bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of DPIE [2-(1,2-Diphenyl-1H-indol-3-yl)ethanamine] Derivatives and Their Regulatory Effects on Pro-Inflammatory Cytokine Production in IL-1β-Stimulated Primary Human Oral Cells
Authors: Lim Jeongah , Seong Jihyoun , Jung Seunggon , Lee Tae-Hoon , Kim Eunae , Lee Sunwoo
Published: January 2022

Interleukin-1 beta (IL-1β) has diverse physiological functions and plays important roles in health and disease. In this report, we focus on its function in the production of pro-inflammatory cytokines, including IL-6 and IL-8, which are implicated in several autoimmune diseases and host defense against infection. IL-1β activity is markedly dependent on the binding affinity toward IL-1 receptors (IL-1Rs). Several studies have been conducted to identify suitable small molecules that can modulate the interactions between 1L-1β and 1L-1R1. Based on our previous report, where DPIE [2-(1,2-Diphenyl-1H-indol-3-yl)ethanamine] exhibited such modulatory activity, three types of DPIE derivatives were synthesized by introducing various substituents at the 1, 2, and 3 positions of the indole group in DPIE. To predict a possible binding pose in complex with IL-1R1, a docking simulation was performed. The effect of the chemicals was determined in human gingival fibroblasts (GFs) following IL-1β induction. The DPIE derivatives affected different aspects of cytokine production. Further, a group of the derivatives enabled synergistic pro-inflammatory cytokine production, while another group caused diminished cytokine production compared to DPIE stimulation. Some groups displayed no significant difference after stimulation. These findings indicate that the modification of the indole site could modulate IL-1β:IL1R1 binding affinity to reduce or enhance pro-inflammatory cytokine production.
Effects of MN4-Type Coordination Structure in Metallophthalocyanine for Bio-Inspired Oxidative Desulfurization Performance
Authors: Zhang Gai , Zhang Yufan , Tan Amin , Yang Yan , Tian Min
Published: January 2022

Oxidative desulfurization (ODS) is the promising new method for super deep desulfurization of fuel oil. The oxidative desulfurization performance of the metal-N4-chelates metallophthalocyanines (MPcs) is related to the chemical properties of conjugate structures and the central metal ions. Herein, a biomimetic catalytic system composed of metallophthalocyanines (MPcR4, M = Mn(II), Fe(II), Co(II), Ni(II), Cu(II), Zn(II); R = -H, -COOH, -NO2, -NH2) and molecular O2 was performed to study the influence of MN4-type coordination structure in metallophthalocyanines for the degradation of dibenzothiophene (DBT) in model oil containing n-octane. The results reveal that the conjugate structures and the center metal ions of metallophthalocyanines played key roles in oxidative desulfurization performance. The inductive effect of different R substituents strongly affected the electron cloud distribution of the conjugate structures and the catalytic performance. Moreover, the catalytic activity of MPcs, which is related to the d electronic configuration and ligand-field effects, does not sequentially increase with the increase in the d electron number of central metal ions.
Hydrophobic Eutectic Solvent-Based Dispersive Liquid-Liquid Microextraction Applied to the Analysis of Pesticides in Wine
Authors: Dal Bosco Chiara , Mariani Francesca , Gentili Alessandra
Published: January 2022

A green solvent-based DLLME/HPLC-MS method for the determination of 19 pesticides in wine samples has been developed. The extractant solvent is a hydrophobic eutectic mixture composed of L-menthol and butylated hydroxytoluene in a molar ratio of 3:1. The endogenous ethanol of wine has been used as dispersive solvent, in order to avoid the solidification of the extracts under 19 °C. The mobile phase composition, the elution gradient and the sample injection volume were optimized in order to make this hydrophobic mixture compatible with conventional reversed phase chromatography and electrospray ionization. The method was validated in matrix, using a wine free from the target compounds. Average recovery as high as 80%, precision between 3 and 14%, and limits of detection and quantification much lower than the maximum residue levels (MRLs) for grapes and wines fixed by the EU regulation, make this multiresidue method fitted for the purpose, with the further advantages of being quick, cheap and in compliance with the green analytical chemistry. From the analysis of 11 commercial wines it was found that just in a bio sample the target compounds were not detectable or lower than quantification limit; as for the other samples, the most widespread and abundant pesticides were methoxyfenozide and boscalid, but their levels were much lower than the relative MRLs.
A Comprehensive In Silico Exploration of Pharmacological Properties, Bioactivities, Molecular Docking, and Anticancer Potential of Vieloplain F from Xylopia vielana Targeting B-Raf Kinase
Authors: Hassan Syed Shams ul , Abbas Syed Qamar , Ali Fawad , Ishaq Muhammad , Bano Iqra , Hassan Mubashir , Jin Hui-Zi , Bungau Simona G.
Published: January 2022

Compounds derived from plants have several anticancer properties. In the current study, one guaiane-type sesquiterpene dimer, vieloplain F, isolated from Xylopia vielana species, was tested against B-Raf kinase protein (PDB: 3OG7), a potent target for melanoma. A comprehensive in silico analysis was conducted in this research to understand the pharmacological properties of a compound encompassing absorption, distribution, metabolism, excretion, and toxicity (ADMET), bioactivity score predictions, and molecular docking. During ADMET estimations, the FDA-approved medicine vemurafenib was hepatotoxic, cytochrome-inhibiting, and non-cardiotoxic compared to the vieloplain F. The bioactivity scores of vieloplain F were active for nuclear receptor ligand and enzyme inhibitor. During molecular docking experiments, the compound vieloplain F has displayed a higher binding potential with −11.8 kcal/mol energy than control vemurafenib −10.2 kcal/mol. It was shown that intermolecular interaction with the B-Raf complex and the enzyme’s active gorge through hydrogen bonding and hydrophobic contacts was very accurate for the compound vieloplain F, which was then examined for MD simulations. In addition, simulations using MM-GBSA showed that vieloplain F had the greatest propensity to bind to active site residues. The vieloplain F has predominantly represented a more robust profile compared to control vemurafenib, and these results opened the road for vieloplain F for its utilization as a plausible anti-melanoma agent and anticancer drug in the next era.
In Silico Analysis of Metabolites from Peruvian Native Plants as Potential Therapeutics against Alzheimer’s Disease
Authors: Goyzueta-Mamani Luis Daniel , Barazorda-Ccahuana Haruna Luz , Chávez-Fumagalli Miguel Angel , F. Alvarez Karla Lucia , Aguilar-Pineda Jorge Alberto , Vera-Lopez Karin Jannet , Lino Cardenas Christian Lacks
Published: January 2022

