CD20+ T cells in monoclonal B cell lymphocytosis and chronic lymphocytic leukemia: frequency, phenotype and association with disease progression.

Introduction: In monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), the expansion of malignant B cells disrupts the normal homeostasis and interactions between B cells and T cells, leading to immune dysregulation. CD20+ T cells are a subpopulation of T cells that appear to be involved in autoimmune diseases and cancer. Methods: Here, we quantified and phenotypically characterized CD20+ T cells from MBL subjects and CLL patients using flow cytometry and correlated our findings with the B-cell receptor mutational status and other features of the disease. Results and discussion: CD20+ T cells were more represented within the CD8+ T cell compartment and they showed a predominant memory Tc1 phenotype. CD20+ T cells were less represented in MBL and CLL patients vs healthy controls, particularly among those with unmutated IGVH gene. The expansion of malignant B cells was accompanied by phenotypic and functional changes in CD20+ T cells, including an increase in follicular helper CD4+ CD20+ T cells and CD20+ Tc1 cells, in addition to the expansion of the TCR Vß 5.1 in CD4+ CD20+ T cells in CLL.

Unmasking the Metabolite Signature of Bladder Cancer: A Systematic Review.

Bladder cancer (BCa) research relying on Omics approaches has increased over the last few decades, improving the understanding of BCa pathology and contributing to a better molecular classification of BCa subtypes. To gain further insight into the molecular profile underlying the development of BCa, a systematic literature search was performed in PubMed until November 2023, following the PRISMA guidelines. This search enabled the identification of 25 experimental studies using mass spectrometry or nuclear magnetic resonance-based approaches to characterize the metabolite signature associated with BCa. A total of 1562 metabolites were identified to be altered by BCa in different types of samples. Urine samples displayed a higher likelihood of containing metabolites that are also present in bladder tumor tissue and cell line cultures. The data from these comparisons suggest that increased concentrations of L-isoleucine, L-carnitine, oleamide, palmitamide, arachidonic acid and glycoursodeoxycholic acid and decreased content of deoxycytidine, 5-aminolevulinic acid and pantothenic acid should be considered components of a BCa metabolome signature. Overall, molecular profiling of biological samples by metabolomics is a promising approach to identifying potential biomarkers for early diagnosis of different BCa subtypes. However, future studies are needed to understand its biological significance in the context of BCa and to validate its clinical application.

Oxidized phospholipid-protein adducts: The future targets of interest.

Phospholipids are key biomolecules with important roles as components of membranes, lipoproteins and as signalling molecules. However, phospholipids are quite prone to oxidation. Upon oxidation they generate several types of oxidation products including long chain oxidation products, as hydroperoxyl and hydroxy derivatives, and highly reactive oxidation products, like small aldehydes and truncated oxidized phospholipids. The formation of protein adducts with small electrophilic aldehydes (like malondialdehyde) is now well studied, however, the aggregation of proteins with truncated oxidized phospholipids lacks research. This paper provides a short overview of the formation of protein adducts with truncated oxidized phospholipids as well as a gathering of the research on this topic. The literature found reports the synthesis, detection and fragmentation of this type of adducts, mainly focusing on truncated oxidized phospholipid' products from phosphatidylcholine class and few peptides and proteins, as human serum albumin and Apo B100, leaving unattended the screening in vivo and in disease correlation, thus lacking possible association with their biological role. These adducts are a consequence of oxidative modifications to important biomolecules and their involvement in the organism is still unclear, revealing the urgent need for more investigation in this area.

Effect of physical exercise on immune, inflammatory, cardiometabolic biomarkers, and fatty acids of breast cancer survivors: results from the MAMA_MOVE Gaia After Treatment trial.

