Article
Biochemistry & Molecular Biology
Alicia Ioppolo, Melissa Eccles, David Groth, Giuseppe Verdile, Mark Agostino
Summary: gamma-Secretase is an important intramembrane aspartyl protease that regulates cell physiology by cleaving multiple transmembrane proteins. Aberrant activity of gamma-Secretase is implicated in various diseases. Recent structural evidence provides insight into the binding of gamma-Secretase inhibitors and modulators, facilitating rational drug design. This study successfully identified known inhibitors and modulators and applied screening strategies to discover novel small molecules targeting gamma-Secretase.
Article
Chemistry, Medicinal
Gavin O'Mahony, Jens Petersen, Margareta Ek, Rebecca Rae, Carina Johansson, Liu Jianming, Nina Prokoph, Fredrik Bergstrom, Krister Bamberg, Fabrizio Giordanetto, Bader Zarrouki, Daniel Karlsson, Anders Hogner
Summary: A new compound, 10, has been discovered to be a potent PPARγ binder and inhibitor of CDK-mediated phosphorylation of PPARγ Ser273, without classical PPARγ agonism. In animal models, compound 10 demonstrated an improvement in insulin sensitivity.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Suliman Almahmoud, Catherine C. Elix, Jeremy O. Jones, Corey R. Hopkins, Jonathan L. Vennerstrom, Haizhen A. Zhong
Summary: The PPAR gamma antagonist is crucial for inhibiting prostate cancer cell growth, and residues Arg288, Lys367, and His449 are important for PPAR gamma antagonist binding.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Salvatore Galati, Stefano Sainas, Marta Giorgis, Donatella Boschi, Marco L. Lolli, Gabriella Ortore, Giulio Poli, Tiziano Tuccinardi
Summary: In this study, a novel hDHODH inhibitor with promising inhibitory activity was identified through virtual screening. This compound, structurally different from known ligands, serves as a valuable starting point for future drug optimization studies.
Article
Biochemistry & Molecular Biology
Lianxiang Luo, Huiting Tan, Yinglin Liao
Summary: In this study, virtual screening of 52119 marine natural compounds was performed using PRMT5. Using various analysis methods, 20 pharmacophore models were constructed and the best model, AARR_2, was selected. After screening and docking analysis, 46 compounds were selected for further analysis. The relationship between structure and activity of the compounds was analyzed using 3D-QSAR. Finally, marine natural compounds 36404 and 36405 were identified as candidates for PRMT5 substrate competitive inhibitors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Vibhu Jha, Marzia Biagi, Valeria Spinelli, Miriana Di Stefano, Marco Macchia, Filippo Minutolo, Carlotta Granchi, Giulio Poli, Tiziano Tuccinardi
Summary: Monoacylglycerol lipase (MAGL) is an important enzyme in the endocannabinoid system, associated with various pathological conditions, making it a promising drug design target. A study developed a virtual screening protocol combined with molecular docking and dynamics simulations to identify two promising reversible MAGL inhibitors, VS1 and VS2.
Article
Biology
Yuvaraj Sivamani, Dhivya Shanmugarajan, T. Durai Ananda Kumar, Syed Faizan, Bhavya Channappa, Namburu Lalitha Naishima, B. R. Prashantha Kumar
Summary: A protocol for developing novel PPARγ antagonists was reported in this study, involving virtual screening for ligands with anticancer properties, model validation and screening, as well as synthesis and validation of Cpd31 for binding to PPARγ and anti-cancer effects.
COMPUTATIONAL BIOLOGY AND CHEMISTRY
(2021)
Article
Engineering, Biomedical
Yongzhao Xiong, Xinchang Gao, Daodong Pan, Ting Zhang, Lulu Qi, Ning Wang, Yufen Zhao, Yali Dang
Summary: A novel model combining common feature pharmacophore and molecular docking was established for rapid screening of umami peptides, successfully identifying twenty previously unreported dipeptides with umami taste. Experimental validation confirmed their umami activity, demonstrating the practicality of this screening strategy.
Article
Chemistry, Medicinal
Lei Xu, Lilei Sun, Peng Su, Teng Ma, Yingcong Yu, Haibin Liu, Xianfeng Huang
Summary: In this study, two potential PDE5 inhibitors were discovered through computer-aided virtual screening technique from the ZINC database. These natural compounds could serve as critical starting points for the development of novel PDE5 inhibitors.
