bluuebunny/crossref_metadata_2025 huggingface dataset:
Slow Off-Rate Modified Aptamer (SOMAmer) Proteomic Analysis of Patient-Derived Malignant Glioma Identifies Distinct Cellular Proteomes
Authors: Thanasupawat Thatchawan , Glogowska Aleksandra , Pascoe Christopher , Krishnan Sai Nivedita , Munir Maliha , Begum Farhana , Beiko Jason , Krcek Jerry , Del Bigio Marc R. , Pitz Marshall , Shen Yaoqing , Spicer Victor , Coombs Kevin M. , Wilkins John , Hombach-Klonisch Sabine , Klonisch Thomas
Published: September 2021

Malignant gliomas derive from brain glial cells and represent >75% of primary brain tumors. This includes anaplastic astrocytoma (grade III; AS), the most common and fatal glioblastoma multiforme (grade IV; GBM), and oligodendroglioma (ODG). We have generated patient-derived AS, GBM, and ODG cell models to study disease mechanisms and test patient-centered therapeutic strategies. We have used an aptamer-based high-throughput SOMAscan® 1.3K assay to determine the proteomic profiles of 1307 different analytes. SOMAscan® proteomes of AS and GBM self-organized into closely adjacent proteomes which were clearly distinct from ODG proteomes. GBM self-organized into four proteomic clusters of which SOMAscan® cluster 4 proteome predicted a highly inter-connected proteomic network. Several up- and down-regulated proteins relevant to glioma were successfully validated in GBM cell isolates across different SOMAscan® clusters and in corresponding GBM tissues. Slow off-rate modified aptamer proteomics is an attractive analytical tool for rapid proteomic stratification of different malignant gliomas and identified cluster-specific SOMAscan® signatures and functionalities in patient GBM cells.
Quantitative Analysis of the Potency of Equimolar Two-Drug Combinations and Combi-Molecules Involving Kinase Inhibitors In Vitro: The Concept of Balanced Targeting
Authors: Rao Suman , Thibault Benoît , Peyrard Lisa , Larroque-Lombard Anne-Laure , Rupp Martin , Thauvin Cédric , Jean-Claude Bertrand J.
Published: September 2021

The median-effect principle proposed by Chou and Talalay is the most effective approach to parameterize interactions between several agents in combination. However, this method cannot be used to evaluate the effectiveness of equimolar drug combinations, which are comparative references for dual-targeting molecular design. Here, using data acquired through the development of “combi-molecules” blocking two kinases (e.g., EGFR-c-Src and EGFR-c-Met), we established potency indices for equimolar and dual-targeted inhibitors. If the fold difference (κ) between the IC50 of the two individual kinase inhibitors was >6, the IC50 of their equimolar combination resembled that of the more potent inhibitor. Hence, the “combi-targeting” of the two kinases was considered “imbalanced” and the combination ineffective. However, if κ ≤ 6, the IC50 of the combination fell below that of each individual drug and the combi-targeting was considered “balanced” and the combination effective. We also showed that combi-molecules should be compared with equimolar combinations only under balanced conditions and propose a new parameter Ω for validating their effectiveness. A multi-targeted drug is effective if Ω < 1, where Ω is defined as the IC50 of the drug divided by that of the corresponding equimolar combination. Our study provides a methodology to determine the in vitro potency of equimolar two-drug combinations as well as combi-/hybrid molecules inhibiting two different kinase targets.
Culturomics Approach to Identify Diabetic Foot Infection Bacteria
Authors: Złoch Michał , Maślak Ewelina , Kupczyk Wojciech , Jackowski Marek , Pomastowski Paweł , Buszewski Bogusław
Published: September 2021

The main goal of the study was to evaluate the usefulness of the culturomics approach in the reflection of diabetic foot infections (DFIs) microbial compositions in Poland. Superficial swab samples of 16 diabetic foot infection patients (Provincial Polyclinical Hospital in Toruń, Poland) were subjected to culturing using 10 different types of media followed by the identification via the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and Biotyper platform. Identified 204 bacterial isolates representing 18 different species—mostly Enterococcus faecalis (63%) and Staphylococcus aureus (44%). Most of the infections (81%) demonstrated a polymicrobial character. Great differences in the species coverage, the number of isolated Gram-positive and Gram-negative bacteria, and the efficiency of the microbial composition reflection between the investigated media were revealed. The use of commonly recommended blood agar allowed to reveal only 53% of the entire microbial composition of the diabetic foot infection samples, which considerably improved when the chromagar orientation and vancomycin-resistant enterococi agar were applied. In general, efficiency increased in the following order: selective < universal < enriched < differential media. Performed analysis also revealed the impact of the culture media composition on the molecular profiles of some bacterial species, such as Corynebacterium striatum, Proteus mirabilis or Morganella morganii that contributed to the differences in the identification quality. Our results indicated that the culturomics approach can significantly improve the accuracy of the reflection of the diabetic foot infections microbial compositions as long as an appropriate media set is selected. The chromagar orientation and vancomycin-resistant enterococi agar media which were used for the first time to study diabetic foot infection microbial profiles demonstrate the highest utility in the culturomics approach and should be included in further studies directed to find a faster and more reliable diabetic foot infection diagnostic tool.
Modeling In Vitro Osteoarthritis Phenotypes in a Vascularized Bone Model Based on a Bone-Marrow Derived Mesenchymal Cell Line and Endothelial Cells
Authors: Pirosa Alessandro , Tankus Esma Bahar , Mainardi Andrea , Occhetta Paola , Dönges Laura , Baum Cornelia , Rasponi Marco , Martin Ivan , Barbero Andrea
Published: September 2021

