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JOURNAL ARTICLE
Tatsuya Koreeda, Hiroshi Honda
Glycans have attracted much attention in cancer therapeutic strategies, and cell surface proteins and lipids with glycans are known to be altered during the carcinogenic process. However, our understanding of how the glycogenes profile responds to drug stimulation remains incomplete. In this study, we search public databases for Sequence Read Archive data on drug-treated liver cancer cells, with the aim to comprehensively analyze the drug responses of glycogenes via bioinformatic meta-analysis. The study comprised 86 datasets, encompassing eight distinct liver cancer cell lines and 13 different drugs...
April 24, 2024: Glycoconjugate Journal
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JOURNAL ARTICLE
Yuki Hitomi, Kazuko Ueno, Yoshihiro Aiba, Nao Nishida, Michihiro Kono, Mitsuki Sugihara, Yosuke Kawai, Minae Kawashima, Seik-Soon Khor, Kazuhiro Sugi, Hirotaka Kouno, Hiroshi Kouno, Atsushi Naganuma, Satoru Iwamoto, Shinji Katsushima, Kiyoshi Furuta, Toshiki Nikami, Tomohiko Mannami, Tsutomu Yamashita, Keisuke Ario, Tatsuji Komatsu, Fujio Makita, Masaaki Shimada, Noboru Hirashima, Shiro Yokohama, Hideo Nishimura, Rie Sugimoto, Takuya Komura, Hajime Ota, Motoyuki Kojima, Makoto Nakamuta, Naoyuki Fujimori, Kaname Yoshizawa, Yutaka Mano, Hironao Takahashi, Kana Hirooka, Satoru Tsuruta, Takeaki Sato, Kazumi Yamasaki, Yuki Kugiyama, Yasuhide Motoyoshi, Tomoyuki Suehiro, Akira Saeki, Kosuke Matsumoto, Shinya Nagaoka, Seigo Abiru, Hiroshi Yatsuhashi, Masahiro Ito, Kazuhito Kawata, Akinobu Takaki, Kuniaki Arai, Teruko Arinaga, Masanori Abe, Masaru Harada, Makiko Taniai, Mikio Zeniya, Hiromasa Ohira, Shinji Shimoda, Atsumasa Komori, Atsushi Tanaka, Kazuyoshi Ishigaki, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura
BACKGROUND AIMS: Previous genome-wide association studies (GWAS) have indicated the involvement of shared (population-non-specific) and non-shared (population-specific) susceptibility genes in the pathogenesis of primary biliary cholangitis (PBC) among European and East-Asian populations. Although a meta-analysis of these distinct populations has recently identified more than 20 novel PBC susceptibility loci, analyses of population-specific genetic architecture are still needed for a more comprehensive search for genetic factors in PBC...
April 23, 2024: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
#3
REVIEW
Arriana Gkouvi, Sotirios G Tsiogkas, Dimitrios P Bogdanos, Helen Gika, Dimitrios G Goulis, Maria G Grammatikopoulou
PURPOSE OF REVIEW: Fibromyalgia syndrome (FMS) is a disease of unknown pathophysiology, with the diagnosis being based on a set of clinical criteria. Proteomic analysis can provide significant biological information for the pathophysiology of the disease but may also reveal biomarkers for diagnosis or therapeutic targets. The present systematic review aims to synthesize the evidence regarding the proteome of adult patients with FMS using data from observational studies. RECENT FINDINGS: An extensive literature search was conducted in MEDLINE/PubMed, CENTRAL, and clinicaltrials...
April 23, 2024: Current Pain and Headache Reports
#4
JOURNAL ARTICLE
Keith L Sanders, Astrid M Manuel, Andi Liu, Boyan Leng, Xiangning Chen, Zhongming Zhao
Alzheimer's Disease (AD) is a complex disease and the leading cause of dementia in older people. We aimed to uncover aspects of AD's pathogenesis that may contribute to drug repurposing efforts by integrating DNA methylation and genetic data. Implementing the network-based tool, a dense module search of genome-wide association studies (dmGWAS), we integrated a large-scale GWAS dataset with DNA methylation data to identify gene network modules associated with AD. Our analysis yielded 286 significant gene network modules...
