-
An update of isoprostanoid nomenclature Prog. Lipid. Res. (IF 14.0) Pub Date : 2024-09-14 Camille Oger, Tereza Pavlíčková, Valérie Bultel-Poncé, Alexandre Guy, Jean-Marie Galano, Ullrich Jahn, Thierry Durand
Polyunsaturated fatty acids (PUFAs) play numerous roles in living organisms but are also prone to rapid aerobic oxidation, resulting in the production of a wide range of isomeric metabolites called oxylipins. Among these, isoprostanes, discovered in the 1990s, are formed non-enzymatically from ω–3 and ω–6 PUFAs with 16 to 22 carbon atoms. Over nearly 35 years of research, two nomenclature systems for
-
ERK5 suppression overcomes FAK inhibitor resistance in mutant KRAS-driven non-small cell lung cancer. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-09-13 Chiara Pozzato,Gonçalo Outeiro-Pinho,Mirco Galiè,Giorgio Ramadori,Georgia Konstantinidou
Mutated KRAS serves as the oncogenic driver in 30% of non-small cell lung cancers (NSCLCs) and is associated with metastatic and therapy-resistant tumors. Focal Adhesion Kinase (FAK) acts as a mediator in sustaining KRAS-driven lung tumors, and although FAK inhibitors are currently undergoing clinical development, clinical data indicated that their efficacy in producing long-term anti-tumor responses
-
CRISPR-enabled point-of-care genotyping for APOL1 genetic risk assessment. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-09-13 Robert Greensmith,Isadora T Lape,Cristian V Riella,Alexander J Schubert,Jakob J Metzger,Anand S Dighe,Xiao Tan,Bernhard Hemmer,Josefine Rau,Sarah Wendlinger,Nora Diederich,Anja Schütz,Leonardo V Riella,Michael M Kaminski
Detecting genetic variants enables risk factor identification, disease screening, and initiation of preventative therapeutics. However, current methods, relying on hybridization or sequencing, are unsuitable for point-of-care settings. In contrast, CRISPR-based-diagnostics offer high sensitivity and specificity for point-of-care applications. While these methods have predominantly been used for pathogen
-
Multiomics reveals microbial metabolites as key actors in intestinal fibrosis in Crohn's disease. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-09-13 Xuehua Li,Shixian Hu,Xiaodi Shen,Ruonan Zhang,Caiguang Liu,Lin Xiao,Jinjiang Lin,Li Huang,Weitao He,Xinyue Wang,Lili Huang,Qingzhu Zheng,Luyao Wu,Canhui Sun,Zhenpeng Peng,Minhu Chen,Ziping Li,Rui Feng,Yijun Zhu,Yangdi Wang,Zhoulei Li,Ren Mao,Shi-Ting Feng
Intestinal fibrosis is the primary cause of disability in patients with Crohn's disease (CD), yet effective therapeutic strategies are currently lacking. Here, we report a multiomics analysis of gut microbiota and fecal/blood metabolites of 278 CD patients and 28 healthy controls, identifying characteristic alterations in gut microbiota (e.g., Lachnospiraceae, Ruminococcaceae, Muribaculaceae, Saccharimonadales)
-
An intrinsic mechanism of metabolic tuning promotes cardiac resilience to stress. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-09-13 Matteo Sorge,Giulia Savoré,Andrea Gallo,Davide Acquarone,Mauro Sbroggiò,Silvia Velasco,Federica Zamporlini,Saveria Femminò,Enrico Moiso,Giampaolo Morciano,Elisa Balmas,Andrea Raimondi,Gabrielle Nattenberg,Rachele Stefania,Carlo Tacchetti,Angela Maria Rizzo,Paola Corsetto,Alessandra Ghigo,Emilia Turco,Fiorella Altruda,Lorenzo Silengo,Paolo Pinton,Nadia Raffaelli,Nathan J Sniadecki,Claudia Penna,Pasquale
Defining the molecular mechanisms underlying cardiac resilience is crucial to find effective approaches to protect the heart. A physiologic level of ROS is produced in the heart by fatty acid oxidation, but stressful events can boost ROS and cause mitochondrial dysfunction and cardiac functional impairment. Melusin is a muscle specific chaperone required for myocardial compensatory remodeling during
-
B Cell Responses to the Placenta and Fetus Ann. Review Paleopathol. Mech. Disease (IF 28.4) Pub Date : 2024-09-12 Gabrielle Rizzuto
Pregnancy has fascinated immunologists ever since Peter Medawar's observation that reproduction runs contrary to the founding tenets of immunology. During healthy pregnancy, maternal B cells interact with antigens of the foreign conceptus (placenta and fetus) yet do not elicit rejection. Instead, robust, and redundant fetomaternal tolerance pathways generally prevent maternal B cells and antibodies
-
O-GlcNAcylation regulation of RIPK1-dependent apoptosis dictates sensitivity to sunitinib in renal cell carcinoma Drug Resist. Updat. (IF 15.8) Pub Date : 2024-09-12 Xiangbo Zeng, Zhiliang Chen, Yuanchao Zhu, Lei Liu, Zhiyong Zhang, Yongyuan Xiao, Qiong Wang, Shiyu Pang, Fengjin Zhao, Bihong Xu, Mengxin Leng, Xiaocen Liu, Chenxi Hu, Siying Zeng, Fei Li, Wenlian Xie, Wanlong Tan, Zaosong Zheng
Receptor interacting protein kinase 1 (RIPK1) has emerged as a key regulatory molecule that influences the balance between cell death and cell survival. Under external stress, RIPK1 determines whether a cell undergoes RIPK-dependent apoptosis (RDA) or survives by activating NF-κB signaling. However, the role and mechanisms of RIPK1 on sunitinib sensitivity in renal cell carcinoma (RCC) remain elusive
-
