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Insects, the most varied group of known organisms on Earth, are arousing great interest also for the possibility to use them as a feed and food source. The mass rearing of some species, defined as “bioconverters”, is spreading worldwide, thanks to their sustainability. At the end of the bioconversion process, breeders obtain eco-friendly biomolecules of high biological and economic value, including proteins and lipids, from larvae of bioconverter insects, in particular Hermetia illucens. Besides the most classical use of insect lipids as food additives, they are also used in the formulation of several products for personal care. The composition of insect lipids depends on the substrate on which the insects are reared but also on the insect species, so the cosmetic producers should consider these features to choose their insect starting point. The most abundant fatty acids detected in H. illucens are lauric, myristic, palmitic, and oleic acids, regardless of feed substrate; its fatty acids composition is favorable for soap composition, while their derivatives are used for detergent and shampoo. Here, we offer an overview of insect lipids, their extraction methods, and their application in cosmetics and personal care products.

Friedreich ataxia (FRDA) is a rare, inherited neurodegenerative disease caused by an expanded GAA repeat in the first intron of the FXN gene, leading to transcriptional silencing and reduced expression of frataxin. Frataxin participates in the mitochondrial assembly of FeS clusters, redox cofactors of the respiratory complexes I, II and III. To date it is still unclear how frataxin deficiency culminates in the decrease of bioenergetics efficiency in FRDA patients’ cells. We previously demonstrated that in healthy cells frataxin is closely attached to the mitochondrial cristae, which contain both the FeS cluster assembly machinery and the respiratory chain complexes, whereas in FRDA patients’ cells with impaired respiration the residual frataxin is largely displaced in the matrix. To gain novel insights into the function of frataxin in the mitochondrial pathophysiology, and in the upstream metabolic defects leading to FRDA disease onset and progression, here we explored the potential interaction of frataxin with the FeS cluster-containing respiratory complexes I, II and III. Using healthy cells and different FRDA cellular models we found that frataxin interacts with these three respiratory complexes. Furthermore, by EPR spectroscopy, we observed that in mitochondria from FRDA patients’ cells the decreased level of frataxin specifically affects the FeS cluster content of complex I. Remarkably, we also found that the frataxin-like protein Nqo15 from T. thermophilus complex I ameliorates the mitochondrial respiratory phenotype when expressed in FRDA patient’s cells. Our data point to a structural and functional interaction of frataxin with complex I and open a perspective to explore therapeutic rationales for FRDA targeted to this respiratory complex.

Although glucocorticoids (GC) represent the most frequently used immunosuppressive drugs, their effects are still not well understood. In our previous studies, we have shown that treatment of monocytes with GC does not cause a global suppression of monocytic effector functions, but rather induces differentiation of a specific anti-inflammatory phenotype. The anti-inflammatory role of peroxisome proliferator-activated receptor (PPAR)-γ has been extensively studied during recent years. However, a relationship between GC treatment and PPAR-γ expression in macrophages has not been investigated so far. Studies using PPAR-γ-deficient mice have frequently provided controversial results. A potential reason is the use of primary cells, which commonly represent inhomogeneous populations burdened with side effects and influenced by bystander cells. To overcome this constraint, we established ER-Hoxb8-immortalized bone marrow-derived macrophages from and mice in this study. In contrast to primary macrophages, the ER-Hoxb8 system allows the generation of a homogeneous and well-defined population of resting macrophages. We could show that the loss of PPAR-γ resulted in delayed kinetic of differentiation of monocytes into macrophages as assessed by reduced F4/80, but increased Ly6C expression in early phases of differentiation. As expected, PPAR-γ-deficient macrophages displayed an increased pro-inflammatory phenotype upon long-term LPS stimulation characterized by an elevated production of pro-inflammatory cytokines TNF-α, IL1-β, IL-6, IL-12 and a reduced production of anti-inflammatory cytokine IL-10 compared to PPAR-γ WT cells. Moreover, PPAR-γ-deficient macrophages showed impaired phagocytosis. GC treatment of macrophages led to the upregulation of PPAR-γ expression. However, there were no differences in GC-induced suppression of cytokines between both cell types, implicating a PPAR-γ-independent mechanism. Intriguingly, GC treatment resulted in an increased migration only in PPAR-γ-deficient macrophages. Performing a newly developed cell-tracking experiment, we could confirm that GC induces an increased recruitment of PPAR-γ KO, but not PPAR-γ WT macrophages to the site of inflammation. Our findings suggest a specific effect of PPAR-γ on GC-induced migration in macrophages. In conclusion, we could demonstrate that PPAR-γ exerts anti-inflammatory activities and shapes macrophage functions. Moreover, we identified a molecular link between GC and PPAR-γ and could show for the first time that PPAR-γ modulates GC-induced migration in macrophages.