Background: Despite research on the molecular bases of Alzheimer’s disease (AD), effective therapies against its progression are still needed. Recent studies have shown direct links between AD progression and neurovascular dysfunction, highlighting it as a potential target for new therapeutics development. In this work, we screened and evaluated the inhibitory effect of natural compounds from native Peruvian plants against tau protein, amyloid beta, and angiotensin II type 1 receptor (AT1R) pathologic AD markers. Methods: We applied in silico analysis, such as virtual screening, molecular docking, molecular dynamics simulation (MD), and MM/GBSA estimation, to identify metabolites from Peruvian plants with inhibitory properties, and compared them to nicotinamide, telmisartan, and grapeseed extract drugs in clinical trials. Results: Our results demonstrated the increased bioactivity of three plants’ metabolites against tau protein, amyloid beta, and AT1R. The MD simulations indicated the stability of the AT1R:floribundic acid, amyloid beta:rutin, and tau:brassicasterol systems. A polypharmaceutical potential was observed for rutin due to its high affinity to AT1R, amyloid beta, and tau. The metabolite floribundic acid showed bioactivity against the AT1R and tau, and the metabolite brassicasterol showed bioactivity against the amyloid beta and tau. Conclusions: This study has identified molecules from native Peruvian plants that have the potential to bind three pathologic markers of AD.
Recent Advances in Hole-Transporting Layers for Organic Solar Cells
Authors: Anrango-Camacho Cinthya , Pavón-Ipiales Karla , Frontana-Uribe Bernardo A. , Palma-Cando Alex
Published: January 2022

Global energy demand is increasing; thus, emerging renewable energy sources, such as organic solar cells (OSCs), are fundamental to mitigate the negative effects of fuel consumption. Within OSC’s advancements, the development of efficient and stable interface materials is essential to achieve high performance, long-term stability, low costs, and broader applicability. Inorganic and nanocarbon-based materials show a suitable work function, tunable optical/electronic properties, stability to the presence of moisture, and facile solution processing, while organic conducting polymers and small molecules have some advantages such as fast and low-cost production, solution process, low energy payback time, light weight, and less adverse environmental impact, making them attractive as hole transporting layers (HTLs) for OSCs. This review looked at the recent progress in metal oxides, metal sulfides, nanocarbon materials, conducting polymers, and small organic molecules as HTLs in OSCs over the past five years. The endeavors in research and technology have optimized the preparation and deposition methods of HTLs. Strategies of doping, composite/hybrid formation, and modifications have also tuned the optical/electrical properties of these materials as HTLs to obtain efficient and stable OSCs. We highlighted the impact of structure, composition, and processing conditions of inorganic and organic materials as HTLs in conventional and inverted OSCs.
Catalytic Neutralization of Water Pollutants Mediated by Dendritic Polymers
Authors: Arkas Michael , Anastopoulos Ioannis , Giannakoudakis Dimitrios A. , Pashalidis Ioannis , Katsika Theodora , Nikoli Eleni , Panagiotopoulos Rafael , Fotopoulou Anna , Vardavoulias Michail , Douloudi Marilina
Published: January 2022

Radially polymerized dendritic compounds are nowadays an established polymer category next to their linear, branched, and cross-linked counterparts. Their uncommon tree-like architecture is characterized by adjustable internal cavities and external groups. They are therefore exceptional absorbents and this attainment of high concentrations in their interior renders them ideal reaction media. In this framework, they are applied in many environmentally benign implementations. One of the most important among them is water purification through pollutant decomposition. Simple and composite catalysts and photo-catalysts containing dendritic polymers and applied in water remediation will be discussed jointly with some unconventional solutions and prospects.
Significant Surface Spin Effects and Exchange Bias in Iron Oxide-Based Hollow Magnetic Nanoparticles
Authors: García Acevedo Pelayo , González Gómez Manuel A. , Arnosa Prieto Ángela , Garitaonandia Jose S. , Piñeiro Yolanda , Rivas José
Published: January 2022

Exchange bias (EB) properties have become especially important in hollow magnetic nanoparticles (MNPs) due to the versatility and reduced size of these materials. In this work, we present the synthesis and study of the EB properties of iron-oxide-based hollow MNPs and their precursors Fe/iron oxide MNPs with core/void/shell structure. The two mechanisms involved in EB generation were investigated: the frozen spins present in the nanograins that form the nanoparticles and the surface spins. The effect of external parameters on the coercivity (HC), remanence (MR), exchange bias field (HEB) and frozen spins, such as cooling field (HFC) and temperature, was investigated. Both HC and HEB present a maximum threshold above which their values begin to decrease with HFC, showing a new trend of HEB with HFC and allowing modulation on demand. The existence of surface spins, present on the outer and inner surfaces, was demonstrated, and an intrinsic EB phenomenon (HEB = 444 Oe for hollow iron oxide-based MNPs of 13.1 nm) with significant magnetization (MS~50 emu/g) was obtained. Finally, core/void/shell MNPs of 11.9 nm prior to the formation of the hollow MNPs showed a similar behavior, with non-negligible HEB, highlighting the importance of surface spins in EB generation.
Review on Nanoparticles and Nanostructured Materials: Bioimaging, Biosensing, Drug Delivery, Tissue Engineering, Antimicrobial, and Agro-Food Applications
Authors: Harish Vancha , Tewari Devesh , Gaur Manish , Yadav Awadh Bihari , Swaroop Shiv , Bechelany Mikhael , Barhoum Ahmed
Published: January 2022