Wnt/β-Catenin Signaling in Liver Pathobiology Ann. Review Paleopathol. Mech. Disease (IF 28.4) Pub Date : 2024-09-11 Matthew D. Carson, Kari Nejak-Bowen
The liver has a critical role in regulating host metabolism, immunity, detoxification, and homeostasis. Proper liver function is essential for host health, and dysregulation of hepatic signaling pathways can lead to the onset of disease. The Wnt/β-catenin signaling pathway is an important regulator of liver homeostasis and function. Throughout life, hepatic Wnt/β-catenin signaling contributes to liver
-
Trained immunity of intestinal tuft cells during infancy enhances host defense against enteroviral infections in mice. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-09-11 Deyan Chen,Jing Wu,Fang Zhang,Ruining Lyu,Qiao You,Yajie Qian,Yurong Cai,Xiaoyan Tian,Hongji Tao,Yating He,Waqas Nawaz,Zhiwei Wu
Innate immune cells have been acknowledged as trainable in recent years. While intestinal tuft cells are recognized for their crucial roles in the host defense against intestinal pathogens, there remains uncertainty regarding their trainability. Enterovirus 71 (EV71), a prevalent enterovirus that primarily infects children but rarely infects adults. At present, there is a significant expansion of intestinal
-
A critical role for HNF4α in polymicrobial sepsis-associated metabolic reprogramming and death. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-09-11 Céline Van Dender,Steven Timmermans,Ville Paakinaho,Tineke Vanderhaeghen,Jolien Vandewalle,Maarten Claes,Bruno Garcia,Bart Roman,Jan De Waele,Siska Croubels,Karolien De Bosscher,Philip Meuleman,Antoine Herpain,Jorma J Palvimo,Claude Libert
In sepsis, limited food intake and increased energy expenditure induce a starvation response, which is compromised by a quick decline in the expression of hepatic PPARα, a transcription factor essential in intracellular catabolism of free fatty acids. The mechanism upstream of this PPARα downregulation is unknown. We found that sepsis causes a progressive hepatic loss-of-function of HNF4α, which has
-
RGS5+ lymphatic endothelial cells facilitate metastasis and acquired drug resistance of breast cancer through oxidative stress-sensing mechanism Drug Resist. Updat. (IF 15.8) Pub Date : 2024-09-06 Caixin Qiu, Chaoyi Tang, Yujun Tang, Ka Su, Xiao Chai, Zexu Zhan, Xing Niu, Jiehua Li
Oxidative stress reflected by elevated reactive oxygen species (ROS) in the tumor ecosystem, is a hallmark of human cancers. The mechanisms by which oxidative stress regulate the metastatic ecosystem and resistance remain elusive. This study aimed to dissect the oxidative stress-sensing machinery during the evolvement of early dissemination and acquired drug resistance in breast cancer.
-
The important role of lactylation in regulating DNA damage repair and tumor chemotherapy resistance Drug Resist. Updat. (IF 15.8) Pub Date : 2024-09-06 Jia Li, Zhe-Sheng Chen, Yihang Pan, Leli Zeng
-
The influence of AHR on immune and tissue biology. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-09-06 Brigitta Stockinger,Oscar E Diaz,Emma Wincent
The aryl hydrocarbon receptor is a ligand dependent transcription factor which functions as an environmental sensor. Originally discovered as the sensor for man made pollutants such as 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) it has recently gained prominence as an important mediator for environmental triggers via the diet or microbiota which influences many physiological functions in different cell
-
Next generation of "magic bullets", solutions from the microbial pangenome. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-09-06 Vega Masignani,Rino Rappuoli,Mariagrazia Pizza
-
Somatic Mosaicism in Brain Disorders Ann. Review Paleopathol. Mech. Disease (IF 28.4) Pub Date : 2024-09-04 Rachel R. Corrigan, Lauren M. Mashburn-Warren, Hyojung Yoon, Tracy A. Bedrosian
Research efforts over the past decade have defined the genetic landscape of somatic variation in the brain. Neurons accumulate somatic mutations from development through aging with potentially profound functional consequences. Recent studies have revealed the contribution of somatic mosaicism to various brain disorders including focal epilepsy, neuropsychiatric disease, and neurodegeneration. One notable
-
Can we manipulate the ovary's own metabolism to protect it from chemotherapy-induced damage? EMBO Mol. Med. (IF 9.0) Pub Date : 2024-09-03 Adomas Liugaila,Agnes Stefansdottir,Norah Spears
-
Plasmid-borne tigecycline resistance gene tet(X4) in Salmonella enterica and Escherichia coli isolates from a pediatric patient with diarrhea Drug Resist. Updat. (IF 15.8) Pub Date : 2024-09-02 Zelin Yan, Yan Li, Yingling Ni, Xiaoni Xia, Yanyan Zhang, Yuchen Wu, Jing Zhang, Gongxiang Chen, Ruichao Li, Rong Zhang
-
Mechanism of staphylococcal resistance to clinically relevant antibiotics Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-31 Daniela Brdová, Tomáš Ruml, Jitka Viktorová
, a notorious pathogen with versatile virulence, poses a significant challenge to current antibiotic treatments due to its ability to develop resistance mechanisms against a variety of clinically relevant antibiotics. In this comprehensive review, we carefully dissect the resistance mechanisms employed by against various antibiotics commonly used in clinical settings. The article navigates through
