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Portimine A toxin causes skin inflammation through ZAKα-dependent NLRP1 inflammasome activation. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-02-13 Léana Gorse,Loïc Plessis,Stephen Wearne,Margaux Paradis,Miriam Pinilla,Rae Chua,Seong Soo Lim,Elena Pelluz,Gee-Ann Toh,Raoul Mazars,Caio Bomfim,Fabienne Hervé,Korian Lhaute,Damien Réveillon,Bastien Suire,Léa Ravon-Katossky,Thomas Benoist,Léa Fromont,David Péricat,Kenneth Neil Mertens,Amélie Derrien,Aouregan Terre-Terrillon,Nicolas Chomérat,Gwenaël Bilien,Véronique Séchet,Liliane Carpentier,Mamadou
In 2020-2021, a "mysterious illness" struck Senegalese fishermen, causing severe acute dermatitis in over one thousand individuals following exposure through drift-net fishing activity. Here, by performing deep analysis of the environmental samples we reveal the presence of the marine dinoflagellate Vulcanodinium rugosum and its associated cyclic imine toxins. Specifically, we show that the toxin PortimineA
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Model systems to study tumor-microbiome interactions in early-onset colorectal cancer. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-02-13 Katharina M Richter,Marius Wrage,Carolin Krekeler,Tiago De Oliveira,Lena-Christin Conradi,Kerstin Menck,Annalen Bleckmann
Colorectal cancer (CRC) is a major health problem, with an alarming increase of early-onset CRC (EO-CRC) cases among individuals under 50 years of age. This trend shows the urgent need for understanding the underlying mechanisms leading to EO-CRC development and progression. There is significant evidence that the gut microbiome acts as a key player in CRC by triggering molecular changes in the colon
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Immune Dysregulation in Obesity Ann. Review Paleopathol. Mech. Disease (IF 28.4) Pub Date : 2025-02-11 Zewen Jiang, Chihiro Tabuchi, Sarah G. Gayer, Sagar P. Bapat
The immune system plays fundamental roles in maintaining physiological homeostasis. With the increasing prevalence of obesity—a state characterized by chronic inflammation and systemic dyshomeostasis—there is growing scientific and clinical interest in understanding how obesity reshapes immune function. In this review, we propose that obesity is not merely an altered metabolic state but also a fundamentally
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Targeting Protein–Protein Interactions in Hematologic Malignancies Ann. Review Paleopathol. Mech. Disease (IF 28.4) Pub Date : 2025-02-11 Tomasz Cierpicki, Jolanta Grembecka
Over the last two decades, there have been extensive efforts to develop small-molecule inhibitors of protein–protein interactions (PPIs) as novel therapeutics for cancer, including hematologic malignancies. Despite the numerous challenges associated with developing PPI inhibitors, a significant number of them have advanced to clinical studies in hematologic patients in recent years. The US Food and
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Pathogenesis of Focal Segmental Glomerulosclerosis and Related Disorders Ann. Review Paleopathol. Mech. Disease (IF 28.4) Pub Date : 2025-02-11 Mehmet M. Altintas, Shivangi Agarwal, Yashwanth Sudhini, Ke Zhu, Changli Wei, Jochen Reiser
Focal segmental glomerulosclerosis (FSGS) is the morphologic manifestation of a spectrum of kidney diseases that primarily impact podocytes, cells that create the filtration barrier of the glomerulus. As its name implies, only parts of the kidney and glomeruli are affected, and only a portion of the affected glomerulus may be sclerosed. Although the diagnosis is based primarily on microscopic features
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Role of Fungi in Tumorigenesis: Promises and Challenges Ann. Review Paleopathol. Mech. Disease (IF 28.4) Pub Date : 2025-02-11 Silvia Guglietta, Xin Li, Deepak Saxena
The mycobiome plays a key role in the host immune responses in homeostasis and inflammation. Recent studies suggest that an imbalance in the gut's fungi contributes to chronic, noninfectious diseases such as obesity, metabolic disorders, and cancers. Pathogenic fungi can colonize specific organs, and the gut mycobiome has been linked to the development and progression of various cancers, including
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Roles of Cellular Neighborhoods in Hepatocellular Carcinoma Pathogenesis Ann. Review Paleopathol. Mech. Disease (IF 28.4) Pub Date : 2025-02-11 Lichun Ma, Cherry Caiyi Li, Xin Wei Wang
The development of hepatocellular carcinoma (HCC) involves an intricate interplay among various cell types within the liver. Unraveling the orchestration of these cells, particularly in the context of various etiologies, may hold the key to deciphering the underlying mechanisms of this complex disease. The advancement of single-cell and spatial technologies has revolutionized our ability to determine
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Apoptosis in Cancer Biology and Therapy Ann. Review Paleopathol. Mech. Disease (IF 28.4) Pub Date : 2025-02-11 Allison Moyer, Kosuke Tanaka, Emily H. Cheng
Since its inception, the study of apoptosis has been intricately linked to the field of cancer. The term apoptosis was coined more than five decades ago following its identification in both healthy tissues and malignant neoplasms. The subsequent elucidation of its molecular mechanisms has significantly enhanced our understanding of how cancer cells hijack physiological processes to evade cell death
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Unraveling Mechanisms of Genetic Risks in Metabolic Dysfunction–Associated Steatotic Liver Diseases: A Pathway to Precision Medicine Ann. Review Paleopathol. Mech. Disease (IF 28.4) Pub Date : 2025-02-11 Xiang Zhang, Kyong-Mi Chang, Jun Yu, Rohit Loomba
Metabolic dysfunction–associated steatotic liver disease (MASLD) is a growing global health problem, affecting ∼1 billion people. This condition is well established to have a heritable component with strong familial clustering. With the extraordinary breakthroughs in genetic research techniques coupled with their application to large-scale biobanks, the field of genetics in MASLD has expanded rapidly
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Sciatic nerve stimulation enhances NK cell cytotoxicity through dopamine signaling and synergizes immunotherapy in triple-negative breast cancer Drug Resist. Updat. (IF 15.8) Pub Date : 2025-02-10 Guangqi Li, Yuting Jiang, Huan Tong, Jifeng Liu, Zedong Jiang, Yunuo Zhao, Keqin Tan, Yu Zhang, Xiaomeng Yin, Hong Yun, Yuxin He, Hu Liao, Jiangjiang Qin, Xuelei Ma
Triple-negative breast cancer (TNBC) has shown resistance to immunotherapy. Stimulating ProkR2-bearing sensory neurons of the sciatic nerve has been reported to regulate immune function by catecholamine release through the vagal-adrenal axis. We aimed to investigate the impact of sciatic nerve stimulation on anti-tumor immune responses and immunotherapy efficacy in TNBC.
