Long-chain polyunsaturated fatty acids (LC-PUFAs), especially very long-chain polyunsaturated fatty acids (VLC-PUFAs), are highly beneficial to human health including brain development, cardiovascular health and the immune system. Plant-derived edible oils serve as crucial dietary sources of PUFAs for humans. However, oilseed crops such as soybean, peanut, rapeseed, sesame and flax, generally contain

Inhibition of the epidermal growth factor receptor (EGFR) shows clinical benefit in metastatic colorectal cancer (CRC) patients, but KRAS-mutations are known to confer resistance. However, recent reports highlight EGFR as a crucial target to be co-inhibited with RAS inhibitors for effective treatment of KRAS mutant CRC. Here, we investigated the tumor cell-intrinsic contribution of EGFR in KRASG12D

Glioblastoma remains incurable and recurs in all patients. Here we design and characterize a novel induced-recurrence model in which mice xenografted with primary patient-derived glioma initiating/stem cells (GIC) are treated with a therapeutic regimen closely recapitulating patient standard of care, followed by monitoring until tumours recur (induced recurrence patient-derived xenografts, IR-PDX)

Liver fibrosis is a major cause of death worldwide. As a progressive step in chronic liver disease, fibrosis is almost always diagnosed too late with limited treatment options. Here, we uncover the spatial transcriptional landscape driving human liver fibrosis using single nuclei RNA and Assay for Transposase-Accessible Chromatin (ATAC) sequencing to deconvolute multi-cell spatial transcriptomic profiling

The therapeutic efficacy of osimertinib (OSI) in EGFR-mutant lung cancer is ultimately limited by the onset of acquired resistance, of which the mechanisms remain poorly understood. Here, we identify a novel long non-coding RNA, LRTOR, as a key driver of OSI resistance in non-small cell lung cancer (NSCLC). Clinical data indicate that elevated LRTOR expression correlates with poor prognosis in OSI-resistant

Primary cilia are solitary organelles formed by a microtubule-based skeleton protruding in a single copy on the surface of most cells. Alterations in their function cause a plethora of human conditions collectively called the ciliopathies. The kidney is frequently and severely affected in the ciliopathies, presenting with a spectrum of phenotypes. Cyst formation is a common trait of all renal ciliopathies

Lactate plays a crucial role as an energy substrate, metabolite, and signaling molecule in cancer. Lactate has long been considered a byproduct of glycolysis. Still, the lactate shuttle hypothesis has changed the lactate paradigm, revealing the implications of lactate in cellular metabolism and cellular communications that can transcend the compartment barrier and occur within and between different

Resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) poses a significant challenge to enhancing the efficacy of cancer treatments. Beyond the cellular mechanisms intrinsic to tumor cells, the modulation of the tumor immune microenvironment is crucial in dictating the responsiveness to pharmacological interventions. Thus, there is a pressing need to elucidate the intricate interplay between

RNA-binding proteins (RBPs) are critical regulators in tumorigenesis and therapy resistance by modulating RNA metabolism. However, the role of RBPs in hepatocarcinogenesis and progression remains elusive. Here, RBPs screening and integrating analyses identify major vault protein (MVP) as an oncogenic RBP in the occurrence of hepatocellular carcinoma (HCC) and sorafenib resistance via suppressing ferroptosis

Fibrosis is a key feature of a broad spectrum of cystic kidney diseases, especially autosomal recessive kidney disorders such as nephronophthisis (NPHP). However, its contribution to kidney function decline and the underlying molecular mechanism(s) remains unclear. Here, we show that kidney-specific deletion of Fbxw7, the recognition receptor of the SCFFBW7 E3 ubiquitin ligase, results in a juvenile-adult

Mutations in the mitochondrial genome (mtDNA) often lead to clinical pathologies. Mitochondrially-targeted zinc finger nucleases (mtZFNs) have been successful in reducing the levels of mutation-bearing mtDNA both in vivo and in vitro, resulting in a shift in the genetic makeup of affected mitochondria and subsequently to phenotypic rescue. Given the uneven distribution in the mtDNA mutation load across

Hypervirulent and carbapenem-resistant pathogens posed a significant and growing threat to global public health. This study focused on the rapid spread of a hypervirulent carbapenem-resistant E. coli (hv-CREC) subclone and its genomic resembles with hypervirulent carbapenem-resistant K. pneumoniae (hv-CRKP), driven by recombination impacting both chromosomal and plasmid gene content.

