bluuebunny/crossref_metadata_2025 huggingface dataset:
Food Waste Biorefinery: Pathway towards Circular Bioeconomy
Authors: Tsegaye Bahiru , Jaiswal Swarna , Jaiswal Amit K.
Published: May 2021

Food waste biorefineries for the production of biofuels, platform chemicals and other bio-based materials can significantly reduce a huge environmental burden and provide sustainable resources for the production of chemicals and materials. This will significantly contribute to the transition of the linear based economy to a more circular economy. A variety of chemicals, biofuels and materials can be produced from food waste by the integrated biorefinery approach. This enhances the bioeconomy and helps toward the design of more green, ecofriendly, and sustainable methods of material productions that contribute to sustainable development goals. The waste biorefinery is a tool to achieve a value-added product that can provide a better utilization of materials and resources while minimizing and/or eliminating environmental impacts. Recently, food waste biorefineries have gained momentum for the production of biofuels, chemicals, and bio-based materials due to the shifting of regulations and policies towards sustainable development. This review attempts to explore the state of the art of food waste biorefinery and the products associated with it.
Choice Drivers for Quality-Labelled Food: A Cross-Cultural Comparison on PDO Cheese
Authors: Menozzi Davide , Giraud Georges , Saïdi Monia , Yeh Ching-Hua
Published: May 2021

This study aims at examining the consumers’ preferences and drivers affecting the choice of quality-labelled food products, i.e., protected designation of origin (PDO) labelled cheese. We applied the theory of planned behaviour (TPB) to analyse the purchase of Parmigiano Reggiano PDO and Comté PDO hard cheeses in Italy and France, respectively. A cross-sectional sample of 808 consumers (400 French and 408 Italian) completed a questionnaire. Structural equation modelling (SEM) indicated perceived behavioural control (PBC) and attitude to be significant predictors of intention to purchase PDO-labelled cheese in France and Italy. Subjective and moral norms affected intention in France. Intention significantly influenced the hard cheese purchase behaviour. The results confirm that the TPB model predicted the self-reported measure of behaviour more than the observed one, measured with a discrete choice experiment, in both countries. The TPB interrelationships varied between countries, suggesting that food systems operators and public authorities should carefully target their intervention to stimulate the demand of PDO-labelled products.
Clinical and Genetic Characteristics of Korean Congenital Stationary Night Blindness Patients
Authors: Kim Hyeong-Min , Joo Kwangsic , Han Jinu , Woo Se-Joon
Published: May 2021

In this study, we investigated the clinical and genetic characteristics of 19 Korean patients with congenital stationary night blindness (CSNB) at two tertiary hospitals. Clinical evaluations, including fundus photography, spectral-domain optical coherence tomography, and electroretinography, were performed. Genetic analyses were conducted using targeted panel sequencing or whole exome sequencing. The median age was 5 (3–21) years at the initial examination, 2 (1–8) years at symptom onset, and 11 (5–28) years during the final visit. Genetic mutations were identified as CNGB1 and GNAT1 for the Riggs type (n = 2), TRPM1 and NYX for the complete type (n = 3), and CACNA1F (n = 14) for the incomplete type. Ten novel variants were identified, and best-corrected visual acuity (BCVA) and spherical equivalents (SE) were related to each type of CSNB. The Riggs and TRPM1 complete types presented mild myopia and good BCVA without strabismus and nystagmus, whereas the NYX complete and incomplete types showed mixed SE and poor BCVA with strabismus and nystagmus. This is the first case series of Korean patients with CSNB, and further studies with a larger number of subjects should be conducted to correlate the clinical and genetic aspects of CSNB.
Selection and Verification of Appropriate Reference Genes for Expression Normalization in Cryptomeria fortunei under Abiotic Stress and Hormone Treatments
Authors: Zhang Yingting , Zhu Lijuan , Xue Jinyu , Yang Junjie , Hu Hailiang , Cui Jiebing , Xu Jin
Published: May 2021