April 1, 2024: Epigenomes
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JOURNAL ARTICLE
Hui Chen, Xiangna Guan, Chi He, Tingting Lu, Xingyu Lin, Xuebin Liao
INTRODUCTION: Hematopoietic progenitor kinase 1 (HPK1), a 97-kDa serine/threonine Ste20-related protein kinase, functions as an intracellular negative regulator, primarily in hematopoietic lineage cells, where it regulates T cells, B cells, dendritic cells and other immune cells. Loss of HPK1 kinase activity results in exacerbated cytokine secretion, enhanced T cell signaling, improved viral clearance, and thus increased restraint of tumor growth. These findings highlight HPK1 as a promising target for immuno-oncology treatments, culminating in the advancement of candidate compounds targeting HPK1 to clinical trials by several biotech enterprises...
April 22, 2024: Expert Opinion on Therapeutic Targets
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REVIEW
Yuichi Hattori, Kohshi Hattori, Kuniaki Ishii, Masanobu Kobayashi
Heart failure (HF) is a major global health problem afflicting millions worldwide. Despite the significant advances in therapies and prevention, HF still carries very high morbidity and mortality, requiring enormous healthcare-related expenditure, and the search for new weapons goes on. Following initial treatment strategies targeting inotropism and congestion, attention has focused on offsetting the neurohormonal overactivation and three main therapies, including angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor antagonists, β-adrenoceptor antagonists, and mineralocorticoid receptor antagonists, have been the foundation of standard treatment for patients with HF...
April 20, 2024: Biochemical Pharmacology
#7
REVIEW
Wenhao Guo, Hanwen Liu, Yong Yan, Di Wu, Hequan Yao, Kejiang Lin, Xuanyi Li
INTRODUCTION: The TGF-β signaling pathway is a complex network that plays a crucial role in regulating essential biological functions and is implicated in the onset and progression of multiple diseases. This review highlights the recent advancements in developing inhibitors targeting the TGF-β signaling pathway and their potential therapeutic applications in various diseases. AREA COVERED: The review discusses patents on active molecules related to the TGF-β signaling pathway, focusing on three strategies: TGF-β activity inhibition, blocking TGF-β receptor binding, and disruption of the signaling pathway using small molecule inhibitors...
April 22, 2024: Expert Opinion on Therapeutic Patents
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JOURNAL ARTICLE
Lorenzo Olivi, Cleo Bagchus, Victor Pool, Ezra Bekkering, Konstantin Speckner, Hidde Offerhaus, Wen Y Wu, Martin Depken, Koen J A Martens, Raymond H J Staals, Johannes Hohlbein
CRISPR-Cas systems have widely been adopted as genome editing tools, with two frequently employed Cas nucleases being SpyCas9 and LbCas12a. Although both nucleases use RNA guides to find and cleave target DNA sites, the two enzymes differ in terms of protospacer-adjacent motif (PAM) requirements, guide architecture and cleavage mechanism. In the last years, rational engineering led to the creation of PAM-relaxed variants SpRYCas9 and impLbCas12a to broaden the targetable DNA space. By employing their catalytically inactive variants (dCas9/dCas12a), we quantified how the protein-specific characteristics impact the target search process...
April 22, 2024: Nucleic Acids Research
#9
JOURNAL ARTICLE
Yutao Peng, Chanjuan Zhou
AIM: Scutellaria baicalensis , a traditional Chinese medicinal herb renowned for its anti-inflammatory, antioxidant, and anti-tumor properties, has shown promise in alleviating cognitive impairment associated with Alzheimer's disease. Nonetheless, the exact neuroprotective mechanism of Scutellaria baicalensis against Alzheimer's disease remains unclear. In this study, network pharmacology was employed to explore the possible mechanisms by which Scutellaria baicalensis protects against Alzheimer's disease...