The subchondral bone and its associated vasculature play an important role in the onset of osteoarthritis (OA). Integration of different aspects of the OA environment into multi-cellular and complex human, in vitro models is therefore needed to properly represent the pathology. In this study, we exploited a mesenchymal stromal cell line/endothelial cell co-culture to produce an in vitro human model of vascularized osteogenic tissue. A cocktail of inflammatory cytokines, or conditioned medium from mechanically-induced OA engineered microcartilage, was administered to this vascularized bone model to mimic the inflamed OA environment, hypothesizing that these treatments could induce the onset of specific pathological traits. Exposure to the inflammatory factors led to increased network formation by endothelial cells, reminiscent of the abnormal angiogenesis found in OA subchondral bone, demineralization of the constructs, and increased collagen production, signs of OA related bone sclerosis. Furthermore, inflammation led to augmented expression of osteogenic (alkaline phosphatase (ALP) and osteocalcin (OCN)) and angiogenic (vascular endothelial growth factor (VEGF)) genes. The treatment, with a conditioned medium from the mechanically-induced OA engineered microcartilage, also caused increased demineralization and expression of ALP, OCN, ADAMTS5, and VEGF; however, changes in network formation by endothelial cells were not observed in this second case, suggesting a possible different mechanism of action in inducing OA-like phenotypes. We propose that this vascularized bone model could represent a first step for the in vitro study of bone changes under OA mimicking conditions and possibly serve as a tool in testing anti-OA drugs.
Pharmacokinetic Drug–Drug Interactions among Antiepileptic Drugs, Including CBD, Drugs Used to Treat COVID-19 and Nutrients
Authors: Karaźniewicz-Łada Marta , Główka Anna K. , Mikulska Aniceta A. , Główka Franciszek K.
Published: September 2021

Anti-epileptic drugs (AEDs) are an important group of drugs of several generations, ranging from the oldest phenobarbital (1912) to the most recent cenobamate (2019). Cannabidiol (CBD) is increasingly used to treat epilepsy. The outbreak of the SARS-CoV-2 pandemic in 2019 created new challenges in the effective treatment of epilepsy in COVID-19 patients. The purpose of this review is to present data from the last few years on drug–drug interactions among of AEDs, as well as AEDs with other drugs, nutrients and food. Literature data was collected mainly in PubMed, as well as google base. The most important pharmacokinetic parameters of the chosen 29 AEDs, mechanism of action and clinical application, as well as their biotransformation, are presented. We pay a special attention to the new potential interactions of the applied first-generation AEDs (carbamazepine, oxcarbazepine, phenytoin, phenobarbital and primidone), on decreased concentration of some medications (atazanavir and remdesivir), or their compositions (darunavir/cobicistat and lopinavir/ritonavir) used in the treatment of COVID-19 patients. CBD interactions with AEDs are clearly defined. In addition, nutrients, as well as diet, cause changes in pharmacokinetics of some AEDs. The understanding of the pharmacokinetic interactions of the AEDs seems to be important in effective management of epilepsy.
Air-Spun Silk-Based Micro-/Nanofibers and Thin Films for Drug Delivery
Authors: Gough Christopher R. , Hu Xiao
Published: September 2021

Micro-/nanofibers have shown high promise as drug delivery vehicles due to their high porosity and surface-area-to-volume ratio. The current study utilizes air-spraying, a novel fiber fabrication technique, to create silk micro-/nanofibers without the need for a high voltage power source. Air-spraying was used to create silk fibrous mats embedded with several model drugs with high efficiency. In order to compare the effect of biomaterial geometry on the release of the model drugs, silk films were also created and characterized. Fourier-transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and a drug release study were performed on both fiber and film samples to study how the model drugs interact with the protein structure. FTIR analysis showed that while drugs could interact with the protein structure of porous silk fibers, they could not interact with the flat geometry of silk films. As a result, fibers could protect select model drugs from thermal degradation and slow their release from the fiber network with more control than the silk films. A trend was also revealed where hydrophobic drugs were better protected and had a slower release than hydrophilic drugs. The results suggest that the physical and chemical properties of drugs and protein-based biomaterials are important for creating drug delivery vehicles with tailored release profiles and that fibers provide better tunability than films do.
An Overview of the Nrf2/ARE Pathway and Its Role in Neurodegenerative Diseases
Authors: Zgorzynska Emilia , Dziedzic Barbara , Walczewska Anna
Published: September 2021

Nrf2 is a basic region leucine-zipper transcription factor that plays a pivotal role in the coordinated gene expression of antioxidant and detoxifying enzymes, promoting cell survival in adverse environmental or defective metabolic conditions. After synthesis, Nrf2 is arrested in the cytoplasm by the Kelch-like ECH-associated protein 1 suppressor (Keap1) leading Nrf2 to ubiquitin-dependent degradation. One Nrf2 activation mechanism relies on disconnection from the Keap1 homodimer through the oxidation of cysteine at specific sites of Keap1. Free Nrf2 enters the nucleus, dimerizes with small musculoaponeurotic fibrosarcoma proteins (sMafs), and binds to the antioxidant response element (ARE) sequence of the target genes. Since oxidative stress, next to neuroinflammation and mitochondrial dysfunction, is one of the hallmarks of neurodegenerative pathologies, a molecular intervention into Nrf2/ARE signaling and the enhancement of the transcriptional activity of particular genes are targets for prevention or delaying the onset of age-related and inherited neurogenerative diseases. In this study, we review evidence for the Nrf2/ARE-driven pathway dysfunctions leading to various neurological pathologies, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, as well as amyotrophic lateral sclerosis, and the beneficial role of natural and synthetic molecules that are able to interact with Nrf2 to enhance its protective efficacy.
One-Pot Process: Microwave-Assisted Keratin Extraction and Direct Electrospinning to Obtain Keratin-Based Bioplastic
Authors: Pulidori Elena , Micalizzi Simone , Bramanti Emilia , Bernazzani Luca , Duce Celia , De Maria Carmelo , Montemurro Francesca , Pelosi Chiara , De Acutis Aurora , Vozzi Giovanni , Tinè Maria Rosaria
Published: September 2021

