Article
Biochemistry & Molecular Biology
Alice H. Grant, Alejandro C. Rodriguez, Omar J. Rodriguez J. Moncivais, Shengjie Sun, Lin Li, Jonathon E. Mohl, Ming-Ying Leung, Robert A. Kirken, Georgialina Rodriguez
Summary: Overactive Janus kinases (JAKs) are potential targets for leukemia treatment. However, a JAK1-inactivating pseudokinase mutation, V666G, was discovered instead of new JAK-activating mutations. Unlike other pseudokinase mutations, the JAK1 V666G mutation led to under-activation. It not only inhibited its own activity but also other JAK kinases. These findings provide insights into the potential modulation of JAK kinases by the JAK1 pseudokinase and the opportunity to allosterically inhibit overactive JAKs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Tinglei Huang, Biying Chen, Feng Wang, Weiyang Cai, Xinxin Wang, Bo Huang, Feng Liu, Bin Jiang, Yanjie Zhang
Summary: This study found that Rab1A overexpression in non-small cell lung cancer is significantly correlated with aggressive tumor growth and metastasis by activating the JAK1/STAT6 signaling pathway. Additionally, Rab1A levels also impact sensitivity to JAK1 inhibitors, potentially enhancing the efficacy of JAK1-targeted cancer therapy.
Article
Immunology
Holly Bachus, Erin McLaughlin, Crystal Lewis, Amber M. Papillion, Etty N. Benveniste, Dave Durell Hill, Alexander F. Rosenberg, Andre Ballesteros-Tato, Beatriz Leon
Summary: Defective IL-6 signaling is linked to Th2 bias and elevated IgE levels. The study reveals that IL-6 signaling in allergen-specific T cells is necessary to prevent Th2 cell differentiation, IgE response, and allergic inflammation. IL-6 inhibits IL-2 signaling through upregulation of SOCS3, thus preventing Th2 priming.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Zhiping Liu, Wen Xu, Xiansheng Tan, Chunhua Li
Summary: Lung cancer stem cells (CSCs) have self-renewal capability and SH3BGRL plays a role in suppressing lung CSCs self-renewal, showing potential as a therapeutic target and prognostic marker for lung cancer patients.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Endocrinology & Metabolism
Yen-Shuo Chiu, Oluwaseun Adebayo Bamodu, Iat-Hang Fong, Wei-Hwa Lee, Chih-Cheng Lin, Chen-Hsu Lu, Chi-Tai Yeh
Summary: Research has revealed that miR-149-5p is downregulated in clinical OA samples, contributing to chronic inflammation by increasing TNF-alpha/IL-6 signaling within the synovium and OA progression. Additionally, therapeutic effects of tofacitinib, a JAK inhibitor, were evaluated in in vitro and in vivo OA models, showing potential in suppressing inflammation and restoring miR-149-5p expression.
Article
Multidisciplinary Sciences
Uddhav Timilsina, Supawadee Umthong, Emily B. Ivey, Brandon Waxman, Spyridon Stavrou
Summary: The cellular protein SERINC5, which restricts retroviruses, has been found to also inhibit the entry of SARS-CoV-2 by blocking virus-cell fusion. However, the viral protein ORF7a counteracts the antiviral effect of SERINC5 by preventing its incorporation into newly formed viral particles.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Yinan Wang, Chuanhe Yang, Michelle M. Sims, Joshua R. Sacher, Mithun Raje, Hemantkumar Deokar, Peibin Yue, James Turkson, John K. Buolamwini, Lawrence M. Pfeffer
Summary: In this study, a novel small molecule SS-4 was designed to specifically interact with STAT3 and showed strong inhibition of Y705 phosphorylation. SS-4 induced apoptosis and inhibited proliferation in GBM cells in a Y705 phosphorylation-dependent manner. It also had anti-tumor effects in vivo, suggesting its potential as a therapeutic agent for GBM.