CURRENT COMPUTER-AIDED DRUG DESIGN
(2023)
Article
Biochemistry & Molecular Biology
David Bacelar Costa Junior, Janay Stefany Carneiro Araujo, Larissa de Mattos Oliveira, Flavio Simas Moreira Neri, Paulo Otavio Lourenco Moreira, Alex Gutterres Taranto, Amanda Luisa Fonseca, Fernando de Pilla Varotti, Franco Henrique Andrade Leite
Summary: Malaria, caused by Plasmodium spp., remains a significant public health issue with drug resistance limiting chemotherapy. By exploring essential therapeutic targets of the parasite, a potential new antimalarial molecule with activity comparable to artemether was identified through virtual screening. This molecule, previously used in traditional Chinese medicine, may offer a repurposing opportunity to expedite drug development. Molecular dynamics studies confirmed the stability of molecular interactions, paving the way for further research on new derivatives for in vitro and in vivo evaluation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Immunology
Da Li, Long He, Chang Yuan, Yanqiu Ai, Jian-Jun Yang
Summary: The PPAR gamma agonist pioglitazone can alleviate hemorrhage-induced thalamic pain by suppressing the NF-kappa B inflammasome and activating the STAT6 signal pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Miah Roney, A. K. M. Moyeenul Huq, Abdul Rashid Issahaku, Mahmoud E. S. Soliman, Md. Sanower Hossain, Abu Hasnat Mustafa, Md. Alimul Islam, Amit Dubey, Aisha Tufail, Mohd Fadhlizil Fasihi Mohd Aluwi, Saiful Nizam Tajuddin
Summary: Dengue fever is a significant global public health concern, causing hundreds of thousands of hospitalizations and deaths each year. This study aimed to discover a new anti-dengue therapy by using computer-based approaches. Natural products were screened using a pharmacophore model, and compounds with potential inhibitory effects were identified through molecular docking. The lead compound demonstrated promising characteristics for further development as a drug candidate.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Chia-Wei Weng, Chi-Hsuan Wei, Jeng-Yuan Tsai, Yi-Hua Lai, Gee-Chen Chang, Jeremy J. W. Chen
Summary: In this study, a hybrid virtual screening approach was used to identify a compound with significant inhibitory effects on EGFR activity, and its mechanism of action in lung cancer cells was investigated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yue Zhang, Jiankun Song, Yuanzhang Zhou, Huijun Jia, Tianyu Zhou, Yingbo Sun, Qiong Gao, Yue Zhao, Yujie Pan, Zhaolin Sun, Peng Chu
Summary: Ubiquitin-specific protease 22 (USP22) plays a prominent role in tumor development and immune reprogramming, and has been proposed as a potential therapeutic target for cancer. Rottlerin and Morusin were discovered as selective and potent USP22 inhibitors, which can increase histone ubiquitination levels and reduce the expression of Sirt1 and PD-L1 proteins. These findings suggest that Rottlerin and Morusin may have potential as drugs for anticancer therapy.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Shizhen Zhao, Xinping Li, Wenjing Peng, Le Wang, Wenling Ye, Yang Zhao, Wenbo Yin, Wei-Dong Chen, Weiguo Li, Yan-Dong Wang
Summary: TGR5 is an emerging target for anti-diabetic drug development, and in this study, common feature pharmacophore models and molecular docking were used to identify novel nonsteroidal TGR5 agonists. Among the 20 compounds screened, V12 and V14 showed promising TGR5 agonistic activity with EC50 values of 19.5 mu M and 7.7 mu M, respectively. These compounds could be potential candidates for TGR5 agonists development.
Letter
Rheumatology
Maja Skov Kragsnaes, Jens Kjeldsen, Hans Christian Horn, Heidi Lausten Munk, Jens Kristian Pedersen, Soren Andreas Just, Palle Ahlquist, Jesper Romhild Davidsen, Anna Christine Nilsson, Richard Rottger, Mogens Kruhoffer, Julian R. Marchesi, Karsten Kristiansen, Robin Christensen, Torkell Ellingsen
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Biology
Ke-Xu Xiong, Han-Lin Zhou, Cong Lin, Jian-Hua Yin, Karsten Kristiansen, Huan-Ming Yang, Gui-Bo Li
Summary: An ensemble machine learning algorithm called Chord was developed to address the unmet need for a suitable doublet detection method in scRNA-seq analysis. Chord integrates multiple methods and achieves higher accuracy and stability on different datasets. It offers a general solution to the doublet detection problem, with a modular architecture for flexibility and adaptability to incorporate new tools.
COMMUNICATIONS BIOLOGY
(2022)
Article
Nutrition & Dietetics
Chong Wang, Fan Zhao, Yun Bai, Chunbao Li, Xinglian Xu, Karsten Kristiansen, Guanghong Zhou
Summary: In this study, we evaluated the protective effects of six polyphenols on BaP-induced cytotoxicity in Caco-2 cells. Our results showed that eriodictyol was superior to naringenin in protecting against BaP-induced toxicity. Proteomics analysis revealed several key proteins involved in the protective mechanisms of eriodictyol.