Poultry feathers are among the most abundant and polluting keratin-rich waste biomasses. In this work, we developed a one-pot microwave-assisted process for eco-friendly keratin extraction from poultry feathers followed by a direct electrospinning (ES) of the raw extract, without further purification, to obtain keratin-based bioplastics. This microwave-assisted keratin extraction (MAE) was conducted in acetic acid 70% v/v. The effects of extraction time, solvent/feathers ratio, and heating mode (MAE vs. conventional heating) on the extraction yield were investigated. The highest keratin yield (26 ± 1% w/w with respect to initial feathers) was obtained after 5 h of MAE. Waste-derived keratin were blended with gelatin to fabricate keratin-based biodegradable and biocompatible bioplastics via ES, using 3-(Glycidyloxypropyl)trimethoxysilane (GPTMS) as a cross-linking agent. A full characterization of their thermal, mechanical, and barrier properties was performed by differential scanning calorimetry, thermogravimetric analysis, uniaxial tensile tests, and water permeability measurements. Their morphology and protein structure were investigated using scanning electron microscopy and attenuated total reflection-infrared spectroscopy. All these characterizations highlighted that the properties of the keratin-based bioplastics can be modulated by changing keratin and GPTMS concentrations. These bioplastics could be applied in areas such as bio-packaging and filtration/purification membranes.
Brain Metabolic Profile after Intranasal vs. Intraperitoneal Clomipramine Treatment in Rats with Ultrasound Model of Depression
Authors: Abramova Olga , Zorkina Yana , Syunyakov Timur , Zubkov Eugene , Ushakova Valeria , Silantyev Artemiy , Soloveva Kristina , Gurina Olga , Majouga Alexander , Morozova Anna , Chekhonin Vladimir
Published: September 2021

Background: Molecular mechanisms of depression remain unclear. The brain metabolome after antidepressant therapy is poorly understood and had not been performed for different routes of drug administration before the present study. Rats were exposed to chronic ultrasound stress and treated with intranasal and intraperitoneal clomipramine. We then analyzed 28 metabolites in the frontal cortex and hippocampus. Methods: Rats’ behavior was identified in such tests: social interaction, sucrose preference, forced swim, and Morris water maze. Metabolic analysis was performed with liquid chromatography. Results: After ultrasound stress pronounced depressive-like behavior, clomipramine had an equally antidepressant effect after intranasal and intraperitoneal administration on behavior. Ultrasound stress contributed to changes of the metabolomic pathways associated with pathophysiology of depression. Clomipramine affected global metabolome in frontal cortex and hippocampus in a different way that depended on the route of administration. Intranasal route was associated with more significant changes of metabolites composition in the frontal cortex compared to the control and ultrasound groups while the intraperitoneal route corresponded with more profound changes in hippocampal metabolome compared to other groups. Since far metabolic processes in the brain can change in many ways depending on different routes of administration, the antidepressant therapy should also be evaluated from this point of view.
The Transcriptional Landscape and Hub Genes Associated with Physiological Responses to Drought Stress in Pinus tabuliformis
Authors: Pervaiz Tariq , Liu Shuang-Wei , Uddin Saleem , Amjid Muhammad Waqas , Niu Shi-Hui , Wu Harry X.
Published: September 2021

Drought stress has an extensive impact on regulating various physiological, metabolic, and molecular responses. In the present study, the Pinus tabuliformis transcriptome was studied to evaluate the drought-responsive genes using RNA- Sequencing approache. The results depicted that photosynthetic rate and H2O conductance started to decline under drought but recovered 24 h after re-watering; however, the intercellular CO2 concentration (Ci) increased with the onset of drought. We identified 84 drought-responsive transcription factors, 62 protein kinases, 17 transcriptional regulators, and 10 network hub genes. Additionally, we observed the expression patterns of several important gene families, including 2192 genes positively expressed in all 48 samples, and 40 genes were commonly co-expressed in all drought and recovery stages compared with the control samples. The drought-responsive transcriptome was conserved mainly between P. tabuliformis and A. thaliana, as 70% (6163) genes had a homologous in arabidopsis, out of which 52% homologous (3178 genes corresponding to 2086 genes in Arabidopsis) were also drought response genes in arabidopsis. The collaborative network exhibited 10 core hub genes integrating with ABA-dependent and independent pathways closely conserved with the ABA signaling pathway in the transcription factors module. PtNCED3 from the ABA family genes had shown significantly different expression patterns under control, mild, prolonged drought, and recovery stages. We found the expression pattern was considerably increased with the prolonged drought condition. PtNCED3 highly expressed in all drought-tested samples; more interestingly, expression pattern was higher under mild and prolonged drought. PtNCED3 is reported as one of the important regulating enzymes in ABA synthesis. The continuous accumulation of ABA in leaves increased resistance against drought was due to accumulation of PtNCED3 under drought stress in the pine needles.
Cilia, Centrosomes and Skeletal Muscle
Authors: Ng Dominic C. H. , Ho Uda Y. , Grounds Miranda D.
Published: September 2021