Article
Virology
Qiaoshuai Lan, Jasper Fuk-Woo Chan, Wei Xu, Lijue Wang, Fanke Jiao, Guangxu Zhang, Jing Pu, Jie Zhou, Shuai Xia, Lu Lu, Kwok-Yung Yuen, Shibo Jiang, Qian Wang
Summary: Cholesterol-conjugated, peptide-based pan-coronavirus fusion inhibitors have been shown to effectively inhibit human coronavirus infection. A newly developed lipopeptide drug called EK1-C16, modified with palmitic acid (C16), has demonstrated potent inhibition against SARS-CoV-2 and its variants, as well as other human CoVs and bat SARS-related CoVs. This suggests that EK1-C16 could be a promising candidate for the prevention and treatment of current and future coronaviruses.
Article
Orthopedics
Yunzhou Zuo, Changjun Xiong, Xuewen Gan, Wei Xie, Xiaokang Yan, Yanzhao Chen, Xugui Li
Summary: This study reveals that lncRNA HAGLR can play a role in osteoarthritis (OA) through the miR-130a-3p/JAK1 axis.
JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Petra Luschnig, Melanie Kienzl, David Roula, Johannes Pilic, Reham Atallah, Akos Heinemann, Eva M. Sturm
Summary: Baricitinib, a JAK1/2 inhibitor, was found to be more potent in suppressing eosinophil effector function compared to the JAK3 inhibitor tofacitinib.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Medicine, General & Internal
Zhanying Hou, Xuehan Su, Guangming Han, Ruzeng Xue, Yangxia Chen, Ye Chen, Huan Wang, Bin Yang, Yunsheng Liang, Suyun Ji
Summary: This study found that JAK1 and JAK2 inhibitors have significant efficacy in alleviating skin fibrosis and digital ulcers in systemic sclerosis (SSc) patients. Baricitinib, an oral JAK1/2 inhibitor, is a potentially effective treatment for SSc patients with skin fibrosis and ulcers, with good tolerability. Further large-scale clinical trials are needed to confirm these preliminary findings.
FRONTIERS IN MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Lian Lu, Yun Peng, Huiqiao Yao, Yanqun Wang, Jinyu Li, Yang Yang, Zhonghui Lin
Summary: This study identified a novel coronavirus helicase inhibitor punicalagin (PUG) through high-throughput screening. The research showed that PUG directly binds to NSP13 and inhibits its activity, effectively suppressing the replication of SARS-CoV-2. This work demonstrates the potential application of PUG in the treatment of COVID-19 and provides an allosteric inhibition mechanism for future drug design targeting viral helicases.
ANTIVIRAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Wei Wei, Ni Kong, Meng-Zhen Liu, Ting Han, Jun-Feng Xu, Chong Liu
Summary: This study found that anisodamine suppressed SARS-CoV-2 infection in Vero E6 cells and reduced SARS-CoV-2 pseudovirus entry in HEK293/hACE2 cells. Molecular docking studies suggested that anisodamine may target SARS-CoV-2 main protease (Mpro) with a docking score of -6.63 kcal/mol and form three hydrogen bonds at the predicted active site of Mpro.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Xing-Kai Qian, Jing Zhang, Pei-Fang Song, Yi-Su Zhao, Hong-Ying Ma, Qiang Jin, Dan-Dan Wang, Xiao-Qing Guan, Shi-Yang Li, XiaoZe Bao, Li-Wei Zou