It is well known that DNA replication affects the stability of several trinucleotide repeats, but whether replication profiles of human loci carrying an expanded repeat differ from those of normal alleles is poorly understood in the endogenous context. We investigated this issue using cell lines from Friedreich's ataxia patients, homozygous for a GAA-repeat expansion in intron 1 of the Frataxin gene. By interphase, FISH we found that in comparison to the normal Frataxin sequence the replication of expanded alleles is slowed or delayed. According to molecular combing, origins never fired within the normal Frataxin allele. In contrast, in mutant alleles dormant origins are recruited within the gene, causing a switch of the prevalent fork direction through the expanded repeat. Furthermore, a global modification of the replication profile, involving origin choice and a differential distribution of unidirectional forks, was observed in the surrounding 850 kb region. These data provide a wide-view of the interplay of events occurring during replication of genes carrying an expanded repeat.

There is little information about cardiovascular adverse event (CV-AE) incidence in chronic myeloid leukemia (CML) patients treated with bosutinib in the real-life practice. We identified 54 consecutive CML patients treated with bosutinib, stratified according to the Systematic Coronary Risk Evaluation (SCORE) assessment, based on sex, age, smoking habits, systolic blood pressure, and total cholesterol levels. The 40-month cumulative incidence of CV-AEs was 25.2 ± 8.1%. Patients with the SCORE of high–very high showed a significantly higher incidence of CV-AEs (55 ± 12.9% vs 9 ± 9.5%; p = 0.002). Overall, 9 CV-AEs were reported, with 2 deaths attributed to CV-AE. In conclusion, the SCORE assessment before starting treatment is helpful in identifying CV-AE high-risk patients during bosutinib treatment.

An innovative and eco-friendly one-pot synthesis of bio-based polyurethanes is proposed via the epoxy-ring opening of epoxidized soybean oil (ESO) with methanol, followed by the reaction of methoxy bio-polyols intermediates with 2,6-tolyl-diisocyanate (TDI). Both synthetic steps, methanolysis and polyurethane linkage formation, are promoted by a unique catalyst, molybdenum(VI) dichloride dioxide (MoCl2O2), which makes this procedure an efficient, cost-effective, and environmentally safer method amenable to industrial scale-up.

