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Abstract Obesity is associated with fatty liver disease. Available therapies show modest efficacy, and nutraceuticals with good effectiveness and safety are largely investigated. We focused on five natural compounds, three plant phenolic compounds (carvacrol, rosmarinic acid, silybin), and two thyroid hormones (T2: 3,5-diiodo-l-thyronine; T3: 3,5,3’-triiodo-L-thyronine) as comparison, to assess their beneficial effects on two cellular models of hepatosteatosis and adipogenesis. All compounds ameliorated the lipid accumulation and oxidative stress in both models, but with different potencies. The peroxisome proliferator-activated receptors (PPARs) are pivotal controllers of adipogenesis and lipid metabolism. For the main isoforms, PPARγ and PPARa, we assessed their possible binding to the compounds by molecular docking calculations, and their expression pattern by real-time PCR. All compounds bind both PPARs with different affinity, while not all compounds affect their expression. The results may clarify the distinctive molecular mechanisms underlying the action of the five compounds in the different cell models with possible applications to treat obesity.

Abstract Spike (S) glycoprotein is the largest structural protein of SARS‐CoV‐2 virus and the main one involved in anchoring of the host receptor ACE2 through the receptor binding domain (RBD). S protein secondary structure is of great interest for shedding light on various aspects, from functionality to pathogenesis, finally to spectral fingerprint for the design of optical biosensors. In this paper, the secondary structure of SARS‐CoV‐2 S protein and its constituting components, namely RBD, S1 and S2 regions, are investigated at serological pH by measuring their amide I infrared absorption bands through Attenuated Total Reflection Infrared (ATR‐IR) spectroscopy. Experimental data in combination with MultiFOLD predictions, Define Secondary Structure of Proteins (DSSP) web server and Gravy value calculations, provide a comprehensive understanding of RBD, S1, S2, and S proteins in terms of their secondary structure content, conformational order, and interaction with the solvent.

Abstract Mitogen-activated protein kinases 1 and 3 (MAPK1 and MAPK3), also called extracellular regulated kinases (ERK2 and ERK1), are serine/threonine kinase activated downstream by the Ras/Raf/MEK/ERK signal transduction cascade that regulates a variety of cellular processes. A dysregulation of MAPK cascade is frequently associated to missense mutations on its protein components and may be related to many pathologies, including cancer. In this study we selected from COSMIC database a set of MAPK1 and MAPK3 somatic variants found in cancer tissues carrying missense mutations distributed all over the MAPK1 and MAPK3 sequences. The proteins were expressed as pure recombinant proteins, and their biochemical and biophysical properties have been studied in comparison with the wild type. The missense mutations lead to changes in the tertiary arrangements of all the variants. The thermodynamic stability of the wild type and variants has been investigated in the non-phosphorylated and in the phosphorylated form. Significant differences in the thermal stabilities of most of the variants have been observed, as well as changes in the catalytic efficiencies. The energetics of the catalytic reaction is affected for all the variants for both the MAPK proteins. The stability changes and the variation in the enzyme catalysis observed for most of MAPK1/3 variants suggest that a local change in a residue, distant from the catalytic site, may have long-distance effects that reflect globally on enzyme stability and functions.

Infrared (IR) spectroscopy is a valuable tool to obtain information about protein secondary structure. The far-infrared (FIR) spectrum is characterized by a complex combination of different molecular contributions which, for small molecules, may be interpreted with the help of quantum-mechanical (QM) calculations. Unfortunately, the high computational cost of QM calculations makes them inapplicable to larger molecules, such as proteins and peptides. In this work, we present a theoretical study on the secondary structure, molecular properties, and vibrational spectra of different peptides, using both a classical and a QM approach. Our results show that the amide I main peak value, and related quantities, such as dipole strength (DS) and transition dipole moment (TDM), depends on protein secondary structure; in particular, from QM calculations arises that α-rich molecular systems present lower intensities than β-rich ones. Furthermore, it is possible to decouple and identify the intensity of the different contributions of the inter- and intra-molecular motions which characterize the FIR spectrum, starting from the results obtained with QM calculations.

TNF Receptor-Associated Factor 2 (TRAF2) is a homo-trimer belonging to the TNF-receptor-associated factor family (TRAFs). The TRAF2 oligomeric state is crucial for receptor binding, the interaction with other proteins (involved in the TNFR signaling), and the interaction with biological membranes. In this study, we present a computational analysis of the Molecular Dynamics of TRAF2-C (a truncated and soluble TRAF2 form) to identify patterns in the interactions between the three chains. We have performed a canonical analysis of the motion applied to molecular dynamics starting from the available crystal structure to identify correlated motions in TRAF2 dynamics. We have computed the displacement matrix, providing a frame-by-frame displacement for each residue in the dynamic. We provide the results in terms of the correlation matrix, which represents a detailed map of the correlated motions of residues. Eventually, we computed the so-called dynamical clusters, based on the Principal Component Analysis (PCA) of the motion (displacement) and the k means application on the first two principal components space. The results clearly indicate that, most of the time, two chains move in a strongly correlated motion, while the third chain follows a freer motion. A detailed analysis of the correlation matrix also shows that a few specific interface residues characterize the interaction of the more independent subunit with the other two. These findings suggest that the equilibrium between the trimer and the dissociated species (dimers and monomers) might be finely tuned by controlling a few critical residues in the protein quaternary structure, probably facilitating the regulation of oligomerization and dissociation in vivo.