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Low miR-224–5p in exosomes confers colorectal cancer 5-FU resistance by upregulating S100A4 Drug Resist. Updat. (IF 15.8) Pub Date : 2025-02-06 Yan-yan Yan, Zhuo-fen Deng, Xing-tao Wu, Yu Lu, Zhuang-yan Zhu, Qing Wen, Wei Zhang, Hai-yan Zhang, Xin-zhu Chen, Yu-song Wu, Xue-bing He, Zi-ang Ma, Jin-shuo Li, Hong Bi, Jian-ye Zhang
This study aimed to identify molecular markers that mediate 5-fluorouracil (5-FU) resistance in colorectal cancer (CRC). Exosomes from 5-FU resistant CRC cells (HCT-15/FU) significantly enhanced the resistance to 5-FU and the malignant properties of HCT-15 cells. Double screening of miRNAs in CRC cell-exosomes and serum-exosomes from clinical CRC patients revealed that miR-224–5p was expressed at significantly
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Microbial metabolites tune amygdala neuronal hyperexcitability and anxiety-linked behaviors. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-02-05 Weonjin Yu,Yixin Xiao,Anusha Jayaraman,Yi-Chun Yen,Hae Ung Lee,Sven Pettersson,H Shawn Je
Changes in gut microbiota composition have been linked to anxiety behavior in rodents. However, the underlying neural circuitry linking microbiota and their metabolites to anxiety behavior remains unknown. Using male C57BL/6J germ-free (GF) mice, not exposed to live microbes, increased anxiety-related behavior was observed correlating with a significant increase in the immediate early c-Fos gene in
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Lipid dysregulation in triple negative breast cancer: Insights from mass spectrometry-based approaches Prog. Lipid. Res. (IF 14.0) Pub Date : 2025-02-04 Xiaoyue Huang, Ahmed Ali, Dounia E.I. Yachioui, Sylvia E. Le Dévédec, Thomas Hankemeier
Triple negative breast cancer (TNBC) has the worst prognosis among breast cancers due to its aggressive nature and the absence of targeted treatments. Development of novel anti-cancer drugs for TNBC faces challenges stemming from its heterogeneity and high potential for metastasis. Metabolomics can be a useful technology in finding novel therapeutic targets and probing the heterogeneity of TNBC. Metabolomics
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An AI-assisted morphoproteomic approach is a supportive tool in esophagitis-related precision medicine. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-02-03 Sven Mattern,Vanessa Hollfoth,Eyyub Bag,Arslan Ali,Philip Riemenschneider,Mohamed A Jarboui,Karsten Boldt,Mihaly Sulyok,Anabel Dickemann,Julia Luibrand,Stefano Fusco,Mirita Franz-Wachtel,Kerstin Singer,Benjamin Goeppert,Oliver Schilling,Nisar Malek,Falko Fend,Boris Macek,Marius Ueffing,Stephan Singer
Esophagitis is a frequent, but at the molecular level poorly characterized condition with diverse underlying etiologies and treatments. Correct diagnosis can be challenging due to partially overlapping histological features. By proteomic profiling of routine diagnostic FFPE biopsy specimens (n = 55) representing controls, Reflux- (GERD), Eosinophilic-(EoE), Crohn's-(CD), Herpes simplex (HSV) and Candida
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Exploiting metabolic vulnerability in glioblastoma using a brain-penetrant drug with a safe profile. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-02-03 Audrey Burban,Cloe Tessier,Mathieu Larroquette,Joris Guyon,Cloe Lubiato,Mathis Pinglaut,Maxime Toujas,Johanna Galvis,Benjamin Dartigues,Emmanuelle Georget,H Artee Luchman,Samuel Weiss,David Cappellen,Nathalie Nicot,Barbara Klink,Macha Nikolski,Lucie Brisson,Thomas Mathivet,Andreas Bikfalvi,Thomas Daubon,Ahmad Sharanek
Glioblastoma is one of the most treatment-resistant and lethal cancers, with a subset of self-renewing brain tumour stem cells (BTSCs), driving therapy resistance and relapse. Here, we report that mubritinib effectively impairs BTSC stemness and growth. Mechanistically, bioenergetic assays and rescue experiments showed that mubritinib targets complex I of the electron transport chain, thereby impairing
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Harnessing phytochemicals: Innovative strategies to enhance cancer immunotherapy Drug Resist. Updat. (IF 15.8) Pub Date : 2025-02-01 Qianru Zhu, Ruonan Zhang, Ziming Zhao, Tian Xie, Xinbing Sui
Cancer immunotherapy has revolutionized cancer treatment, but therapeutic ineffectiveness—driven by the tumor microenvironment and immune evasion mechanisms—continues to limit its clinical efficacy. This challenge underscores the need to explore innovative approaches, such as multimodal immunotherapy. Phytochemicals, bioactive compounds derived from plants, have emerged as promising candidates for
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Rational design of peptides to overcome drug resistance by metabolic regulation Drug Resist. Updat. (IF 15.8) Pub Date : 2025-01-31 Min Sun, Le He, Ran Chen, Mingchen Lv, Zhe-Sheng Chen, Zhen Fan, Yuxiao Zhou, Jinlong Qin, Jianzhong Du
