RET inhibition overcomes resistance to combined CDK4/6 inhibitor and endocrine therapy in ER+ breast cancer by Charlotte K. Kindt, Sidse Ehmsen, Sidse Ehmsen, Sidse Ehmsen, Sofie Traynor, Benedetta Policastro, Nikoline Nissen, Mie K. Jakobsen, Monique F. Hundebøl, Lene E. Johansen, Martin Bak, Elsa Arbajian, Johan Staaf, Henrik J. Ditzel, Henrik J. Ditzel, Henrik J. Ditzel, Carla L. Alves

“…High expression of the receptor tyrosine kinase REarranged during Transfection (RET) has been associated with resistance to endocrine therapy in breast cancer, but the role of RET in CDK4/6i treatment response/resistance remains unexplored.MethodsTo identify gene expression alterations associated with resistance to combined endocrine therapy and CDK4/6i, we performed RNA sequencing of two ER+ breast cancer cell models resistant to this combined therapy. …”
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Effect and Mechanism of Swimming Exercise Preconditioning on Neurological Function of Mice with Intracerebral Hemorrhage by LI Yongxu, LIN Libin, LU Taotao, WEI Wei, LIN Zhicheng, XUE Xiehua

“…ObjectiveTo observe the effect of swimming exercise preconditioning on neurological function and expression levels of brain derived neurotrophic factor (BDNF), serine-threonine kinase (Akt) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) proteins in perihematoma tissues of mice with intracerebral hemorrhage (ICH).MethodsA total of 60 male C57BL/6 mice were randomly divided into sham group, ICH 7 d group, SEP+ICH 7 d group (preconditioning group 1), ICH 14 d group and SEP+ICH 14 d group (preconditioning group 2), with 12 cases in each group. …”
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Efficacy and safety of jaktinib hydrochloride tablets in active axial spondyloarthritis: a multicentre, randomised, double-blind, placebo-controlled phase II clinical trial by Xiaomei Li, Xiaoxia Wang, Jian Wu, Xiao Zhang, Chunde Bao, Shengqian Xu, Lingyun Sun, Juan Wang, Guixiu Shi, Xiaofei Wang, Qing Dai, Antao Xu, Huaxiang Wu, YongQing Wang, Yan Ye, Yongfu Wang, Huaxiang Liu, Chenyin Lv, Jun Miao, Weiqi Min, Kuanting Wang, Luan Xue, Shanhui Ye

“…Objective The objective of this study is to evaluate the efficacy and safety of jaktinib hydrochloride tablets (jaktinib), a Janus kinase inhibitor, in patients with active radiographic axial spondyloarthritis (r-axSpA).Methods Adults with active r-axSpA who met modified New York criteria and had an inadequate response to non-steroidal anti-inflammatory drugs were randomised 1:1:1 to receive jaktinib 75 mg two times per day, 100 mg two times per day, or placebo. …”
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Lactobacillus salivarius metabolite succinate enhances chicken intestinal stem cell activities via the SUCNR1-mitochondria axis by Danni Luo, Minyao Zou, Xi Rao, Mingping Wei, Lingzhi Zhang, Yuping Hua, Lingzi Yu, Jiajia Cao, Jinyi Ye, Sichao Qi, Huanan Wang, Yuling Mi, Caiqiao Zhang, Jian Li

“…Accordingly, succinate could accelerate intestinal epithelial turnover, as indicated by the increased levels of cyclin-dependent kinase 2 (Cdk2) mRNA and proliferating cell nuclear antigen protein (PCNA), as well as ISC differentiation-related protein leucine-rich repeat containing G protein-coupled receptor 5 (LGR5). …”
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Solid Predominant Histology and High Podoplanin Expression in Cancer-Associated Fibroblast Predict Primary Resistance to Osimertinib in EGFR-Mutated Lung Adenocarcinoma by Yuji Uehara, MD, Hiroki Izumi, MD, PhD, Tetsuro Taki, MD, PhD, Tetsuya Sakai, MD, PhD, Hibiki Udagawa, MD, PhD, Eri Sugiyama, MD, PhD, Shigeki Umemura, MD, PhD, Yoshitaka Zenke, MD, PhD, Shingo Matsumoto, MD, PhD, Kiyotaka Yoh, MD, PhD, Shoko Kubota, MD, PhD, Keiju Aokage, MD, PhD, Naoya Sakamoto, MD, PhD, Shingo Sakashita, MD, PhD, Motohiro Kojima, MD, PhD, Michiko Nagamine, MD, PhD, Yukio Hosomi, MD, PhD, Masahiro Tsuboi, MD, PhD, Koichi Goto, MD, PhD, Genichiro Ishii, MD, PhD