FRONTIERS IN NUTRITION
(2022)
Article
Chemistry, Applied
Chong Wang, Fan Zhao, Yun Bai, Chunbao Li, Xinglian Xu, Karsten Kristiansen, Guanghong Zhou
Summary: Among the physiological functions declining with aging, decreased secretion of gastric fluid, achlorhydria, is commonly observed. We evaluated the digestion of meat and soy proteins using in vitro conditions mimicking gastrointestinal digestion in adults (control, C) and elderly individuals with achlorhydria (EA). Our results showed significant decrease in protein digestion, particularly for soy proteins, under EA conditions. We also found that myofibrillar/sarcoplasmic proteins from meat and glycinin/beta-conglycinin from soy were most affected by digestion conditions. Our work provides new insight for dietary recommendations for elderly individuals.
Article
Microbiology
Timothy James Russell, Erandi K. De Silva, Valerie M. Crowley, Kathryn Shaw-Saliba, Namita Dube, Gabrielle Josling, Charisse Flerida A. Pasaje, Irene Kouskoumvekaki, Gianni Panagiotou, Jacquin C. Niles, Marcelo Jacobs-Lorena, C. Denise Okafor, Francisco-Javier Gamo, Manuel Llinas
Summary: This study identifies a novel set of antimalarial compounds that interact with the AP2 DNA binding domains, offering potential targets for future antimalarial therapeutics or chemical genetic interrogation of ApiAP2 proteins.
Review
Biochemistry & Molecular Biology
Finn E. von Eyben, Karsten Kristiansen, Daniel S. Kapp, Rong Hu, Ovidiu Preda, Francisco F. Nogales
Summary: This review summarizes the literature on the gene expression and epigenetic regulation of germ cell tumors of the testis type II (TGCT). The seminoma subtype of TGCT expresses a panel of induced pluripotent stem cell (iPSC) with four upregulated genes, while the embryonal carcinoma (EC) subtype has a different set of four upregulated genes. The epigenetic mechanisms, such as DNA methylation and histone modifications, regulate the expression of these driver genes and contribute to the clinical characteristics of TGCT.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Ecology
Jacob A. Rasmussen, Pia Kiilerich, Abdullah S. Madhun, Rune Waagbo, Erik-Jan R. Lock, Lise Madsen, M. Thomas P. Gilbert, Karsten Kristiansen, Morten T. Limborg
Summary: Understanding the evolutionary relationships between a host and its intestinal resident bacteria can transform our understanding of adaptive phenotypic traits. This study reveals a strong co-evolution between the population structure of Atlantic salmon and nucleotide variability of the intestinal Mycoplasma populations, indicating an interplay between the host and its resident bacteria.
Article
Immunology
Daniel Andersen, Janne Marie Moll, Pankaj Arora, Niels Banhos Danneskiold-Samsoe, Si Brask Sonne, Christopher Thomas Workman, Andrew Richard Williams, Karsten Kristiansen, Susanne Brix
Summary: Intestinal tuft cells and immune responses were examined in mice fed a high-fat diet and gavaged with helminth PCF. Helminth PCF upregulated gene expression in tuft cells and increased levels of innate lymphoid cells and eosinophils. Network analyses revealed immunometabolic cues linking tuft cell response to fat mass ratio and eosinophils in eWAT to body fat mass regulation.
PARASITE IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Xiaoqian Lin, Tongyuan Hu, Jianwei Chen, Hewei Liang, Jianwei Zhou, Zhinan Wu, Chen Ye, Xin Jin, Xun Xu, Wenwei Zhang, Xiaohuan Jing, Tao Yang, Jian Wang, Huanming Yang, Karsten Kristiansen, Liang Xiao, Yuanqiang Zou
Summary: The authors present an expanded version of the Cultivated Genome Reference (CGR), termed CGR2, which includes 3324 high-quality draft genomes based on gut bacterial isolates from Chinese individuals. They classify 527 species from 8 phyla, including 179 previously unidentified species, and provide information on secondary metabolite biosynthetic gene clusters and gut phage-bacteria interactions.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Valdemar Brimnes Ingemann Johansen, Daisy Faero, Karsten Buschard, Karsten Kristiansen, Flemming Pociot, Pia Kiilerich, Knud Josefsen, Martin Haupt-Jorgensen, Julie Christine Antvorskov
Summary: The incidence of type 1 diabetes is increasing and environmental factors are believed to contribute to it. A gluten-free diet has been shown to improve autoimmune diabetes in non-obese diabetic (NOD) mice and humans. This study conducted analysis of gut microbiota and pancreatic immune environment in NOD mice fed a gluten-free (GF) diet and a gluten-containing standard (STD) diet. The results revealed distinct microbiota compositions and reduced insulitis in GF mice, suggesting a protective effect of a GF diet in humans.