PURPOSE: Physical exercise has positive effects on clinical outcomes of breast cancer survivors such as quality of life, fatigue, anxiety, depression, body mass index, and physical fitness. We aimed to study its impact on immune, inflammatory, cardiometabolic, and fatty acids (FA) biomarkers. METHODS: An exploratory sub-analysis of the MAMA_MOVE Gaia After Treatment trial (NCT04024280, registered July 18, 2019) was performed. Blood sample collections occurred during the control phase and at eight weeks of the intervention phase. Samples were subjected to complete leukocyte counts, cytokine, and cardiometabolic marker evaluation using flow cytometry, enzyme-linked immunoassays, and gas chromatography. RESULTS: Ninety-three percent of the 15 participants had body mass index ≥ 25 kg/m2. We observed a decrease of the plasmatic saturated FA C20:0 [median difference - 0.08% (p = 0.048); mean difference - 0.1 (95%CI - 0.1, - 0.0)], positively associated with younger ages. A tendency to increase the saturated FA C18:0 and the ratio of unsaturated/saturated FA and a tendency to decrease neutrophils (within the normal range) and interferon-gamma were observed. CONCLUSIONS: Positive trends of physical exercise on circulating immune cells, inflammatory cytokines, and plasmatic FA were observed. Larger studies will further elucidate the implications of physical exercise on metabolism. These exploratory findings may contribute to future hypothesis-driven research and contribute to meta-analyses.

Polar Lipids of Marine Microalgae Nannochloropsis oceanica and Chlorococcum amblystomatis Mitigate the LPS-Induced Pro-Inflammatory Response in Macrophages.

Microalgae are recognized as a relevant source of bioactive compounds. Among these bioactive products, lipids, mainly glycolipids, have been shown to present immunomodulatory properties with the potential to mitigate chronic inflammation. This study aimed to evaluate the anti-inflammatory effect of polar lipids isolated from Nannochloropsis oceanica and Chlorococcum amblystomatis. Three fractions enriched in (1) digalactosyldiacylglycerol (DGDG) and sulfoquinovosyldiacylglycerol (SQDG), (2) monogalactosyldiacylglycerol (MGDG), and (3) diacylglyceryl-trimethylhomoserine (DGTS) and phospholipids (PL) were obtained from the total lipid extracts (TE) of N. oceanica and C. amblystomatis, and their anti-inflammatory effect was assessed by analyzing their capacity to counteract nitric oxide (NO) production and transcription of pro-inflammatory genes Nos2, Ptgs2, Tnfa, and Il1b in lipopolysaccharide (LPS)-activated macrophages. For both microalgae, TE and Fractions 1 and 3 strongly inhibited NO production, although to different extents. A strong reduction in the LPS-induced transcription of Nos2, Ptgs2, Tnfa, and Il1b was observed for N. oceanica and C. amblystomatis lipids. The most active fractions were the DGTS-and-PL-enriched fraction from N. oceanica and the DGDG-and-SQDG-enriched fraction from C. amblystomatis. Our results reveal that microalgae lipids have strong anti-inflammatory capacity and may be explored as functional ingredients or nutraceuticals, offering a natural solution to tackle chronic inflammation-associated diseases.

Lipidomic assessment of the impact of Nannochloropsis oceanica microalga lipid extract on human skin keratinocytes exposed to chronic UVB radiation.

Considerable attention has been devoted to investigating the biological activity of microalgal extracts, highlighting their capacity to modulate cellular metabolism. This study aimed to assess the impact of Nannochloropsis oceanica lipid extract on the phospholipid profile of human keratinocytes subjected to UVB radiation. The outcomes revealed that treatment of keratinocytes with the lipid extract from microalgae led to a reduction in sphingomyelin (SM) levels, with a more pronounced effect observed in UVB-irradiated cells. Concomitantly, there was a significant upregulation of ceramides CER[NDS] and CER[NS], along with increased sphingomyelinase activity. Pathway analysis further confirmed that SM metabolism was the most significantly affected pathway in both non-irradiated and UVB-irradiated keratinocytes treated with the microalgal lipid extract. Additionally, the elevation in alkylacylPE (PEo) and diacylPE (PE) species content observed in UVB-irradiated keratinocytes following treatment with the microalgal extract suggested the potential induction of pro-survival mechanisms through autophagy in these cells. Conversely, a noteworthy reduction in LPC content in UVB-irradiated keratinocytes treated with the extract, indicated the anti-inflammatory properties of the lipid extract obtained from microalgae. However, to fully comprehend the observed alterations in the phospholipid profile of UVB-irradiated keratinocytes, further investigations are warranted to identify the specific fraction of compounds responsible for the activity of the Nannochloropsis oceanica extract.