Mechanisms keeping leukocytes distant of local inflammatory processes in a resting state despite systemic release of inflammatory triggers are a pivotal requirement for avoidance of overwhelming inflammation but are ill defined. Dimers of the alarmin S100A8/S100A9 activate Toll‐like receptor‐4 (TLR4) but extracellular calcium concentrations induce S100A8/S100A9‐tetramers preventing TLR4‐binding and limiting their inflammatory activity. So far, only antimicrobial functions of released S100A8/S100A9‐tetramers (calprotectin) are described. It is demonstrated that extracellular S100A8/S100A9 tetramers significantly dampen monocyte dynamics as adhesion, migration, and traction force generation in vitro and immigration of monocytes in a cutaneous granuloma model and inflammatory activity in a model of irritant contact dermatitis in vivo. Interestingly, these effects are not mediated by the well‐known binding of S100A8/S100A9‐dimers to TLR‐4 but specifically mediated by S100A8/S100A9‐tetramer interaction with CD69. Thus, the quaternary structure of these S100‐proteins determines distinct and even antagonistic effects mediated by different receptors. As S100A8/S100A9 are released primarily as dimers and subsequently associate to tetramers in the high extracellular calcium milieu, the same molecules promote inflammation locally (S100‐dimer/TLR4) but simultaneously protect the wider environment from overwhelming inflammation (S100‐tetramer/CD69). Mechanisms restricting local inflammation and preventing systemic spreading of diseases are hardly understood. Release of S100A8/S100A9‐dimers at local sites of inflammation leads to monocyte activation via TLR4 while calcium‐induced S100A8/S100A9‐tetramer formation in the extracellular space mitigates monocyte dynamics via CD69. Thus, different quaternary structures of the same molecules promote inflammation locally (S100‐dimer/TLR4) but simultaneously protect systemic spreading of inflammation (S100‐tetramer/CD69).

Background: We previously showed that peptides encompassing the unique b3a2 or b2a2 breakpoint amino-acid sequence of oncogenic p210 induced peptide-specific T-cell responses in chronic myeloid leukemia (CML) patients. Methods: From 2007 to 2011, two multicenter peptide vaccine phase II studies, GIMEMA CML0206 and SI0207, enrolling overall 109 CML patients (68 b3a2 and 41 b2a2) with persistence of molecular disease during imatinib treatment, were carried out. Peptide vaccination schedule included the following: “immunization phase” (six vaccinations every 2 weeks); “reinforcement” phase (three monthly boosts) and “maintenance” phase (two boosts at 3-month intervals). GM-CSF (granulocyte-macrophage-colony-stimulating factor, sarmograstim) served as the immunological adjuvant. Results: The short-term results (at completion of vaccine protocol—12 months) and long-term follow-up are reported. All patients completed the vaccination schedule with no toxicity. After vaccinations, the BCR::ABL1 peptide-specific CD4+ T-cell response was documented in 80% of patients. In the short term, 30% of patients achieved a reduction in BCR::ABL1, while the majority showed stable molecular disease with fluctuations. The median follow-up since diagnosis and last vaccination are 18 and 10 years, respectively, with an overall survival (OS) rate at 18 years of 89%. In addition, 97/109 (89%) patients are alive, while 12/109 (11%) died of CML-unrelated reasons. Overall, 18/109 (16.5%) patients are in treatment-free remission (TFR) for a median time of 48 months. Conclusions: The long-term results of p210 peptide vaccinations in CML patients with persisting disease during imatinib treatment showed its feasibility, safety, absence of off-targets events, high OS and not negligible rate of successful TFR. Active immunotherapeutic approaches in CML patients with low disease burden, eventually employing newer vaccine strategies such as mRNA vaccines, may be reconsidered.

Terminally differentiated cells are defined by their inability to proliferate. When forced to re-enter the cell cycle, they generally cannot undergo long-term replication. Our previous work with myotubes has shown that these cells fail to proliferate because of their intrinsic inability to complete DNA replication. Moreover, we have reported pronounced modifications of deoxynucleotide metabolism during myogenesis. Here we investigate the causes of incomplete DNA duplication in cell cycle-reactivated myotubes (rMt). We find that rMt possess extremely low levels of thymidine triphosphate (dTTP), resulting in very slow replication fork rates. Exogenous administration of thymidine or forced expression of thymidine kinase increases deoxynucleotide availability, allowing extended and faster DNA replication. Inadequate dTTP levels are caused by selective, differentiation-dependent, cell cycle-resistant suppression of genes encoding critical synthetic enzymes, chief among which is thymidine kinase 1. We conclude that lack of dTTP is at least partially responsible for the inability of myotubes to proliferate and speculate that it constitutes an emergency barrier against unwarranted DNA replication in terminally differentiated cells.