Cryptomeria fortunei has become one of the main timber afforestation species in subtropical high-altitude areas of China due to its fast growth, good material quality, and strong adaptability, showing broad application prospects. Quantitative real-time PCR (qRT-PCR) is the most accurate and widely used gene expression evaluation technique, and selecting appropriate reference genes (RGs) is essential for normalizing qRT-PCR results. However, suitable RGs for gene expression normalization in C. fortunei have not been reported. Here, we tested the expression stability for 12 RGs in C. fortunei under various experimental conditions (simulated abiotic stresses (cold, heat, drought, and salinity) and hormone treatments (methyl jasmonate, abscisic acid, salicylic acid, and gibberellin) and in different tissues (stems, tender needles, needles, cones, and seeds) using four algorithms (delta Ct, geNorm, NormFinder, and BestKeeper). Then, geometric mean rankings from these algorithms and the RefFinder program were used to comprehensively evaluate RG stability. The results indicated CYP, actin, UBC, and 18S as good choices for studying C. fortunei gene expression. qRT-PCR analysis of the expression patterns of three target genes (CAT and MAPK1/6) further verified that the selected RGs were suitable for gene expression normalization. This study provides an important basis for C. fortunei gene expression standardization and quantification.
Self-Perceived Physical Activity and Adherence to the Mediterranean Diet in Healthy Adolescents during COVID-19: Findings from the DIMENU Pilot Study
Authors: Galluccio Angelo , Caparello Giovanna , Avolio Ennio , Manes Emanuele , Ferraro Simona , Giordano Cinzia , Sisci Diego , Bonofiglio Daniela
Published: May 2021

The global pandemic coronavirus disease (COVID-19) resulted in restrictions which forced adolescents to stay at home and influenced their food habits and lifestyles with potential negative health impact. This study aims to investigate the self-reported physical activity (PA) and eating habits related to the consumption of Mediterranean foods in a sample of adolescents during the COVID-19 lockdown enrolled into the DIMENU study. A web survey was launched for 91 adolescents (aged 15–17 years) to assess their adherence to the Mediterranean Diet using the KIDMED test and lifestyle habits using a questionnaire designed following recommendations by Italian National Institute of Health (ISS score). Our results indicate that most of the sample declared no changes in eating habits and PA without sex differences. After dividing the sample into active and sedentary groups based on the self-perceived PA, we found that KIDMED and ISS scores were significantly higher (p = 0.0028 and p = 0.0001, respectively) in active adolescents. Moreover, KIDMED was positively correlated with ISS only in active adolescents (r = 0.311, p = 0.0185). In conclusion, our data underline the impact of the PA on the Mediterranean diet adherence in adolescents during the lockdown, suggesting the usefulness of promoting wellness programs directed towards inactive individuals to increase their awareness on the importance of healthy lifestyles.
Single Nucleotide Polymorphism rs17173608 in the Chemerin Encoding Gene: Is It a Predictor of Insulin Resistance and Severity of Coronary Artery Disease in Non-Obese Type 2 Diabetes?
Authors: Perumalsamy Sangeetha , Wan Ahmad Wan Azman , Zaman Huri Hasniza
Published: May 2021

(1) Background: Chemerin, or the RARRES2 (Retinoic Acid Receptor Responder 2) gene, is found to be associated with an increased incidence of insulin resistance, endothelial dysfunction, type 2 diabetes (T2D), and coronary artery disease (CAD). This study investigates associations of RARRES2rs17173608 with insulin resistance and the severity of CAD in non-obese T2D patients in relation to the clinical and genetic factors. (2) Methods: A total of 300 patients with T2D and CAD were recruited in this study. The associations of insulin resistance and the severity of CAD with RARRES2rs17173608 and clinical factors were assessed. The genotyping procedures were performed using the TaqMan method. The significant associations (p ≤ 0.05) from preliminary tests were employed to carry out the secondary analysis. (3) Results: RARRES2rs17173608 (TT, TG, and GG polymorphisms in the preliminary analysis; TG and GG polymorphisms in a secondary analysis) was associated with insulin resistance and the severity of CAD in both the preliminary and secondary analysis (all p-values were < 0.05). Additionally, in the secondary analysis, FPG and ACEI were also associated with insulin resistance and the severity of CAD (all p-values were < 0.05). (4) Conclusion: From the preliminary findings, rs17173608 is a significant predictor of insulin resistance and the severity of CAD.
A Catalogue of Tropical Cyclone Induced Instantaneous Peak Flows Recorded in Puerto Rico and a Comparison with the World’s Maxima
Authors: Ramos-Scharrón Carlos E. , Garnett Caroline T. , Arima Eugenio Y.
Published: May 2021

Peak streamflow rates from the Insular Caribbean have received limited attention in worldwide catalogues in spite of their potential for exceptionality given many of the islands’ steep topographic relief and proneness to high rainfall rates associated with tropical cyclones. This study compiled 1922 area-normalized peak streamflow rates recorded during tropical cyclones in Puerto Rico from 1899 to 2020. The results show that the highest peak flow values recorded on the island were within the range of the world’s maxima for watersheds with drainage areas from 10 to 619 km2. Although higher tropical cyclone rainfall and streamflow rates were observed on average for the central–eastern half of Puerto Rico, the highest of all cyclone-related peaks occurred throughout the entire island and were caused by tropical depressions, tropical storms, or hurricanes. Improving our understanding of instantaneous peak flow rates in Puerto Rico and other islands of the Caribbean is locally important due to their significance in terms of flooding extent and its associated impacts, but also because these could serve as indicators of the implications of a changing climate on tropical cyclone intensity and the associated hydrologic response.
Angiogenic Properties of Placenta-Derived Extracellular Vesicles in Normal Pregnancy and in Preeclampsia
Authors: Gebara Natalia , Correia Yolanda , Wang Keqing , Bussolati Benedetta
Published: May 2021