Bioconversion of olive oil pomace by black soldier fly increases eco-efficiency in solid waste stream reduction producing tailored value-added insect meals.

Olive oil is one of the most important agricultural products in Mediterranean areas, and currently the European Union is the largest producer. Due to technological innovations, Portugal has become one of the main olive oil producing countries over the last few years, accompanied by large amounts of olive oil pomace (OOP), the most representative residue of the olive oil extraction process. This is causing serious waste management problems since current management solutions also present environmental impacts. Here we explored the black soldier fly (Hermetia illucens) potential to biotransform OOP into valuable insect meals by feeding them OOP-based diets as substrates. Results show that despite survival rates not being affected by higher replacement (75% and 50%) levels of OOP, there was an increase in larval instar duration. Substrate reduction was significantly lower for higher replacement levels but was not affected up to the 50% replacement level. Feed conversion rate differed among all the treatments, increasing as the replacement level increased, while bioconversion rate, which also differed among all the treatments, decreased as replacement level increased. Differences in larval protein content were only seen at higher replacement levels (75%), with an increase in protein content for replacements of up to 25%. One of the most striking results was the change in fatty acid profile, which became more abundant in monounsaturated fatty acids (mostly oleic acid) as the olive pomace replacement levels increased in comparison with the control substrate, rich in saturated fatty acids (palmitic acid). These results show that BSF can be an effective OOP bioconversion agent, and resulting insect meals can be used as alternatives to currently available saturated fatty acid insect meals.

An overview on lipids in nuts and oily fruits: oil content, lipid composition, health effects, lipidomic fingerprinting and new biotechnological applications of their by-products.

Tree nuts and oily fruits are used as a diet complement and are highly consumed worldwide. The production and consumption of these foods have been increasing, and an enormous global market value is forecasted for 2023. Besides their high nutritional value and lipid content, they provide health benefits to fat metabolism, heart, skin, and brain. The industrial by-products of these oily foods represent promising raw materials for many industries. However, the lipidomic analysis of nuts and oily fruits is still in its early stages. State-of-the-art analytical approaches for the lipid profiling and fingerprinting of nuts and oily fruits have been developed using high-performance liquid chromatography and high-resolution mass spectrometry for the accurate identification and structural characterization at the molecular species level. It is expected to bring a new understanding of these everyday foods' nutritional and functional value. This review comprises the oil content and lipid composition of various nuts and oily fruits, particularly those mostly consumed worldwide and having recognized beneficial health effects, biological activities associated with the lipids from different oily foodstuffs, analytical methodologies to analyze lipids in nuts and oily fruits, and the potential biotechnological applications of their industrial by-products for a lipid-based commercial valorization.

Microbial Conjugated Linolenic Acid-Enriched Fermented Milk Using Lipase-Hydrolyzed Flaxseed Oil: Biochemical, Organoleptic and Storage Traits.