Neoantigen vaccine is a promising breakthrough in tumor immunotherapy. However, the application of this highly personalized strategy in the treatment of solid tumors is hindered by several obstacles, including very costly and time-consuming preparation steps, uncertainty in prediction algorithms and tumor heterogeneity. Universalization of neoantigen vaccine is an ideal yet currently unattainable solution

Genomics has transformed the diagnostic landscape of pediatric malignancies by identifying and integrating actionable features that refine diagnosis, classification, and treatment. Yet, translating precision oncology data into effective therapies for hard-to-cure childhood, adolescent, and young adult malignancies remains a significant challenge. We present the case for combining proteomics with patient-derived

Saccharin has been part of the human diet for over 100 years, and there is a comprehensive body of evidence demonstrating that it can influence the gut microbiome, ultimately impacting human health. However, the precise mechanisms through which saccharin can impact bacteria have remained elusive. In this work, we demonstrate that saccharin inhibits cell division, leading to cell filamentation with

Circulating neutrophils are responsible for poor neurological outcomes and have been implicated in respiratory morbidity after acute ischemic stroke (AIS). However, the molecular mechanisms regulating neutrophil responses and their pathological relevance in post-stroke complications remain unclear. In this study, we investigated the involvement of hematopoietic progenitor kinase 1 (HPK1) in neutrophil

Global hepatic DNA methylation change has been linked to human patients with metabolic dysfunction-associated steatotic liver disease (MASLD). DNA demethylation is regulated by the TET family proteins, whose enzymatic activities require 2-oxoglutarate (2-OG) and iron that both are elevated in human MASLD patients. We aimed to investigate liver TET1 in MASLD progression. Depleting TET1 using two different

Relapse in acute myeloid leukemia (AML) is driven by resistant subclones that survive chemotherapy. It is assumed that these resilient leukemic cells can modify their proliferative behavior by entering a quiescent-like state, similar to healthy hematopoietic stem cells (HSCs). These dormant cells can evade the effects of cytostatic drugs that primarily target actively dividing cells. Although quiescence

Metastatic melanoma can be treated with anti-PD-1 monotherapy or in combination with anti-CTLA-4 or anti-Lag3. However, combination therapy is associated with a high risk of toxicity. Recently, we reported that high plasma soluble CD27 (sCD27) levels reflect the intratumoral interaction of CD70-CD27 and dysfunctional T cells in the tumor microenvironment of renal cell carcinoma. In this study, we first

The oncogenic mechanisms by which TFE3 fusion proteins drive translocation renal cell carcinoma (tRCC) are poorly characterized. Here, we integrated loss and gain of function experiments with multi-omics analyses in tRCC cell lines and patient tumors. High nuclear accumulation of NONO-TFE3 or PRCC-TFE3 fusion proteins promotes their broad binding across the genome at H3K27ac-marked active chromatin

The intratumoral immune milieu is crucial for the success of anti-cancer immunotherapy. We show here that stromal modulation by the tubulin-binding anti-cancer drugs combretastatin A4 (CA-4) and eribulin improved tumor perfusion and anti-tumor immunity. This was achieved by reverting highly proliferative, angiogenic pericytes into a quiescent, contractile state which durably normalized the vascular

Myotonic dystrophy type 2 (DM2), caused by CCTG repeat expansion, is a common adult-onset disorder characterized by myotonia and progressive muscle degeneration with no effective treatment. Here, we identified Tyrosyl-DNA phosphodiesterase 1 (TDP1) as a novel modifier for DM2 therapeutic intervention through a high-throughput chemical screening of 2160 compounds. Moreover, we detailed how both genetic

Lipids besides being components of membranes and storage molecules are also involved in signalling processes and have proven to be vital components in plant defence mechanisms. Over the past decades, the intricate lipid-signalling pathways that underlie the establishment of defence responses have been extensively studied. These molecules can act directly as signalling agents in plant defence or serve

ADP-ribosyl transferases (ARTs) are a family of enzymes which catalyze the addition of a chain (PARylation) or a single moiety (MARylation) of ADP-ribose to their substrates. PARP7 is a mono-ADP-ribosyl transferase (mono-ART) which has recently gained attention due to its emerging role as a negative regulator of the type I interferon (IFN-I) and nuclear receptor signaling, and due to its aberrant expression

Current therapeutic strategies for pancreatic ductal adenocarcinoma (PDAC) have limited efficacy in increasing patient survival rates, largely due to ferroptosis resistance and immunosuppression. The aim of this study is to identify molecular mechanisms associated with ferroptosis resistance and immunosuppression in PDAC tumour cells.

