Differential and Overlapping Effects of Melatonin and Its Metabolites on Keratinocyte Function: Bioinformatics and Metabolic Analyses.

We investigated the effects of melatonin and its selected metabolites, i.e., -Acetyl--formyl-5-methoxykynurenamine (AFMK) and 6-hydroxymelatonin (6(OH)Mel), on cultured human epidermal keratinocytes (HEKs) to assess their homeostatic activities with potential therapeutic implications.

Combination of PKCδ Inhibition with Conventional TKI Treatment to Target CML Models.

Numerous combinations of signaling pathway blockades in association with tyrosine kinase inhibitor (TKI) treatment have been proposed for eradicating leukemic stem cells (LSCs) in chronic myeloid leukemia (CML), but none are currently clinically available. Because targeting protein kinase Cδ (PKCδ) was demonstrated to eliminate cancer stem cells (CSCs) in solid tumors, we evaluated the efficacy of PKCδ inhibition in combination with TKIs for CML cells. We observed that inhibition of PKCδ by a pharmacological inhibitor, by gene silencing, or by using K562 CML cells expressing dominant-negative (DN) or constitutively active (CA) PKCδ isoforms clearly points to PKCδ as a regulator of the expression of the stemness regulator BMI1.

Influenza Virus Infection Impairs the Gut's Barrier Properties and Favors Secondary Enteric Bacterial Infection through Reduced Production of Short-Chain Fatty Acids.

Along with respiratory tract disease , viral respiratory infections can also cause extrapulmonary complications with a potentially critical impact on health. In the present study, we used an experimental model of influenza A virus (IAV) infection to investigate the nature and outcome of the associated gut disorders. In IAV-infected mice, the signs of intestinal injury and inflammation, altered gene expression, and compromised intestinal barrier functions peaked on day 7 postinfection.

Analysis of Matched Skin and Gut Microbiome of Patients with Vitiligo Reveals Deep Skin Dysbiosis: Link with Mitochondrial and Immune Changes.

Vitiligo is an autoimmune disease characterized by patchy, white skin owing to melanocyte loss. Commensal cutaneous or gut dysbiosis has been linked to various dermatological disorders. In this study, we studied the skin and gut microbiota of patients with vitiligo compared with those of healthy controls.

Memory B Cells Predict Relapse in Rituximab-Treated Myasthenia Gravis.

Myasthenia gravis can be efficiently treated with rituximab but there is no consensus regarding administration and dose schedules in this indication. No marker has yet been described to predict the clinical relapse of patients. Our objective was to identify the B cell subpopulations predicting clinical relapse in patients suffering from generalized myasthenia gravis and treated with rituximab.

Proteinuria as a Biomarker for COVID-19 Severity.

Background: Renal involvement in syndrome coronavirus 2 (SARS-CoV-2) infection has been retrospectively described, especially acute kidney injury (AKI). However, quantitative proteinuria assessment and its implication in coronavirus disease 2019 (COVID-19) remain unknown.

Methods: In this prospective, multicenter study in France, we collected clinical and biological data including urinary protein to creatine ratio (UPCR) in patients presenting with moderate to severe COVID-19.

Mitochondrial function is controlled by melatonin and its metabolites in vitro in human melanoma cells.

Melanoma is a leading cause of cancer deaths worldwide. Although immunotherapy has revolutionized the treatment for some patients, resistance towards therapy and unwanted side effects remain a problem for numerous individuals. Broad anti-cancer activities of melatonin are recognized; however, additional investigations still need to be elucidated.

Functional Exhaustion of Type I and II Interferons Production in Severe COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged in Wuhan in December 2019 and has since spread across the world. Even though the majority of patients remain completely asymptomatic, some develop severe systemic complications. In this prospective study we compared the immunological profile of 101 COVID-19 patients with either mild, moderate or severe form of the disease according to the WHO classification, as well as of 50 healthy subjects, in order to identify functional immune factors independently associated with severe forms of COVID-19.

Germline variants in exonic regions have limited impact on immune checkpoint blockade clinical outcomes in advanced melanoma.

Immune checkpoint inhibition (ICI) treatments improve outcomes for metastatic melanoma; however, up to 60% of treated patients do not respond to ICI and/or develop immune-related adverse events (irAEs). Currently, robust and reliable biomarker to predict response and/or occurrence of irAEs to ICI are missing. Herein, we wanted to explore whether germline variants (SNPs) could predict the clinical outcomes of melanoma patients treated with ICIs.

Discovery of a new molecule inducing melanoma cell death: dual AMPK/MELK targeting for novel melanoma therapies.