-
Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-30 Ashu Shah, Koelina Ganguly, Sanchita Rauth, Shamema S. Sheree, Imran Khan, Apar K. Ganti, Moorthy P. Ponnusamy, Sushil Kumar, Maneesh Jain, Surinder K. Batra
Despite the ongoing advances in interventional strategies (surgery, chemotherapy, radiotherapy, and immunotherapy) for managing pancreatic ductal adenocarcinoma (PDAC), the development of therapy refractory phenotypes remains a significant challenge. Resistance to various therapeutic modalities in PDAC emanates from a combination of inherent and acquired factors and is attributable to cancer cell-intrinsic
-
The gray boundaries of aberrant shortening of the cellular timekeepers' edges. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-08-28 Guillermo Guenechea,Nestor W Meza
-
The evolving genetic landscape of telomere biology disorder dyskeratosis congenita. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-08-28 Hemanth Tummala,Amanda J Walne,Mohsin Badat,Manthan Patel,Abigail M Walne,Jenna Alnajar,Chi Ching Chow,Ibtehal Albursan,Jennifer M Frost,David Ballard,Sally Killick,Peter Szitányi,Anne M Kelly,Manoj Raghavan,Corrina Powell,Reinier Raymakers,Tony Todd,Elpis Mantadakis,Sophia Polychronopoulou,Nikolas Pontikos,Tianyi Liao,Pradeep Madapura,Upal Hossain,Tom Vulliamy,Inderjeet Dokal
Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome, caused by genetic mutations that principally affect telomere biology. Approximately 35% of cases remain uncharacterised at the genetic level. To explore the genetic landscape, we conducted genetic studies on a large collection of clinically diagnosed cases of DC as well as cases exhibiting features resembling DC, referred
-
Un-methylation of NUDT21 represses docosahexaenoic acid biosynthesis contributing to enzalutamide resistance in prostate cancer Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-24 Shin-Chih Lin, Ya-Chuan Tsai, Ying-Lan Chen, Hui-Kuan Lin, Yun-Chen Huang, Yi-Syuan Lin, Yu-Sheng Cheng, Hsing-Yi Chen, Chia-Jung Li, Tsung-Yen Lin, Shih-Chieh Lin
The recent approval of enzalutamide for metastatic castration-sensitive prostate cancer underscores its growing clinical significance, raising concerns about emerging resistance and limited treatment options. While the reactivation of the androgen receptor (AR) and other genes plays a role in enzalutamide resistance, identifications of novel underlying mechanism with therapeutic potential in enzalutamide-resistant
-
CRISPR-AMRtracker: A novel toolkit to monitor the antimicrobial resistance gene transfer in fecal microbiota Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-24 Gong Li, Teng-Fei Long, Shi-Ying Zhou, Li-Juan Xia, Ang Gao, Lei Wan, Xiao-Yuan Diao, Yu-Zhang He, Ruan-Yang Sun, Jin-Tao Yang, Sheng-Qiu Tang, Hao Ren, Liang-Xing Fang, Xiao-Ping Liao, Ya-Hong Liu, Liang Chen, Jian Sun
The spread of antibiotic resistance genes (ARGs), particularly those carried on plasmids, poses a major risk to global health. However, the extent and frequency of ARGs transfer in microbial communities among human, animal, and environmental sectors is not well understood due to a lack of effective tracking tools. We have developed a novel fluorescent tracing tool, CRISPR-AMRtracker, to study ARG transfer
-
Human breast tissue engineering in health and disease. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-08-23 Maj-Britt Buchholz,Demi I Scheerman,Riccardo Levato,Ellen J Wehrens,Anne C Rios
The human mammary gland represents a highly organized and dynamic tissue, uniquely characterized by postnatal developmental cycles. During pregnancy and lactation, it undergoes extensive hormone-stimulated architectural remodeling, culminating in the formation of specialized structures for milk production to nourish offspring. Moreover, it carries significant health implications, due to the high prevalence
-
Revolutionising infection control: building the next generation of phage banks Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-22 Braira Wahid, Muhammad Salman Tiwana, Akhtar Ali
-
Novel immunotherapeutics against LGR5 to target multiple cancer types. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-08-21 Hung-Chang Chen,Nico Mueller,Katherine Stott,Chrysa Kapeni,Eilidh Rivers,Carolin M Sauer,Flavio Beke,Stephen J Walsh,Nicola Ashman,Louise O'Brien,Amir Rafati Fard,Arman Godsinia,Changtai Li,Fadwa Joud,Olivier Giger,Inti Zlobec,Ioana Olan,Sarah J Aitken,Matthew Hoare,Richard Mair,Eva Serrao,James D Brenton,Alicia Garcia-Gimenez,Simon E Richardson,Brian Huntly,David R Spring,Mikkel-Ole Skjoedt,Karsten
We have developed and validated a highly specific, versatile antibody to the extracellular domain of human LGR5 (α-LGR5). α-LGR5 detects LGR5 overexpression in >90% of colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pre-B-ALL tumour cells and was used to generate an Antibody-Drug Conjugate (α-LGR5-ADC), Bispecific T-cell Engager (α-LGR5-BiTE) and Chimeric Antigen Receptor (α-LGR5-CAR).