In the last few decades, the vast potential of nanomaterials for biomedical and healthcare applications has been extensively investigated. Several case studies demonstrated that nanomaterials can offer solutions to the current challenges of raw materials in the biomedical and healthcare fields. This review describes the different nanoparticles and nanostructured material synthesis approaches and presents some emerging biomedical, healthcare, and agro-food applications. This review focuses on various nanomaterial types (e.g., spherical, nanorods, nanotubes, nanosheets, nanofibers, core-shell, and mesoporous) that can be synthesized from different raw materials and their emerging applications in bioimaging, biosensing, drug delivery, tissue engineering, antimicrobial, and agro-foods. Depending on their morphology (e.g., size, aspect ratio, geometry, porosity), nanomaterials can be used as formulation modifiers, moisturizers, nanofillers, additives, membranes, and films. As toxicological assessment depends on sizes and morphologies, stringent regulation is needed from the testing of efficient nanomaterials dosages. The challenges and perspectives for an industrial breakthrough of nanomaterials are related to the optimization of production and processing conditions.
Interplay between Thickness, Defects, Optical Properties, and Photoconductivity at the Centimeter Scale in Layered GaS
Authors: Dicorato Stefano , Gutiérrez Yael , Giangregorio Maria M. , Palumbo Fabio , Bianco Giuseppe V. , Losurdo Maria
Published: January 2022

From the group-III monochalcogenide (MX, M  =  Ga, In; X  =  S, Se, Te) layered semiconductors, gallium monosulfide, GaS, has emerged as a promising material for electronics, optoelectronics, and catalysis applications. In this work, GaS samples of various thicknesses in the range from 38 to 1665 nm have been obtained by mechanical exfoliation to study the interplay between structural, morphological, optical, and photoresponsivity properties as a function of thickness. This interplay has been established by analyzing the structure through Raman spectroscopy and X-ray diffraction, the morphology through scanning electron microscopy and atomic force microscopy, the density and optical properties through spectroscopic ellipsometry, and the photoresponsivity through current–voltage measurements under UV light. This work shows that photoresponsivity increases with increases in GaS thickness, resulting in a UV photoresponsivity of 1.5·10−4 AW−1 stable over several on/off cycles.
Peptide Self-Assembled Nanostructures: From Models to Therapeutic Peptides
Authors: Gatto Emanuela , Toniolo Claudio , Venanzi Mariano
Published: January 2022

Self-assembly is the most suitable approach to obtaining peptide-based materials on the nano- and mesoscopic scales. Applications span from peptide drugs for personalized therapy to light harvesting and electron conductive media for solar energy production and bioelectronics, respectively. In this study, we will discuss the self-assembly of selected model and bioactive peptides, in particular reviewing our recent work on the formation of peptide architectures of nano- and mesoscopic size in solution and on solid substrates. The hierarchical and cooperative characters of peptide self-assembly will be highlighted, focusing on the structural and dynamical properties of the peptide building blocks and on the nature of the intermolecular interactions driving the aggregation phenomena in a given environment. These results will pave the way for the understanding of the still-debated mechanism of action of an antimicrobial peptide (trichogin GA IV) and the pharmacokinetic properties of a peptide drug (semaglutide) currently in use for the therapy of type-II diabetes.
The Effect of Surface Hydroxyls on the Humidity-Sensitive Properties of LiCl-Doped ZnSn(OH)6 Sphere-Based Sensors
Authors: Li Zhenjiang , Zhang Min , Yang Linyu , Wu Rong , Wu Zhaofeng , Jiang Youquan , Zhou Lina , Liu Yanan
Published: January 2022

Pure zinc hydroxystannate (ZnSn(OH)6) and LiCl-doped ZnSn(OH)6 have been synthesized through a facile wet chemical method. The LiCl-doped samples keep their original spherical morphology as pure ZnSn(OH)6, with some LiCl particles stuck to its surface, providing more active sites for the adsorption and desorption of water molecules. The influence of LiCl doping on the humidity-sensing properties was explored by varying the dopant concentration. The 16 wt% LiCl/ZnSn(OH)6 showed a better humidity-sensing performance than that of the pure ZnSn(OH)6 and other doped samples, including a high resistive sensitivity, a relatively small hysteresis, and a fast response speed. Through the FTIR analysis, the number of hydroxyl groups on the surface structure after aging has been found to decline markedly. These hydroxyl groups provide a platform for the adsorption of water molecules on the surface and promote the dissociation of water molecules. The detriment of aging to sensor performance should not be underrated. The complex impedance spectrum explains the mechanism of the sensor. These results demonstrate that ZnSn(OH)6 has potential application in fabricating humidity sensors, and the sensing performance of the sensor is enhanced by the dopant LiCl.
Enhancement of Ferroelectricity in 5 nm Metal-Ferroelectric-Insulator Technologies by Using a Strained TiN Electrode
Authors: Wu Cheng-Hung , Wang Kuan-Chi , Wang Yu-Yun , Hu Chenming , Su Chun-Jung , Wu Tian-Li
Published: January 2022