RNA metabolism has been extensively studied in DNA double-strand break (DSB) repair. The RNA acetyltransferase N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4C) modification in DSB repair remains largely elusive. In this study, we aim to decipher the role for ac4C modification by NAT10 in DSB repair in hepatocellular carcinoma (HCC).

Molecular changes underlying the persistent health effects after SARS-CoV-2 infection remain poorly understood. To discern the gene regulatory landscape in the upper respiratory tract of COVID-19 patients, we performed enzymatic DNA methylome and single-cell RNA sequencing in nasal cells of COVID-19 patients (n = 19, scRNA-seq n = 14) and controls (n = 14, scRNA-seq n = 10). In addition, we resampled

Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality, with maternal stress-related disorders, such as depression and anxiety, linked to idiopathic PTB (iPTB). At the maternal-fetal interface, decidualized stromal cells (DSCs) exclusively express the progesterone receptor (PR) and play pivotal roles in maintaining pregnancy and initiating labor. DSCs also express FKBP51, a protein

Despite global efforts, antimicrobial resistance persists. Mechanisms like heterotolerance further undermine antibiotic effectiveness. Testing > 1000 clinical strains revealed widespread heterotolerance largely missed by conventional MIC-based diagnostics. Since AMR alone does not predict treatment success, new tests and strategies incorporating tolerance data are urgently needed to significantly improve

We aimed to restore MHC-I expression on the surface of solid tumors including breast cancer and melanoma cells to regain sensitivity to immunotherapy and suppress metastatic progression. We screened a natural compound library and identified macbecin II as a reagent that upregulates MHC-I expression and induces antigen-dependent cell death in pre-invasive and invasive breast cancer models. Furthermore

Viral infections pose a significant global burden. Host susceptibility to pathogens is determined by many factors including genetic variation that can lead to immunodeficient or dysregulated antiviral immune responses. Pax5 heterozygosity (Pax5-/+), resulting in reduced PAX5 levels in mice, mimics germline or somatic PAX5 dysregulation contributing to diseases such as childhood B-cell precursor acute

Chemotherapeutic drug resistance remains a major barrier to effective cancer treatment. Drug resistance could be driven in part by adaptive redox remodeling of cancer cells. Paradoxically, drug-resistant malignancies exhibit elevated reactive oxygen species (ROS), as well as amplified antioxidant defenses, which enable cancer cell survival under therapeutic stress. Central to this adaptation is glutathione

To investigate the role of CD105 in mediating drug resistance to EGFR-targeted therapy in non-small cell lung cancer (NSCLC).

The phospholipase A and acyltransferase (PLAAT) family is a group of structurally related proteins that are conserved among vertebrates. In humans, the family comprises five members (PLAAT1–5), which share common domain structures, and functions as phospholipase A1/A2 and acyltransferase enzymes. Regarding acyltransferase activities, PLAATs produce N-acyl-phosphatidylethanolamines, which serve as the

Host-microbiome communication is frequently perturbed in gut pathologies due to microbiome dysbiosis, leading to altered production of bacterial metabolites. Among these, 7α-dehydroxylated bile acids are notably diminished in inflammatory bowel disease patients. Herein, we investigated whether restoration of 7α-dehydroxylated bile acids levels by Clostridium scindens, a human-derived 7α-dehydroxylating

Taxanes are effective in several solid tumors. Paclitaxel, the main clinically available taxane, was approved in the early nineties, for the treatment of ovarian cancer and later on, together with the analogs docetaxel and cabazitaxel, for other malignancies. By interfering with microtubule function and impairing the separation of sister cells at mitosis, taxanes act as antimitotic agents, thereby

One of the major limitations of cancer therapy is the emergence of drug resistance. This review amis to provide a focused analysis of the multifactorial mechanisms underlying therapy resistance,with an emphasis on actionable insights for developing novel therapeutic strategies. It concisely outlines key factors contributing to therapy resistance, including drug delivery barriers, cancer stem cells

Prostate cancer (PCa) remains a significant challenge in oncology due to high rates of drug resistance following standard treatment with docetaxel-based chemotherapy. Asporin (ASPN) has been regarded as an oncogene and its upregulation is closely associated with malignant behavior and poor prognosis in multiple cancers. Studies indicated that abnormal activation of the Wnt/β-catenin signaling pathway