Summary: Carboxylesterase 2 (CES2) is a crucial Phase I drug metabolizing enzyme with significant roles in mediating the effects of certain anticancer drugs. Through synthesizing a series of pyrazolones and analyzing their inhibitory effects against CES2, researchers identified compound 27 as a potent inhibitor with the ability to also inhibit adipocyte adipogenesis. These findings suggest compound 27 could serve as a valuable lead compound for developing more powerful CES2 inhibitors and exploring CES2's biological functions in humans.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Wei-Chung Chiou, Guan-Jhong Huang, Tein-Yao Chang, Tzu-Lan Hsia, Hao-You Yu, Jir-Mehng Lo, Pin-Kuei Fu, Cheng Huang
Summary: The study found that OVA can effectively inhibit SARS-CoV-2 infection and improve pulmonary fibrosis. The results showed that OVA is an effective 3CLpro inhibitor of SARS-CoV-2 and has remarkable inhibitory activity against SARS-CoV-2 infection. In addition, OVA can reduce inflammatory cell infiltration and collagen deposition, as well as the levels of pulmonary hydroxyproline, myeloperoxidase, TNF-alpha, IL-1 beta, IL-6, and TGF-beta in the lung. In other words, OVA not only helps fight against SARS-CoV-2 infection, but also helps manage injury-induced pulmonary fibrosis.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Ileana Montoya Perez, Harri Merisaari, Ivan Jambor, Otto Ettala, Pekka Taimen, Juha Knaapila, Henna Kekki, Ferdhos L. Khan, Elise Syrjala, Aida Steiner, Kari T. Syvanen, Janne Verho, Marjo Seppanen, Antti Rannikko, Jarno Riikonen, Tuomas Mirtti, Tarja Lamminen, Jani Saunavaara, Ugo Falagario, Alberto Martini, Tapio Pahikkala, Kim Pettersson, Peter J. Bostrom, Hannu J. Aronen
Summary: This study aimed to develop and validate radiomics and kallikrein models for the detection of clinically significant prostate cancer. The results showed that the use of radiomics and kallikreins did not outperform PI-RADSv2.1/IMPROD bpMRI Likert, and their combination did not lead to further performance gains.
JOURNAL OF MAGNETIC RESONANCE IMAGING
(2022)
Article
Urology & Nephrology
Utku Lokman, Hanna Vasarainen, Kanerva Lahdensuo, Andrew Erickson, Timo Muhonen, Tuomas Mirtti, Antti Rannikko
Summary: This study aimed to prospectively study long-term changes in quality of life (QoL) in a contemporary active surveillance (AS) patient cohort with low-risk prostate cancer. The results showed that AS does not impair general QoL and patients undergoing treatment change also did not experience a decrease in QoL.
EUROPEAN UROLOGY FOCUS
(2022)
Article
Urology & Nephrology
Antti Rannikko, Mare Leht, Tuomas Mirtti, Anu Kenttamies, Teemu Tolonen, Irina Rinta-Kiikka, Tuomas P. Kilpelainen, Kari Natunen, Hans Lilja, Terho Lehtimaki, Jani Raitanen, Paula Kujala, Johanna Ronkainen, Mika Matikainen, Anssi Petas, Kimmo Taari, Teuvo Tammela, Anssi Auvinen
Summary: This study evaluated the feasibility of a population-based screening trial using PSA, a kallikrein panel, and MRI. The findings showed that the screening protocol was able to minimize overdiagnosis while retaining mortality benefit, and achieved a substantial detection rate for clinically significant prostate cancer. However, participation rate needs improvement.