In this work, the ferroelectric characteristic of a 5 nm Hf0.5Zr0.5O2 (HZO) metal-ferroelectric-insulator-semiconductor (MFIS) device is enhanced through strained complementary metal oxide semiconductor (CMOS)-compatible TiN electrode engineering. Strained TiN top-layer electrodes with different nitrogen (N) concentrations are deposited by adjusting the sputtering process conditions. The TiN electrode with 18% N exhibits a compressive characteristic, which induces tensile stress in a 5 nm HZO film. A device with 18% N in TiN shows a higher remanent polarization (2Pr) and larger capacitance value than the compared sample, indicating that the strained TiN is promising for enhancing the ferroelectricity of sub-5 nm HZO devices.
Transplantation of Olfactory Ensheathing Cells: Properties and Therapeutic Effects after Transplantation into the Lesioned Nervous System
Authors: Delarue Quentin , Guérout Nicolas
Published: January 2022

The primary olfactory system (POS) is in permanent renewal, especially the primary olfactory neurons (PON) are renewed with a turnover of around four weeks, even in adulthood. The re-growth of these axons is helped by a specific population of glial cells: the olfactory ensheathing cells (OECs). In the POS, OECs constitute an “open-channel” in which the axons of PON cause regrowth from peripheral nervous system (PNS) to central nervous system (CNS). The remarkable role played by OECs into the POS has led scientists to investigate their properties and potential beneficial effects after transplantation in different lesion models of the CNS and PNS. In this review, we will resume and discuss more than thirty years of research regarding OEC studies. Indeed, after discussing the embryonic origins of OECs, we will describe the in vitro and in vivo properties exert at physiological state by these cells. Thereafter, we will present and talk over the effects of the transplantation of OECs after spinal cord injury, peripheral injury and other CNS injury models such as demyelinating diseases or traumatic brain injury. Finally, the mechanisms exerted by OECs in these different CNS and PNS lesion paradigms will be stated and we will conclude by presenting the innovations and future directions which can be considered to improve OECs properties and allow us to envisage their use in the near future in clinical applications.
Neuroimaging and CSF Findings in Patients with Autoimmune Encephalitis: A Report of Eight Cases in a Single Academic Center
Authors: Wu Hongyan , Yu Hongxuyang , Joseph Joe , Jaiswal Shruti , Pasham Shreya R. , Sriwastava Shitiz
Published: January 2022

Autoimmune Encephalitis (AIE) is a rare and complex group of disorders wherein the body’s immune system attacks and causes inflammatory changes in the central nervous system (CNS). It presents with altered mental status and a diverse range of typical and atypical symptoms and neuroimaging and cerebrospinal fluid (CSF) findings. The objective of this article is to highlight the importance of early identification of neurological symptoms, prompt diagnosis with neuroimaging and CSF findings, and timely management for early and complete resolution of the disease and long-term benefits. We report eight AIE cases from a single academic center confirmed by the presence of specific serum and CSF autoantibodies. The patients were mostly women, with imaging findings showing T2-weighted (T2), fluid-attenuated inversion recovery (FLAIR), hyperintensities/changes in cortical/mesio-temporal regions on a magnetic resonance imaging (MRI), and delta brush wave patterns or epileptogenic patterns on an electroencephalogram (EEG). Among the antibodies, the N-methyl-D-aspartate receptor (NMDA-R) antibody (AB) was most frequently identified, and CSF lymphocytosis and elevated CSF glucose were found in majority of the cases, CSF pleocytosis and elevated protein only in a minority of patients, and oligoclonal bands (OCBs) only in NMDA-R encephalitis. Early treatment with intravenous immune globulin (IVIG), steroids, plasmapheresis (PLEX), and rituximab was started in most cases, and all of them responded well and survived, but some had residual symptoms or relapses.
Acute Effects of Low Dose of Caffeine Ingestion Combined with Conditioning Activity on Psychological and Physical Performances of Male and Female Taekwondo Athletes
Authors: Ouergui Ibrahim , Mahdi Nourhene , Delleli Slaheddine , Messaoudi Hamdi , Chtourou Hamdi , Sahnoun Zouheir , Bouassida Anissa , Bouhlel Ezdine , Nobari Hadi , Ardigò Luca Paolo , Franchini Emerson
Published: January 2022

This study investigated low-dose caffeine ingestion, conditioning activity (CA) effects on psycho-physical performances in young taekwondo athletes. In a randomized, double-blind, counterbalanced, crossover design, 20 athletes (10 males; 17.5 ± 0.7 yrs) performed taekwondo-specific agility test (TSAT), 10 s/multiple frequency speed of kick test (FSKT-10s/FSKT-mult) after ingesting 3 mg·kg−1 caffeine (CAF) or placebo (PL) 60 min before performing standard warm-up without (NoCA) or with CA (3 × 10 vertical jumps above 40 cm), resulting in four experimental (PL + NoCA, CAF + NoCA, PL + CA, and CAF + CA) and one control (warm-up session without CAF or CA) conditions. Mood/physical symptoms (MPSS), subjective vitality (SVS), and feeling (FS) scales were analyzed post-to-pre for all conditions. Ratings of perceived-exertion and perceived-recovery status were determined after tests. For TSAT, CAF + CA induced better performance compared with all conditions (p < 0.001). For FSKT-10s and FSKT-mult, CAF + CA induced better performance compared with all conditions (p < 0.001). For MPSS, FS, CAF + NoCA induced higher scores than PL + NoCA and PL + CA (p = 0.002, 0.009 for MPSS; p = 0.014, 0.03 for FS). For SVS, PL + CA elicited lower scores than PL + NoCA and CAF + NoCA (p = 0.01, 0.004). Sex comparisons resulted in better performances for males for TSAT (p = 0.008), FSKT-10s (p < 0.001), FSKT-mult (p < 0.01), MPSS (p = 0.02), SVS (p = 0.028), and FS (p = 0.020) scores. Caffeine and conditioning activity are two efficient performance-enhancing strategies, which could synergistically result in greater psycho-physical performances.
Chewing the Fat with Microbes: Lipid Crosstalk in the Gut
Authors: Lemons Johanna M. S. , Liu LinShu
Published: January 2022