A distinct set of channels and transporters regulates the ion fluxes across the lysosomal membrane. Malfunctioning of these transport proteins and the resulting ionic imbalance is involved in various human diseases, such as lysosomal storage disorders, cancer, as well as metabolic and neurodegenerative diseases. As a consequence, these proteins have stimulated strong interest for their suitability as possible drug targets. A detailed functional characterization of many lysosomal channels and transporters is lacking, mainly due to technical difficulties in applying the standard patch-clamp technique to these small intracellular compartments. In this review, we focus on current methods used to unravel the functional properties of lysosomal ion channels and transporters, stressing their advantages and disadvantages and evaluating their fields of applicability.

Symmetry is an intrinsic property of homo-oligomers. Amine oxidases are multidomain homodimeric enzymes that contain one catalytic site per subunit, and that share a high homology degree. In this paper, we investigated, by fluorescence spectroscopy measurements, the conformational dynamics and resiliency in solutions of two amine oxidases, one from lentil seedlings, and one from Euphorbia characias latex, of which the crystallographic structure is still unknown. The data demonstrate that slight but significant differences exist at the level of the local tridimensional structure, which arise from the presence of large internal cavities, which are characterized by different hydration extents. Molecular dynamics and a contact network methodology were also used to further explore, in silico, the structural features of the two proteins. The analysis demonstrates that the two proteins show similar long-range symmetrical connectivities, but that they differ in their local (intra-subunit) contact networks, which appear mostly asymmetric. These features have been interpreted to suggest a new rationale for the functioning of amino oxidases as obligate homodimers.

EuPRAXIA is a leading European project aimed at the development of a dedicated, ground-breaking, ultra-compact accelerator research infrastructure based on novel plasma acceleration concepts and laser technology and on the development of their users’ communities. Within this framework, the Laboratori Nazionali di Frascati (LNF, INFN) will be equipped with a unique combination of an X-band RF LINAC generating high-brightness GeV-range electron beams, a 0.5 PW class laser system and the first fifth-generation free electron laser (FEL) source driven by a plasma-based accelerator, the EuPRAXIA@SPARC_LAB facility. Wiggler-like radiation emitted by electrons accelerated in plasma wakefields gives rise to brilliant, ultra-short X-ray pulses, called betatron radiation. Extensive studies have been performed at the FLAME laser facility at LNF, INFN, where betatron radiation was measured and characterized. The purpose of this paper is to describe the betatron spectrum emitted by particle wakefield acceleration at EuPRAXIA@SPARC_LAB and provide an overview of the foreseen applications of this specific source, thus helping to establish a future user community interested in (possibly coupled) FEL and betatron radiation experiments. In order to provide a quantitative estimate of the expected betatron spectrum and therefore to present suitable applications, we performed simple simulations to determine the spectrum of the betatron radiation emitted at EuPRAXIA@SPARC_LAB. With reference to experiments performed exploiting similar betatron sources, we highlight the opportunities offered by its brilliant femtosecond pulses for ultra-fast X-ray spectroscopy and imaging measurements, but also as an ancillary tool for designing and testing FEL instrumentation and experiments.

The flavonoid naringenin (Nar), present in citrus fruits and tomatoes, has been identified as a blocker of an emerging class of human intracellular channels, namely the two-pore channel (TPC) family, whose role has been established in several diseases. Indeed, Nar was shown to be effective against neoangiogenesis, a process essential for solid tumor progression, by specifically impairing TPC activity. The goal of the present review is to illustrate the rationale that links TPC channels to the mechanism of coronavirus infection, and how their inhibition by Nar could be an efficient pharmacological strategy to fight the current pandemic plague COVID-19.

Our study showed that in formula-fed babies, the use of mixture X (containing 2'-FL (2'-fucosyllactose) - a type of milk oligosaccharide, as well as carefully studied Bifidobacterium lactis, DHA, ARA, and nucleotides) as the main product for feeding could ensure children's body with all the necessary nutrients. Furthermore, it can minimize the progression of clinical signs of atopic dermatitis and reduce the use of drugs. In addition, there was an improvement in height and weight parameters, proportional development of the child (p<0.05), an increase in the number of erythrocytes (erythrocytes), hemoglobin (Hb), mean cell volume (MCV) (p<0.05), a decrease in the number of leukocytes (WBC) (p<0.05), and leveling of skin signs of atopic dermatitis (AD) (according to SCORAD a decrease from 32.8±5.5 to 16.1±2.2, p<0.05). Based on these results, it is possible to recommend using mixture (X) with a preventive and rational purpose as a product of artificial feeding of children with a hereditary predisposition to allergies., Competing Interests: The authors declare no conflict of interest., (©2022 JOURNAL of MEDICINE and LIFE.)