Chemotherapy is widely used clinically, however, its efficacy is often compromised by the development of drug resistance, which arises from prolonged administration of drugs or other stimuli. One of the driven causes of drug resistance in tumors or bacterial infections is metabolic reprogramming, which alters mitochondrial metabolism, disrupts metabolic pathways and causes ion imbalance. Bioactive
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The uptake of extracellular vesicles: Research progress in cancer drug resistance and beyond Drug Resist. Updat. (IF 15.8) Pub Date : 2025-01-31 Luomeng Qian, Pangzhou Chen, Shiwu Zhang, Zhenglu Wang, Yuan Guo, Vasili Koutouratsas, Joshua S. Fleishman, Chuanqiang Huang, Sihe Zhang
Extracellular vesicles (EVs) are heterogeneous vesicles released by donor cells that can be taken up by recipient cells, thus inducing cellular phenotype changes. Since their discovery decades ago, roles of EVs in modulating initiation, growth, survival and metastasis of cancer have been revealed. Recent studies from multifaceted perspectives have further detailed the contribution of EVs to cancer
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Structural and functional analyses of STM14_5441-STM14_5442: A potential mechanism for persister formation against aminoglycosides Drug Resist. Updat. (IF 15.8) Pub Date : 2025-01-29 Hyun-Jong Eun, Seok-Won Jang, Ju-Hyun Park, Jooyeon Lee, Ki-Young Lee, Eun-Jin Lee, Bong-Jin Lee
The ability to eliminate bacterial persister cells is still a medical challenge that has yet to be overcome. These cells represent a unique subpopulation within bacterial communities and are characterized by a reduced susceptibility to antibiotics with growth retardation. In this study, we investigated the molecular basis of persister formation in Salmonella Typhimurium 14028 s under aminoglycoside
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B7-H3-liquid biopsy for the characterization and monitoring of the dynamic biology of prostate cancer Drug Resist. Updat. (IF 15.8) Pub Date : 2025-01-28 Yong Ju, Joshua Watson, Jasmine J. Wang, Ying-Tzu Yen, Lilit Gevorkian, Zijing Chen, Kai Han Tu, Brenda Salumbides, Aaron Phung, Chen Zhao, Hyoyong Kim, You-Ren Ji, Ryan Y. Zhang, Junseok Lee, Jun Gong, Kevin Scher, Sungyong You, Jie-Fu Chen, Hsian-Rong Tseng, Yazhen Zhu, Edwin M. Posadas
B7-H3 is a promising target for cancer therapy, notably in prostate cancer (PCa), particularly in metastatic, castration-resistant PCa (mCRPC). With the development of B7-H3-targeted therapies, there is a need for a rapid, reliable, and cost-effective method to detect and monitor B7-H3 expression. Leveraging their abundance and stability, we developed a liquid biopsy assay using extracellular vesicles
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Exposomics: a review of methodologies, applications, and future directions in molecular medicine. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-01-27 Melissa Wan,Elisabeth M Simonin,Mary Margaret Johnson,Xinyue Zhang,Xiangping Lin,Peng Gao,Chirag J Patel,Aroub Yousuf,Michael P Snyder,Xiumei Hong,Xiaobin Wang,Vanitha Sampath,Kari C Nadeau
The exposome is the measure of all the exposures of an individual in a lifetime and how those exposures relate to health. Exposomics is the emerging field of research to measure and study the totality of the exposome. Exposomics can assist with molecular medicine by furthering our understanding of how the exposome influences cellular and molecular processes such as gene expression, epigenetic modifications
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Boosting human immunology: harnessing the potential of immune organoids. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-01-27 Maximilian Moll,Dirk Baumjohann
Studying the human immune system in vivo is challenging and often not possible. Therefore, most human immunology studies have been predominantly confined to peripheral blood analyses, which by themselves have inherent limitations, as many immune reactions take place within tissues. For example, potent antibody responses that contribute to fighting infections and provide protection following vaccination
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Dynamic evolution of KPC-230-mediated resistance to ceftazidime-avibactam during the treatment of carbapenem-resistant Klebsiella pnenmoniae Drug Resist. Updat. (IF 15.8) Pub Date : 2025-01-25 Xi Li, Longjie Zhou, Huaqiong Huang
The molecular mechanisms driving the development of KPC-230-mediated resistance to ceftazidime-avibactam during treatment of carbapenem-resistant Klebsiella pneumoniae infection was elucidated by analyzing specimens collected from a patient, including one blaKPC-230-positive and three blaKPC-2-positive Klebsiella pnenmoniae isolates.