Article
Oncology
Veronique Ouellet, Andrew Erickson, Kathy Wiley, Colm Morrissey, Viktor Berge, Carlos S. Moreno, Kristin Austlid Tasken, Dominique Trudel, Lawrence D. True, Michael S. Lewis, Aud Svindland, Onur Ertunc, Igor Damasceno Vidal, Adeboye O. Osunkoya, Tracy Jones, G. Steven Bova, Tarja Lamminen, Ariel H. Achtman, Mark Buzza, Michelle M. Kouspou, Steven A. Bigler, Xinchun Zhou, Stephen J. Freedland, Anne-Marie Mes-Masson, Isla P. Garraway, Bruce J. Trock, Pekka Taimen, Fred Saad, Tuomas Mirtti, Beatrice S. Knudsen, Angelo M. De Marzo
Summary: This study has successfully constructed a unique and richly annotated tissue microarray using prostate cancer samples from multiple institutions. It aims to validate biomarkers and address important clinical questions regarding prostate cancer progression and treatment response.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Multidisciplinary Sciences
Lassi Luomala, Juhana Rautiola, Petrus Jarvinen, Tuomas Mirtti, Harry Nisen
Summary: This study evaluated and compared the oncological and pathological outcomes of Bosniak IIF-IV complex cystic renal masses (CRM) treated by initial surgery or active surveillance. The results showed that active surveillance is safe for Bosniak IIF and III categories, while surgery remains the primary treatment for Bosniak IV due to its high malignancy rate.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Moon Hee Lee, Essi Laajala, Anna Kreutzman, Petrus Jarvinen, Harry Nisen, Tuomas Mirtti, Maija Hollmen, Satu Mustjoki
Summary: This study comprehensively investigated the cytokine landscape of renal cell carcinoma (RCC) tumors and explored the correlation between tumor infiltrating lymphocytes (TILs) and cytokine expressions. The results showed distinct differences in cytokine profiles between tumor and adjacent renal tissue samples, with most tumor cytokines positively correlated with each other. The quantity of lymphocytes in tumor samples was positively correlated with specific chemokine-family cytokines.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Hannu Koistinen, Ruusu-Maaria Kovanen, Morley D. Hollenberg, Antoine Dufour, Evette S. Radisky, Ulf-Hakan Stenman, Jyotsna Batra, Judith Clements, John D. Hooper, Eleftherios Diamandis, Oliver Schilling, Antti Rannikko, Tuomas Mirtti
Summary: Since the proposition of the pro-invasive activity of proteolytic enzymes over 70 years ago, several roles for proteases in cancer progression have been established. About half of the 473 active human proteases are expressed in the prostate and many of the most well-characterized members of this enzyme family are regulated by androgens, hormones essential for development of prostate cancer. Most notably, several kallikrein-related peptidases, including KLK3 (prostate-specific antigen, PSA), the most well-known prostate cancer marker, and type II transmembrane serine proteases, such as TMPRSS2 and matriptase, have been extensively studied and found to promote prostate cancer progression. Recent findings also suggest a critical role for proteases in the development of advanced and aggressive castration-resistant prostate cancer (CRPC). Perhaps the most intriguing evidence for this role comes from studies showing that the protease-activated transmembrane proteins, Notch and CDCP1, are associated with the development of CRPC.
Article
Oncology
Anna Aakula, Aleksi Isomursu, Christian Rupp, Andrew Erickson, Nikhil Gupta, Otto Kauko, Pragya Shah, Artur Padzik, Yuba Raj Pokharel, Amanpreet Kaur, Song-Ping Li, Lloyd Trotman, Pekka Taimen, Antti Rannikko, Jan Lammerding, Ilkka Paatero, Tuomas Mirtti, Johanna Ivaska, Jukka Westermarck
Summary: This study found that prostate cancer tumors with concomitant inhibition of PP2A and PTEN are particularly aggressive, with low patient survival rates. Overexpression of PME-1 inhibits anoikis in PTEN-deficient prostate cancer cells. The results suggest that PME-1 may be a candidate biomarker for particularly aggressive PTEN-deficient prostate cancer.
MOLECULAR ONCOLOGY
(2023)
Article
Oncology
Timo-Pekka K. Lehto, Ruusu-Maaria Kovanen, Susanna Lintula, Adrian Malen, Carolin Sturenberg, Andrew Erickson, Olli-Pekka Pulkka, Ulf-Hakan Stenman, Eleftherios P. Diamandis, Antti Rannikko, Tuomas Mirtti, Hannu Koistinen
Summary: This study aimed to investigate the mRNA levels and prognostic impact of all 15 human kallikrein-related peptidases (KLKs) and their targets, proteinase-activated receptors (PARs), in surgically treated prostate cancer (PCa). The results showed that the expression of KLK2, KLK3, KLK4, and KLK15 was closely associated with tumor aggressiveness and prognosis, suggesting their potential as prognostic biomarkers for PCa.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Biochemical Research Methods
Anni S. S. Halkola, Kaisa Joki, Tuomas Mirtti, Marko M. M. Maekelae, Tero Aittokallio, Teemu D. D. Laajala
Summary: This paper presents a novel methodology for feature subset selection based on the L-0 pseudonorm, which has advantages in clinical applicability, selection of grouped features, and analysis of high-dimensional transcriptomics data. The methodology is benchmarked against existing regularization methods and shows superior performance.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Cell Biology
Rim Bouslama, Vincent Dumont, Sonja Lindfors, Lassi Paavolainen, Jukka Tienari, Harry Nisen, Tuomas Mirtti, Moin A. Saleem, Daniel Gordin, Per-Henrik Groop, Shiro Suetsugu, Sanna Lehtonen
Summary: Changes in the podocytes, the glomerular epithelial cells, can lead to kidney dysfunction. The phosphorylation of PACSIN2 at serine 313 (S313) is increased in the glomeruli of rats with diabetic kidney disease, and this phosphorylation is associated with kidney dysfunction and increased free fatty acids. PACSIN2 phosphorylation is a dynamic process that regulates cell morphology and cytoskeletal arrangement in cooperation with N-WASP. The phosphorylation of PACSIN2 at S313 is important for regulating cytoskeletal reorganization.