2024: Drug Design, Development and Therapy
#10
REVIEW
Yilin Tao, Ruixiang Luo, Yuanbing Xiang, Min Lei, Xuan Peng, Yao Hu
The Bailing Capsule is a commonly used traditional Chinese medicine for the treatment of chronic kidney disease (CKD). However, its therapeutic effects and pharmacological mechanisms have not been fully explored. In this study, we integrated meta-analysis and network pharmacology to provide scientific evidence for the efficacy and pharmacological mechanism of Bailing Capsule in treating CKD. We conducted searches for randomized controlled studies matching the topic in PubMed, the Cochrane Library, Embase, Web of Science, and the Wanfang Database, and screened them according to predefined inclusion and exclusion criteria...
2024: Frontiers in Pharmacology
#11
REVIEW
Christina Morgenstern, Isabel Lastres-Becker, Birsen Can Demirdöğen, Vera Marisa Costa, Andreas Daiber, Roberta Foresti, Roberto Motterlini, Sibel Kalyoncu, Burak I Arioz, Sermin Genc, Monika Jakubowska, Ioannis P Trougakos, Aleksandra Piechota-Polanczyk, Michel Mickael, Marlene Santos, Thomas W Kensler, Antonio Cuadrado, Ian M Copple
The cytoprotective transcription factor NRF2 regulates the expression of several hundred genes in mammalian cells and is a promising therapeutic target in a number of diseases associated with oxidative stress and inflammation. Hence, an ability to monitor basal and inducible NRF2 signalling is vital for mechanistic understanding in translational studies. Due to some caveats related to the direct measurement of NRF2 levels, the modulation of NRF2 activity is typically determined by measuring changes in the expression of one or more of its target genes and/or the associated protein products...
March 30, 2024: Redox Biology
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JOURNAL ARTICLE
Sujeet Kumar Mishra, Sangeeta, Dieter W Heermann, Arnab Bhattacherjee
Preserving the genomic integrity stands a fundamental necessity, primarily achieved by the DNA repair proteins through their continuous patrolling on the DNA in search of lesions. However, comprehending how even a single base-pair lesion can be swiftly and specifically recognized amidst millions of base-pair sites remains a formidable challenge. In this study, we employ extensive molecular dynamics simulations using an appropriately tuned model of both protein and DNA to probe the underlying molecular principles...
April 17, 2024: Biochimica et Biophysica Acta. Gene Regulatory Mechanisms
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JOURNAL ARTICLE
Leonardo Y Tanaka, Sandeep Kumar, Lucas F Gutierre, Celso Magnun, Daniela Kajihara, Dong-Won Kang, Francisco R M Laurindo, Hanjoong Jo
Redox processes can modulate vascular pathophysiology. The endoplasmic reticulum redox chaperone protein disulfide isomerase A1 (PDIA1) is overexpressed during vascular proliferative diseases, regulating thrombus formation, endoplasmic reticulum stress adaptation, and structural remodeling. However, both protective and deleterious vascular effects have been reported for PDIA1, depending on the cell type and underlying vascular condition. Further understanding of this question is hampered by the poorly studied mechanisms underlying PDIA1 expression regulation...
2024: Frontiers in Physiology
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JOURNAL ARTICLE
Aman Kumar Saini, Neha Anil, Ardra N Vijay, Bharti Mangla, Shamama Javed, Pankaj Kumar, Waquar Ahsan
BACKGROUND: Friedreich's ataxia (FRDA) is a rare hereditary neurodegenerative disorder characterized by progressive ataxia, cardiomyopathy, and diabetes. The disease is caused by a deficiency of frataxin, a mitochondrial protein involved in iron-sulfur cluster synthesis and iron metabolism. OBJECTIVE: This review aims to summarize recent advances in the development of treatment strategies for FRDA, with a focus on potential drug candidates and their mechanisms of action...
April 17, 2024: Current Pharmaceutical Design
#15
JOURNAL ARTICLE
Jianwei Ren, Zhiting Mo, Zhengsha Huang, Shangze Li
BACKGROUND: Network pharmacology is a novel approach that uses bioinformatics to predict multitarget drugs and ingredient-target interactions in various diseases. A thorough search of previously published studies revealed that Hedyotis diffusa Willd (HDW) and Astragalus membranaceus (AM) possess anticancer activity. Colon cancer (CC) is one of the most common malignant tumors of the digestive tract and occurs in the colon. Herein, we explored the effect of two drugs in the treatment of CC...