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Improving the odds of survival: transgenerational effects of infections. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-01-22 Victoria M Spanou,Theano P Andriopoulou,Evangelos J Giamarellos-Bourboulis,Mihai G Netea
Recent studies argue for a novel concept of the role of chromatin as a carrier of epigenetic memory through cellular and organismal generations, defining and coordinating gene activity states and physiological functions. Environmental insults, such as exposures to unhealthy diets, smoking, toxic compounds, and infections, can epigenetically reprogram germ-line cells and influence offspring phenotypes
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Global dissemination of Klebsiella pneumoniae in surface waters: Genomic insights into drug resistance, virulence, and clinical relevance Drug Resist. Updat. (IF 15.8) Pub Date : 2025-01-21 Damian Rolbiecki, Edyta Kiedrzyńska, Małgorzata Czatzkowska, Marcin Kiedrzyński, Ewa Korzeniewska, Monika Harnisz
The aquatic environment is a major pathway for the spread of antibiotic resistance (AR) among microorganisms. Among these, Klebsiella pneumoniae reveals high genome plasticity, adaptability, and the ability to colonize humans, animals, and the natural environment, awarding it a significant role in the spread of AR. This work presents an in-depth analysis of the whole sequences of 149 K. pneumoniae
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Osmotic stress influences microtubule drug response via WNK1 kinase signaling Drug Resist. Updat. (IF 15.8) Pub Date : 2025-01-18 Ana Monfort-Vengut, Natalia Sanz-Gómez, Sandra Ballesteros-Sánchez, Beatriz Ortigosa, Aitana Cambón, Maria Ramos, Ángela Montes-San Lorenzo, María Escribano-Cebrián, Juan Manuel Rosa-Rosa, Joaquín Martínez-López, Ricardo Sánchez-Prieto, Rocío Sotillo, Guillermo de Cárcer
Ion homeostasis is critical for numerous cellular processes, and disturbances in ionic balance underlie diverse pathological conditions, including cancer progression. Targeting ion homeostasis is even considered as a strategy to treat cancer. However, very little is known about how ion homeostasis may influence anticancer drug response. In a genome-wide CRISPR-Cas9 resistance drug screen, we identified
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Gut microbiota interact with breast cancer therapeutics to modulate efficacy. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-01-16 Alana A Arnone,Katherine Ansley,Arielle L Heeke,Marissa Howard-McNatt,Katherine L Cook
The gut microbiome, or the community of microorganisms residing in the gastrointestinal tract, has emerged as an important factor in breast cancer etiology and treatment. Specifically, the impact of gut bacterial populations on breast cancer therapeutic outcomes is an emerging area of research. The microbiota's role in modifying the pharmacokinetics of chemotherapy and endocrine-targeting therapies
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Female sex is linked to a stronger association between sTREM2 and CSF p-tau in Alzheimer's disease. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-01-10 Davina Biel,Marc Suárez-Calvet,Anna Dewenter,Anna Steward,Sebastian N Roemer,Amir Dehsarvi,Zeyu Zhu,Julia Pescoller,Lukas Frontzkowski,Annika Kreuzer,Christian Haass,Michael Schöll,Matthias Brendel,Nicolai Franzmeier
In Alzheimer's disease (AD), Aβ triggers p-tau secretion, which drives tau aggregation. Therefore, it is critical to characterize modulators of Aβ-related p-tau increases which may alter AD trajectories. Here, we assessed whether factors known to alter tau levels in AD modulate the association between fibrillar Aβ and secreted p-tau181 determined in the cerebrospinal fluid (CSF). To assess potentially
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Peptide-based PET/CT imaging visualizes PD-L1-driven radioresistance in glioblastoma Drug Resist. Updat. (IF 15.8) Pub Date : 2025-01-09 Yong Wang, Zhiguo Liu, Yang Li, Kelin Wang, Chunhui Yuan, Jian Shi, Jiazhong Ren, Shijie Wang, Jinping Wang, Miaoqing Zhao, Man Hu
Radioresistance remains a great challenge for radiotherapy in the treatment of glioblastoma (GBM). PD-L1 expression is a key contributor to radioresistance and immune escape in GBM. The lack of effective methods to monitor the change of PD-L1 during radiotherapy in patients limits timely intervention and management of the resistance. Here, we developed a novel peptide tracer [18F]AlF-NOTA-PCP2 for
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Oncolytic viruses expressing MATEs facilitate target-independent T-cell activation in tumors. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-01-09 Malin Peter,Bettina Mundt,Arne Menze,Norman Woller,Valery Volk,Amanda M Ernst,Leon A Öhler,Steven R Talbot,Heiner Wedemeyer,Christine Falk,Friedrich Feuerhake,Thomas C Wirth,Florian Kühnel
Oncolytic viruses (OV) expressing bispecific T-cell engagers (BiTEs) are promising tools for tumor immunotherapy but the range of target tumors is limited. To facilitate effective T-cell stimulation with broad-range applicability, we established membrane-associated T-cell engagers (MATEs) harboring the protein transduction domain of the HIV-Tat protein to achieve non-selective binding to target cells
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Betaine lipids: Biosynthesis, functional diversity and evolutionary perspectives Prog. Lipid. Res. (IF 14.0) Pub Date : 2025-01-08 Sarah Salomon, Océane Oliva, Alberto Amato, Olivier Bastien, Morgane Michaud, Juliette Jouhet