The bioactive conjugated linolenic acid (CLNA) can be microbiologically produced by different probiotic strains when in the presence of α-linolenic acid (α-LNA). Food matrices are a good vector, such as has been previously demonstrated with fermented milk enriched with microbial CLNA by Bifidobacterium breve DSM 20091 from lipase-hydrolyzed flaxseed oil. The aim of the present work was to further assess the nutritional, biochemical and organoleptic properties of the developed dairy product, as well as its storage stability throughout 28 days at 4 °C, proving its suitability for consumption. Milk lactose hydrolyzed into glucose (0.89 g/100 g) and galactose (0.88 g/100 g), which were further metabolized into lactic (0.42 g/100 g), acetic (0.44 g/100 g) and propionic (0.85 g/100 g) acids. Titratable acidity reached 0.69% and pH 4.93. Compared with the control (no CLNA), fat content was slightly higher (2.0 g/100 g). Acetic acid was the major volatile (83.32%), lacking important dairy flavor contributors, like acetaldehyde. Sensory analysis revealed predominant astringency and bitterness. No microbial concerns arose during storage, but the CLNA content increased, and some saturated fatty acids seemed to oxidize. In conclusion, the CLNA-enriched fermented milk revealed reasonable compositional properties, yet further improvements are needed for optimal consumer acceptance and a prolonged shelf-life.

Major anthocyanins in elderberry effectively trap methylglyoxal and reduce cytotoxicity of methylglyoxal in HepG2 cell line.

The accumulation of advanced glycation end-products (AGEs) in the body is implicated in numerous diseases, being methylglyoxal (MGO) one of the main precursors. One of the strategies to reduce AGEs accumulation might be acting in an early stage of glycation by trapping MGO. Thus, this work aimed to evaluate, for the first time, the potential of elderberries polyphenols to trap MGO, access the formation of MGO adducts, and evaluate the cytoprotection effect in HepG2 and Caco-2 cells. The results demonstrated that monoglycosylated anthocyanins (cyanidin-3-glucoside and cyanidin-3-sambubioside) are very efficient in trapping MGO, forming mono- and di-adducts. Quercetin-3-glucoside and quercetin-3-rutinoside reacted slowly, while diglycosylated anthocyanins did not react. The trapping of MGO by elderberry monoglycosylated anthocyanins significantly decreased the MGO cytotoxicity in HepG2 cells (∼70 % of cell viability), while the effect in Caco-2 cells was lower (∼50 %). Thus, elderberry phenolics present antiglycation potential by trapping MGO.

Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a disabling autoimmune disease whose treatment is ineffective for one-third of patients. Thus, the immunomodulatory potential of mesenchymal stromal/stem cells (MSCs) makes MSC-based therapy a promising approach to RA. This study aimed to explore the immunomodulatory action of human bone marrow (BM)-MSCs on myeloid dendritic cells (mDCs) and monocytes, especially on cytokines/chemokines involved in RA physiopathology. For that, LPS plus IFNγ-stimulated peripheral blood mononuclear cells from RA patients (n = 12) and healthy individuals (n = 6) were co-cultured with allogeneic BM-MSCs. TNF-α, CD83, CCR7 and MIP-1ß protein levels were assessed in mDCs, classical, intermediate, and non-classical monocytes. mRNA expression of other cytokines/chemokines was also evaluated. BM-MSCs effectively reduced TNF-α, CD83, CCR7 and MIP-1ß protein levels in mDCs and all monocyte subsets, in RA patients. The inhibition of TNF-α production was mainly achieved by the reduction of the percentage of cellsproducing this cytokine. BM-MSCs exhibited a remarkable suppressive action over antigen-presenting cells from RA patients, potentially affecting their ability to stimulate the immune adaptive response at different levels, by hampering their migration to the lymph node and the production of proinflammatory cytokines and chemokines. Accordingly, MSC-based therapies can be a valuable approach for RA treatment, especially for non-responder patients.

Algal Lipids as Modulators of Skin Disease: A Critical Review.