April 17, 2024: Current Computer-aided Drug Design
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JOURNAL ARTICLE
Marinus J Hagens, Pim J van Leeuwen, Maurits Wondergem, Thierry N Boellaard, Francesco Sanguedolce, Daniela E Oprea-Lager, Axel Bex, André N Vis, Henk G van der Poel, Laura S Mertens
In contemporary oncologic diagnostics, molecular imaging modalities are pivotal for precise local and metastatic staging. Recent studies identified fibroblast activation protein as a promising target for molecular imaging across various malignancies. Therefore, we aimed to systematically evaluate the current literature on the utility of fibroblast activation protein inhibitor (FAPI) PET/CT for staging patients with genitourinary malignancies. Methods: A systematic Embase and Medline search was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) process, on August 1, 2023...
April 18, 2024: Journal of Nuclear Medicine
#17
Esthika Dewiasty, Siti Setiati, Rina Agustina, Siti Rizny F Saldi, Nove Zain Wisuda, Arvin Pramudita, Meutia Kumaheri, Gracia Fensynthia, Fariza Rahmah, Reganedgary Jonlean, Lisette C P G M de Groot
INTRODUCTION: Data on the prevalence of malnutrition and nutrient intakes among Indonesian older aduls in institutionalized care setting are scattered and scarce. Thus, we conducted a systematic review of published and grey literature to estimate (1) the prevalence of malnutrition, (2) the level and distribution of habitual energy and nutrient intakes, and (3) the prevalence of inadequacy of energy and nutrient intakes among hospitalized and institutionalized older adults in Indonesia...
April 18, 2024: Annals of Nutrition & Metabolism
#18
JOURNAL ARTICLE
Shannon T Smith, Jackson B Cassada, Lukas Von Bredow, Kevin Erreger, Emma M Webb, Trevor A Trombley, Jacob J Kalbfleisch, Brian J Bender, Irene Zagol-Ikapitte, Valerie M Kramlinger, Jacob L Bouchard, Sidnee G Mitchell, Maik Tretbar, Brian K Shoichet, Craig W Lindsley, Jens Meiler, Heidi E Hamm
Here, we demonstrate a structure-based small molecule virtual screening and lead optimization pipeline using a homology model of a difficult-to-drug G-protein-coupled receptor (GPCR) target. Protease-activated receptor 4 (PAR4) is activated by thrombin cleavage, revealing a tethered ligand that activates the receptor, making PAR4 a challenging target. A virtual screen of a make-on-demand chemical library yielded a one-hit compound. From the single-hit compound, we developed a novel series of PAR4 antagonists...
April 12, 2024: ACS Pharmacology & Translational Science
#19
REVIEW
Shizhe Li, He Zhang, Ting Chen, Xiaowen Zhang, Guanning Shang
BACKGROUND: The proto-oncogene ROS1 encodes an intrinsic type I membrane protein of the tyrosine kinase/insulin receptor family. ROS1 facilitates the progression of various malignancies via self-mutations or rearrangements. Studies on ROS1-directed tyrosine kinase inhibitors have been conducted, and some have been approved by the FDA for clinical use. However, the adverse effects and mechanisms of resistance associated with ROS1 inhibitors remain unknown. In addition, next-generation ROS1 inhibitors, which have the advantage of treating central nervous system metastases and alleviating endogenous drug resistance, are still in the clinical trial stage...
April 2024: Cancer Medicine
#20
REVIEW
Behjat Javadi, Zahra Sobhani
Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that has a high prevalence worldwide. Apigenin is a flavonoid present in several vegetables and fruits and has anti-inflammatory, anti-oxidant, and anti-MetS properties. This study aims to systematically review the effects of apigenin against MetS and the relevant molecular and cellular mechanisms of action, pharmacokinetics features, and potential structure-activity relationship. Electronic databases including Scopus, PubMed, Science Direct and Cochrane Library were searched for in vivo, and in vitro, and human studies with the following keywords: "apigenin" and "metabolic syndrome or insulin resistance syndrome", "fatty liver", "hypertension or blood pressure", "diabetes or blood glucose", "dyslipidemia", "heart or cardiovascular " and "obesity" in title/abstract...
2024: Iranian Journal of Basic Medical Sciences
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