It is becoming increasingly important for any project aimed at understanding the effects of diet on human health, to also consider the combined effect of the trillions of microbes within the gut which modify and are modified by dietary nutrients. A healthy microbiome is diverse and contributes to host health, partly via the production and subsequent host absorption of secondary metabolites. Many of the beneficial bacteria in the gut rely on specific nutrients, such as dietary fiber, to survive and thrive. In the absence of those nutrients, the relative proportion of good commensal bacteria dwindles while communities of opportunistic, and potentially pathogenic, bacteria expand. Therefore, it is unsurprising that both diet and the gut microbiome have been associated with numerous human diseases. Inflammatory bowel diseases and colorectal cancer are associated with the presence of certain pathogenic bacteria and risk increases with consumption of a Western diet, which is typically high in fat, protein, and refined carbohydrates, but low in plant-based fibers. Indeed, despite increased screening and better care, colorectal cancer is still the 2nd leading cause of cancer death in the US and is the 3rd most diagnosed cancer among US men and women. Rates are rising worldwide as diets are becoming more westernized, alongside rising rates of metabolic diseases like obesity and diabetes. Understanding how a modern diet influences the microbiota and how subsequent microbial alterations effect human health will become essential in guiding personalized nutrition and healthcare in the future. Herein, we will summarize some of the latest advances in understanding of the three-way interaction between the human host, the gut microbiome, and the specific class of dietary nutrients, lipids.
Lysophosphatidylethanolamine Affects Lipid Accumulation and Metabolism in a Human Liver-Derived Cell Line
Authors: Yamamoto Yusuke , Sakurai Toshihiro , Chen Zhen , Inoue Nao , Chiba Hitoshi , Hui Shu-Ping
Published: January 2022

The physiological functions of lysophosphatidylethanolamine (lysoPE) have not been fully elucidated. In this study, the effects of lysoPE on lipogenesis and lipolysis were investigated in a cultured human liver-derived cell line. The intracellular lipid profile was investigated in detail using liquid chromatography–tandem mass spectrometry (LC-MS/MS) to better understand the underlying mechanism. The expression of genes related to lipid metabolism and catabolism was analyzed using real-time PCR. LysoPE supplementation induced cellular lipid droplet formation and altered triacylglycerol (TAG) profiles. Furthermore, lysoPE downregulated expression of the TAG hydrolyzation regulation factor ATGL, and reduced the expression of fatty acid biosynthesis-related genes SREBP1 and SCD1. LC-MS/MS-based lipidomic profiling revealed that the addition of lysoPE 18:2 increased the PE species containing linoleic acyl, as well as the CE 18:2 species, likely due to the incorporation of linoleic acyl from lysoPE 18:2. Collectively, these findings suggest that lysoPE 18:2 is involved in lipid droplet formation by suppressing lipolysis and fatty acid biosynthesis. Thus, lysoPE might play a pathological role in the induction of fatty liver disease.
Supplementing Soy-Based Diet with Creatine in Rats: Implications for Cardiac Cell Signaling and Response to Doxorubicin
Authors: Kay Laurence , Potenza Lucia , Hininger-Favier Isabelle , Roth Hubert , Attia Stéphane , Tellier Cindy , Zuppinger Christian , Calcabrini Cinzia , Sestili Piero , Wallimann Theo , Schlattner Uwe , Tokarska-Schlattner Malgorzata
Published: January 2022

Nutritional habits can have a significant impact on cardiovascular health and disease. This may also apply to cardiotoxicity caused as a frequent side effect of chemotherapeutic drugs, such as doxorubicin (DXR). The aim of this work was to analyze if diet, in particular creatine (Cr) supplementation, can modulate cardiac biochemical (energy status, oxidative damage and antioxidant capacity, DNA integrity, cell signaling) and functional parameters at baseline and upon DXR treatment. Here, male Wistar rats were fed for 4 weeks with either standard rodent diet (NORMAL), soy-based diet (SOY), or Cr-supplemented soy-based diet (SOY + Cr). Hearts were either freeze-clamped in situ or following ex vivo Langendorff perfusion without or with 25 μM DXR and after recording cardiac function. The diets had distinct cardiac effects. Soy-based diet (SOY vs. NORMAL) did not alter cardiac performance but increased phosphorylation of acetyl-CoA carboxylase (ACC), indicating activation of rather pro-catabolic AMP-activated protein kinase (AMPK) signaling, consistent with increased ADP/ATP ratios and lower lipid peroxidation. Creatine addition to the soy-based diet (SOY + Cr vs. SOY) slightly increased left ventricular developed pressure (LVDP) and contractility dp/dt, as measured at baseline in perfused heart, and resulted in activation of the rather pro-anabolic protein kinases Akt and ERK. Challenging perfused heart with DXR, as analyzed across all nutritional regimens, deteriorated most cardiac functional parameters and also altered activation of the AMPK, ERK, and Akt signaling pathways. Despite partial reprogramming of cell signaling and metabolism in the rat heart, diet did not modify the functional response to supraclinical DXR concentrations in the used acute cardiotoxicity model. However, the long-term effect of these diets on cardiac sensitivity to chronic and clinically relevant DXR doses remains to be established.
Lactose Malabsorption and Presumed Related Disorders: A Review of Current Evidence
Authors: Usai-Satta Paolo , Lai Mariantonia , Oppia Francesco
Published: January 2022

