Differential targeting of immune-cells by Pixantrone in experimental myasthenia gravis

n/

Microfluidic fiber spinning for 3D bioprinting: Harnessing microchannels to build macrotissues

Microfluidics is rapidly revolutionizing the scientific panorama, providing unmatched high-throughput platforms that find application in numerous areas of physics, chemistry, biology, and materials science. Recently, microfluidic chips have been proposed, in combination with bioactive materials, as promising tools for spinning cell-laden fibers with on-demand characteristics. However, cells encapsulated in filaments produced via microfluidic spinning technology are confined in a quasi-three-dimensional (3D) environment that fails to replicate the intricate 3D architecture of biological tissues. Thanks to the recent synergistic combination of microfluidic devices with 3D bioprinting technologies that enable the production of sophisticated microfibers serving as the backbone of 3D structures, a new age of tissue engineering is emerging. This review looks at how combining microfluidics with 3D printing is contributing to the biofabrication of relevant human substitutes and implants. This paper also describes the whole manufacturing process from the production of the microfluidic tool to the printing of tissue models, focusing on cutting-edge fabrication technologies and emphasizing the most noticeable achievements for microfluidic spinning technology. A theoretical insight for thixotropic hydrogels is also proposed to predict the fiber size and shear stress developing within microfluidic channels. The potential of using microfluidic chips as bio-printheads for multi-material and multi-cellular bioprinting is discussed, highlighting the challenges that microfluidic bioprinting still faces in advancing the field of biofabrication for tissue engineering and regenerative medicine purposes

Linking gene expression to productivity to unravel long-and short-term responses of seagrasses exposed to CO2 in volcanic vents

Ocean acidification is a major threat for marine life but seagrasses are expected to benefit from high CO2. In situ (long-term) and transplanted (short-term) plant incubations of the seagrass Cymodocea nodosa were performed near and away the influence of volcanic CO2 vents at Vulcano Island to test the hypothesis of beneficial effects of CO2 on plant productivity. We relate, for the first time, the expression of photosynthetic, antioxidant and metal detoxification-related genes to net plant productivity (NPP). Results revealed a consistent pattern between gene expression and productivity indicating water origin as the main source of variability. However, the hypothesised beneficial effect of high CO2 around vents was not supported. We observed a consistent long-and short-term pattern of gene downregulation and 2.5-fold NPP decrease in plants incubated in water from the vents and a generalized upregulation and NPP increase in plants from the vent site incubated with water from the Reference site. Contrastingly, NPP of specimens experimentally exposed to a CO2 range significantly correlated with CO2 availability. The down-regulation of metal-related genes in C. nodosa leaves exposed to water from the venting site suggests that other factors than heavy metals, may be at play at Vulcano confounding the CO2 effects.ESF COST Action [ES0906]; Portuguese Foundation for Science and Technology (FCT) [PTDC/MAR-EST/3687/2012]; Italian MIUR Flagship project RITMARE (NRP); FCT [UID/Multi/04326/2013, SFRH/BPD/71129/2010, SFRH/BD/64590/2009]info:eu-repo/semantics/publishedVersio

Non-Ischemic Scar Underlines Ventricular Arrhythmias in Kearns-Sayre Syndrome

Kearns-Sayre syndrome (KSS) is a rare mitochondrial disease in which cardiac involvement has been associated with poor prognosis. Although the most common clinical manifestation is progressive conduction system impairment, patients can suffer from ventricular arrhythmias. Yet, they show a high prevalence of sudden cardiac death, whose etiopathological mechanism is not completely understood. Cardiac magnetic resonance is a rising tool to detect subclinical heart involvement in many heart diseases and was recently able to detect nonischemic scar, which is an arrhythmogenic substrate, in patients affected by KSS

Efficacy and tolerability of a specific blend of amino acids in patients with anorexia nervosa treated in a hospital setting: study protocol for a randomized controlled trial