Primary cilia are non-motile, cell cycle-associated organelles that can be found on most vertebrate cell types. Comprised of microtubule bundles organised into an axoneme and anchored by a mature centriole or basal body, primary cilia are dynamic signalling platforms that are intimately involved in cellular responses to their extracellular milieu. Defects in ciliogenesis or dysfunction in cilia signalling underlie a host of developmental disorders collectively referred to as ciliopathies, reinforcing important roles for cilia in human health. Whilst primary cilia have long been recognised to be present in striated muscle, their role in muscle is not well understood. However, recent studies indicate important contributions, particularly in skeletal muscle, that have to date remained underappreciated. Here, we explore recent revelations that the sensory and signalling functions of cilia on muscle progenitors regulate cell cycle progression, trigger differentiation and maintain a commitment to myogenesis. Cilia disassembly is initiated during myoblast fusion. However, the remnants of primary cilia persist in multi-nucleated myotubes, and we discuss their potential role in late-stage differentiation and myofiber formation. Reciprocal interactions between cilia and the extracellular matrix (ECM) microenvironment described for other tissues may also inform on parallel interactions in skeletal muscle. We also discuss emerging evidence that cilia on fibroblasts/fibro–adipogenic progenitors and myofibroblasts may influence cell fate in both a cell autonomous and non-autonomous manner with critical consequences for skeletal muscle ageing and repair in response to injury and disease. This review addresses the enigmatic but emerging role of primary cilia in satellite cells in myoblasts and myofibers during myogenesis, as well as the wider tissue microenvironment required for skeletal muscle formation and homeostasis.
Formation of Multicolor Nanogels Based on Cationic Polyfluorenes and Poly(methyl vinyl ether-alt-maleic monoethyl ester): Potential Use as pH-Responsive Fluorescent Drug Carriers
Authors: Rubio-Camacho Marta , Martínez-Tomé María José , Mira Amalia , Mallavia Ricardo , Mateo Carmen Reyes
Published: September 2021

In this study, we employed the copolymer poly(methyl vinyl ether-alt-maleic monoethyl ester) (PMVEMA-Es) and three fluorene-based cationic conjugated polyelectrolytes to develop fluorescent nanoparticles with emission in the blue, green and red spectral regions. The size, Zeta Potential, polydispersity, morphology, time-stability and fluorescent properties of these nanoparticles were characterized, as well as the nature of the interaction between both PMVEMA-Es and fluorescent polyelectrolytes. Because PMVEMA-Es contains a carboxylic acid group in its structure, the effects of pH and ionic strength on the nanoparticles were also evaluated, finding that the size is responsive to pH and ionic strength, largely swelling at physiological pH and returning to their initial size at acidic pHs. Thus, the developed fluorescent nanoparticles can be categorized as pH-sensitive fluorescent nanogels, since they possess the properties of both pH-responsive hydrogels and nanoparticulate systems. Doxorubicin (DOX) was used as a model drug to show the capacity of the blue-emitting nanogels to hold drugs in acidic media and release them at physiological pH, from changes in the fluorescence properties of both nanoparticles and DOX. In addition, preliminary studies by super-resolution confocal microscopy were performed, regarding their potential use as image probes.
Methotrexate Ameliorates Systemic Inflammation and Septic Associated-Lung Damage in a Cecal Ligation and Puncture Septic Rat Model
Authors: Bringué Josep , Guillamat-Prats Raquel , Martinez Maria , Torrents Eva , Camprubí-Rimblas Marta , Blanch Lluís , Artigas Antonio
Published: September 2021

Background: Sepsis is a serious, heterogeneous clinical entity produced by a severe and systemic host inflammatory response to infection. Methotrexate (MTX) is a folate-antagonist that induces the generation of adenosine and also inhibits JAK/STAT pathway; MTX it is widely used as an anti-inflammatory drug to control the immune system. Objective: The aim of this study was to assess the beneficial effects of a single and low dose of MTX in the systemic response and acute lung injury (ALI) induced by sepsis. As in the clinics, we treated our animals with antibiotics and fluids and performed the source control to mimic the current clinic treatment. Methods and main results: Sepsis was induced in rats by a cecal ligation puncture (CLP) procedure. Six hours after induction of sepsis, we proceeded to the source control; fluids and antibiotics were administered at 6 h and 24 h after CLP. MTX (2.5 mg/Kg) was administered 6 h after the first surgery in one CLP experimental group and to one Sham group. A protective effect of MTX was observed through a significant reduction of pro-inflammatory cytokines and a decrease infiltration of inflammatory cells in the lung. In addition, we found a regulation in adenosine receptor A2aR and the metalloproteinases by MTX. Conclusion: A single, low dose of MTX attenuates sepsis lung-associated damage by decreasing pro-inflammatory response, infiltration of pro-inflammatory cells and avoiding defective tissue lung remodeling.
Pathogenic Effects of Mineralocorticoid Pathway Activation in Retinal Pigment Epithelium
Authors: Canonica Jérémie , Zhao Min , Favez Tatiana , Gelizé Emmanuelle , Jonet Laurent , Kowalczuk Laura , Guegan Justine , Le Menuet Damien , Viengchareun Say , Lombès Marc , Pussard Eric , Arsenijevic Yvan , Behar-Cohen Francine
Published: September 2021