The prevalence of inflammatory skin diseases continues to increase with a high incidence in children and adults. These diseases are triggered by environmental factors, such as UV radiation, certain chemical compounds, infectious agents, and in some cases, people with a genetic predisposition. The pathophysiology of inflammatory skin diseases such as psoriasis or atopic dermatitis, but also of skin cancers, is the result of the activation of inflammation-related metabolic pathways and the overproduction of pro-inflammatory cytokines observed in in vitro and in vivo studies. Inflammatory skin diseases are also associated with oxidative stress, overproduction of ROS, and impaired antioxidant defense, which affects the metabolism of immune cells and skin cells (keratinocytes and fibroblasts) in systemic and skin disorders. Lipids from algae have been scarcely applied to modulate skin diseases, but they are well known antioxidant and anti-inflammatory agents. They have shown scavenging activities and can modulate redox homeostasis enzymes. They can also downmodulate key inflammatory signaling pathways and transcription factors such as NF-κB, decreasing the expression of pro-inflammatory mediators. Thus, the exploitation of algae lipids as therapeutical agents for the treatment of inflammatory skin diseases is highly attractive, being critically reviewed in the present work.

Comprehensive Metabolomics and Lipidomics Profiling of Prostate Cancer Tissue Reveals Metabolic Dysregulations Associated with Disease Development.

Prostate cancer (PCa) is a global health problem that affects millions of men every year. In the past decade, metabolomics and related subareas, such as lipidomics, have demonstrated an enormous potential to identify novel mechanisms underlying PCa development and progression, providing a good basis for the development of new and more effective therapies and diagnostics. In this study, a multiplatform metabolomics and lipidomics approach, combining untargeted mass spectrometry (MS) and nuclear magnetic resonance (NMR)-based techniques, was applied to PCa tissues to investigate dysregulations associated with PCa development, in a cohort of 40 patients submitted to radical prostatectomy for PCa. Results revealed significant alterations in the levels of 26 metabolites and 21 phospholipid species in PCa tissue compared with adjacent nonmalignant tissue, suggesting dysregulation in 13 metabolic pathways associated with PCa development. The most affected metabolic pathways were amino acid metabolism, nicotinate and nicotinamide metabolism, purine metabolism, and glycerophospholipid metabolism. A clear interconnection between metabolites and phospholipid species participating in these pathways was observed through correlation analysis. Overall, these dysregulations may reflect the reprogramming of metabolic responses to produce high levels of cellular building blocks required for rapid PCa cell proliferation.

Hydrophobic Starch-Based Films Using Potato Washing Slurries and Spent Frying Oil.

Starch is a promising candidate for preparing biodegradable films with useful gas barriers and thermoplastic capabilities. However, these materials are hydrophilic and brittle, thus limiting their application range. To overcome these drawbacks, it has been hypothesized that starch can be hydrophobized and plasticized during the starch-based film production using a single-step approach and following transesterification principles. In this work, KOH powder and spent frying oil (SFO) were used as an alkaline catalyst and a source for triacylglycerides, respectively, to promote the modification of starch. Different ratios of SFO (w/w related to the dried starch weight) were tested. When compared to the neat films (without a catalyst and SFO), the incorporation of at least 15% SFO/KOH gave rise to transparent, hydrophobic (water contact angles of ca. 90∘), stretchable (ca. 20×), elastic (ca. 5×), and water tolerant starch-based films, contrary to the films produced without the catalyst. ATR-FTIR and 1H NMR revealed structural differences among the produced films, suggesting that starch was modified with the SFO-derived fatty acids. Therefore, adding KOH during the potato starch/spent frying oil-based film's production was determined to be a promising in situ strategy to develop starch-based materials with improved hydrophobicity and flexibility, while valorizing the potato chip industry's byproducts.

Microalgal Lipid Extracts Have Potential to Modulate the Inflammatory Response: A Critical Review.