“…Introduction: Resistance to EGFR tyrosine kinase inhibitors is influenced by tumor-intrinsic and -extrinsic factors. …”
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Evaluation of rheumatoid arthritis-associated interstitial lung disease in patients treated with JAK inhibitors: a MAJIK-SFR cohort study by Adeline Ruyssen-Witrand, Jacques-Eric Gottenberg, Philippe Dieude, Rene-Marc Flipo, Jerome Avouac, Emanuelle Dernis, Anne Tournadre, Marie-Elise Truchetet, Raphaele Seror, André Ramon, Nicolas Roux, André Basch, Pascal Chazerain, Fabienne Coury-Lucas, Richard Damade, Pierre-Antoine Juge, Thao Pham, Clément Prati, Olivier Brocq, Jean Hugues Salmon, Christian hubert roux, Félicien Triboulet, Charles Leské, Émilie Shipley

“…Objective To examine the course of interstitial lung disease associated with rheumatoid arthritis (RA-ILD) in France on treatment with Janus kinase inhibitors (JAKis) using the MAJIK-SFR registry.Methods Prospective national multicentre observational study identifying patients with RA-ILD from the MAJIK-SFR registry. …”
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Monitoring of Circulating Tumor DNA and Indication of De-Escalation Adjuvant Targeted Therapy for EGFR-Mutated NSCLC After Complete Resection by Song Dong, PhD, Bingfa Yan, PhD, Si-Yang Liu, PhD, Xuan Gao, PhD, Hui-Zhao Hong, MD, Hong-Ji Li, MD, Wei Gao, PhD, Hong-Hong Yan, PhD, Si-Yang Maggie Liu, PhD, Hai-Yan Tu, PhD, Yi Pan, PhD, Qing Zhou, PhD, Xue-Ning Yang, PhD, Xue-Feng Xia, PhD, Xin Yi, PhD, Wen-Zhao Zhong, PhD, Yi-Long Wu, MD, Jia-Tao Zhang, PhD

“…Introduction: EGFR tyrosine kinase inhibitor (TKI) is the standard adjuvant treatment for patients with stages IB to IIIA EGFR-mutated NSCLC. …”
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Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosine by Juliana Escher Toller-Kawahisa, Paula Ramos Viacava, Eva Margareta Palsson-McDermott, Daniele Carvalho Nascimento, Mariana Patricia Cervantes-Silva, Shane Myles O'Carroll, Alessia Zotta, Luis Eduardo Alves Damasceno, Gabriel Azevedo Públio, Pedro Forti, João Paulo Mesquita Luiz, Bruno Marcel Silva de Melo, Timna Varela Martins, Vitor Marcel Faça, Annie Curtis, Thiago Mattar Cunha, Fernando de Queiroz Cunha, Luke Anthony John O'Neill, José Carlos Alves-Filho

“…The tetramerization of the glycolytic enzyme pyruvate kinase M2 (PKM2) induces the production of the anti-inflammatory cytokine interleukin (IL)-10 in vivo, but the underlying mechanism remains elusive. …”
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Activity of CDK4/6 inhibitors and parameters affecting survival in elderly patients in age-subgroups: Turkish Oncology Group (TOG) retrospective study by Seda Kahraman, Mutlu Hizal, Burcin Cakan Demirel, Deniz Can Guven, Ozge Gumusay, Basak Oyan Uluc, Ertugrul Bayram, Burcu Gulbagci, Alper Yasar, Sena Ece Davarci, Eda Eylemer Mocan, Omer Acar, Deniz Isik, Esra Aydin, Yusuf Karakas, Melike Ozcelik, Murat Keser, Sadi Kerem Okutur, Onder Eren, Serkan Menekse, Dincer Aydin, Funda Yilmaz, Ozlem Dogan, Gulhan Ozkanli, Hakan Yucel, Veli Sunar, Musa Baris Aykan, Ozlem Ozdemir, Berna Bozkurt Duman, Merve Keskinkilic, Teoman Sakalar, Ali Inal, Muge Karaoglanoglu, Asude Aksoy, Muhammed Muhiddin Er, Nazim Serdar Turhal, Nurhan Onal Kalkan, Mehmet Ali Nahit Sendur

“…Abstract Highly selective inhibitors of cyclin-dependent kinase 4 and 6 (CDK4/6is) have emerged as a standart of care for first- and second-line therapies in combination with endocrine therapy (ET) for HR+/HER2- metastatic breast cancer (MBC) patients. …”
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Biosynthesis inhibition of miR-142-5p in a N 6-methyladenosine-dependent manner induces neuropathic pain through CDK5/TRPV1 signaling by Jinshi Li, Yang Guo, Chen Zhu, Dongxu Wang, Yuan Li, Xiaotong Hao, Linyan Cao, Yiting Fan, Bo Fang