Background. Lactose malabsorption (LM) is a frequent clinical problem associated with several digestive and extra-digestive diseases. The aim of this manuscript was to clarify the real clinical impact of LM on these disorders. Methods. A literature search for digestive and extra-digestive disorders related to LM was carried out using PubMed, Medline and Cochrane. Results. A transient lactase deficiency is present in celiac disease (CD) on a normal diet. The persistence of symptoms in CD on a gluten-free diet may be instead, in part, attributed to a primary LM. Similar circumstances are present in inflammatory bowel diseases (IBD), in which LM can be responsible for a part of persistent symptoms in IBD on clinical remission. LM and irritable bowel syndrome (IBS) are instead independent conditions. On the other hand, a lactose-restricted diet may be useful for some IBS patients. A reduced lactose intake can lead to low bone mass and limited risk of fragility fractures. Finally, the absorption of levothyroxine could be conditioned by LM. Conclusions. LM can be responsible for persistent symptoms in CD and IBD. The association with IBS seems to be casual. Bone mass and levothyroxine absorption can be affected by LM.
Creatine as a Promising Component of Paternal Preconception Diet
Authors: Ostojic Sergej M. , Stea Tonje Holte , Engeset Dagrun
Published: January 2022

Male fertility has been declining globally over the past several decades, advancing from a personal issue to a public health problem. Beyond any doubt, a reduction in fertility (often characterized by low sperm count or motility) can severely threaten reproductive health and lifecourse framework in a long-term fashion. Aside from uncovering the currently unknown etiology of modern-day male infertility, the scientific and medical community faces a double burden: finding an efficient biomarker of impaired fertility and exploring any intervention that can act to enhance fertility. A plethora of nutritional compounds have been recognized as possible modulators of semen quality, and specific dietary patterns and nutrients appear to be accompanied by a lower risk of male infertility. Creatine, a conditionally essential nutrient, has caught attention as a male fertility-promoting candidate due to its role in sperm energy metabolism. This mini-review describes the creatine-related bioenergetics of spermatozoa, explores a connection between creatine levels and sperm quality in men, and critically examines available evidence for interventional studies with creatine to affect sperm viability.
Taiwanese Vegetarians Are Associated with Lower Dementia Risk: A Prospective Cohort Study
Authors: Tsai Jui-Hsiu , Huang Ching-Feng , Lin Ming-Nan , Chang Chiao-Erh , Chang Chia-Chen , Lin Chin-Lon
Published: January 2022

The number of people living with dementia globally is increasing rapidly, and there is no effective therapy. Dietary pattern is one important risk factor for the development and progression of dementia. We undertake this study to determine whether Taiwanese vegetarian diet in midlife affects dementia incidence in later years in a prospective cohort. We followed 5710 participants (average age less than 60) in the Tzu Chi Vegetarian Study (TCVS). We started recruiting in 2005 and followed until the end of 2014 when the database changed from ICD-9-CM to ICD-10-CM codes. The incidence of dementia was obtained through linkage to the National Health Insurance Research Database. We used Cox proportional hazards regression to estimate the hazard ratio of dementia between vegetarians and nonvegetarians. There were 121 cases of dementia (37 vegetarians and 84 nonvegetarians) diagnosed. Vegetarians were associated with reduced risk of clinically overt dementia compared with nonvegetarians (hazard ratio = 0.671, confidence interval: 0.452–0.996, p < 0.05) after adjusting for gender, age, smoking, drinking, education level, marriage, regular exercise, and comorbidities with stepwise regression.
New Evidence for a Nonclassical Behavior of Laser Multimode Light
Authors: Lebedev Michael , Demenev Andrey , Parakhonsky Andrey , Misochko Oleg
Published: January 2022

In this work, we present new experimental evidence of a nonclassical behavior of a multimode Fabry–Perot (FP) semiconductor laser by the measurements of intensity correlation functions. Due to the multimode quantum state occurrence, instead of expected correlations between the intensities of the laser modes (a semiclassical theory), their anticorrelations were revealed.
Molecular Characterization of Bovine Leukemia Virus with the Evidence of a New Genotype Circulating in Cattle from Kazakhstan
Authors: Sultanov Akhmetzhan , Rola-Łuszczak Marzena , Mamanova Saltanat , Ryło Anna , Osiński Zbigniew , Saduakassova Meruyert A. , Bashenova Elvira , Kuźmak Jacek
Published: January 2022

Bovine leukemia virus (BLV) is a retrovirus that causes enzootic bovine leukosis (EBL) and has worldwide distribution. Infections with BLV have been reported in cattle from Kazakhstan but the virus has not yet been thoroughly characterized. In this study, we detect and estimate the level of BLV proviral DNA by qPCR in DNA samples from 119 cattle naturally infected with BLV, from 18 farms located in four different geographical regions of Kazakhstan. Furthermore, we conducted the phylogenetic and molecular analysis of 41 BLV env-gp51 gene sequences from BLV infected cattle. Phylogenetic analysis showed the affiliation of sequences to two already known genotypes G4 and G7 and also to a new genotype, classified as genotype G12. In addition, a multivariate method was employed for analysis of the association between proviral load and different variables such as the geographical location of the herd, cattle breeds, age of animals, and the presence of particular BLV genotypes. In summary, the results of this study provide the first evidence on molecular characterization of BLV circulating in cattle from Kazakhstan.
Bartonella henselae Recombinant Pap31 for the Diagnosis of Canine and Human Bartonelloses
Authors: Neupane Pradeep , Maggi Ricardo G. , Basnet Manoj , Lashnits Erin , Andrews Gerard P. , Breitschwerdt Edward B.
Published: January 2022