Noncommunicable diseases (NCD) and age-associated diseases (AAD) are some of the gravest health concerns worldwide, accounting for up to 70% of total deaths globally. NCD and AAD, such as diabetes, obesity, cardiovascular disease, and cancer, are associated with low-grade chronic inflammation and poor dietary habits. Modulation of the inflammatory status through dietary components is a very appellative approach to fight these diseases and is supported by increasing evidence of natural and dietary components with strong anti-inflammatory activities. The consumption of bioactive lipids has a positive impact on preventing chronic inflammation and consequently NCD and AAD. Thus, new sources of bioactive lipids have been sought out. Microalgae are rich sources of bioactive lipids such as omega-6 and -3 polyunsaturated fatty acids (PUFA) and polar lipids with associated anti-inflammatory activity. PUFAs are enzymatically and non-enzymatically catalyzed to oxylipins and have a significant role in anti and pro-resolving inflammatory responses. Therefore, a large and rapidly growing body of research has been conducted in vivo and in vitro, investigating the potential anti-inflammatory activities of microalgae lipids. This review sought to summarize and critically analyze recent evidence of the anti-inflammatory potential of microalgae lipids and their possible use to prevent or mitigate chronic inflammation.

Structural and Functional Alterations in Mitochondria-Associated Membranes (MAMs) and in Mitochondria Activate Stress Response Mechanisms in an In Vitro Model of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by the accumulation of extracellular plaques composed by amyloid-ß (Aß) and intracellular neurofibrillary tangles of hyperphosphorylated tau. AD-related neurodegenerative mechanisms involve early changes of mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) and impairment of cellular events modulated by these subcellular domains. In this study, we characterized the structural and functional alterations at MAM, mitochondria, and ER/microsomes in a mouse neuroblastoma cell line (N2A) overexpressing the human amyloid precursor protein (APP) with the familial Swedish mutation (APPswe). Proteins levels were determined by Western blot, ER-mitochondria contacts were quantified by transmission electron microscopy, and Ca2+ homeostasis and mitochondria function were analyzed using fluorescent probes and Seahorse assays. In this in vitro AD model, we found APP accumulated in MAM and mitochondria, and altered levels of proteins implicated in ER-mitochondria tethering, Ca2+ signaling, mitochondrial dynamics, biogenesis and protein import, as well as in the stress response. Moreover, we observed a decreased number of close ER-mitochondria contacts, activation of the ER unfolded protein response, reduced Ca2+ transfer from ER to mitochondria, and impaired mitochondrial function. Together, these results demonstrate that several subcellular alterations occur in AD-like neuronal cells, which supports that the defective ER-mitochondria crosstalk is an important player in AD physiopathology.

Microalgae as Sustainable Bio-Factories of Healthy Lipids: Evaluating Fatty Acid Content and Antioxidant Activity.

The demand for sustainable and environmentally friendly food sources and food ingredients is increasing, and microalgae are promoted as a sustainable source of essential and bioactive lipids, with high levels of omega-3 fatty acids (ω-3 FA), comparable to those of fish. However, most FA screening studies on algae are scattered or use different methodologies, preventing a true comparison of its content between microalgae. In this work, we used gas-chromatography mass-spectrometry (GC-MS) to characterize the FA profile of seven different commercial microalgae with biotechnological applications (Chlorella vulgaris, Chlorococcum amblystomatis, Scenedesmus obliquus, Tetraselmis chui, Phaeodactylum tricornutum, Spirulina sp., and Nannochloropsis oceanica). Screening for antioxidant activity was also performed to understand the relationship between FA profile and bioactivity. Microalgae exhibited specific FA profiles with a different composition, namely in the ω-3 FA profile, but with species of the same phylum showing similar tendencies. The different lipid extracts showed similar antioxidant activities, but with a low activity of the extracts of Nannochloropsis oceanica. Overall, this study provides a direct comparison of FA profiles between microalgae species, supporting the role of these species as alternative, sustainable, and healthy sources of essential lipids.

Fruit seeds and their oils as promising sources of value-added lipids from agro-industrial byproducts: oil content, lipid composition, lipid analysis, biological activity and potential biotechnological applications.