Glucocorticoids are amongst the most used drugs to treat retinal diseases of various origins. Yet, the transcriptional regulations induced by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation in retinal pigment epithelium cells (RPE) that form the outer blood–retina barrier are unknown. Levels of endogenous corticoids, ligands for MR and GR, were measured in human ocular media. Human RPE cells derived from induced pluripotent stem cells (iRPE) were used to analyze the pan-transcriptional regulations induced by aldosterone—an MR-specific agonist, or cortisol or cortisol + RU486—a GR antagonist. The retinal phenotype of transgenic mice that overexpress the human MR (P1.hMR) was analyzed. In the human eye, the main ligand for GR and MR is cortisol. The iRPE cells express functional GR and MR. The subset of genes regulated by aldosterone and by cortisol + RU-486, and not by cortisol alone, mimics an imbalance toward MR activation. They are involved in extracellular matrix remodeling (CNN1, MGP, AMTN), epithelial–mesenchymal transition, RPE cell proliferation and migration (ITGB3, PLAUR and FOSL1) and immune balance (TNFSF18 and PTX3). The P1.hMR mice showed choroidal vasodilation, focal alteration of the RPE/choroid interface and migration of RPE cells together with RPE barrier function alteration, similar to human retinal diseases within the pachychoroid spectrum. RPE is a corticosteroid-sensitive epithelium. MR pathway activation in the RPE regulates genes involved in barrier function, extracellular matrix, neural regulation and epithelial differentiation, which could contribute to retinal pathology.
New Glycosylated Dihydrochalcones Obtained by Biotransformation of 2′-Hydroxy-2-methylchalcone in Cultures of Entomopathogenic Filamentous Fungi
Authors: Krawczyk-Łebek Agnieszka , Dymarska Monika , Janeczko Tomasz , Kostrzewa-Susłow Edyta
Published: September 2021

Flavonoids, including chalcones, are more stable and bioavailable in the form of glycosylated and methylated derivatives. The combined chemical and biotechnological methods can be applied to obtain such compounds. In the present study, 2′-hydroxy-2-methylchalcone was synthesized and biotransformed in the cultures of entomopathogenic filamentous fungi Beauveria bassiana KCH J1.5, Isaria fumosorosea KCH J2 and Isaria farinosa KCH J2.6, which have been known for their extensive enzymatic system and ability to perform glycosylation of flavonoids. As a result, five new glycosylated dihydrochalcones were obtained. Biotransformation of 2′-hydroxy-2-methylchalcone by B. bassiana KCH J1.5 resulted in four glycosylated dihydrochalcones: 2′-hydroxy-2-methyldihydrochalcone 3′-O-β-d-(4″-O-methyl)-glucopyranoside, 2′,3-dihydroxy-2-methyldihydrochalcone 3′-O-β-d-(4″-O-methyl)-glucopyranoside, 2′-hydroxy-2-hydroxymethyldihydrochalcone 3′-O-β-d-(4″-O-methyl)-glucopyranoside, and 2′,4-dihydroxy-2-methyldihydrochalcone 3′-O-β-d-(4″-O-methyl)-glucopyranoside. In the culture of I. fumosorosea KCH J2 only one product was formed—3-hydroxy-2-methyldihydrochalcone 2′-O-β-d-(4″-O-methyl)-glucopyranoside. Biotransformation performed by I. farinosa KCH J2.6 resulted in the formation of two products: 2′-hydroxy-2-methyldihydrochalcone 3′-O-β-d-(4″-O-methyl)-glucopyranoside and 2′,3-dihydroxy-2-methyldihydrochalcone 3′-O-β-d-(4″-O-methyl)-glucopyranoside. The structures of all obtained products were established based on the NMR spectroscopy. All products mentioned above may be used in further studies as potentially bioactive compounds with improved stability and bioavailability. These compounds can be considered as flavor enhancers and potential sweeteners.
High Incidence of Related Wolbachia across Unrelated Leaf-Mining Diptera
Authors: Xu Xuefen , Ridland Peter M. , Umina Paul A. , Gill Alex , Ross Perran A. , Pirtle Elia , Hoffmann Ary A.
Published: September 2021

The maternally inherited endosymbiont, Wolbachia pipientis, plays an important role in the ecology and evolution of many of its hosts by affecting host reproduction and fitness. Here, we investigated 13 dipteran leaf-mining species to characterize Wolbachia infections and the potential for this endosymbiont in biocontrol. Wolbachia infections were present in 12 species, including 10 species where the Wolbachia infection was at or near fixation. A comparison of Wolbachia relatedness based on the wsp/MLST gene set showed that unrelated leaf-mining species often shared similar Wolbachia, suggesting common horizontal transfer. We established a colony of Liriomyza brassicae and found adult Wolbachia density was stable; although Wolbachia density differed between the sexes, with females having a 20-fold higher density than males. Wolbachia density increased during L. brassicae development, with higher densities in pupae than larvae. We removed Wolbachia using tetracycline and performed reciprocal crosses between Wolbachia-infected and uninfected individuals. Cured females crossed with infected males failed to produce offspring, indicating that Wolbachia induced complete cytoplasmic incompatibility in L. brassicae. The results highlight the potential of Wolbachia to suppress Liriomyza pests based on approaches such as the incompatible insect technique, where infected males are released into populations lacking Wolbachia or with a different incompatible infection.
Myzus persicae Management through Combined Use of Beneficial Insects and Thiacloprid in Pepper Seedlings
Authors: Lin Qingcai , Chen Hao , Dai Xiaoyan , Yin Shuyan , Shi Chenghao , Yin Zhenjuan , Zhang Jinping , Zhang Feng , Zheng Li , Zhai Yifan
Published: September 2021

