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JOURNAL ARTICLE
Yan Jia, Rui-Ning Zhang, Yong-Jun Li, Bing-Yan Guo, Jian-Long Wang, Su-Yun Liu
Nonischemic cardiomyopathy (NICM) is a major cause of advanced heart failure, and the morbidity and mortality associated with NICM are serious medical problems. However, the etiology of NICM is complex and the related mechanisms involved in its pathogenesis remain unclear. The microarray datasets GSE1869 and GSE9128 retrieved from the Gene Expression Omnibus database were used to identify differentially expressed genes (DEGs) between NICM and normal samples. The co-expressed genes were identified using Venn diagrams...
April 26, 2024: Medicine (Baltimore)
#2
JOURNAL ARTICLE
Viraj Muthye, Dennis V Lavrov
Mitochondrial proteomes have been experimentally characterized for only a handful of animal species. However, the increasing availability of genomic and transcriptomic data allows one to infer mitochondrial proteins using computational tools. MitoPredictor is a novel random forest classifier, which utilizes orthology search, mitochondrial targeting signal (MTS) identification, and protein domain content to infer mitochondrial proteins in animals. MitoPredictor's output also includes an easy-to-use R Shiny applet for the visualization and analysis of the results...
2024: Methods in Molecular Biology
#3
REVIEW
Kalyan Naik Gugulothu, Pampatti Anvesh Sai, Sonika Suraparaju, Sai Prasad Karuturi, Ganesh Pendli, Ravi Babu Kamma, Kethana Nimmagadda, Alekhya Modepalli, Mahesh Mamilla, Shambhavi Vashist
Advanced pancreatic cancer is one of the prominent contributors to cancer-related mortality globally. Chemotherapy, especially gemcitabine, is generally used for the treatment of advanced pancreatic cancer. Despite the treatment, the fatality rate for advanced pancreatic cancer is alarmingly high. Thus, the dire need for better treatment alternatives has drawn focus to cancer vaccinations. The Wilms tumor gene (WT1), typically associated with Wilms tumor, is found to be excessively expressed in some cancers, such as pancreatic cancer...
March 2024: Curēus
#4
JOURNAL ARTICLE
Chen-Yan Li, Li-Juan Liao, Shi-Xian Yang, Lu-Yao Wang, Hao Chen, Peipei Luo, Gan-Rong Huang, Yan-Qiang Huang
ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia Presl (Cinnamomum cassia) is a common traditional Chinese medicine, which can promote the secretion and digestion of gastric juice, improve the function of gastrointestinal tract. Cinnamaldehyde (CA) is a synthetic food flavoring in the Chinese Pharmacopoeia. AIM OF THE STUDY: This study aimed to search for the active ingredient (CA) of inhibiting H. pylori from Cinnamomum cassia, and elucidate mechanism of action, so as to provide the experimental basis for the treatment of H...
April 23, 2024: Journal of Ethnopharmacology
#5
JOURNAL ARTICLE
Chaojun Zhai, Yunfeng Wang, Shenao Qi, Muhan Yang, Shian Wu
Yorkie (Yki) is a key effector of the Hippo pathway that activates the expression of targets by associating with the transcription factor Scalloped (Sd). Various upstream signals, such as cell polarity and mechanical cues, control transcriptional programs by regulating Yki activity. Searching for Yki regulatory factors has far-reaching significance for studying the Hippo pathway in animal development and human diseases. In this study, we identify Calpain-A (CalpA) and Calpain-B (CalpB), two calcium (Ca2+ )-dependent modulatory proteases of the calpain family, as critical regulators of Yki in Drosophila that interact with Yki respectively...
April 23, 2024: Journal of Genetics and Genomics
#6
JOURNAL ARTICLE
Kevin T Militello, Jennifer Leigh, Matthew Pusateri, Laurie K Read, Dineen Vogler
In Trypanosoma brucei, gene expression is primarily regulated posttranscriptionally making RNA metabolism critical. T. brucei has an epitranscriptome containing modified RNA bases. Yet, the identity of the enzymes catalyzing modified RNA base addition and the functions of the enzymes and modifications remain unclear. Homology searches indicate the presence of numerous T. brucei cytosine RNA methyltransferase homologs. One such homolog, TbNop2 was studied in detail. TbNop2 contains the six highly conserved motifs found in cytosine RNA methyltransferases and is evolutionarily related to the Nop2 protein family required for rRNA modification and processing...
2024: PloS One
#7
REVIEW
Alexandra Indeglia, Maureen E Murphy
TP53 encodes a transcription factor that is centrally-involved in several pathways, including the control of metabolism, the stress response, DNA repair, cell cycle arrest, senescence, programmed cell death, and others. Since the discovery of TP53 as the most frequently-mutated tumor suppressor gene in cancer over four decades ago, the field has focused on uncovering target genes of this transcription factor that are essential for tumor suppression. This search has been fraught with red herrings, however. Dozens of p53 target genes were discovered that had logical roles in tumor suppression, but subsequent data showed that most were not tumor suppressive, and were dispensable for p53-mediated tumor suppression...
April 25, 2024: Critical Reviews in Biochemistry and Molecular Biology
#8
JOURNAL ARTICLE
Remkes A Scheele, Yanik Weber, Friederike E H Nintzel, Michael Herger, Tomasz S Kaminski, Florian Hollfelder
Tryptophan synthase catalyzes the synthesis of a wide array of noncanonical amino acids and is an attractive target for directed evolution. Droplet microfluidics offers an ultrahigh throughput approach to directed evolution (up to 107 experiments per day), enabling the search for biocatalysts in wider regions of sequence space with reagent consumption minimized to the picoliter volume (per library member). While the majority of screening campaigns in this format on record relied on an optically active reaction product, a new assay is needed for tryptophan synthase...
April 19, 2024: ACS Catalysis
#9
Marwah Karim, Manjari Mishra, Chieh-Wen Lo, Sirle Saul, Halise Busra Cagirici, Do Hoang Nhu Tran, Aditi Agrawal, Luca Ghita, Amrita Ojha, Michael P East, Karen Anbro Gammeltoft, Malaya Kumar Sahoo, Gary L Johnson, Soumita Das, Dirk Jochmans, Courtney A Cohen, Judith Gottwein, John Dye, Norma Neff, Benjamin A Pinsky, Tuomo Laitinen, Tatu Pantsar, Antti Poso, Fabio Zanini, Steven De Jonghe, Christopher R M Asquith, Shirit Einav
In search for broad-spectrum antivirals, we discovered a small molecule inhibitor, RMC-113, that potently suppresses the replication of multiple RNA viruses including SARS-CoV-2 in human lung organoids. We demonstrated selective dual inhibition of the lipid kinases PIP4K2C and PIKfyve by RMC-113 and target engagement by its clickable analog. Advanced lipidomics revealed alteration of SARS-CoV-2-induced phosphoinositide signature by RMC-113 and linked its antiviral effect with functional PIP4K2C and PIKfyve inhibition...
April 17, 2024: bioRxiv
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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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