“…This study aims to investigate the regulation of transient receptor potential vanilloid 1 (TRPV1) and cyclin-dependent kinase 5 (CDK5) expression levels by miR-142-5p as a common upstream molecule, and to delve into the mature process of miR-142-5p from the perspective of N 6-methyladenosine (m6A) modification. …”
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Dual specific STAT3/5 degraders effectively block acute myeloid leukemia and natural killer/T cell lymphoma by Daniel Pölöske, Helena Sorger, Anna Schönbichler, Elvin D. deAraujo, Heidi A. Neubauer, Anna Orlova, Sanna H. Timonen, Diaaeldin I. Abdallah, Aleksandr Ianevski, Heikki Kuusanmäki, Marta Surbek, Elisabeth Heyes, Thomas Eder, Christina Wagner, Tobias Suske, Martin L. Metzelder, Michael Bergmann, Maik Dahlhoff, Florian Grebien, Roman Fleck, Christine Pirker, Walter Berger, Emir Hadzijusufovic, Wolfgang R. Sperr, Lukas Kenner, Peter Valent, Tero Aittokallio, Marco Herling, Satu Mustjoki, Patrick T. Gunning, Richard Moriggl

“…Current therapeutic strategies focus on blocking upstream tyrosine kinases to inhibit STAT3/5, but these kinase blockers are not selective against STAT3/5 activation and frequent resistance causes relapse, emphasizing the need for targeted drugs. …”
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Natural products targeting AMPK signaling pathway therapy, diabetes mellitus and its complications by Min Li, Lu Ding, Lu Ding, Liyan Cao, Zepeng Zhang, Xueyan Li, Zirui Li, Qinjing Xia, Kai Yin, Siyu Song, Zihan Wang, Haijian Du, Daqing Zhao, Xiangyan Li, Zeyu Wang, Zeyu Wang

“…The adenylate-activated protein kinase (AMPK) signaling pathway is crucial in regulating cellular energy metabolism, marking it as a significant therapeutic target for diabetes and related complications. …”
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Durvalumab, Tremelimumab, and Platinum Chemotherapy in EGFR Mutation–Positive NSCLC: An Open-Label Phase 2 Trial (ILLUMINATE) by Chee Khoon Lee, PhD, Bin-Chi Liao, MD, Shalini Subramaniam, MMed (Clin Epi), Chao-Hua Chiu, MD, Antony J. Mersiades, MMed (Clin Epi), Chao-Chi Ho, MD, PhD, Chris Brown, MBiostats, Chun-Liang Lai, MD, PhD, Brett G.M. Hughes, M.B.B.S. (Hons), Tsung-Ying Yang, MD, PhD, Ken O’Byrne, MD, Yung-Hung Luo, MD, PhD, Sonia Yip, PhD, Ching-Liang Ho, MD, Victoria Bray, PhD, Wu-Chou Su, MD, PhD, Melissa Moore, PhD, Wei-Lien Feng, MS, Ya-Ying Bai, MS, Kate Ford, MHSc, Michelle M. Cummins, PhD, Martin R. Stockler, MSc (Clin Epi), Benjamin J. Solomon, PhD, Thomas John, PhD, James Chih-Hsin Yang, MD, PhD

“…We conducted a phase 2 trial to determine the efficacy of durvalumab, tremelimumab, and platinum-pemetrexed in EGFR-mutant NSCLC after progression with EGFR tyrosine kinase inhibitors (TKIs). Methods: Participants were treated with induction durvalumab, tremelimumab, and platinum-pemetrexed, followed by durvalumab-pemetrexed maintenance. …”
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VCP downstream metabolite glycerol-3-phosphate (G3P) inhibits CD8+T cells function in the HCC microenvironment by Cheng Cheng, Qingrui Zha, Linmao Sun, Tianming Cui, Xinyu Guo, Changjian Xing, Zhengxiang Chen, Changyong Ji, Shuhang Liang, Shengwei Tao, Junhui Chu, Chenghui Wu, Qi Chu, Xuetian Gu, Ning Zhang, Yumin Fu, Shumin Deng, Yitong Zhu, Jiabei Wang, Yao Liu, Lianxin Liu