Aging plays a critical role in the development, progression, and therapeutic challenges associated with brain tumors, particularly glioblastomas (GBM). As the population ages, the incidence of brain tumors, including GBM, increases, with aging emerging as a significant prognostic factor influencing survival outcomes. This review examines the molecular mechanisms linking aging and brain tumor progression

Tumors often recapitulate programs to acquire invasive and dissemination abilities, during which pro-metastatic proteins are distinctively stabilized in cancer cells to drive further progression. Whether failed protein degradation affects the metastatic programs of cancer remains unknown. Here, we show that the human cancer cell-specific knockout (KO) of LAMP-2A, a limiting protein for chaperone-mediated

Methotrexate (MTX) is a critical antimetabolite drug in treating various pediatric diseases, including acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), brain tumors, osteosarcoma, inflammatory myofibroblastic tumor (IMT), juvenile scleroderma (JS), and juvenile idiopathic arthritis (JIA). MTX acts as a folate antagonist by inhibiting dihydrofolate reductase (DHFR), an enzyme essential

Mycobacterial infections pose a significant global health concern, requiring precise identification for effective treatment. However, diagnosing them is challenging due to inaccurate identifications and prolonged times. In this study, we aimed to develop a novel peptidome-based method using mycobacterial growth indicator tube (MGIT) cultures for faster and more accurate identification. We created the

TRAP1 is involved in metabolic reprogramming and promotes drug resistance. We aimed to explore whether a novel HSP90 inhibitor, C210, overcomes doxorubicin (DOX) resistance of quiescent breast cancer cells by targeting TRAP1.

Emerging resistance to Lenvatinib, which is used as a first-line agent for the treatment of advanced hepatocellular carcinoma (HCC), is still a concern. The aim of this study was to determine core factors of Lenvatinib resistance (LR) and their underlying molecular mechanisms.

Patients with breast cancer (BC) who benefit from the PD-1/PD-L1 inhibitor (PDi) is limited, necessitating novel strategies to improve immunotherapy efficacy of BC. Here we aimed to investigate the inhibitory effects of flaxseed lignans (FL) on the biological behaviors of BC and evaluate the roles of FL in enhancing the anticancer effects of PDi.

As a common and severe cerebrovascular disease, ischemic stroke casts a significant shadow over global health. Unfortunately, the mechanisms regulating neuronal death in the affected areas remain largely unclear. Here, we found that deletion of the deubiquitinating enzyme Otubain-2 (OTUB2) significantly alleviated ischemia-induced cerebral infarction and neurological deficits, accompanied by a reduction

Over the last two decades, advancements in deciphering the intricate interactions between oncology and immunity have fueled a meteoric rise in immunotherapy for non-small cell lung cancer, typified by an explosive growth of immune checkpoint inhibitors. However, resistance to immunotherapy remains inevitable. Herein we unravel the labyrinthine mechanisms of resistance to immunotherapy, characterized

After the Covid-19 pandemic, pertussis has made a spectacular comeback in Europe and many other parts of the world, while during the pandemic it had essentially disappeared because of the social distancing requirements. However, even before the Covid-19 pandemic, the disease was on the rise in many countries, especially those that have replaced whole-cell pertussis vaccines by acellular pertussis vaccines

X-linked myopathy with excessive autophagy (XMEA), a rare childhood-onset autophagic vacuolar myopathy caused by mutations in VMA21, is characterized by proximal muscle weakness and progressive vacuolation. VMA21 encodes a protein chaperone of the vacuolar hydrogen ion ATPase, the loss of which leads to lysosomal neutralization and impaired function. At present, there is an incomplete understanding

Temozolomide (TMZ) is the first-line chemotherapeutic agent for glioblastoma (GBM) therapy; however, resistance to TMZ remains a major obstacle in GBM treatment. The aim of this study is to elucidate the mechanisms underlying TMZ resistance and explore how to enhance the sensitivity of GBM to TMZ.

Regulatory T cells (Tregs) play critical roles in inhibiting antitumor immunity, which is dependent on FOXP3-mediated transcriptional activity. However, no Treg-specific therapeutics has been approved for clinical use. We performed a high-throughput screen of FDA-approved drugs for potential inhibitors of FOXP3 transcriptional activity. These efforts identified Lanatoside C (Lac), which potently inhibits