-
Fertility protection during chemotherapy treatment by boosting the NAD(P)+ metabolome. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-08-21 Wing-Hong Jonathan Ho,Maria B Marinova,Dave R Listijono,Michael J Bertoldo,Dulama Richani,Lynn-Jee Kim,Amelia Brown,Angelique H Riepsamen,Safaa Cabot,Emily R Frost,Sonia Bustamante,Ling Zhong,Kaisa Selesniemi,Derek Wong,Romanthi Madawala,Maria Marchante,Dale M Goss,Catherine Li,Toshiyuki Araki,David J Livingston,Nigel Turner,David A Sinclair,Kirsty A Walters,Hayden A Homer,Robert B Gilchrist,Lindsay
Chemotherapy induced ovarian failure and infertility is an important concern in female cancer patients of reproductive age or younger, and non-invasive, pharmacological approaches to maintain ovarian function are urgently needed. Given the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) as an essential cofactor for drug detoxification, we sought to test whether boosting the NAD(P)+
-
Restoration of defective oxidative phosphorylation to a subset of neurons prevents mitochondrial encephalopathy. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-08-21 Brittni R Walker,Lise-Michelle Theard,Milena Pinto,Monica Rodriguez-Silva,Sandra R Bacman,Carlos T Moraes
Oxidative Phosphorylation (OXPHOS) defects can cause severe encephalopathies and no effective treatment exists for these disorders. To assess the ability of gene replacement to prevent disease progression, we subjected two different CNS-deficient mouse models (Ndufs3/complex I or Cox10/complex IV conditional knockouts) to gene therapy. We used retro-orbitally injected AAV-PHP.eB to deliver the missing
-
Immunotherapies targeting the oncogenic fusion gene CLDN18-ARHGAP in gastric cancer. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-08-20 Yue Wang,Hanbing Wang,Tao Shi,Xueru Song,Xin Zhang,Yue Zhang,Xuan Wang,Keying Che,Yuting Luo,Lixia Yu,Baorui Liu,Jia Wei
The CLDN18-ARHGAP fusion gene is an oncogenic driver newly discovered in gastric cancer. It was detected in 9% (8/87) of gastric cancer patients in our center. An immunogenic peptide specifically targeting CLDN18-ARHGAP fusion gene was generated to induce neoantigen-reactive T cells, which was proved to have specific and robust anti-tumor capacity both in in vitro coculture models and in vivo xenograft
-
An enhanced intracellular delivery platform based on a distant diphtheria toxin homolog that evades pre-existing antitoxin antibodies. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-08-19 Shivneet K Gill,Seiji N Sugiman-Marangos,Greg L Beilhartz,Elizabeth Mei,Mikko Taipale,Roman A Melnyk
Targeted intracellular delivery of therapeutic proteins remains a significant unmet challenge in biotechnology. A promising approach is to leverage the intrinsic capabilities of bacterial toxins like diphtheria toxin (DT) to deliver a potent cytotoxic enzyme into cells with an associated membrane translocation moiety. Despite showing promising clinical efficacy, widespread deployment of DT-based therapeutics
-
Fusion event mediated by IS903B between chromosome and plasmid in two MCR-9- and KPC-2-co-producing Klebsiella pneumoniae isolates Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-17 Ruishan Liu, Yingying Chen, Hao Xu, Huanran Zhang, Yi Liu, Xiaojing Liu, Haowei Ye, Mantao Chen, Beiwen Zheng
Herein, we first isolated two MCR-9- and KPC-2-co-producing isolates. Notably, we observed a fusion event between the chromosome and plasmid, mediated by IS, in these two strains. This cointegration of chromosomes and plasmids introduces a new mode of transmission for antimicrobial resistance genes.