Bartonella spp. comprise a genus of Gram-negative alphaproteobacteria that are slow growing, fastidious, and facultative intracellular pathogens with zoonotic potential. Immunofluorescent antibody assays (IFAs), Western blot (WB), and enzyme-linked immunosorbent assays (ELISAs), the frequently used modalities for the serological diagnosis of canine and human Bartonelloses, generate numerous false negative results. Therefore, the development of a reliable serodiagnostic assay for Bartonelloses is of clinical and epidemiological importance. Pap31, a heme binding surface protein of B. henselae, is associated with bacterial adhesion and related to bacterial colonization. To our knowledge, B. henselae Pap31 and its fragments (N-terminal (NTD), middle (MD), and C-terminal (CTD) domains) have not been investigated for the serodiagnosis of canine and human Bartonelloses. In this study, we evaluate the diagnostic utility of B. henselae recombinant whole Pap31 (rPap31) and Pap31 fragments by ELISA using sera from 70 dogs (36 Bartonella spp. IFA-positive (naturally infected), and 34 Bartonella spp. IFA- and PCR-negative (control dogs)) and 36 humans (18 Bartonella spp. IFA-positive (naturally infected) and 18 controls)). In the dogs, the area under the curve (AUC) score of recombinant whole Pap31 was 0.714 with a sensitivity of 42% and specificity of 94% at an OD cutoff value of 0.8955. Among the evaluated recombinant Pap31 proteins for the diagnosis of canine Bartonelloses, rPap31-NTD yielded the highest AUC score of 0.792 (95% CI 0.688–0.895) with a sensitivity of 44% and specificity of 100% at a cutoff value of 1.198. In concordance with this finding, rPap31-NTD also had the highest AUC score of 0.747 (95% CI 0.581–0.913) among the Pap31 recombinant proteins for the diagnosis of human Bartonelloses, with 39% sensitivity and 94% specificity at a cutoff value of 1.366. Recombinant whole Pap31 (rPap31) resulted in 72% sensitivity and 61% specificity at a cutoff value of 0.215 for human Bartonelloses. Due to either low sensitivity or questionable specificity, our findings indicate that recombinant Pap31 and the selected fragments may not be appropriate diagnostic targets in detecting anti-Bartonella antibodies in Bartonella-infected dogs and humans. The findings from this study can be used to further assess the antigenicity and immunogenicity of B. henselae Pap31 as a diagnostic target.
Toxoplasma gondii Infections in Animals and Humans in Southern Africa: A Systematic Review and Meta-Analysis
Authors: Omonijo Adejumoke O. , Kalinda Chester , Mukaratirwa Samson
Published: January 2022

Background: Toxoplasma gondii is an apicomplexan parasite with zoonotic importance worldwide especially in pregnant women and immunocompromised people. This study is set to review the literature on T. gondii infections in humans and animals in southern Africa. Methods: We extracted data regarding T. gondii infections from published articles from southern Africa from 1955 to 2020 from four databases, namely Google Scholar, PubMed, EBSCO Host, and Science Direct. Forty articles from eight southern African countries were found eligible for the study. Results: This review revealed a paucity of information on T. gondii infection in southern African countries, with an overall prevalence of 17% (95% CI: 7–29%). Domestic felids had a prevalence of 29% (95% CI: 7–54%), wild felids 79% (95% CI: 60–94), canids (domestic and wild) 69% (95% CI: 38–96%), cattle 20% (95% CI: 5–39%), pigs 13% (95% CI: 1–29%), small ruminants (goats and sheep) 11% (95% CI: 0–31%), chicken and birds 22% (95% CI: 0–84%), and humans 14% (95% CI: 5–25%). Enzyme-linked immunosorbent assay (ELISA) and immunofluorescence antibody test (IFAT) constituted the most frequently used diagnostic tests for T. gondii. Conclusions: We recommend more focused studies be conducted on the epidemiology of T. gondii in the environment, food animals and human population, most especially the at-risk populations.
Role of Cellular Metabolism during Candida-Host Interactions
Authors: Pellon Aize , Begum Neelu , Sadeghi Nasab Shervin Dokht , Harzandi Azadeh , Shoaie Saeed , Moyes David L.
Published: January 2022

Microscopic fungi are widely present in the environment and, more importantly, are also an essential part of the human healthy mycobiota. However, many species can become pathogenic under certain circumstances, with Candida spp. being the most clinically relevant fungi. In recent years, the importance of metabolism and nutrient availability for fungi-host interactions have been highlighted. Upon activation, immune and other host cells reshape their metabolism to fulfil the energy-demanding process of generating an immune response. This includes macrophage upregulation of glucose uptake and processing via aerobic glycolysis. On the other side, Candida modulates its metabolic pathways to adapt to the usually hostile environment in the host, such as the lumen of phagolysosomes. Further understanding on metabolic interactions between host and fungal cells would potentially lead to novel/enhanced antifungal therapies to fight these infections. Therefore, this review paper focuses on how cellular metabolism, of both host cells and Candida, and the nutritional environment impact on the interplay between host and fungal cells.
Behavioral, Anti-Inflammatory, and Neuroprotective Effects of a Novel FPR2 Agonist in Two Mouse Models of Autism
Authors: Cristiano Claudia , Volpicelli Floriana , Crispino Marianna , Lacivita Enza , Russo Roberto , Leopoldo Marcello , Calignano Antonio , Perrone-Capano Carla
Published: January 2022

