Thus, lactoferrin peptides limit pro-inflammatory signaling and cytokine production by LPS-activated human macrophages and thereby enhance the resolution of inflammation.Mitochondria are double-membrane organelles that continuously undergo fission and fusion. Outer mitochondrial membrane fusion is mediated by the membrane proteins mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2), carrying a GTP hydrolyzing domain (GTPase) and two coiled-coil repeats. The detailed mechanism on how the GTP hydrolysis allows Mfns to approach adjacent membranes into proximity and promote their fusion is currently under debate. Using model membranes built up as giant unilamellar vesicles (GUVs), we show here that Mfn1 promotes membrane adhesion of apposing lipid vesicles. The adhesion forces were sustained by the GDP-bound state of Mfn1 after GTP hydrolysis. In contrast, the incubation with the GDPAlF 4 – , which mimics the GTP transition state, did not induce membrane adhesion. Due to the flexible nature of lipid membranes, the adhesion strength depended on the surface concentration of Mfn1 through a cooperative binding mechanism. We discuss a possible scenario for the outer mitochondrial membrane fusion based on the modulated action of Mfn1.Background Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated to asbestos exposure. One of the most frequent genetic alteration in MPM patients is CDKN2A/ARF loss, leading to aberrant activation of the Rb pathway. In MPM cells, we previously demonstrated the therapeutic efficacy of targeting this signaling with the CDK4/6 inhibitor palbociclib in combination with PI3K/mTOR inhibitors. Here, we investigated whether such combination may have an impact on cell energy metabolism. Methods The study was performed in MPM cells of different histotypes; metabolic analyses were conducted by measuring GLUT-1 expression and glucose uptake/consumption, and by SeaHorse technologies. Results MPM cell models differed for their ability to adapt to metabolic stress conditions, such as glucose starvation and hypoxia. Independently of these differences, combined treatments with palbociclib and PI3K/mTOR inhibitors inhibited cell proliferation more efficaciously than single agents. The drugs alone reduced glucose uptake/consumption as well as glycolysis, and their combination further enhanced these effects under both normoxic and hypoxic conditions. Moreover, the drug combinations significantly impaired mitochondrial respiration as compared with individual treatments. These metabolic effects were mediated by the concomitant inhibition of Rb/E2F/c-myc and PI3K/AKT/mTOR signaling. Conclusions Dual blockade of glycolysis and respiration contributes to the anti-tumor efficacy of palbociclib-PI3K/mTOR inhibitors combination.NKp30 is one of the main human natural killer (NK) cell activating receptors used in directed immunotherapy. The oligomerization of the NKp30 ligand binding domain depends on the length of the C-terminal stalk region, but our structural knowledge of NKp30 oligomerization and its role in signal transduction remains limited. Moreover, ligand binding of NKp30 is affected by the presence and type of N-glycosylation. In this study, we assessed whether NKp30 oligomerization depends on its N-glycosylation. Our results show that NKp30 forms oligomers when expressed in HEK293S GnTI- cell lines with simple N-glycans. However, NKp30 was detected only as monomers after enzymatic deglycosylation. Furthermore, we characterized the interaction between NKp30 and its best-studied cognate ligand, B7-H6, with respect to glycosylation and oligomerization, and we solved the crystal structure of this complex with glycosylated NKp30, revealing a new glycosylation-induced mode of NKp30 dimerization. Overall, this study provides new insights into the structural basis of NKp30 oligomerization and explains how the stalk region and glycosylation of NKp30 affect its ligand affinity. This furthers our understanding of the molecular mechanisms involved in NK cell activation, which is crucial for the successful design of novel NK cell-based targeted immunotherapeutics.Brown seaweeds are known to present components with appealing bioactive properties eliciting great interest for industrial applications. However, their lipid content is generally disregarded beyond their fatty acid (FA) composition. This study thoroughly characterized the lipid profile of two brown seaweeds collected from Portuguese coast, the native Bifurcaria bifurcata and the invasive Sargassum muticum species, and bioprospecting for antioxidant activity. An integrated state-of-the-art approach including gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (HILIC-ESI-MS/MS), allowed a comprehensive picture of FA and polar lipid content. Polar lipid profile of B. bifurcata and S. muticum included 143 and 217 lipid species respectively, distributed between glycolipids, phospholipids, and betaine lipids. Some of the lipid species found have been assigned biological activity and contain of n-3 and n-6 FA. Sargassum muticum presented the highest n-3 FA content. Low concentrations of extracts of both seaweeds displayed antioxidant activity, with S. muticum presenting more promising results. These findings contribute to the nutritional and industrial exploitation of both seaweeds, highlighting their relevance as viable sources of bioactive and added-value compounds. Sargassum muticum presented interesting lipid composition and bioactivity, which may represent an accessible opportunity for the exploitation of this invasive seaweed, especially taking advantage of Sargassum blooms.The integration of copper