Betaine lipids (BL) are relatively understudied non‑phosphorus glycerolipids. They are predominantly found in algae but have also been detected in other unicellular eukaryotes, fungi, bacteria, and some bryophytes and pteridophytes. These extraplastidial lipids are considered as substitute for phospholipids in organisms, particularly under phosphate (Pi) deficiency. This review provides a broader perspective
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Organoid models of drug resistant gastric adenosquamous carcinoma: Recapitulating tumor features and refining precision treatment Drug Resist. Updat. (IF 15.8) Pub Date : 2025-01-07 Kuan Li, Wenchao Li, Shuying Fu, Chen Wang, Kexin Wang, Huan Yang, Yumei Xian, Tengfei Hao, Shiwei Zhang, Tianshun Gao, Jie Zhou, Jia Li, Changhua Zhang, Wei Chen, Leli Zeng, Yulong He
Organoids were successfully established from primary tumor and its metastatic lymph nodes of a patient. These organoids faithfully replicated tumor pathology and genetic characteristics. Organoid-based drug screening was conducted, which revealed significant difference in sensitivity to drugs between organoids dervived from primary tumor versus metastatic lymph nodes. The results guided clinical decisions
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CAR T-cell-associated secondary malignancies challenge current pharmacovigilance concepts. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-01-06 Philipp Berg,Gabriele Ruppert-Seipp,Susanne Müller,Gabriele D Maurer,Jessica Hartmann,Udo Holtick,Christian J Buchholz,Markus B Funk
Suspected adverse reactions following chimeric antigen receptor T-cell (CAR T) treatment include more and more cases of secondary T-cell malignancies. The causality assessment of such suspected reactions challenges established evaluation practices due to (i) patient and product-specific risk factors and (ii) incomplete data available with post-marketing reports submitted to competent authorities. This
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Macrophage-induced enteric neurodegeneration leads to motility impairment during gut inflammation. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-01-06 Mona Breßer,Kevin D Siemens,Linda Schneider,Jonah E Lunnebach,Patrick Leven,Tim R Glowka,Kristin Oberländer,Elena De Domenico,Joachim L Schultze,Joachim Schmidt,Jörg C Kalff,Anja Schneider,Sven Wehner,Reiner Schneider
Current studies pictured the enteric nervous system and macrophages as modulators of neuroimmune processes in the inflamed gut. Expanding this view, we investigated the impact of enteric neuron-macrophage interactions on postoperative trauma and subsequent motility disturbances, i.e., postoperative ileus. In the early postsurgical phase, we detected strong neuronal activation, followed by transcriptional
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To image or not to image: Use of imaging mass spectrometry in biomedical lipidomics Prog. Lipid. Res. (IF 14.0) Pub Date : 2025-01-05 Albert Maimó-Barceló, Karim Pérez-Romero, Ramón M. Rodríguez, Cristina Huergo, Ibai Calvo, José A. Fernández, Gwendolyn Barceló-Coblijn
Lipid imaging mass spectrometry (LIMS) allows for establishing the bidimensional distribution of lipid species within a tissue section. One of the main advantages is the generation of spatial information on lipid species distribution at a spatial (lateral) resolution bordering on single-cell resolution with no need to isolate cells. Thus, LIMS images demonstrate, with a level of detail never described
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Exploring treatment-driven subclonal evolution of prognostic triple biomarkers: Dual gene fusions and chimeric RNA variants in novel subtypes of acute myeloid leukemia patients with KMT2A rearrangement Drug Resist. Updat. (IF 15.8) Pub Date : 2025-01-02 Yi Xu, Shengwen Calvin Li, Jeffrey Xiao, Qian Liu, Durga Cherukuri, Yan Liu, Saied Mirshahidi, Jane Xu, Xuelian Chen, Dadrastoussi Homa, Julian Olea, Kaijin Wu, Kevin R. Kelly, Fengzhu Sun, Ruihao Huang, Xiaoqi Wang, Qin Wen, Xi Zhang, Cristina M. Ghiuzeli, Esther Chong, Hisham Abdel-Azim, Mark E. Reeves, David J. Baylink, Huynh Cao, Jiang F. Zhong
Chromosomal rearrangements (CR) initiate leukemogenesis in approximately 50 % of acute myeloid leukemia (AML) patients; however, limited targeted therapies exist due to a lack of accurate molecular and genetic biomarkers of refractory mechanisms during treatment. Here, we investigated the pathological landscape of treatment resistance and relapse in 16 CR-AML patients by monitoring cytogenetic, RNAseq
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YTHDF2-mediated m6A modification of ONECUT2 promotes stemness and oxaliplatin resistance in gastric cancer through transcriptionally activating TFPI Drug Resist. Updat. (IF 15.8) Pub Date : 2025-01-02 Xingdi Fan, Fangyi Han, Haocheng Wang, Zhilin Shu, Bowen Qiu, Fanan Zeng, Hongzhen Chen, Ziying Wu, Yongwei Lin, Zhien Lan, Zhiwei Ye, Yao Ying, Tiansu Geng, Ziqian Xian, Xing Niu, Junming Wu, Ke Mo, Kehong Zheng, Yaping Ye, Chunhui Cui
Chemoresistance results in poor outcomes of patients with gastric cancer (GC). This study aims to identify oxaliplatin resistance-related cell subpopulations in the tumor microenvironment (TME) and decipher the involved molecular mechanisms.