BackgroundSpecific blends of essential amino acids (EAA) containing a high percentage of branched-chain amino acids preserves mitochondrial metabolism and higher physical resistance in elderly mice, increasing their survival and improving physical performance and cognitive functions in malnourished elderly patients. However, no study has been yet done on patients with anorexia nervosa (AN) who regain weight with specialized intensive treatment. The present study aims to evaluate the efficacy of supplementation with EAA on the change in lean body mass (LBM) and other physical and psychological outcomes in patients with AN who are undergoing specialist treatment for eating disorders.MethodsThis is a 13-week randomized, double-blind, placebo-controlled study. Patients will be randomized to either a mixture of a complex blend of EAA and intermediates of the tricarboxylic acid (TCA) cycle (citrate, malate, succinate) supplementation (or placebo) upon admission at the intensive residential and day-hospital treatment for eating disorders. Ninety-two participants with AN aged 16-50 years will be recruited from a specialized intensive treatment of eating disorders. Double-blind assessment will be conducted at baseline (T0) and the end of the 13 weeks of treatment (T1). The study's primary aim is to evaluate the efficacy of supplementation with EAA and TCA intermediates on the change in lean body mass (LBM) with weight restoration in patients with AN who are undergoing specialist treatment for eating disorders. The secondary aims of the study are to assess the effect of dietary supplementation on physical fitness, weight restoration, modification of AN and general psychopathology, and psychosocial impairment.DiscussionThe study's results will inform researchers and clinicians on whether supplementing a mixture of EAA and TCA cycle intermediates will improve the increase of LBM and other important physical and psychological outcomes in patients with AN who regain weight with specialized intensive treatment

Role of Portion Size in the Context of a Healthy, Balanced Diet: A Case Study of European Countries

Over the past decades, a generalised increase in food portion sizes has probably contributed to the growing global obesity epidemic. Increasing awareness of appropriate portion sizes could contribute to reversing this trend through better control of calorie intake. In this study, a comparison of standard portion sizes in European countries for various food categories shows a wide variability of their importance for food, nutrient, and energy consumption according to government and institutional websites. On the other hand, the overall averages appear to be largely in line with the values indicated by the Italian Society of Human Nutrition, which is the most comprehensive and detailed document among those evaluated. The exceptions are milk and yoghurt, for which the reference portions in Europe are generally higher, and vegetables and legumes, for which portions are smaller than those reported in the Italian document. Moreover, the portion sizes of staple foods (e.g., pasta and potatoes) vary according to different food traditions. It is reasonable to consider that the creation of harmonised standard reference portions common to the European countries, based on international guidelines and scientific evidence, would significantly contribute to consumers' nutritional education and ability to make informed choices for a healthy diet

A peculiar formula of essential amino acids prevents rosuvastatin myopathy in mice

Aims: Myopathy, characterized by mitochondrial oxidative stress, occurs in ∼10% of statin-treated patients, and a major risk exists with potent statins such as rosuvastatin (Rvs). We sought to determine whether a peculiar branched-chain amino acid-enriched mixture (BCAAem), found to improve mitochondrial function and reduce oxidative stress in muscle of middle-aged mice, was able to prevent Rvs myopathy. Results: Dietary supplementation of BCAAem was able to prevent the structural and functional alterations of muscle induced by Rvs in young mice. Rvs-increased plasma 3-methylhistidine (a marker of muscular protein degradation) was prevented by BCAAem. This was obtained without changes of Rvs ability to reduce cholesterol and triglyceride levels in blood. Rather, BCAAem promotes de novo protein synthesis and reduces proteolysis in cultured myotubes. Morphological alterations of C2C12 cells induced by statin were counteracted by amino acids, as were the Rvs-increased atrogin-1 mRNA and protein levels. Moreover, BCAAem maintained mitochondrial mass and density and citrate synthase activity in skeletal muscle of Rvs-treated mice beside oxygen consumption and ATP levels in C2C12 cells exposed to statin. Notably, BCAAem assisted Rvs to reduce oxidative stress and to increase the anti-reactive oxygen species (ROS) defense system in skeletal muscle. Innovation and Conclusions: The complex interplay between proteostasis and antioxidant properties may underlie the mechanism by which a specific amino acid formula preserves mitochondrial efficiency and muscle health in Rvs-treated mice. Strategies aimed at promoting protein balance and controlling mitochondrial ROS level may be used as therapeutics for the treatment of muscular diseases involving mitochondrial dysfunction, such as statin myopathy

Dietary essential amino acids for the treatment of heart failure with reduced ejection fraction

