PIM2 inhibition promotes MCL1 dependency in plasma cells involving integrated stress response-driven NOXA expression.

Our study explores the complex dynamics of the integrated stress response (ISR) axis, highlighting PIM2 kinase's critical role and its interaction with the BCL2 protein family, uncovering key mechanisms of cell survival and tumor progression. Elevated PIM2 expression, a marker of various cancers, often correlates with disease aggressiveness. Using a model of normal and malignant plasma cells, we show that inhibiting PIM2 kinase inhibits phosphorylated BAD production and activates ISR-mediated NOXA expression.

Haematometabolism rewiring in atherosclerotic cardiovascular disease.

Atherosclerotic cardiovascular diseases are the most frequent cause of death worldwide. The clinical complications of atherosclerosis are closely linked to the haematopoietic and immune systems, which maintain homeostatic functions and vital processes in the body. The nodes linking metabolism and inflammation are receiving increasing attention because they are inextricably linked to inflammatory manifestations of non-communicable diseases, including atherosclerosis.

Disrupting USP39 deubiquitinase function impairs the survival and migration of multiple myeloma cells through ZEB1 degradation.

Background: Multiple Myeloma (MM) is the second most common hematological malignancy, characterized by the accumulation of monoclonal plasmocytes in the bone marrow. Despite advancements with proteasome inhibitors, immunomodulatory agents, and CD38-targeting antibodies, MM remains largely incurable due to resistant clones and frequent relapses. The success of the proteasome inhibitor bortezomib (BTZ) in MM treatment highlights the critical role of the ubiquitin-proteasome system (UPS) in this disease.

CLEC12B regulates melanocyte immunity and homeostasis in the skin through the STAT1/IRF1 axis.

CLEC12B is a C-type lectin receptor involved in the inhibition of natural killers-mediated cytotoxicity. We have previously shown that CLEC12B is predominantly expressed on melanocytes, inhibits melanin production and pigmentation as well as proliferation of melanoma. To date, the role of CLEC12B in skin immunity is unknown.

A ganglioside-based immune checkpoint enables senescent cells to evade immunosurveillance during aging.

Although senescent cells can be eliminated by the immune system, they tend to accumulate with age in various tissues. Here we show that senescent cells can evade immune clearance by natural killer (NK) cells by upregulating the expression of the disialylated ganglioside GD3 at their surface. The increased level of GD3 expression on senescent cells that naturally occurs upon aging in liver, lung, kidney or bones leads to a strong suppression of NK-cell-mediated immunosurveillance.

Free Methylglyoxal as a Metabolic New Biomarker of Tumor Cell Proliferation in Cancers.

Background: A fundamental property of cancer cells is their metabolic reprogramming, allowing them to increase glucose uptake and glycolysis. Using a rat colon adenocarcinoma model, we previously showed that blood levels of free methylglyoxal (MG), a side-product of glycolysis, remained normal in animals grafted with a non-growing tumor cell clone, while MG levels were significantly increased and positively correlated with tumor growth in animals grafted with a tumorigenic cell clone issued from the same tumor.

Methods: We measured free MG in the blood of cancerous non-diabetic patients and compared the results to healthy subjects and non-cancerous diabetic patients.

Metabolism and mRNA translation: a nexus of cancer plasticity.

Tumors often face energy deprivation due to mutations, hypoxia, and nutritional deficiencies within the harsh tumor microenvironment (TME), and as an effect of anticancer treatments. This metabolic stress triggers adaptive reprogramming of mRNA translation, which in turn adjusts metabolic plasticity and associated signaling pathways to ensure tumor cell survival. Emerging evidence is beginning to reveal the complex interplay between metabolism and mRNA translation, shedding light on the mechanisms that synchronize ribosome assembly and reconfigure translation programs under metabolic stress.

GLS2 links glutamine metabolism and atherosclerosis by remodeling artery walls.

Metabolic dysregulation, including perturbed glutamine-glutamate homeostasis, is common among patients with cardiovascular diseases, but the underlying mechanisms remain largely unknown. Using the human MESA cohort, here we show that plasma glutamine-glutamate ratio is an independent risk factor for carotid plaque progression. Mice deficient in glutaminase-2 (Gls2), the enzyme that mediates hepatic glutaminolysis, developed accelerated atherosclerosis and susceptibility to catastrophic cardiac events, while Gls2 overexpression partially protected from disease progression.