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A therapeutic regimen using neoantigen-specific TCR-T cells for HLA-A*2402-positive solid tumors. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-01-02 Yuncheng Bei,Ying Huang,Nandie Wu,Yishan Li,Ruihan Xu,Baorui Liu,Rutian Li
The adoptive transfer of TCR-T cells specific to neoantigens preferentially exhibits potent cytotoxicity to tumor cells and has shown promising efficacy in various preclinical human cancers. In this study, we first identified a functional TCR, Tcr-1, which selectively recognized the SYT-SSX fusion neoantigen shared by most synovial sarcomas. Engineered T-cell expressing Tcr-1 (Tcr-T1) demonstrated
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PlexinD1 is a driver and a therapeutic target in advanced prostate cancer. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-01-02 Jing Wei,Jing Wang,Wen Guan,Jingjing Li,Tianjie Pu,Eva Corey,Tzu-Ping Lin,Allen C Gao,Boyang Jason Wu
Aggressive prostate cancer (PCa) variants associated with androgen receptor signaling inhibitor (ARSI) resistance and metastasis remain poorly understood. Here, we identify the axon guidance semaphorin receptor PlexinD1 as a crucial driver of cancer aggressiveness in metastatic castration-resistant prostate cancer (CRPC). High PlexinD1 expression in human PCa is correlated with adverse clinical outcomes
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Bioavailability of EPA and DHA in humans – A comprehensive review Prog. Lipid. Res. (IF 14.0) Pub Date : 2024-12-28 Sepideh Alijani, Andreas Hahn, William S. Harris, Jan Philipp Schuchardt
The bioavailability of long-chain omega-3 fatty acids is a critical yet often overlooked factor influencing their efficacy. This review evaluates the bioavailability of EPA/DHA from acute (single-dose) and chronic human studies, focusing on (a) chemical forms such as triacylglycerols (TAG, natural and re-esterified, rTAG), non-esterified fatty acids (NEFA), and phospholipids (PL) from sources like
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N6-methyladenosine modification of 3'tRF-AlaAGC impairs PD-1 blockade efficacy by promoting lactic acid accumulation in the tumor microenvironment of gastric carcinoma Drug Resist. Updat. (IF 15.8) Pub Date : 2024-12-26 Weiguo Xu, Bin Zhou, Ping Wang, Yuyan Ma, Yu Jiang, Dongping Mo, Jun Wu, Jingjing Ma, Xiao Wang, Yinxing Miao, Yong Nian, Junyu Zheng, Jie Li, Feng Yan, Gang Li
The balance between CD8+ T cells and regulatory T (Treg) cells in the tumor microenvironment (TME) plays a crucial role in the immune checkpoint inhibition (ICI) therapy in gastric carcinoma (GC). However, related factors leading to the disturbance of TME and resistance to ICI therapy remain unknown. In this study, we applied N6-methyladenosine (m6A) small RNA Epitranscriptomic Microarray and screened
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Molecular subtype changes after acquiring resistance to tarlatamab in small cell lung cancer Drug Resist. Updat. (IF 15.8) Pub Date : 2024-12-26 Hyung-Min Ahn, Seog-Yun Park, Yura Choi, Jaemin Kim, Youngjoo Lee
Tarlatamab, a novel bispecific T-cell engager, has demonstrated unprecedented efficacy in patients with small cell lung cancer. However, there is no known mechanism of resistance to tarlatamab. This study suggests that a transcriptional expression shift might be associated with acquired resistance to tarlatamab.