Excessive insecticide application has posed a threat to pollinators and has also increased insecticide resistance of Myzus persicae Sulzer. Therefore, it is urgent to develop an economical and effective strategy, especially for greenhouse vegetables. Firstly, we selected a neonicotinoid insecticide that is specifically fatal to M. persicae but relatively safe to predators and bumblebees by laboratory toxicity tests and risk assessments. Then, we tested the effectiveness of the neonicotinoid insecticide under different temperature conditions. According to the LC50 values and the hazard quotients, thiacloprid met the requirements. Greenhouse trails indicated that thiacloprid was quite efficient, while control dropped to 80% without the application of thiacloprid. As for biological control, Harmonia axyridis effectively controlled 90% of aphids with thiacloprid or not. However, Aphidoletes aphidimyza performed better above 20 °C. Our results indicated that it is cost-effective to control M. persicae with A. aphidimyza in suitable temperature conditions and H. axyridis was more effective at low temperatures. Practically, thiacloprid could be used either as an emergency option to control aphids’ abundance alone or in combination with natural enemies.
A Historical Collection of Termites in Ferrara: Recovery, Cataloguing and Geographical Analyses
Authors: Curci Davide , Scapoli Chiara , Marchetti Maria Gabriella , Chicca Milvia , Leis Marilena , Vicentini Chiara Beatrice , Bonacci Teresa , Pezzi Marco
Published: September 2021

Termites are an insect group relevant for recycling of organic matter, but they are also biodeteriogenic and may cause serious damages to wooden structures (including historical buildings and ancient libraries) in anthropogenic environments. The collection of Italian and foreign termites gathered over the years by Antonio Springhetti, Professor of Zoology at the University of Ferrara (Ferrara, Italy) and internationally renowned entomologist, contains over 44,000 specimens, collected by Springhetti during his field campaigns or donated by other entomologists from all over the world. The collection is currently preserved at the Department of Life Sciences and Biotechnology of the University of Ferrara. Unfortunately, all documents, publications and notes concerning the Springhetti Collection were lost; thus, in 2020, the collection was completely re-catalogued within the University Museum System and analyzed in detail. The collection contains specimens dating back to 1878 and represents not only a valuable scientific tool for studies on these ecologically relevant insects that may cause damages to historical buildings, ancient books and artworks but also an important cultural asset for the University Museum System.
Comparative Mitogenomes of Two Coreamachilis Species (Microcoryphia: Machilidae) along with Phylogenetic Analyses of Microcoryphia
Authors: Guan Jia-Yin , Shen Shi-Qi , Zhang Zi-Yi , Xu Xiao-Dong , Storey Kenneth B. , Yu Dan-Na , Zhang Jia-Yong
Published: September 2021

The order Microcoryphia, commonly known as bristletails, is considered as the most primitive one among living insects. Within this order, two species, Coreamachilis coreanus and C. songi (Machilidae: Machilinae), display the following contrasting reproductive strategies: parthenogenesis occurs in C. coreanus, whereas sexual reproduction is found in C. songi. In the present study, the complete mitogenomes of C. coreanus and C. songi were sequenced to compare their mitogenome structure, analyze relationships within the Microcoryphia, and assess adaptive evolution. The length of the mitogenomes of C. coreanus and C. songi were 15,578 bp and 15,570 bp, respectively, and the gene orders were those of typical insects. A long hairpin structure was found between the ND1 and 16S rRNA genes of both species that seem to be characteristic of Machilinae and Petrobiinae species. Phylogenetic assessment of Coreamachilis was conducted using BI and ML analyses with concatenated nucleotide sequences of the 13 protein-coding genes. The results showed that the monophyly of Machilidae, Machilinae, and Petrobiinae was not supported. The genus Coreamachilis (C. coreanus and C. songi) was a sister clade to Allopsontus helanensis, and then the clade of ((C. coreanus + C. songi) + A. helanensis) was a sister clade to A. baii, which suggests that the monophyly of Allopsontus was not supported. Positive selection analysis of the 13 protein-coding genes failed to reveal any positive selection in C. coreanus or C. songi. The long hairpin structures found in Machilinae and Petrobiinae were highly consistent with the phylogenetic results and could potentially be used as an additional molecular characteristic to further discuss relationships within the Microcoryphia.
Awareness of Rheumatic Heart Disease in Egypt: A National Multicenter Study
Authors: Sayed Ahmed Kamal , Se’eda Hussien , Eltewacy Nael Kamel , El Sherif Loalo’a , Ghalioub Hagar Samy , Sayed Ahmed , Afifi Ahmed M. , Almoallim Hesham S. , Alharbi Sulaiman Ali , Abushouk Abdelrahman I.
Published: September 2021