nanoparticles as antifungal agents in polymeric matrices to produce copper polymer nanocomposites has shown excellent results in preventing the growth of a wide variety of toxigenic fungi. Copper-chitosan nanocomposite-based chitosan hydrogels (Cu-Chit/NCs hydrogel) were prepared using a metal vapor synthesis (MVS) and the resulting samples were described by transmission electron microscopy (TEM), X-ray fluorescence analysis (XRF), and small-angle X-ray scattering (SAXS). Aflatoxin-producing medium and VICAM aflatoxins tests were applied to evaluate their ability to produce aflatoxins through various strains of Aspergillus flavus associated with peanut meal and cotton seeds. Aflatoxin production capacity in four fungal media outlets revealed that 13 tested isolates were capable of producing both aflatoxin B1 and B2. Only 2 A. flavus isolates (Af11 and Af 20) fluoresced under UV light in the A. flavus and parasiticus Agar (AFPA) medium. PCR was completed using two specific primers tarlates. Additionally, microscopic measurements of scanning electron microscopy (SEM) showed damage to the fungal cell membranes. Cu-Chit/NCS hydrogel is an innovative nano-biopesticide produced by MVS is employed in food and feed to induce plant defense against toxigenic fungi.Nuclear factor kappa B (NF-κB) signaling is implicated in all major human chronic diseases, with its role in transcription of hundreds of gene well established in the literature. This has propelled research into targeting the NF-κB pathways for modulating expression of those genes and the diseases mediated by them. In-spite of the critical, but often promiscuous role played by this pathway and the inhibition causing adverse drug reaction, currently many biologics, macromolecules, and small molecules that modulate this pathway are in the market or in clinical trials. Furthermore, many marketed drugs that were later found to also have NF-κB targeting activity were repurposed for new therapeutic interventions. Despite the rising importance of biologics in drug discovery, small molecules got around 76% of US-FDA (Food and Drug Administration-US) approval in the last decade. This encouraged us to review information regarding clinically relevant small molecule inhibitors of the NF-κB pathway from cell surface receptor stimulation to nuclear signaling. We have also highlighted the underexplored targets in this pathway that have potential to succeed in clinic.MicroRNAs (miRNAs) are a class of short non-coding RNAs involved in the regulation of gene expression and the control of several cellular processes at physiological and pathological levels. Furthermore, extracellular vesicles (EV), which are small membrane-bound vesicles secreted by cells in the extracellular environment, contain functional miRNAs. The remarkable deregulation of many miRNAs has been demonstrated in respiratory diseases. Among them, miR-206, miR-133a-5p, and miR-133a-3p are striated muscle-specific miRNAs (myo-miRNA), related to skeletal muscle dysfunction, one of the commonest systemic manifestations in patients with chronic obstructive pulmonary disease (COPD). Nevertheless, their circulating expression in COPD patients is not demonstrated. For these reasons, we performed a pilot study to analyze the expression profiles of myo-miRNAs in plasma-derived EV from patients with COPD. We analyzed the expression profiles of selected myo-miRNAs in plasma-derived EV from COPD. Receiver operating characteristic analyses were carried out to evaluate whether selected plasma miRNAs were able to discriminate between different groups of COPD patients. We found EV-embedded myo-miRNAs in the bloodstream of COPD patients. Specifically, miR-206, miR-133a-5p and miR-133a-3p were significantly upregulated in group B patients. Receiver operating characteristic analyses of the combination of these selected miRNAs showed their high capacity to discriminate group B from other COPD patients. Our data provide evidence that myo-miRNA are present in EV in the plasma of COPD patients and their expression (miR-206, miR-133a-5p, and miR-133a-3p) can discriminate group B from group C patients. The future analysis of a larger number of patients should allow us to obtain more refined correlations.In this report, we present a detailed comparison of the lipid composition of human milk (HM) and formula milk (FM) targeting different lactation stages and infant age range. We studied HM samples collected from 26 Polish mothers from colostrum to 19 months of lactation, along with FM from seven brands available on the Polish market (infant formula, follow-on formula and growing-up formula). Lipid extracts were analysed using liquid chromatography coupled to high-resolution mass spectrometry (LC-Q-TOF-MS). We found that the lipid composition of FM deviates significantly from the HM lipid profile in terms of qualitative and quantitative differences. FM had contrasting lipid profiles mostly across brands and accordingly to the type of fat added but not specific to the target age range. The individual differences were dominant in HM; however, differences according to the lactation stage were also observed, especially between colostrum and HM collected in other lactation stages. Biologically and nutritionally important lipids, such as long-chain polyunsaturated fatty acids (LC-PUFAs) containing lipid species, sphingomyelines or ether analogues of glycerophosphoethanoloamines were detected in HM collected in all studied lactation stages. The observed differences concerned all the major HM lipid classes and highlight the importance of the detailed compositional studies of both HM and FM.