Thousands of tons of fruit seeds are discarded every year worldwide as agro-industrial byproducts. Fruit seeds have a high oil content, are rich in monounsaturated fatty acids (FA) and in n-6 and n-3 polyunsaturated essential FA. Sterols, phospholipids, glycolipids, carotenoids, tocopherols and polyphenols are other seed phytochemicals that make them interesting from a commercial viewpoint. Fruit seeds have high potential as raw material for several industries, but their lipid profile remains poorly studied. Current analytical approaches for the analysis of lipids that are based on high-performance liquid chromatography and high-resolution mass spectrometry allow the separation and analysis of compounds with the accurate identification and structural characterization of molecular species in very small quantities. Even though lipidomic analysis of fruit seeds' lipids is still in its infancy, it will bring a new look over these value-added byproducts. This review covers the following topics: (a) the lipid content of various fruit seed oils; (b) their lipid composition (FA, triacylglycerol, sterol, phospholipid and glycolipid profiles), (c) current and future analytical methodologies for the analysis of lipids in fruit seeds; (d) biological activities of fruit seeds' extracts; and (e) potential biotechnological applications of fruit seed oils for their commercial valorization based on lipids.

Cannabidiol-Mediated Changes to the Phospholipid Profile of UVB-Irradiated Keratinocytes from Psoriatic Patients.

UVB phototherapy is treatment for psoriasis, which increases phospholipid oxidative modifications in the cell membrane of the skin. Therefore, we carried out lipidomic analysis on the keratinocytes of healthy individuals and patients with psoriasis irradiated with UVB and treated with cannabidiol (CBD), phytocannabinoid with antioxidant and anti-inflammatory properties. Our results showed that, in psoriatic keratinocytes phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylserine (PS), and ether-linked phosphoethanolamine (PEo), were downregulated, while SM (d41:2) was upregulated. These changes were accompanied by an increase in negative zeta potential, which indicates translocation of PS to the outer layer of the membrane. CBD treatment of psoriatic keratinocytes led to downregulation of PC, PS, and upregulation of certain PEo and an SM species, SM (d42:2), and the zeta potential. However, UVB irradiation of psoriatic keratinocytes resulted in upregulation of PC, PC plasmalogens (PCp), PEo, and a decrease in the negative zeta potential. The exposure of UVB-irradiated cells to CBD led to a decrease in the level of SM (d42:2). Our results suggest that CBD induces pro-apoptotic mechanisms in psoriatic keratinocytes while simultaneously improving the antioxidant properties and preventing the loss of transepidermal water of keratinocytes of patients irradiated with UVB. Thus, CBD has potential therapeutic value in the treatment of psoriasis.

Differential Modulation of the Phospholipidome of Proinflammatory Human Macrophages by the Flavonoids Quercetin, Naringin and Naringenin.

The immunomodulatory activity of flavonoids is increasingly appreciated. Macrophage phospholipids (PLs) play crucial roles in cell-mediated inflammatory responses. However, little is known on how these PLs are affected upon flavonoid treatment. In this work, we have used mass-spectrometry-based lipidomics to characterize the changes in the phospholipidome of proinflammatory human-macrophage-like cells (THP-1-derived and LPS+IFN-γ-stimulated) incubated with non-cytotoxic concentrations of three flavonoids: quercetin, naringin and naringenin. One hundred forty-seven PL species belonging to various classes were identified, and their relative abundances were determined. Each flavonoid displayed its own unique signature of induced effects. Quercetin produced the strongest impact, acting both on constitutive PLs (phosphatidylcholines, phosphatidylethanolamines and sphingomyelins) and on minor signaling lipids, such as phosphatidylinositol (PI) and phosphatidylserine (PS) species. Conversely, naringin hardly affected structural PLs, producing changes in signaling molecules that were opposite to those seen in quercetin-treated macrophages. In turn, albeit sharing some effects with quercetin, naringenin did not change PI and PS levels and interfered with a set of phosphatidylcholines distinct from those modulated by quercetin. These results demonstrate that flavonoids bioactivity involves profound and specific remodeling of macrophage phospholipidome, paving the way to future studies on the role of cellular phospholipids in flavonoid-mediated immunomodulatory effects.