In the search of biguanide-derived molecules against melanoma, we have discovered and developed a series of bioactive products and identified the promising new compound CRO15. This molecule exerted anti-melanoma effects on cells lines and cells isolated from patients including the ones derived from tumors resistant to BRAF inhibitors. Moreover, CRO15 was able to decrease viability of cells lines from a broad range of cancer types.

Monocyte Recruitment, Specification, and Function in Atherosclerosis.

Atherosclerotic lesions progress through the continued recruitment of circulating blood monocytes that differentiate into macrophages within plaque. Lesion-associated macrophages are the primary immune cells present in plaque, where they take up cholesterol and store lipids in the form of small droplets resulting in a unique morphology termed foam cell. Recent scientific advances have used single-cell gene expression profiling, live-cell imaging, and fate mapping approaches to describe macrophage and monocyte contributions to pro- or anti-inflammatory mechanisms, in addition to functions of motility and proliferation within lesions.

Liquid Biopsy for Solid Ophthalmic Malignancies: An Updated Review and Perspectives.

Tissue biopsy is considered the gold standard when establishing a diagnosis of cancer. However, tissue biopsies of intraocular ophthalmic malignancies are hard to collect and are thought to be associated with a non-negligible risk of extraocular dissemination. Recently, the liquid biopsy (LB) has emerged as a viable, non-invasive, repeatable, and promising way of obtaining a diagnosis, prognosis, and theragnosis of patients with solid tumors.

Mitochondria orchestrate macrophage effector functions in atherosclerosis.

Macrophages are pivotal in the initiation and development of atherosclerotic cardiovascular diseases. Recent studies have reinforced the importance of mitochondria in metabolic and signaling pathways to maintain macrophage effector functions. In this review, we discuss the past and emerging roles of macrophage mitochondria metabolic diversity in atherosclerosis and the potential avenue as biomarker.

Limited proliferation capacity of aortic intima resident macrophages requires monocyte recruitment for atherosclerotic plaque progression.

Early atherosclerosis depends upon responses by immune cells resident in the intimal aortic wall. Specifically, the healthy intima is thought to be populated by vascular dendritic cells (DCs) that, during hypercholesterolemia, initiate atherosclerosis by being the first to accumulate cholesterol. Whether these cells remain key players in later stages of disease is unknown.

Metabolic Reprogramming of Macrophages in Atherosclerosis: Is It All about Cholesterol?

Hypercholesterolemia contributes to the chronic inflammatory response during the progression of atherosclerosis, in part by favoring cholesterol loading in macrophages and other immune cells. However, macrophages encounter a substantial amount of other lipids and nutrients after ingesting atherogenic lipoprotein particles or clearing apoptotic cells, increasing their metabolic load and impacting their behavior during atherosclerosis plaque progression. This review examines whether and how fatty acids and glucose shape the cellular metabolic reprogramming of macrophages in atherosclerosis to modulate the onset phase of inflammation and the later resolution stage, in which the balance is tipped toward tissue repair.

Hepatic Rab24 controls blood glucose homeostasis via improving mitochondrial plasticity.

Non-alcoholic fatty liver disease (NAFLD) represents a key feature of obesity-related type 2 diabetes with increasing prevalence worldwide. To our knowledge, no treatment options are available to date, paving the way for more severe liver damage, including cirrhosis and hepatocellular carcinoma. Here, we show an unexpected function for an intracellular trafficking regulator, the small Rab GTPase Rab24, in mitochondrial fission and activation, which has an immediate impact on hepatic and systemic energy homeostasis.

Impaired Kupffer Cell Self-Renewal Alters the Liver Response to Lipid Overload during Non-alcoholic Steatohepatitis.

Kupffer cells (KCs) are liver-resident macrophages that self-renew by proliferation in the adult independently from monocytes. However, how they are maintained during non-alcoholic steatohepatitis (NASH) remains ill defined. We found that a fraction of KCs derived from Ly-6C monocytes during NASH, underlying impaired KC self-renewal.

Interplay between Clonal Hematopoiesis of Indeterminate Potential and Metabolism.

Clonal hematopoiesis of indeterminate potential (CHIP), defined as a clone of hematopoietic cells consisting of a single acquired mutation during a lifetime, has recently been discovered to be a major risk factor for atherosclerotic cardiovascular disease (CVD). As such, this phenomenon has sparked interest into the role that these single mutations may play in CVD. Atherosclerotic CVD is a complex disease and we have previously shown that atherosclerosis can be accelerated by metabolic- or autoimmune-related risk factors such as diabetes, obesity, and rheumatoid arthritis.