-
Unraveling the secrets: Evolution of resistance mediated by membrane proteins Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-16 Xue Yang, Min Li, Zi-Chang Jia, Yan Liu, Shun-Fan Wu, Mo-Xian Chen, Ge-Fei Hao, Qing Yang
Membrane protein-mediated resistance is a multidisciplinary challenge that spans fields such as medicine, agriculture, and environmental science. Understanding its complexity and devising innovative strategies are crucial for treating diseases like cancer and managing resistant pests in agriculture. This paper explores the dual nature of resistance mechanisms across different organisms: On one hand
-
Folylpolyglutamate synthetase inactivation in relapsed ALL induces a druggable folate metabolic vulnerability Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-16 Hui Li, Yao Chen, Ming Ding, Jingjing Liu, Huiying Sun, Houshun Fang, Samuel W. Brady, Yan Xu, Fabian Glaser, Xiaotu Ma, Yabin Tang, Liang Du, Xiaoyu Wu, Shuxuan Wang, Liang Zhu, Benshang Li, Shuhong Shen, Jinghui Zhang, Liang Zheng, Jiyang Yu, Yehuda G. Assaraf, Bin-Bing S. Zhou
The antifolate methotrexate (MTX) is an anchor drug used in acute lymphoblastic leukemia (ALL) with poorly understood chemoresistance mechanisms in relapse. Herein we find decreased folate polyglutamylation network activities and inactivating mutations, both of which could induce MTX resistance and folate metabolic vulnerability in relapsed ALL. We utilized integrated systems biology analysis of transcriptomic
-
Ultrastructural, metabolic and genetic characteristics of determinants facilitating the acquisition of macrolide resistance by Streptococcus pneumoniae Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-16 Xueqing Wu, Babek Alibayov, Xi Xiang, Santiago M. Lattar, Fuminori Sakai, Austin A. Medders, Brenda S. Antezana, Lance E. Keller, Ana G.J. Vidal, Yih-Ling Tzeng, D. Ashley Robinson, David S. Stephens, Yunsong Yu, Jorge E. Vidal
To investigate the molecular events associated with acquiring macrolide resistance genes [/ (Mega) or ] in () during nasopharyngeal colonization. Genomic analysis of 128 macrolide-resistant isolates revealed recombination events in genes of the conjugation apparatus, or the competence system, in strains carrying Tn-related elements. Studies using confocal and electron microscopy demonstrated that during
-
Histidine-rich glycoprotein modulates neutrophils and thrombolysis-associated hemorrhagic transformation. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-08-15 Wei Jiang,Yuexin Zhao,Rongrong Liu,Bohao Zhang,Yuhan Xie,Bin Gao,Kaibin Shi,Ming Zou,Dongmei Jia,Jiayue Ding,Xiaowei Hu,Yanli Duan,Ranran Han,DeRen Huang,Luc Van Kaer,Fu-Dong Shi
Intravenous thrombolysis using recombinant tissue plasminogen activator (tPA) remains the primary treatment for patients with acute ischemic stroke (AIS). However, the mechanism of tPA-related hemorrhagic transformation (HT) remains poorly understood. Elevation of histidine-rich glycoprotein (HRG) expression was detected by nano-liquid chromatography tandem mass spectrometry at 1 h following tPA infusion
-
The key role of iroBCDN-lacking pLVPK-like plasmid in the evolution of the most prevalent hypervirulent carbapenem-resistant ST11-KL64 Klebsiella pneumoniae in China Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-14 Xinmiao Jia, Ying Zhu, Peiyao Jia, Cuidan Li, Xiaobing Chu, Tianshu Sun, Xiaoyu Liu, Wei Yu, Fei Chen, Yingchun Xu, Qiwen Yang
Hypervirulent carbapenem-resistant (hv-CRKP), coharboring hypervirulence and carbapenem-resistance genes mediated by plasmids, causes infections with extremely high mortality and seriously impacts public health. Exploring the transfer mechanisms of virulence/carbapenem-resistance plasmids, as well as the formation and evolution pathway of hv-CRKP is of great significance to the control of hv-CRKP infections
-
CBX4 counteracts cellular senescence to desensitize gastric cancer cells to chemotherapy by inducing YAP1 SUMOylation Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-12 Yunru Gu, Tingting Xu, Yuan Fang, Jun Shao, Tong Hu, Xi Wu, Haoyang Shen, Yangyue Xu, Jingxin Zhang, Yu Song, Yang Xia, Yongqian Shu, Pei Ma
As our comprehension of the intricate relationship between cellular senescence and tumor biology continues to evolve, the therapeutic potential of cellular senescence is gaining increasing recognition. Here, we identify chromobox 4 (CBX4), a Small Ubiquitin-related Modifier (SUMO) E3 ligase, as an antagonist of cellular senescence and elucidate a novel mechanism by which CBX4 promotes drug resistance
-
Editorial: ABC transporters and drug resistance Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-10 Qisi Lu, Suresh V. Ambudkar, Dong-Hua Yang
-
Comprehensive molecular characterization of collecting duct carcinoma for therapeutic vulnerability. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-08-09 Peiyong Guan,Jianfeng Chen,Chengqiang Mo,Tomoya Fukawa,Chao Zhang,Xiuyu Cai,Mei Li,Jing Han Hong,Jason Yongsheng Chan,Cedric Chuan Young Ng,Jing Yi Lee,Suet Far Wong,Wei Liu,Xian Zeng,Peili Wang,Rong Xiao,Vikneswari Rajasegaran,Swe Swe Myint,Abner Ming Sun Lim,Joe Poh Sheng Yeong,Puay Hoon Tan,Choon Kiat Ong,Tao Xu,Yiqing Du,Fan Bai,Xin Yao,Bin Tean Teh,Jing Tan