Background: While the prevalence of rheumatic heart disease (RHD) in Egypt is relatively high, data on the awareness of Egyptians about the cause of RHD are lacking. Methods: Using a pre-tested questionnaire, we performed a multicenter survey of outpatients attending 15 university hospitals across Egypt. Results: A total of 6958 participants were interviewed. Most subjects (81.7%) reported a previous experience of sore throat. Seeking treatment, most patients (69.3%) consulted a medical professional, while the others relied on self/peer medication. Individuals consulting a physician received antibiotics more frequently than those who did not (89.1 vs. 38.7%; OR: 12.4, 95% CI 10.8–14.1). The median RHD knowledge score in our sample was 4 (IQR = 6). While most subjects (56.3%) claimed knowledge of the complications of an untreated sore throat, only a third (34%) were aware of the association between sore throat and RHD. In a multivariate analysis, older age (Mean Difference [MD]: 1.58, 95% CI 1.37–1.79), female gender (MD: 0.89, 95% CI 0.75–1.04), higher education (MD: 1.10, 95% CI 0.90–1.30), and being interviewed outside Cairo (MD: 0.67, 95% CI 0.51–0.82) were significant predictors of knowledge about RHD. Conclusion: The current study showed low levels of awareness on the cause of RHD among Egyptians and highlights a pressing need for interventions to address this public knowledge gap.
Psychiatric History and Overactive Bladder Symptom Severity in Ambulatory Urogynecological Patients
Authors: Rogowski Artur , Krowicka-Wasyl Maria , Chotkowska Ewa , Kluz Tomasz , Wróbel Andrzej , Berent Dominika , Mierzejewski Paweł , Sienkiewicz-Jarosz Halina , Wichniak Adam , Wojnar Marcin , Samochowiec Jerzy , Kilis-Pstrusinska Katarzyna , Bienkowski Przemyslaw
Published: September 2021

Introduction and hypothesis: A link between psychiatric comorbidities and overactive bladder symptomatology has been suggested by preclinical and clinical studies. Given this, we hypothesized that a psychiatric history and current treatment with psychotropic medications could be related to the severity of overactive bladder and incontinence symptoms in patients referred to a tertiary care urogynecological center. Methods: One hundred and twenty-seven female patients diagnosed with an overactive bladder were screened for a lifetime history of psychiatric disorders and the type and number of psychotropic medications currently taken. The overall severity of overactive bladder symptoms was assessed using the Indevus Urgency Severity Scale. The severity and impact of urinary incontinence on the quality of life were quantified with the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form. Urinary incontinence was further quantified with the aid of the Urinary Distress Inventory-6. The patients were screened for stress urinary incontinence using the Stamey Incontinence Score. Results: A psychiatric history, as well as current use of at least two psychotropic medications, was associated with increased severity of overactive bladder symptoms. A history of depression and current treatment with any selective serotonin reuptake inhibitor was associated with increased severity of stress urinary incontinence symptoms. Current treatment with other psychotropic medications, including sedative-hypnotics and drugs with anticholinergic properties was not related to the severity of overactive bladder and incontinence symptoms.
Differential Impact of Cytochrome 2C19 Allelic Variants on Three Different Platelet Function Tests in Clopidogrel-Treated Patients
Authors: Olie Renske H. , Hensgens Rachelle R. K. , Wijnen Petal A. H. M. , Veenstra Leo F. , de Greef Bianca T. A. , Vries Minka J. A. , van der Meijden Paola E. J. , ten Berg Jurriën M. , ten Cate Hugo , Bekers Otto , Henskens Yvonne M. C.
Published: September 2021

On-treatment platelet reactivity in clopidogrel-treated patients can be measured with several platelet function tests (PFTs). However, the agreement between different PFTs is only slight to moderate. Polymorphisms of the CYP2C19 gene have an impact on the metabolization of clopidogrel and, thereby, have an impact on on-treatment platelet reactivity. The aim of the current study is to evaluate the differential effects of the CYP2C19 genotype on three different PFTs. Methods: From a prospective cohort study, we included patients treated with clopidogrel following percutaneous coronary intervention (PCI). One month after PCI, we simultaneously performed three different PFTs; light transmission aggregometry (LTA), VerifyNow P2Y12, and Multiplate. In whole EDTA blood, genotyping of the CYP2C19 polymorphisms was performed. Results: We included 308 patients treated with clopidogrel in combination with aspirin (69.5%) and/or anticoagulants (33.8%) and, based on CYP2C19 genotyping, classified them as either extensive (36.4%), rapid (34.7%), intermediate (26.0%), or poor metabolizers (2.9%). On-treatment platelet reactivity as measured by LTA and VerifyNow is significantly affected by CYP2C19 metabolizer status (p < 0.01); as metabolizer status changes from rapid, via extensive and intermediate, to poor, the mean platelet reactivity increases accordingly (p < 0.01). On the contrary, for Multiplate, no such ordering of metabolizer groups was found (p = 0.10). Conclusions: For VerifyNow and LTA, the on-treatment platelet reactivity in clopidogrel-treated patients correlates well with the underlying CYP2C19 polymorphism. For Multiplate, no major effect of genetic background could be shown, and effects of other (patient-related) variables prevail. Thus, besides differences in test principles and the influence of patient-related factors, the disagreement between PFTs is partly explained by differential effects of the CYP2C19 genotype.
The Incidence of Inflammatory Bowel Disease in the Paediatric Population in the District of Lower Silesia, Poland
Authors: Krzesiek Elzbieta , Kofla-Dlubacz Anna , Akutko Katarzyna , Stawarski Andrzej
Published: September 2021