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Research progress on gene mutations and drug resistance in leukemia Drug Resist. Updat. (IF 15.8) Pub Date : 2024-12-26 Xiangyu Ma, Jiamin Xu, Yanan Wang, Joshua S. Fleishman, Hao Bing, Boran Yu, Yanming Li, Letao Bo, Shaolong Zhang, Zhe-Sheng Chen, Libo Zhao
Leukemia is a type of blood cancer characterized by the uncontrolled growth of abnormal cells in the bone marrow, which replace normal blood cells and disrupt normal blood cell function. Timely and personalized interventions are crucial for disease management and improving survival rates. However, many patients experience relapse following conventional chemotherapy, and increasing treatment intensity
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Silent circulation of plasmid-borne tet(X6) and blaOXA-58 genes in a community-acquired Acinetobacter baumannii strain Drug Resist. Updat. (IF 15.8) Pub Date : 2024-12-25 Huiqiong Jia, Qingchao Tong, Le Wang, Yuye Wu, Xinyang Li, Shuangshuang Li, Yingying Kong, Yingying Zhang, João Pedro Rueda Furlan, Nwai Oo Khine, Patrick Butaye, Jun Zhang, Qing Yang, Zhi Ruan
To characterize the genomic features of a community-acquired Acinetobacter baumannii strain, co-carrying tet(X6) and blaOXA-58 genes, but was susceptible to tigecycline and carbapenems. The tet(X6) and blaOXA-58 genes were found on a 149,518 bp non-conjugative plasmid. The blaOXA-58 gene was silent, due to the presence of an intact ISAba3-like element upstream, which rendered the strain susceptible
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Wip1 phosphatase activator QGC-8–52 specifically sensitizes p53-negative cancer cells to chemotherapy while protecting normal cells Drug Resist. Updat. (IF 15.8) Pub Date : 2024-12-24 Ke Wu, Xiao-xiao Ge, Xiao-fan Duan, Jie-qing Li, Kun Wang, Qiao-Hong Chen, Zhi-min Huang, Wei-yan Zhang, Yong Wu, Qun Li
PP2C serine-threonine phosphatase Wip1 plays an important role in normal tissue homeostasis, stress signaling and pathogenesis of various human diseases. It is an attractive drug target for cancer treatment and inhibition of its expression or activity constitute a novel therapeutic intervention strategy to prevent the development of various cancers. However, previous strategies for Wip1 suppression
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WITHDRAWN: Low miR-224-5p in exosomes confers colorectal cancer 5-FU resistance by upregulating S100A4 Drug Resist. Updat. (IF 15.8) Pub Date : 2024-12-16 Yan-yan Yan, Zhuo-fen Deng, Xing-tao Wu, Yu Lu, Zhuang-yan Zhu, Qing Wen, Wei Zhang, Hai-yan Zhang, Xin-zhu Chen, Yu-song Wu, Xue-bing He, Zi-ang Ma, Jin-shuo Li, Hong Bi, Jian-ye Zhang
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Navigating the complexity of lipid oxidation and antioxidation: A review of evaluation methods and emerging approaches Prog. Lipid. Res. (IF 14.0) Pub Date : 2024-12-16 Erwann Durand, Mickael Laguerre, Claire Bourlieu-Lacanal, Jérôme Lecomte, Pierre Villeneuve
Lipid oxidative degradation contributes to the deterioration of food quality and poses potential health risks. A promising approach to counteract this is the use of plant-based antioxidants. However, accurately evaluating the antioxidant capacity and effectiveness of these compounds remains a challenge. While many rapid in vitro tests are available, they must be categorized according to their specific
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Association of idealized amphiphiles and protease inhibitors: Conferring antimicrobial peptides with stable antibacterial activity under physiological conditions to combat multidrug-resistant bacteria Drug Resist. Updat. (IF 15.8) Pub Date : 2024-12-09 Yongjie Zhu, Bowen Li, Wanying Xu, Yuanmengxue Wang, Guoyu Li, Chongpeng Bi, Anshan Shan, Changxuan Shao
The unstable antimicrobial activity of antimicrobial peptides (AMPs) under physiological conditions (especially the degradation instigated proteases) seems to be a persistent impediment for their successful implementation in clinical trials. Consequently, our objective was to devise AMP engineering frameworks that could sustain robust antibacterial efficacy within physiological environments.
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Beneficial microbiome and diet interplay in early-onset colorectal cancer. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-12-09 Zhengyuan Zhou,Linda Kleis,Ana Depetris-Chauvin,Stefanie Jaskulski,Victoria Damerell,Karin B Michels,Biljana Gigic,Ute Nöthlings,Gianni Panagiotou
Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Although the risk of developing CRC increases with age, approximately 10% of newly diagnosed cases occur in individuals under the age of 50. Significant changes in dietary habits in young adults since industrialization create a favorable microenvironment for colorectal
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Navigating from cellular phenotypic screen to clinical candidate: selective targeting of the NLRP3 inflammasome. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-12-09 Rosalie Matico,Karolien Grauwen,Dhruv Chauhan,Xiaodi Yu,Irini Abdiaj,Suraj Adhikary,Ine Adriaensen,Garcia Molina Aranzazu,Jesus Alcázar,Michela Bassi,Ellen Brisse,Santiago Cañellas,Shubhra Chaudhuri,Francisca Delgado,Alejandro Diéguez-Vázquez,Marc Du Jardin,Victoria Eastham,Michael Finley,Tom Jacobs,Ken Keustermans,Robert Kuhn,Josep Llaveria,Jos Leenaerts,Maria Lourdes Linares,Maria Luz Martín,Rosa
The NLRP3 inflammasome plays a pivotal role in host defense and drives inflammation against microbial threats, crystals, and danger-associated molecular patterns (DAMPs). Dysregulation of NLRP3 activity is associated with various human diseases, making it an attractive therapeutic target. Patients with NLRP3 mutations suffer from Cryopyrin-Associated Periodic Syndrome (CAPS) emphasizing the clinical