Collecting duct carcinoma (CDC) is an aggressive rare subtype of kidney cancer with unmet clinical needs. Little is known about its underlying molecular alterations and etiology, primarily due to its rarity, and lack of preclinical models. This study aims to comprehensively characterize molecular alterations in CDC and identify its therapeutic vulnerabilities. Through whole-exome and transcriptome
-
Functional relay between Mph(A) enzyme and Mrx efflux pump mediates azithromycin resistance, a novel mechanism of bacterial antimicrobial resistance Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-08 Xuemei Yang, Haoshuai Zhang, Yang Tang, Heng Heng, Yan-Chu Cheung, Xuejiao Song, Hang-Kin Kong, Edward Wai-Chi Chan, Sheng Chen
-
Immunology of bile acids regulated receptors Prog. Lipid. Res. (IF 14.0) Pub Date : 2024-08-08 Stefano Fiorucci, Silvia Marchianò, Ginevra Urbani, Cristina Di Giorgio, Eleonora Distrutti, Angela Zampella, Michele Biagioli
Bile acids are steroids formed at the interface of host metabolism and intestinal microbiota. While primary bile acids are generated in the liver from cholesterol metabolism, secondary bile acids represent the products of microbial enzymes. Close to 100 different enzymatic modifications of bile acids structures occur in the human intestine and clinically guided metagenomic and metabolomic analyses
-
crVDAC3 alleviates ferroptosis by impeding HSPB1 ubiquitination and confers trastuzumab deruxtecan resistance in HER2-low breast cancer Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-06 Yutian Zou, Anli Yang, Bo Chen, Xinpei Deng, Jindong Xie, Danian Dai, Jinhui Zhang, Hailin Tang, Tao Wu, Zhigang Zhou, Xiaoming Xie, Jin Wang
With the wide application of trastuzumab deruxtecan (T-DXd), the survival of HER2-low breast cancer patients is dramatically improved. However, resistance to T-DXd still exists in a subset of patients, and the molecular mechanism remains unclear. An shRNA lentiviral library functional screening was performed to identify potential circular RNA (crRNA) that mediates T-DXd resistance. RNA pull-down, mass
-
Cellular and molecular mechanisms of gastrointestinal cancer liver metastases and drug resistance Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-06 Daosong Dong, Xue Yu, Jingjing Xu, Na Yu, Zhe Liu, Yanbin Sun
Distant metastases and drug resistance account for poor survival of patients with gastrointestinal (GI) malignancies such as gastric cancer, pancreatic cancer, and colorectal cancer. GI cancers most commonly metastasize to the liver, which provides a unique immunosuppressive tumour microenvironment to support the development of a premetastatic niche for tumor cell colonization and metastatic outgrowth
-
Inhibition of GSK3α,β rescues cognitive phenotypes in a preclinical mouse model of CTNNB1 syndrome. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-08-05 Jonathan M Alexander,Leeanne Vazquez-Ramirez,Crystal Lin,Pantelis Antonoudiou,Jamie Maguire,Florence Wagner,Michele H Jacob
CTNNB1 syndrome is a rare monogenetic disorder caused by CTNNB1 de novo pathogenic heterozygous loss-of-function variants that result in cognitive and motor disabilities. Treatment is currently lacking; our study addresses this critical need. CTNNB1 encodes β-catenin which is essential for normal brain function via its dual roles in cadherin-based synaptic adhesion complexes and canonical Wnt signal
-
The MondoA-dependent TXNIP/GDF15 axis predicts oxaliplatin response in colorectal adenocarcinomas. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-08-05 Jinhai Deng,Teng Pan,Dan Wang,Yourae Hong,Zaoqu Liu,Xingang Zhou,Zhengwen An,Lifeng Li,Giovanna Alfano,Gang Li,Luigi Dolcetti,Rachel Evans,Jose M Vicencio,Petra Vlckova,Yue Chen,James Monypenny,Camila Araujo De Carvalho Gomes,Gregory Weitsman,Kenrick Ng,Caitlin McCarthy,Xiaoping Yang,Zedong Hu,Joanna C Porter,Christopher J Tape,Mingzhu Yin,Fengxiang Wei,Manuel Rodriguez-Justo,Jin Zhang,Sabine Tejpar
Chemotherapy, the standard of care treatment for cancer patients with advanced disease, has been increasingly recognized to activate host immune responses to produce durable outcomes. Here, in colorectal adenocarcinoma (CRC) we identify oxaliplatin-induced Thioredoxin-Interacting Protein (TXNIP), a MondoA-dependent tumor suppressor gene, as a negative regulator of Growth/Differentiation Factor 15 (GDF15)
-
An increased prevalence of carbapenem-resistant hypervirulent Klebsiella pneumoniae associated with the COVID-19 pandemic Drug Resist. Updat. (IF 15.8) Pub Date : 2024-08-02 Chao Liu, Jun Guo, Shuaihua Fan, Wei Guo, Huaiqing Qi, Stephen Baker, Pengcheng Du, Bin Cao
(Kp) is a common community-acquired and nosocomial pathogen. Carbapenem-resistant and hypervirulent (CR-hvKp) variants can emerge rapidly within healthcare facilities and impacted by other infectious agents such as COVID-19 virus. To understand the impact of COVID-19 virus on the prevalence of CR-hvKp, we accessed Kp genomes with corresponding metadata from GenBank. Sequence types (STs), antimicrobial