Angiogenesis is one of the main processes that coordinate the biological events leading to a successful pregnancy, and its imbalance characterizes several pregnancy-related diseases, including preeclampsia. Intracellular interactions via extracellular vesicles (EVs) contribute to pregnancy’s physiology and pathophysiology, and to the fetal–maternal interaction. The present review outlines the implications of EV-mediated crosstalk in the angiogenic process in healthy pregnancy and its dysregulation in preeclampsia. In particular, the effect of EVs derived from gestational tissues in pro and anti-angiogenic processes in the physiological and pathological setting is described. Moreover, the application of EVs from placental stem cells in the clinical setting is reported.
Targeting Lactate Dehydrogenase A with Catechin Resensitizes SNU620/5FU Gastric Cancer Cells to 5-Fluorouracil
Authors: Han Jung Ho , Kim MinJeong , Kim Hyeon Jin , Jang Se Bok , Bae Sung-Jin , Lee In-Kyu , Ryu Dongryeol , Ha Ki-Tae
Published: May 2021

Resistance to anticancer therapeutics occurs in virtually every type of cancer and becomes a major difficulty in cancer treatment. Although 5-fluorouracil (5FU) is the first-line choice of anticancer therapy for gastric cancer, its effectiveness is limited owing to drug resistance. Recently, altered cancer metabolism, including the Warburg effect, a preference for glycolysis rather than oxidative phosphorylation for energy production, has been accepted as a pivotal mechanism regulating resistance to chemotherapy. Thus, we investigated the detailed mechanism and possible usefulness of antiglycolytic agents in ameliorating 5FU resistance using established gastric cancer cell lines, SNU620 and SNU620/5FU. SNU620/5FU, a gastric cancer cell harboring resistance to 5FU, showed much higher lactate production and expression of glycolysis-related enzymes, such as lactate dehydrogenase A (LDHA), than those of the parent SNU620 cells. To limit glycolysis, we examined catechin and its derivatives, which are known anti-inflammatory and anticancer natural products because epigallocatechin gallate has been previously reported as a suppressor of LDHA expression. Catechin, the simplest compound among them, had the highest inhibitory effect on lactate production and LDHA activity. In addition, the combination of 5FU and catechin showed additional cytotoxicity and induced reactive oxygen species (ROS)-mediated apoptosis in SNU620/5FU cells. Thus, based on these results, we suggest catechin as a candidate for the development of a novel adjuvant drug that reduces chemoresistance to 5FU by restricting LDHA.
An Analytical Review of the Structural Features of Pentatricopeptide Repeats: Strategic Amino Acids, Repeat Arrangements and Superhelical Architecture
Authors: Barik Sailen
Published: May 2021

Tricopeptide repeats are common in natural proteins, and are exemplified by 34- and 35-residue repeats, known respectively as tetratricopeptide repeats (TPRs) and pentatricopeptide repeats (PPRs). In both classes, each repeat unit forms an antiparallel bihelical structure, so that multiple such units in a polypeptide are arranged in a parallel fashion. The primary structures of the motifs are nonidentical, but amino acids of similar properties occur in strategic positions. The focus of the present work was on PPR, but TPR, its better-studied cousin, is often included for comparison. The analyses revealed that critical amino acids, namely Gly, Pro, Ala and Trp, were placed at distinct locations in the higher order structure of PPR domains. While most TPRs occur in repeats of three, the PPRs exhibited a much greater diversity in repeat numbers, from 1 to 30 or more, separated by spacers of various sequences and lengths. Studies of PPR strings in proteins showed that the majority of PPR units are single, and that the longer tandems (i.e., without space in between) occurred in decreasing order. The multi-PPR domains also formed superhelical vortices, likely governed by interhelical angles rather than the spacers. These findings should be useful in designing and understanding the PPR domains.
Soluble Epoxide Hydrolase Blockade after Stroke Onset Protects Normal but Not Diabetic Mice
Authors: Davis Catherine M. , Zhang Wenri H. , Allen Elyse M. , Bah Thierno M. , Shangraw Robert E. , Alkayed Nabil J.
Published: May 2021