Urinary tract infections (UTIs) remain an urgent issue in clinical pediatrics. Empirical selection of antibacterial therapy becomes more complicated, and antibacterial drug indication is not always clinically substantiated. This study aimed to compare the antibacterial susceptibility pattern of the main group of urinary tract infectious agents from 2009-2016 with intermediate results from 2020-2021, during the COVID-19 pandemic, among children in the Chernivtsi region. Urine samples were collected from 3089 children (0-17 years old) treated at the health care institutions in the Chernivtsi region (2009-2016). The clinical-laboratory examination of 177 children (0-17 years old) was carried out from 2020 to 2021. The children received specialized medical care at the Department of Nephrology. Preliminary data of regional monitoring (2020-2021) are not considerably different from the previous regional susceptibility of antibiotics: to penicillin (p<0.01), ІІ-ІІІ generation cephalosporin (p<0.01); an increased resistance to levofloxacin (χ 2 =4,338; p<0.01), tetracycline - χ 2 =7,277; p<0.01; doxycycline - χ 2 =5,309; p<0.01) and imipenem - χ 2 =5,594; p<0.01). The data obtained did not explain an increased resistance to fluoroquinolones completely (ofloxacin, pefloxacin, ciprofloxacin), except for levofloxacin (χ 2 =4,338; p<0.01). A reliable difference of susceptibility of tetracycline group was registered (tetracycline - χ 2 =7,277; p<0.01; doxycycline - χ 2 =5,309; p<0.01). Furthermore, there was a regional increase in some UTI-pathogen strains resistant to carbapenems (imipenem - χ 2 =5,594; p<0.01). The use of antibiotics from the group of penicillins and II-III generation cephalosporins as the starting antibacterial therapy for STIs during the COVID-19 pandemic should be justified. A regional increase (2020-2021) of some uropathogenic strains resistant to carbapenems administered to treat severe bacterial infections requires their exclusively designated purpose in everyday pediatric practical work., (© 2022 JOURNAL of MEDICINE and LIFE.)

Increasing requirements of medical aid given to children with infectious-inflammatory diseases of the urinary system stipulate the necessity to improve its quality using evidence-based therapeutic-diagnostic and organization technologies. The aim of the work - to substantiate, develop the improved model of the specialized nephrology care for children with infectious inflammatory diseases of the urinary system at the regional level. The official statistical data have been studied (2006 to 2017); information-analytical and statistical methods have been used. A bacteriological study (2009-2016) of urine samples was carried out for 3089 children (0-17 years old) in the Chernivtsi region. They formed the foundation for substantiation and development of an improved functional-organizational model of the system. In addition to the existing and functionally changed elements contains new elements: regional/inter-regional center of specialized medical aid to children with infectious-inflammatory diseases of the urinary system. Implementation of the elements of the suggested improved model in a part of a rational approach in distribution of functions concerning medical observation of patients at the stages of giving medical aid enabled to make the period of hospitalization of nephrological patients 11,40% shorter and an average period of treatment of patients with infectious-inflammatory diseases of the urinary system 2,93% shorter., (©2021 JOURNAL of MEDICINE and LIFE.)

In a child, cystitis (non-specific microbial inflammation of the mucous membrane of the bladder) is considered to be a dangerous disease; the prolongation of the process is usually associated with a delayed diagnosis. The aim of this work was to analyze the health status of the child population of the Chernivtsi region, especially the dynamics of the prevalence and incidence of cystitis. The official statistical data have been studied (reports on the state of medical care for children in the Chernivtsi region and data from the Center of Medical Statistics of the Ministry of Healthcare from 2006 to 2017); information-analytical and statistical methods have been used for the purpose of this study. Attention should be drawn to the significantly high prevalence of cystitis among children aged 15-17 years, especially in the Chernivtsi region as during period I (8.7±0.6 vs. 4.3±0.3 in Ukraine) and II (11.7±1.0 and 5.7±0.4, respectively, per 1000 people). Moreover, over the years, the growth of indicators acquires intensity, while this process is more than twice as pronounced in Chernivtsi. Thus, the growth rate was 65.0% in 2006-2011 and 90.3% in 2012-2017 vs. 27.2% and 32.8% in Ukraine, respectively. The identified data indicate the need to provide specialized care to children with infectious and inflammatory diseases of the urinary system of the Chernivtsi region and the need to improve regional clinical routes of patients with infectious and inflammatory diseases of the urinary system., (©2021 JOURNAL of MEDICINE and LIFE.)