“…The accumulated G3P diffuses into the TME and directly interacts with SRC-family tyrosine kinase LCK, a critical component of the T-cell receptor (TCR) signaling pathway in CD8+T cells. …”
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AlphaFold-based AI docking reveals AMPK/SIRT1-TFEB pathway modulation by traditional Chinese medicine in metabolic-associated fatty liver disease by Lulu Zhang, Yi Zheng, Mingyan Shao, Aiping Chen, Meiyi Liu, Wenlong Sun, Tianxing Li, Yini Fang, Yang Dong, Shipeng Zhao, Hui Luo, Juan Feng, Qi Wang, Lingru Li, Yanfei Zheng

“…QGJZF upregulated the expressions of phosphorylated -Adenosine 5‘-monophosphate (AMP) - activated protein kinase (p-AMPK), Sirtuin deacetylase 1 (SIRT1) and Transcription factor EB (TFEB), accompanied by the changes in autophagy-related proteins. …”
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Therapeutic role of miR-26a on cardiorenal injury in a mice model of angiotensin-II induced chronic kidney disease through inhibition of LIMS1/ILK pathway by Weijie Ni, Yajie Zhao, Jinxin Shen, Qing Yin, Yao Wang, Zuolin Li, Taotao Tang, Yi Wen, Yilin Zhang, Wei Jiang, Liangyunzi Jiang, Jinxuan Wei, Weihua Gan, Aiqing Zhang, Xiaoyu Zhou, Bin Wang, Bi-Cheng Liu, Yuanyuan Ji

“…Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. …”
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Lactobacillus reuteri LR1 Improved Expression of Genes of Tight Junction Proteins via the MLCK Pathway in IPEC-1 Cells during Infection with Enterotoxigenic Escherichia coli K88 by Hongbo Yi, Li Wang, Yunxia Xiong, Zhilin Wang, Yueqin Qiu, Xiaolu Wen, Zongyong Jiang, Xuefen Yang, Xianyong Ma

“…By using ML-7, a selective inhibitor of myosin light-chain kinase (MLCK), the beneficial effect of L. reuteri LR1 on contents of ZO-1 and occludin was shown to be dependent on the MLCK pathway. …”
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Protective mechanism of safflower yellow injection on myocardial ischemia-reperfusion injury in rats by activating NLRP3 inflammasome by Lingmei Li, Ce Cao, Hao Guo, Li Lin, Lei Li, Yehao Zhang, Gaojie Xin, Zixin Liu, Shujuan Xu, Xiao Han, Qiong Zhang, Jianhua Fu

“…Myocardial enzymes such as aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) were measured by chemiluminescence (CL) method. …”
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Changing Treatment and Metastatic Disease Patterns in Patients with EGFR Mutated NSCLC: An Academic Thoracic Medical Investigator’s Consortium Registry Analysis by Margaret Stalker, MD, Connor B. Grady, MPH, Alex Watts, MS, Wei-Ting Hwang, PhD, Krishna Chandrasekhara, MS, Fangdi Sun, MD, Geoffrey Liu, MD, Devalben Patel, MD, Jorge Nieva, MD, Amanda Herrmann, MD, Kristen Marrone, MD, Vincent K. Lam, MD, Vamsidhar Velcheti, MD, Stephen V. Liu, MD, Gabriela Liliana Bravo Montenegro, MD, William Tompkins, MD, Tejas Patil, MD, Jared Weiss, MD, Kelsey Leigh Miller, MD, William Schwartzman, MD, Jonathan E. Dowell, MD, Khvaramze Shaverdashvili, MD, PhD, Liza Villaruz, MD, Amanda Cass, PharmD, Wade Iams, MD, Dara Aisner, MD, PhD, Charu Aggarwal, MD, MD, D. Ross Camidge, MD, PhD, Lova Sun, MD, Melina E. Marmarelis, MD

“…The predominant first EGFR–tyrosine kinase inhibitor was erlotinib (65%) before 2018 and osimertinib (81%) after 2018. …”
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From Ca2+ dysregulation to heart failure: β-adrenoceptor activation by RKIP postpones molecular damages and subsequent cardiac dysfunction in mice carrying mutant PLNR9C by correct... by Theresa Brand, Bettina Tanitha Baumgarten, Sabrina Denzinger, Yvonne Reinders, Miriam Kleindl, Constanze Schanbacher, Florian Funk, Nilgün Gedik, Mahmood Jabbasseh, Petra Kleinbongard, Jan Dudek, Julia Szendroedi, Elen Tolstik, Kai Schuh, Martina Krüger, Dobromir Dobrev, Friederike Cuello, Albert Sickmann, Joachim P. Schmitt, Kristina Lorenz

“…Early correction of aberrant Ca2+ cycling by cardiac expression of the Raf kinase inhibitor protein (RKIP), an endogenous activator of β-adrenoceptors (βAR), delayed the cellular alterations, functional failure and prolonged lifespan. …”
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