The incidence of IBD has been rising over the last decades. The trend applies not only to well-developed countries but also to the regions with limited number of cases so far, e.g., Asia or Middle East. Aim: The aim of the study was to determine the incidence of paediatric IBD in the district of Lower Silesia, Poland, between 2016 and 2018. Methods: The number of newly diagnosed IBD per 100,000 children, living in the region, was calculated. The characteristics of the group were established. Results: There were 81 cases of paediatric IBD diagnosed between the 1st of January 2016 and 31st of December 2018. The diagnosis of ulcerative colitis (UC) was made for 42 children. In the same period of time 39 cases of Crohn disease (CD) were recognised. The incidences were calculated as 2.57 for UC, and 2.38 for CD. The total incidence of IBD between 2016 and 2018 was 4.96/100,000/year which is rise in the last 20 years. Conclusion: An increase in incidence of IBD in the district of Lower Silesia has been observed.
Fatigue in Systemic Lupus Erythematosus: An Update on Its Impact, Determinants and Therapeutic Management
Authors: Kawka Lou , Schlencker Aurélien , Mertz Philippe , Martin Thierry , Arnaud Laurent
Published: September 2021

Fatigue is a complex and multifactorial phenomenon which is often neglected by clinicians. The aim of this review was to analyze the impact, determinants and management of fatigue in patients with Systemic Lupus Erythematosus (SLE). Fatigue is one of the most prevalent symptoms in SLE, reported by 67% to 90% of patients. It is also described as the most bothersome symptom, considering that it may impair key aspects of health-related quality of life, while also leading to employment disability. It is a multifactorial phenomenon involving psychological factors, pain, lifestyle factors such as reduced physical activity, whereas the contribution of disease activity remains controversial. The management of fatigue in patients with SLE should rely upon a person-centered approach, with targeted interventions. Some pharmacological treatments used to control disease activity have demonstrated beneficial effects upon fatigue and non-pharmacological therapies such as psychological interventions, pain reduction and lifestyle changes, and each of these should be incorporated into fatigue management in SLE.
Neutrophil-to-Lymphocyte, Platelet-to-Lymphocyte Ratios, and Systemic Immune-Inflammation Index as Potential Biomarkers of Chronic Inflammation in Patients with Newly Diagnosed Acromegaly: A Single-Centre Study
Authors: Szydełko Joanna , Szydełko-Gorzkowicz Magdalena , Matyjaszek-Matuszek Beata
Published: September 2021

Acromegaly is a rare disease caused by overproduction of growth hormone (GH) by a pituitary adenoma, and consequently increased insulin-like growth factor 1 (IGF-1) concentration. The GH/IGF-1 axis and immune cells interactions are hypothesized to be involved in subclinical inflammation. This retrospective study aimed to investigate the differences in neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) ratios, and systemic immune-inflammation index (SII) in GH-secreting adenomas compared with non-functioning pituitary adenomas (NFPAs) concerning clinical and radiological findings. After evaluation of 665 patients with pituitary tumors, 62 individuals with newly diagnosed acromegaly and 134 with NFPAs were enrolled in the analysis. The control group consisted of 120 healthy individuals. Fifty-eight patients with acromegaly were re-evaluated after medical or surgical therapies. NLR, PLR, SII values, and neutrophil count were significantly higher (p ≤ 0.001), whereas lymphocyte count was lower in acromegaly than in NFPAs (p = 0.001). No significant differences between NFPAs and controls were observed in analyzed ratios. Higher preoperative NLR, PLR, SII values were found in patients who failed to achieve a cure with surgery (p < 0.05). Although NLR, PLR, and SII values were significantly higher in acromegaly, these indices cannot be used to discriminate GH-secreting pituitary tumors from NFPAs. Treatment of acromegaly decreased the value of NLR and SII, but it requires further studies to consolidate the real clinical role of these inflammation-related ratios.
Model of Care for Microelimination of Hepatitis C Virus Infection among People Who Inject Drugs
Authors: Foschi Francesco , Borghi Alberto , Grassi Alberto , Lanzi Arianna , Speranza Elvira , Vignoli Teo , Napoli Lucia , Olivoni Deanna , Sanza Michele , Polidori Edoardo , Greco Giovanni , Bassi Paolo , Cristini Francesco , Ballardini Giorgio , Altini Mattia , Conti Fabio ,   on behalf of MITH Group
Published: September 2021

Background: People who inject drugs (PWID) are the largest group at risk for HCV infection. Despite the direct acting antivirals (DAA) advancements, HCV elimination has been hindered by real-life difficulties in PWID. Aims: This study aimed to assess the impact of a multidisciplinary intervention strategy where HCV screening, treatment and follow-up were performed at the same location on efficacy and safety of DAA-therapy in real-life PWID population. Methods: All HCV-infected PWID referred to five specialized outpatient centers for drug addicts (SerDs) in Northern Italy were prospectively enrolled from May 2015 to December 2019. Hepatologists and SerDs healthcare workers collaborated together in the management of PWID inside the SerDs. Sustained virologic response (SVR), safety of treatment, proportion of patients lost to follow-up and reinfection rate were evaluated. Results: A total of 358 PWID started antiviral treatment. About 50% of patients had advanced fibrosis/cirrhosis, 69% received opioid substitution treatment, and 20.7% self-reported recent injecting use. SVR was achieved in 338 (94.4%) patients. Two patients died during treatment; one prematurely discontinued, resulting in a non-responder; twelve were lost during treatment/follow-up; and five relapsed. No serious adverse events were reported. SVR was lower in recent PWID than in former ones (89.2% vs. 95.8%; p = 0.028). Seven reinfections were detected, equating to an incidence of 1.25/100 person-years. Reinfection was associated with recent drug use (OR 11.07, 95%CI 2.10–58.38; p = 0.005). Conclusion: Our embedded treatment model could be appropriate to increase the linkage to care of HCV-infected PWID. In this setting, DAA regimens are well tolerated and highly effective, achieving a lower rate of reinfection.