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A novel anti-epileptogenesis strategy of temporal lobe epilepsy based on nitric oxide donor. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-12-09 Xian-Hui Zhu,Ya-Ping Zhou,Qiao Zhang,Ming-Yi Zhu,Xiao-Wei Song,Jun Li,Jiang Chen,Yun Shi,Kang-Jian Sun,Yong-Jie Zhang,Jing Zhang,Tian Xia,Bao-Sheng Huang,Fan Meng,Qi-Gang Zhou
The molecular mechanism underlying the role of hippocampal hilar interneuron degeneration in temporal lobe epilepsy (TLE) remains unclear. Especially, very few studies have focused on the role of neuronal nitric oxide synthase (nNOS, encoded by Nos1) containing hilar interneurons in TLE. In the present study, Nos1 conditional knockout mice were constructed, and we found that selective deletion of Nos1
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Fasting-mimicking diet potentiates anti-tumor effects of CDK4/6 inhibitors against breast cancer by suppressing NRAS- and IGF1-mediated mTORC1 signaling Drug Resist. Updat. (IF 15.8) Pub Date : 2024-12-06 Sebastian Brandhorst, Valter D. Longo
Fasting-mimicking diet (FMD) cycles, defined as 3–5 day periods of a calorie-restricted, low-protein, low-carbohydrate, and high-fat diet, have emerged as a dietary approach to delay cancer initiation and progression in both autograft and xenograft mouse models and as a safe and feasible approach to decrease risk factors for cancer and other age-related pathologies in humans. A substantial number of
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Global phylogeography and antibiotic resistance characteristics of Morganella: An epidemiological, spatial, comparative genomic study Drug Resist. Updat. (IF 15.8) Pub Date : 2024-12-05 Qian Liu, Hong Shen, Ming Wei, Xi Chen, Li Gu, Wentao Zhu
Morganella morganii has been recognized as an important opportunistic pathogen that is becoming increasingly prevalent worldwide. However, the current global evolutionary dynamics and emergence of ARGs remain obscure. The present study determined the global distribution, genomic classification, phylogeny, and monitor longitudinal resistome changes. During 1900–2024, a total of 1027 non-duplicate Morganella
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The inflammasome adaptor protein ASC promotes amyloid deposition in cryopyrin-associated periodic syndromes. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-12-05 Cristina Alarcón-Vila,Laura Hurtado-Navarro,Sandra V Mateo,Alejandro Peñín-Franch,Carlos M Martínez,Cristina Molina-López,María C Baños,Ana I Gómez,Javier Gómez-Román,Alberto Baroja-Mazo,Juan I Arostegui,Natalia Palmou-Fontana,Juan J Martínez-García,Pablo Pelegrin
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5-methylcytosine methylation of MALAT1 promotes resistance to sorafenib in hepatocellular carcinoma through ELAVL1/SLC7A11-mediated ferroptosis Drug Resist. Updat. (IF 15.8) Pub Date : 2024-12-04 Chuan-Jian Shi, Feng-Xiang Pang, Yu-He Lei, Li-Qiang Deng, Fu-Zhen Pan, Zhi-Qing Liang, Tian Xie, Xian-Lin Wu, Yu-Yan Wang, Yan-Fang Xian, Wei-Qiang Zeng, Han-Li Lin, Jin-Fang Zhang
Emerging evidence demonstrates that long non-coding RNAs (lncRNAs) play a crucial role in sorafenib resistance in hepatocellular carcinoma (HCC), and lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a dysregulated lncRNA in sorafenib-resistant HCC cells. However, the underlying regulatory mechanisms of MALAT1 in sorafenib-resistant HCC cells remain unclear. In the present study
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Challenges and Opportunities in the Clinical Translation of High-Resolution Spatial Transcriptomics Ann. Review Paleopathol. Mech. Disease (IF 28.4) Pub Date : 2024-12-03 Tancredi Massimo Pentimalli, Nikos Karaiskos, Nikolaus Rajewsky
Pathology has always been fueled by technological advances. Histology powered the study of tissue architecture at single-cell resolution and remains a cornerstone of clinical pathology today. In the last decade, next-generation sequencing has become informative for the targeted treatment of many diseases, demonstrating the importance of genome-scale molecular information for personalized medicine.
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CEA-induced PI3K/AKT pathway activation through the binding of CEA to KRT1 contributes to oxaliplatin resistance in gastric cancer Drug Resist. Updat. (IF 15.8) Pub Date : 2024-12-03 Yifan Chen, Yulong Mi, Song Tan, Yizhen Chen, Shaolin Liu, Shengtao Lin, Changshun Yang, Weifeng Hong, Weihua Li
The serum level of carcinoembryonic antigen (CEA) has prognostic value in patients with gastric cancer (GC) receiving oxaliplatin-based chemotherapy. As the molecular functions of CEA are increasingly uncovered, its role in regulating oxaliplatin resistance in GC attracts attention.
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Targeting to BMP9 to restrain flare-up of fibrodysplasia ossificans progressiva. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-12-03 Qiwen Li,Quan Yuan
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BMP-9 mediates fibroproliferation in fibrodysplasia ossificans progressiva through TGF-β signaling. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-12-03 Chengzhu Zhao,Yoshiko Inada,Souta Motoike,Daisuke Kamiya,Kyosuke Hino,Makoto Ikeya
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder presenting with progressive heterotopic ossification (HO) in soft tissues. Early-stage FOP is characterized by recurrent episodes of painful tissue swelling (flare-ups), with numerous proliferation-activated mesenchymal stromal cells (MSCs) subsequently causing HO. However, the mechanisms underlying flare-up progression remain unclear
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Reshaping the battlefield: A decade of clonal wars among Staphylococcus aureus in China Drug Resist. Updat. (IF 15.8) Pub Date : 2024-11-29 Wangxiao Zhou, Ye Jin, Pan Chen, Qi Ge, Xu Dong, Yunbo Chen, Minghua Jiang, Yonghong Xiao
Long-term comprehensive studies on the genomic epidemiology of both methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) isolates are limited in China. Here, we aimed to assess the genomic epidemiological characteristics and population dynamics of S. aureus in China.