-
Plant and algal lipidomes: Analysis, composition, and their societal significance Prog. Lipid. Res. (IF 14.0) Pub Date : 2024-07-31 Juliette Jouhet, Eliana Alves, Yohann Boutté, Sylvain Darnet, Frédéric Domergue, Thierry Durand, Pauline Fischer, Laetitia Fouillen, Mara Grube, Jérôme Joubès, Uldis Kalnenieks, Joanna M. Kargul, Inna Khozin-Goldberg, Catherine Leblanc, Sophia Letsiou, Josselin Lupette, Gabriel V. Markov, Isabel Medina, Tânia Melo, Peter Mojzeš, Svetlana Momchilova, Sébastien Mongrand, Ana S.P. Moreira, Bruna B. Neves
Plants and algae play a crucial role in the earth's ecosystems. Through photosynthesis they convert light energy into chemical energy, capture CO2 and produce oxygen and energy-rich organic compounds. Photosynthetic organisms are primary producers and synthesize the essential omega 3 and omega 6 fatty acids. They have also unique and highly diverse complex lipids, such as glycolipids, phospholipids
-
Therapeutic targeting ERRγ suppresses metastasis via extracellular matrix remodeling in small cell lung cancer. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-07-31 Hong Wang,Huizi Sun,Jie Huang,Zhenhua Zhang,Guodi Cai,Chaofan Wang,Kai Xiao,Xiaofeng Xiong,Jian Zhang,Peiqing Liu,Xiaoyun Lu,Weineng Feng,Junjian Wang
Small-cell lung cancer (SCLC) is the most aggressive and lethal type of lung cancer, characterized by limited treatment options, early and frequent metastasis. However, the determinants of metastasis in SCLC are poorly defined. Here, we show that estrogen-related receptor gamma (ERRγ) is overexpressed in metastatic SCLC tumors, and is positively associated with SCLC progression. ERRγ functions as an
-
The RhoB p.S73F mutation leads to cerebral palsy through dysregulation of lipid homeostasis. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-07-30 Xinyu Wu,Ruonan Liu,Zhongtian Zhang,Jie Yang,Xin Liu,Liqiang Jiang,Mengmeng Fang,Shoutang Wang,Liangxue Lai,Yuning Song,Zhanjun Li
Cerebral palsy (CP) is a prevalent neurological disorder that imposes a significant burden on children, families, and society worldwide. Recently, the RhoB p.S73F mutation was identified as a de novo mutation associated with CP. However, the mechanism by which the RhoB p.S73F mutation causes CP is currently unclear. In this study, rabbit models were generated to mimic the human RhoB p.S73F mutation
-
"Cruising together"-ASC specks and SAA, a perfect match in chronic inflammation. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-07-30 Salie Maasewerd,Bernardo Simoes Franklin
-
The ASC inflammasome adapter governs SAA-derived protein aggregation in inflammatory amyloidosis. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-07-30 Marco Losa,Marc Emmenegger,Pierre De Rossi,Patrick M Schürch,Tetiana Serdiuk,Niccolò Pengo,Danaëlle Capron,Dimitri Bieli,Niklas Bargenda,Niels J Rupp,Manfredi C Carta,Karl J Frontzek,Veronika Lysenko,Regina R Reimann,Petra Schwarz,Mario Nuvolone,Gunilla T Westermark,K Peter R Nilsson,Magdalini Polymenidou,Alexandre Pa Theocharides,Simone Hornemann,Paola Picotti,Adriano Aguzzi
Extracellularly released molecular inflammasome assemblies -ASC specks- cross-seed Aβ amyloid in Alzheimer's disease. Here we show that ASC governs the extent of inflammation-induced amyloid A (AA) amyloidosis, a systemic disease caused by the aggregation and peripheral deposition of the acute-phase reactant serum amyloid A (SAA) in chronic inflammatory conditions. Using super-resolution microscopy
-
Emergence of silent NDM-1 carbapenemase gene in carbapenem-susceptible Klebsiella pneumoniae: Clinical implications and epidemiological insights Drug Resist. Updat. (IF 15.8) Pub Date : 2024-07-29 Juanxiu Qin, Yuan Zhu, Yiwei Zhu, Qianqian Gao, Haomin Zhang, Min Li, Zhen Shen
The global dissemination of carbapenemase genes, particularly , poses a significant threat to public health. While research has mainly focused on strains with phenotypic resistance, the impact of silent resistance genes has been largely overlooked. This study documents the first instance of silent in a cluster of clonally related carbapenem-susceptible strains from a single patient. Despite initial
-
Framework nucleic acid-based nanoparticles enhance temozolomide sensitivity in glioblastoma Drug Resist. Updat. (IF 15.8) Pub Date : 2024-07-27 Yufei Lan, Xiaodie Li, Boyang Liu, Jiankun Lu, Boming Zuo, Yue Wang, Shuting Cao, Xin Fu, Qu Yue, Xin Luo, Xiangyang Zhong, Yaoyuan Dong, Zhao Wang, Tao Yang, Xinyun Xie, Tianci Zeng, Manqing Zhang, Yuankai Wang, Yixiong Shen, Huaqin Zuo, Yan Zhao, Chao Zhang, Hongbo Guo
O-methylguanine DNA methyltransferase (MGMT) is a crucial determinant of temozolomide (TMZ) sensitivity in patients with glioblastoma (GBM). The therapeutic potential of small interfering RNA (siRNA) targeting MGMT to enhance TMZ sensitivity has been hampered by serum nuclease degradation, off-target effects, poor accumulation at tumor sites, and low circulation in blood stream. In this study, we developed
-