Article
Food Science & Technology
Atabak M. Azad, Annette Bernhard, Anne Shen, Lene Secher Myrmel, Anne-Katrine Lundebye, Laurene Alicia Lecaudey, Even Fjaere, Quang Tri Ho, Harald Sveier, Karsten Kristiansen, Morten Tonsberg Limborg, Lise Madsen
Summary: Alternative feed ingredients, such as blue mussel meal, can replace fish meal in farmed salmon feed without adversely affecting the fatty acid content of the fish. This study also found that including blue mussel meal in a meat-based diet led to a dose-dependent increase in the fatty acid ratios in mice livers.
FOOD RESEARCH INTERNATIONAL
(2023)
Article
Cell Biology
Mueez U-Din, Vanessa D. de Mello, Marjo Tuomainen, Juho Raiko, Tarja Niemi, Tobias Fromme, Anton Klavus, Nadine Gautier, Kimmo Haimilahti, Marko Lehtonen, Karsten Kristiansen, John W. Newman, Kirsi H. Pietilaeinen, Jussi Pihlajamaeki, Ez-Zoubir Amri, Martin Klingenspor, Pirjo Nuutila, Eija Pirinen, Kati Hanhineva, Kirsi A. Virtanen
Summary: Cold stimulates NAD+ metabolism in humans and may be regulated by multiple tissues.
Article
Food Science & Technology
Maria Marinaki, Ioannis Sampsonidis, Alexandros Nakas, Panagiotis Arapitsas, Andreana N. Assimopoulou, Georgios Theodoridis
Summary: This study aimed to characterize the volatilome of Tsipouro products and found that Tsipouro from different regions and production styles has a high aroma variability. Aniseed spirits from Northern Greece, Macedonia, Limnos Island, and Thessaly were found to be rich in terpenes, terpenoids, and flavored compounds. Different terpenoids were dominant in Muscat distillates from different regions, showing the importance of geographical origin and production process. These results could contribute to better protection of the origin of Tsipouro and improvement of its quality.
Article
Rheumatology
Maja Skov Kragsnaes, Jesus Miguens Blanco, Benjamin H. Mullish, Jose Ivan Contreras-Serrano, Jens Kjeldsen, Hans Christian Horn, Jens Kristian Pedersen, Heidi Lausten Munk, Anna Christine Nilsson, Ash Salam, Matthew R. Lewis, Elena Chekmeneva, Karsten Kristiansen, Julian R. Marchesi, Torkell Ellingsen
Summary: This study investigated the intestinal permeability and metabolomic profiles in methotrexate-treated psoriatic arthritis patients, and their relationship with clinical response. The results showed that intestinal permeability and metabolomic profiles were associated with the primary clinical trial end point.
ACR OPEN RHEUMATOLOGY
(2023)
Article
Cell Biology
Liang Sun, Zhiming Li, Caiyou Hu, Jiahong Ding, Qi Zhou, Guofang Pang, Zhu Wu, Ruiyue Yang, Shenghui Li, Jian Li, Jianping Cai, Yuzhe Sun, Rui Li, Hefu Zhen, Shuqin Sun, Jianmin Zhang, Mingyan Fang, Zhihua Chen, Yuan Lv, Qizhi Cao, Yanan Sun, Ranhui Gong, Zezhi Huang, Yong Duan, Hengshuo Liu, Jun Dong, Junchun Li, Jie Ruan, Haorong Lu, Benjin He, Ninghu Li, Tao Li, Wenbin Xue, Yan Li, Juan Shen, Fan Yang, Cheng Zhao, Qinghua Liang, Mingrong Zhang, Chen Chen, Huan Gong, Yong Hou, Jian Wang, Ying Zhang, Huanming Yang, Shida Zhu, Liang Xiao, Zhen Jin, Haiyun Guo, Peng Zhao, Susanne Brix, Xun Xu, Huijue Jia, Karsten Kristiansen, Ze Yang, Chao Nie
Summary: This study analyzed the gut microbiota and serum metabolome of individuals from a Chinese longevity cohort, as well as two other aging cohorts, and discovered age-dependent differences in both microbiota and serum metabolome. They also found potential causal relationships between specific gut microbes and serum metabolite markers related to impaired renal function and aging. The findings provide valuable insights into the effects of microbiota-metabolite interplay on renal function and healthy aging.