIEW
Mohammad Mahdi Mokhtari Tabar, Mahnaz Fathi, Fatemeh Kazemi, Ghazal Bazregari, Abdolmajid Ghasemian
The stimulator of the interferon genes (STING) signaling pathway plays a crucial role in innate immunity by detecting cytoplasmic DNA and initiating antiviral host defense mechanisms. The STING cascade is triggered when the enzyme cyclic GMP-AMP synthase (cGAS) binds cytosolic DNA and synthesizes the secondary messenger cGAMP. cGAMP activates the endoplasmic reticulum adaptor STING, leading to the activation of kinases TBK1 and IRF3 that induce interferon production. Secreted interferons establish an antiviral state in infected and adjacent cells...
April 5, 2024: Molecular Biology Reports
#12
JOURNAL ARTICLE
Arif Jamal Siddiqui, Arshad Jamal, Mubashir Zafar, Sadaf Jahan
Introduction: The cytosolic Ser/Thr kinase TBK1 is of utmost importance in facilitating signals that facilitate tumor migration and growth. TBK1-related signaling plays important role in tumor progression, and there is need to work on new methods and workflows to identify new molecules for potential treatments for TBK1-affecting oncologies such as breast cancer. Methods: Here, we propose the machine learning assisted computational drug discovery approach to identify TBK1 inhibitors. Through our computational ML-integrated approach, we identified four novel inhibitors that could be used as new hit molecules for TBK1 inhibition...
2024: Frontiers in Pharmacology
#13
JOURNAL ARTICLE
Yang Qu, Siyuan Wang, Hui Jiang, Qingyi Wang, Ying Liao, Xusheng Qiu, Lei Tan, Cuiping Song, Chan Ding, Yingjie Sun, Zengqi Yang
Tumor necrosis factor receptor-associated factor family member-associated NF-κB activator-binding kinase 1 (TBK1) plays a key role in the induction of the type 1 interferon (IFN-I) response, which is an important component of innate antiviral defense. Viruses target calcium (Ca2+ ) signaling networks, which participate in the regulation of the viral life cycle, as well as mediate the host antiviral response. Although many studies have focused on the role of Ca2+ signaling in the regulation of IFN-I, the relationship between Ca2+ and TBK1 in different infection models requires further elucidation...
April 2, 2024: Journal of Virology
#14
JOURNAL ARTICLE
Bo Liu, Huai Wang, Wenhao Xie, Ting Gong
Approximately 2-10% in-stent restenosis (ISR) may occur following percutaneous coronary intervention (PCI) despite the use of modern drug-eluting stents (DES); thus, our study aimed to explore the effects of tripartite motif-containing (TRIM) 27 on ISR and the underlying mechanism. For this purpose, a total of 42 patients undergoing coronary angiography who had prior coronary angiography with DES implantation were recruited. Endothelial progenitor cells (EPCs) markers (defined as CD34 and vascular endothelial growth factoreceptor-2 (VEGFR-2)) in peripheral blood were measured to asses the circulating EPC level...
April 1, 2024: Applied Biochemistry and Biotechnology
#15
JOURNAL ARTICLE
Zhiqiang Chen, Jinyu Zhang, Tingting Feng, Xiujuan Wang, Shimeng Zhou, Wen Pan, Zhengrong Chen, Yongdong Yan, Jianfeng Dai
The DEAD-box (DDX) family comprises RNA helicases characterized by the conserved sequence D(Asp)-E(Glu)-A(Ala)-D(Asp), participating in various RNA metabolism processes. Some DDX family members have been identified for their crucial roles in viral infections. In this study, RNAi library screening of the DDX family unveiled the antiviral activity of DDX20. Knockdown of DDX20 enhanced the replication of viruses such as vesicular stomatitis virus (VSV) and herpes simplex virus type I (HSV-1), while overexpression of DDX20 significantly diminished the replication level of these viruses...