Aims: Heart failure with reduced ejection fraction (HFrEF) is a leading cause of mortality worldwide, requiring novel therapeutic and lifestyle interventions. Metabolic alterations and energy production deficit are hallmarks and thereby promising therapeutic targets for this complex clinical syndrome. We aim to study the molecular mechanisms and effects on cardiac function in rodents with HFrEF of a designer diet in which free essential amino acids - in specifically designed percentages - substituted for protein. Methods and results: Wild-type mice were subjected to transverse aortic constriction (TAC) to induce left ventricle (LV) pressure overload or sham surgery. Whole body glucose homeostasis was studied with glucose tolerance test, while myocardial dysfunction and fibrosis were measured with echocardiogram and histological analysis. Mitochondrial bioenergetics and morphology were investigated with oxygen consumption rate measurement and electron microscopy evaluation. Circulating and cardiac non-targeted metabolite profiles were analyzed by ultrahigh performance liquid chromatography-tandem mass spectroscopy, while RNA sequencing was used to identify signalling pathways mainly affected. The amino acid-substituted diet shows remarkable preventive and therapeutic effects. This dietary approach corrects the whole-body glucose metabolism and restores the unbalanced metabolic substrate usage - by improving mitochondrial fuel oxidation - in the failing heart. In particular, biochemical, molecular, and genetic approaches suggest that renormalization of branched-chain amino acid oxidation in cardiac tissue, which is suppressed in HFrEF, plays a relevant role. Beyond the changes of systemic metabolism, cell-autonomous processes may explain at least in part the diet's cardioprotective impact. Conclusion: Collectively, these results suggest that manipulation of dietary amino acids, and especially essential amino acids, is a potential adjuvant therapeutic strategy to treat systolic dysfunction and HFrEF in humans

Casting light on the European anchovy: from biology to conservation and industry

This manuscript explores the role of European anchovies (Engraulis encrasicolus) in the central Mediterranean Region, shedding light on their ecological significance, conservation challenges, and sustainable utilization. The European anchovy is one of Europe’s most important fish resources in the Mediterranean basin, and it is considered a keystone species, playing a pivotal role in both ecological and socio-economic dimensions. However, in recent decades, European anchovy, together with Sardina pilchardus (commonly known as European sardine), has suffered a population decline for several reasons. Consequently, it is necessary to improve the management of anchovy fisheries by understanding the reproductive modes and characteristics, the influence of currents on the passive transport of eggs and larvae, the feeding habits, the environmental adaptability (e.g., salinity), and the distribution of ecotypes along the Italian coasts. Such information is fundamental for the management of fisheries, especially artisanal ones, and to control frauds, especially in protected, geographically referred, and traditional high-quality commercial products. Various aspects, ranging from their population dynamics to their industrial processing and the ecological implications of these activities were delved, highlighting the knowledge about anchovy populations and ecotypes and its importance in maintaining ecosystem balance and sustaining human communities. The ecological interaction of anchovies within the food web, as essential data in the conservation actions and management of these resources was emphasized. In addition, the metabolic and stomach contents diversity among anchovy populations and ecotypes was discussed, enhancing our understanding of their adaptability to varying environmental conditions. The manuscript then explores the traditional and industrial processing of anchovies, encompassing aspects ranging from fishing techniques (i.e., methods of capture) to their industrial significance, sustainability concerns, issues of fraud, and the establishment of geographical traceability. Finally, the opportunities for sustainable and biotechnological utilization of anchovy discards were also further explored, demonstrating the potential for waste reduction and resource optimization

Protein kinase CK2α is overexpressed in classical hodgkin lymphoma, regulates key signaling pathways, PD-L1 and may represent a new target for therapy

IntroductionIn classical Hodgkin lymphoma (cHL), the survival of neoplastic cells is mediated by the activation of NF-κB, JAK/STAT and PI3K/Akt signaling pathways. CK2 is a highly conserved serine/threonine kinase, consisting of two catalytic (α) and two regulatory (β) subunits, which is involved in several cellular processes and both subunits were found overexpressed in solid tumors and hematologic malignancies.Methods and resultsBiochemical analyses and in vitro assays showed an impaired expression of CK2 subunits in cHL, with CK2α being overexpressed and a decreased expression of CK2β compared to normal B lymphocytes. Mechanistically, CK2β was found to be ubiquitinated in all HL cell lines and consequently degraded by the proteasome pathway. Furthermore, at basal condition STAT3, NF-kB and AKT are phosphorylated in CK2-related targets, resulting in constitutive pathways activation. The inhibition of CK2 with CX-4945/silmitasertib triggered the de-phosphorylation of NF-κB-S529, STAT3-S727, AKT-S129 and -S473, leading to cHL cell lines apoptosis. Moreover, CX-4945/silmitasertib was able to decrease the expression of the immuno-checkpoint CD274/PD-L1 but not of CD30, and to synergize with monomethyl auristatin E (MMAE), the microtubule inhibitor of brentuximab vedotin.ConclusionsOur data point out a pivotal role of CK2 in the survival and the activation of key signaling pathways in cHL. The skewed expression between CK2α and CK2β has never been reported in other lymphomas and might be specific for cHL. The effects of CK2 inhibition on PD-L1 expression and the synergistic combination of CX-4945/silmitasertib with MMAE pinpoints CK2 as a high-impact target for the development of new therapies for cH