Article
Oncology
Timo-Pekka K. Lehto, Juho Pylvalainen, Kevin Sandeman, Anu Kenttamies, Stig Nordling, Ian G. Mills, Jing Tang, Tuomas Mirtti, Antti Rannikko
Summary: Magnetic resonance imaging (MRI) is commonly used for prostate biopsy triage, but a significant number of prostate cancers are not visible using MRI. This study aimed to identify factors associated with MRI visibility and their impact on metastasis and prostate-specific death. The results showed that MRI-visible prostate cancers have more aggressive features and are associated with poor prognosis. Targeted biopsy of visible lesions may be sufficient for risk stratification in MRI-positive patients.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Medicine, Research & Experimental
Tolou Shadbahr, Michael Roberts, Jan Stanczuk, Julian Gilbey, Philip Teare, Soeren Dittmer, Matthew Thorpe, Ramon Vinas Torne, Evis Sala, Pietro Lio, Mishal Patel, Jacobus Preller, James H. F. Rudd, Tuomas Mirtti, Antti Sakari Rannikko, John A. D. Aston, Jing Tang, Carola-Bibiane Schonlieb
Summary: This study demonstrates the importance of evaluating imputation quality when building classification models for incomplete data. The researchers developed a new method for assessing imputation quality and found that a classifier model trained on poorly imputed data can compromise its performance. They also discovered that commonly used measures for assessing imputation quality often result in imputed data that does not match the underlying data distribution.
COMMUNICATIONS MEDICINE
(2023)
Article
Oncology
Moon Hee Lee, Jason Theodoropoulos, Jani Huuhtanen, Dipabarna Bhattacharya, Petrus Jarvinen, Sara Tornberg, Harry Nisen, Tuomas Mirtti, Ilona Uski, Anita Kumari, Karita Peltonen, Arianna Draghi, Marco Donia, Anna Kreutzman, Satu Mustjoki
Summary: In this study, we investigated the expanded tumor-infiltrating lymphocytes (TILs) in patients with renal cell carcinoma (RCC) and explored their characteristics and ability to recognize the tumor using experimental and computational tools.
CANCER RESEARCH COMMUNICATIONS
(2023)
Article
Urology & Nephrology
Magdalena Gongora, Johan Stranne, Eva Johansson, Matteo Bottai, Camilla Thellenberg Karlsson, Klaus Brasso, Steinbjorn Hansen, Henrik Jakobsen, Fredrik Jaderling, Henriette Lindberg, Wolfgang Lilleby, Peter Meidahl Petersen, Tuomas Mirtti, Mats Olsson, Antti Rannikko, Martin Andreas Roder, Per Henrik Vincent, Olof Akre
Summary: The SPCG-15 study provides important evidence for comparing surgery and radiotherapy as primary treatments for locally advanced prostate cancer. The baseline characteristics of the study population demonstrate a high prevalence of advanced disease and well-balanced comparison groups.
EUROPEAN UROLOGY OPEN SCIENCE
(2022)