ATP citrate lyase is an essential player in the metabolic rewiring induced by PTEN loss during T-ALL development.

Alterations inactivating the tumor suppressor gene PTEN drive the development of solid and hematological cancers, such as T-cell acute lymphoblastic leukemia (T-ALL), whereby PTEN loss defines poor-prognosis patients. We investigated the metabolic rewiring induced by PTEN loss in T-ALL, aiming at identifying novel metabolic vulnerabilities. We showed that the enzyme ATP citrate lyase (ACLY) is strictly required for the transformation of thymic immature progenitors and for the growth of human T-ALL, which remain dependent on ACLY activity even upon transformation.

Nitro-fatty acids: promising agents for the development of new cancer therapeutics.

Nitro-fatty acids (NO-FAs) are endogenous pleiotropic lipid mediators regarded as promising drug candidates for treating inflammatory and fibrotic diseases. Over the past two decades, the anti-inflammatory and cytoprotective actions of NO-FAs and several molecular targets have been identified. More recently, preclinical studies have demonstrated their potential as prospective cancer therapeutics with favorable safety and tumor-selective profiles.

Nifuroxazide rescues the deleterious effects due to CHCHD10-associated MICOS defects in disease models.

The identification of a point mutation (p.Ser59Leu) in the CHCHD10 gene was the first genetic evidence that mitochondrial dysfunction can trigger motor neuron disease. Since then, we have shown that this mutation leads to the disorganization of the MItochondrial contact site and Cristae Organizing System (MICOS) complex that maintains the mitochondrial cristae structure.

New Fusarochromanone Derivatives from the Marine Fungus UBOCC-A-117302.

Two new fusarochromanone derivatives, deacetylfusarochromene () and deacetamidofusarochrom-2',3-diene (), along with the previously reported metabolites fusarochromanone TDP-2 (), fusarochromene (), 2,2-dimethyl-5-amino-6-(2'-ene-4'-hydroxylbutyryl)-4-chromone (), fusarochromanone (), (-)-chrysogine (), and equisetin (), were isolated from the marine fungus UBOCC-A-117302. The structures of the compounds were determined by extensive spectrometric (HRMS) and spectroscopic (1D and 2D NMR) analyses, as well as specific rotation. Among them, and showed inhibition of three protein kinases with IC values ranging from 1.

Combined developmental exposure to estrogenic endocrine disruptor and nutritional imbalance induces long term adult prostate inflammation through inflammasome activation.

Increasing number of studies suggested that environmental deleterious impacts (such as estrogen-like endocrine disruptors, EDCs, unhealthy diet) during early human development affect the risk of developing non-communicable diseases including prostate cancer (PCa) later in life. To test if the combination of EDCs and unhealthy induces adult prostate lesions, we developed an experimental model of adult male Sprague Dawley rats exposed during gestation (from day 7) to weaning to high fat diet (HFD 60 % fat), or to a xenoestrogen (estradiol benzoate, EB, 2.5 µg/d) from post-natal days 1-5, or to a combination of both.

Lysosomes in the immunometabolic reprogramming of immune cells in atherosclerosis.

Lysosomes have a central role in the disposal of extracellular and intracellular cargo and also function as metabolic sensors and signalling platforms in the immunometabolic reprogramming of macrophages and other immune cells in atherosclerosis. Lysosomes can rapidly sense the presence of nutrients within immune cells, thereby switching from catabolism of extracellular material to the recycling of intracellular cargo. Such a fine-tuned degradative response supports the generation of metabolic building blocks through effectors such as mTORC1 or TFEB.

RAC2 gain-of-function variants causing inborn error of immunity drive NLRP3 inflammasome activation.

A growing number of patients presenting severe combined immunodeficiencies attributed to monoallelic RAC2 variants have been identified. The expression of the RHO GTPase RAC2 is restricted to the hematopoietic lineage. RAC2 variants have been described to cause immunodeficiencies associated with high frequency of infection, leukopenia, and autoinflammatory features.

Evaluating the Frequency of Mole Checks by a Dermatologist and Correlated Variables in a Global Survey across 17 Countries: HELIOS Project.

Secondary prevention of skin cancer consists in early detection of malignant lesions through patients' mole self-examination and medical examination. The objective of this study was to assess the self-reported  frequency of mole examination in a large, representative sample of the adult general population of 17 countries from all continents. Of a total of 17,001 participants, 4.