March 27, 2024: Antiviral Research
#16
JOURNAL ARTICLE
Zi-Ling Qu, Xiu-Ying Gong, Li-Li An, Hao-Yu Sun, Wen-Hao Guo, Hong-Yu Luan, Meng-Yao Wu, Cheng Dan, Jian-Fang Gui, Yi-Bing Zhang
The development of CRISPR-Cas9 technology introduces an efficient tool for precise engineering of fish genomes. With a short reproduction cycle, zebrafish infection mode can be referenced as antiviral breeding researches in aquaculture fish. Previously we identified a crucian carp-specific gene ftrca1 as an inhibitor of interferon response in vitro . Here, we demonstrate that genome editing of zebrafish ftr42, a homolog of ftrca1 , generates a zebrafish mutant ( ftr42 lof/lof ) with an improved resistance to SVCV infection...
April 19, 2024: IScience
#17
REVIEW
Qixiang Song, Yuhang Fan, Huali Zhang, Nian Wang
Innate immunity is not only the first line of host defense against microbial infections but is also crucial for the host responses against a variety of noxious stimuli. Z-DNA binding protein 1 (ZBP1) is a cytosolic nucleic acid sensor that can induce inflammatory cell death in both immune and nonimmune cells upon sensing of incursive virus-derived Z-form nucleic acids and self-nucleic acids via its Zα domain. Mechanistically, aberrantly expressed or activated ZBP1 induced by pathogens or noxious stimuli enables recruitment of TANK binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and RIPK3 to drive type I interferon (IFN-I) responses and activation of nuclear factor kappa B (NF-κB) signaling...
March 26, 2024: Cytokine & Growth Factor Reviews
#18
JOURNAL ARTICLE
Hongyu Ren, Sheng Wang, Zhixun Xie, Lijun Wan, Liji Xie, Sisi Luo, Meng Li, Zhiqin Xie, Qing Fan, Tingting Zeng, Yanfang Zhang, Minxiu Zhang, Jiaoling Huang, You Wei
Interferon-inducible transmembrane protein 3 (IFITM3) is an antiviral factor that plays an important role in the host innate immune response against viruses. Previous studies have shown that IFITM3 is upregulated in various tissues and organs after avian reovirus (ARV) infection, which suggests that IFITM3 may be involved in the antiviral response after ARV infection. In this study, the chicken IFITM3 gene was cloned and analyzed bioinformatically. Then, the role of chicken IFITM3 in ARV infection was further explored...
February 21, 2024: Viruses
#19
JOURNAL ARTICLE
Shuni Duan, Xin Li, Junsong Han, Yang Yang, Ranyi Luo, Yajie Cai, Xiaojiaoyang Li, Qi Zheng, Jincheng Guo, Runping Liu
Cholangiopathies lack effective medicines and can progress into end-stage liver diseases. Mining natural product transcriptome databases for bioactive ingredients, which can reverse disease-associated transcriptomic phenotypes, holds promise as an effective approach for drug discovery. To identify disease-associated transcriptomic changes, we performed RNA-sequencing on bile duct ligation (BDL)-induced cholestatic liver fibrosis mice, as well as PBC and PSC patients, and found that PANoptosis and activation of type-I interferon (IFN) signaling were observed in BDL mice and patients with PBC and PSC...
February 20, 2024: Antioxidants (Basel, Switzerland)
#20
JOURNAL ARTICLE
Ki Won Lee, Ki-Jun Ryu, Minju Kim, Seyeon Lim, Jisu Kim, Jeong Yoon Kim, Cheol Hwangbo, Jiyun Yoo, Yong-Yeon Cho, Kwang Dong Kim
Melanosomes are specific organelles dedicated to melanin synthesis and accumulation in melanocytes. Autophagy is suggestively involved in melanosome degradation, although the potential underlying molecular mechanisms remain elusive. In selective autophagy, autophagy receptors and E3-ligases are the key factors conferring cargo selectivity. In B16F10 cells, β-mangostin efficiently induced melanosome degradation without affecting other organelles such as mitochondria, peroxisomes, and the endoplasmic reticulum...
April 2, 2024: Proceedings of the National Academy of Sciences of the United States of America
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