Autism spectrum disorders (ASD) are a group of heterogeneous neurodevelopmental conditions characterized by social deficits, repetitive stereotyped behaviors, and altered inflammatory responses. Accordingly, children with ASD show decreased plasma levels of lipoxin A4 (LXA4), a mediator involved in the resolution of inflammation, which is the endogenous ligand of the formyl peptide receptor 2 (FPR2). To investigate the role of FPR2 in ASDs, we have used a new ureidopropanamide derivative able to activate the receptor, named MR-39. The effects of MR-39 (10 mg/kg, for 8 days) on hippocampal pro-inflammatory profile, neuronal plasticity, and social behavior were evaluated in two validated animal models of ASD: BTBR mouse strain and mice prenatally exposed to valproic acid (VPA). Primary cultures of hippocampal neurons from BTBR mice were also used to evaluate the effect of MR-39 on neurite elongation. Our results show that MR-39 treatment reduced several inflammatory markers, restored the low expression of LXA4, and modulated FPR2 expression in hippocampal tissues of both ASD animal models. These findings were accompanied by a significant positive effect of MR-39 on social behavioral tests of ASD mice. Finally, MR-39 stimulates neurite elongation in isolated hippocampal neurons of BTBR mice. In conclusion, these data indicate FPR2 as a potential target for an innovative therapeutical approach for the cure of ASD.
A Convenient Route to New (Radio)Fluorinated and (Radio)Iodinated Cyclic Tyrosine Analogs
Authors: Chao Maria , Chezal Jean-Michel , Debiton Eric , Canitrot Damien , Witkowski Tiffany , Levesque Sophie , Degoul Françoise , Tarrit Sébastien , Wenzel Barbara , Miot-Noirault Elisabeth , Serre Audrey , Maisonial-Besset Aurélie
Published: January 2022

The use of radiolabeled non-natural amino acids can provide high contrast SPECT/PET metabolic imaging of solid tumors. Among them, radiohalogenated tyrosine analogs (i.e., [123I]IMT, [18F]FET, [18F]FDOPA, [123I]8-iodo-L-TIC(OH), etc.) are of particular interest. While radioiodinated derivatives, such as [123I]IMT, are easily available via electrophilic aromatic substitutions, the production of radiofluorinated aryl tyrosine analogs was a long-standing challenge for radiochemists before the development of innovative radiofluorination processes using arylboronate, arylstannane or iodoniums salts as precursors. Surprisingly, despite these methodological advances, no radiofluorinated analogs have been reported for [123I]8-iodo-L-TIC(OH), a very promising radiotracer for SPECT imaging of prostatic tumors. This work describes a convenient synthetic pathway to obtain new radioiodinated and radiofluorinated derivatives of TIC(OH), as well as their non-radiolabeled counterparts. Using organotin compounds as key intermediates, [125I]5-iodo-L-TIC(OH), [125I]6-iodo-L-TIC(OH) and [125I]8-iodo-L-TIC(OH) were efficiently prepared with good radiochemical yield (RCY, 51–78%), high radiochemical purity (RCP, >98%), molar activity (Am, >1.5–2.9 GBq/µmol) and enantiomeric excess (e.e. >99%). The corresponding [18F]fluoro-L-TIC(OH) derivatives were also successfully obtained by radiofluorination of the organotin precursors in the presence of tetrakis(pyridine)copper(II) triflate and nucleophilic [18F]F− with 19–28% RCY d.c., high RCP (>98.9%), Am (20–107 GBq/µmol) and e.e. (>99%).
Identification of Antibacterial Peptide Candidates Encrypted in Stress-Related and Metabolic Saccharomyces cerevisiae Proteins
Authors: Santos Maria Fernanda da Silva , Freitas Cyntia Silva , Verissimo da Costa Giovani Carlo , Pereira Patricia Ribeiro , Paschoalin Vania Margaret Flosi
Published: January 2022

The protein-rich nature of Saccharomyces cerevisiae has led this yeast to the spotlight concerning the search for antimicrobial peptides. Herein, a <10 kDa peptide-rich extract displaying antibacterial activity was obtained through the autolysis of yeast biomass under mild thermal treatment with self-proteolysis by endogenous peptidases. Estimated IC50 for the peptide pools obtained by FPLC gel filtration indicated improved antibacterial activities against foodborne bacteria and bacteria of clinical interest. Similarly, the estimated cytotoxicity concentrations against healthy human fibroblasts, alongside selective indices ≥10, indicates the fractions are safe, at least in a mixture format, for human tissues. Nano-LC-MS/MS analysis revealed that the peptides in FPLC fractions could be derived from both induced-proteolysis and proteasome activity in abundant proteins, up-regulated under stress conditions during S. cerevisiae biomass manufacturing, including those coded by TDH1/2/3, HSP12, SSA1/2, ADH1/2, CDC19, PGK1, PPI1, PDC1, and GMP1, as well as by other non-abundant proteins. Fifty-eight AMP candidate sequences were predicted following an in silico analysis using four independent algorithms, indicating their possible contribution to the bacterial inactivation observed in the peptides pool, which deserve special attention for further validation of individual functionality. S. cerevisiae-biomass peptides, an unconventional but abundant source of pharmaceuticals, may be promissory adjuvants to treat infectious diseases that are poorly sensitive to conventional antibiotics.
Novel Small-Molecule Inhibitors of the SARS-CoV-2 Spike Protein Binding to Neuropilin 1
Authors: Kolarič Anja , Jukič Marko , Bren Urban
Published: January 2022

Furin cleavage of the SARS-CoV-2 spike protein results in a polybasic terminal sequence termed the C-end rule (CendR), which is responsible for the binding to neuropilin 1 (NRP1), enhancing viral infectivity and entry into the cell. Here we report the identification of 20 small-molecule inhibitors that emerged from a virtual screening of nearly 950,000 drug-like compounds that bind with high probability to the CendR-binding pocket of NRP1. In a spike NRP1 binding assay, two of these compounds displayed a stronger inhibition of spike protein binding to NRP1 than the known NRP1 antagonist EG00229, for which the inhibition of the CendR peptide binding to NRP1 was also experimentally confirmed. These compounds present a good starting point for the design of small-molecule antagonists against the SARS-CoV-2 viral entry.