Dantrolene corrects cellular disease features of Darier disease and may be a novel treatment. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-07-26 Matthew Hunt,Nuoqi Wang,Naricha Pupinyo,Philip Curman,Monica Torres,William Jebril,Maria Chatzinikolaou,Julie Lorent,Gilad Silberberg,Ritu Bansal,Teresa Burner,Jing Zhou,Susanne Kimeswenger,Wolfram Hoetzenecker,Keith Choate,Etty Bachar-Wikstrom,Jakob D Wikstrom
Darier disease (DD) is a rare severe acantholytic skin disease caused by mutations in the ATP2A2 gene that encodes for the sarco/endoplasmic reticulum calcium ATPase isoform 2 (SERCA2). SERCA2 maintains endoplasmic reticulum calcium homeostasis by pumping calcium into the ER, critical for regulating cellular calcium dynamics and cellular function. To date, there is no treatment that specifically targets
-
BCL7A inhibits the progression and drug-resistance in acute myeloid leukemia Drug Resist. Updat. (IF 15.8) Pub Date : 2024-07-22 Tushuai Li, Renjie Gao, Kaiwen Xu, Pengpeng Pan, Congcong Chen, Daokuan Wang, Keyi Zhang, Jilei Qiao, Yue Gu
This study aimed to elucidate the biological roles and regulatory mechanisms of B-cell lymphoma 7 protein family member A (BCL7A) in acute myeloid leukemia (AML), particularly its interaction with polypyrimidine tract binding protein 1 (PTBP1) and the effects on cancer progression and drug resistance. BCL7A expression levels were analyzed in AML tissues and cell lines, focusing on associations with
-
PD-1/LAG-3 co-signaling profiling uncovers CBL ubiquitin ligases as key immunotherapy targets. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-07-19 Luisa Chocarro,Ester Blanco,Leticia Fernandez-Rubio,Maider Garnica,Miren Zuazo,Maria Jesus Garcia,Ana Bocanegra,Miriam Echaide,Colette Johnston,Carolyn J Edwards,James Legg,Andrew J Pierce,Hugo Arasanz,Gonzalo Fernandez-Hinojal,Ruth Vera,Karina Ausin,Enrique Santamaria,Joaquin Fernandez-Irigoyen,Grazyna Kochan,David Escors
Many cancer patients do not benefit from PD-L1/PD-1 blockade immunotherapies. PD-1 and LAG-3 co-upregulation in T-cells is one of the major mechanisms of resistance by establishing a highly dysfunctional state in T-cells. To identify shared features associated to PD-1/LAG-3 dysfunctionality in human cancers and T-cells, multiomic expression profiles were obtained for all TCGA cancers immune infiltrates
-
LILRB1-HLA-G axis defines a checkpoint driving natural killer cell exhaustion in tuberculosis. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-07-19 Jing Wang,Qiyao Chai,Zehui Lei,Yiru Wang,Jiehua He,Pupu Ge,Zhe Lu,Lihua Qiang,Dongdong Zhao,Shanshan Yu,Changgen Qiu,Yanzhao Zhong,Bing-Xi Li,Lingqiang Zhang,Yu Pang,George Fu Gao,Cui Hua Liu
Chronic infections, including Mycobacterium tuberculosis (Mtb)-caused tuberculosis (TB), can induce host immune exhaustion. However, the key checkpoint molecules involved in this process and the underlying regulatory mechanisms remain largely undefined, which impede the application of checkpoint-based immunotherapy in infectious diseases. Here, through adopting time-of-flight mass cytometry and transcriptional
-
Reflections on a Career in Pediatric Neuropathology, with a Note of Gratitude Ann. Review Paleopathol. Mech. Disease (IF 28.4) Pub Date : 2024-07-17 Hannah C. Kinney
I am honored to be asked by the journal to write this personal essay about my career in pediatric neuropathology—a life of immense satisfaction, meaning, and fulfillment. My motivation to enter this discipline is highlighted, as is my decision to perform brain research in the sudden infant death syndrome, the leading cause of postneonatal infant mortality in the United States today. I also touch upon
-
DiPRO1 distinctly reprograms muscle and mesenchymal cancer cells. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-07-15 Jeremy Rich,Melanie Bennaroch,Laura Notel,Polina Patalakh,Julien Alberola,Fayez Issa,Paule Opolon,Olivia Bawa,Windy Rondof,Antonin Marchais,Philippe Dessen,Guillaume Meurice,Morgane Le-Gall,Melanie Polrot,Karine Ser-Le Roux,Kamel Mamchaoui,Nathalie Droin,Hana Raslova,Pascal Maire,Birgit Geoerger,Iryna Pirozhkova
We have recently identified the uncharacterized ZNF555 protein as a component of a productive complex involved in the morbid function of the 4qA locus in facioscapulohumeral dystrophy. Subsequently named DiPRO1 (Death, Differentiation, and PROliferation related PROtein 1), our study provides substantial evidence of its role in the differentiation and proliferation of human myoblasts. DiPRO1 operates
-
Immune-enhancing neutrophils reprogrammed by subclinical low-dose endotoxin in cancer treatment. EMBO Mol. Med. (IF 9.0) Pub Date : 2024-07-15 Yao Zhang,Christina Lee,Shuo Geng,Jing Wang,Udipta Bohara,Jacqueline Hou,Ziyue Yi,Liwu Li
Despite the re-emergence of the pioneering "Coley's toxin" concept in anti-cancer immune therapies highlighted by check-point inhibitors and CAR-T approaches, fundamental mechanisms responsible for the immune-enhancing efficacy of low-dose "Coley's toxin" remain poorly understood. This study examines the novel reprogramming of immune-enhancing neutrophils by super-low dose endotoxin conducive for anti-cancer