Soluble epoxide hydrolase (sEH) is abundant in the brain, is upregulated in type 2 diabetes mellitus (DM2), and is possible mediator of ischemic injury via the breakdown of neuroprotective epoxyeicosatrienoic acids (EETs). Prophylactic, pre-ischemic sEH blockade with 4-[[trans-4-[[(tricyclo[3.3.1.13,7]dec-1-ylamino)carbonyl]amino]cyclohexyl]oxy]-benzoic acid (tAUCB) reduces stroke-induced infarct in normal and diabetic mice, with larger neuroprotection in DM2. The present study tested whether benefit occurs in normal and DM2 mice if tAUCB is administered after stroke onset. We performed 60 min middle cerebral artery occlusion in young adult male C57BL mice divided into four groups: normal or DM2, with t-AUCB 2 mg/kg or vehicle 30 min before reperfusion. Endpoints were (1) cerebral blood flow (CBF) by laser Doppler, and (2) brain infarct at 24 h. In nondiabetic mice, t-AUCB reduced infarct size by 30% compared to vehicle-treated mice in the cortex (31.4 ± 4 vs. 43.8 ± 3 (SEM)%, respectively) and 26% in the whole hemisphere (26.3 ± 3 vs. 35.2 ± 2%, both p < 0.05). In contrast, in DM2 mice, tAUCB failed to ameliorate either cortical or hemispheric injury. No differences were seen in CBF. We conclude that tAUCB administered after ischemic stroke onset exerts brain protection in nondiabetic but not DM2 mice, that the neuroprotection appears independent of changes in gross CBF, and that DM2-induced hyperglycemia abolishes t-AUCB-mediated neuroprotection after stroke onset.
Antimicrobial Polymer−Based Assemblies: A Review
Authors: Carmona-Ribeiro Ana Maria , Araújo Péricles Marques
Published: May 2021

An antimicrobial supramolecular assembly (ASA) is conspicuous in biomedical applications. Among the alternatives to overcome microbial resistance to antibiotics and drugs, ASAs, including antimicrobial peptides (AMPs) and polymers (APs), provide formulations with optimal antimicrobial activity and acceptable toxicity. AMPs and APs have been delivered by a variety of carriers such as nanoparticles, coatings, multilayers, hydrogels, liposomes, nanodisks, lyotropic lipid phases, nanostructured lipid carriers, etc. They have similar mechanisms of action involving adsorption to the cell wall, penetration across the cell membrane, and microbe lysis. APs, however, offer the advantage of cheap synthetic procedures, chemical stability, and improved adsorption (due to multipoint attachment to microbes), as compared to the expensive synthetic routes, poor yield, and subpar in vivo stability seen in AMPs. We review recent advances in polymer−based antimicrobial assemblies involving AMPs and APs.
Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation
Authors: Kasatkina Ludmila A. , Rittchen Sonja , Sturm Eva M.
Published: May 2021

Endocannabinoids (eCBs) are lipid-based retrograde messengers with a relatively short half-life that are produced endogenously and, upon binding to the primary cannabinoid receptors CB1/2, mediate multiple mechanisms of intercellular communication within the body. Endocannabinoid signaling is implicated in brain development, memory formation, learning, mood, anxiety, depression, feeding behavior, analgesia, and drug addiction. It is now recognized that the endocannabinoid system mediates not only neuronal communications but also governs the crosstalk between neurons, glia, and immune cells, and thus represents an important player within the neuroimmune interface. Generation of primary endocannabinoids is accompanied by the production of their congeners, the N-acylethanolamines (NAEs), which together with N-acylneurotransmitters, lipoamino acids and primary fatty acid amides comprise expanded endocannabinoid/endovanilloid signaling systems. Most of these compounds do not bind CB1/2, but signal via several other pathways involving the transient receptor potential cation channel subfamily V member 1 (TRPV1), peroxisome proliferator-activated receptor (PPAR)-α and non-cannabinoid G-protein coupled receptors (GPRs) to mediate anti-inflammatory, immunomodulatory and neuroprotective activities. In vivo generation of the cannabinoid compounds is triggered by physiological and pathological stimuli and, specifically in the brain, mediates fine regulation of synaptic strength, neuroprotection, and resolution of neuroinflammation. Here, we review the role of the endocannabinoid system in intrinsic neuroprotective mechanisms and its therapeutic potential for the treatment of neuroinflammation and associated synaptopathy.
The Function of KDEL Receptors as UPR Genes in Disease
Authors: Wires Emily S. , Trychta Kathleen A. , Kennedy Lacey M. , Harvey Brandon K.
Published: May 2021

The KDEL receptor retrieval pathway is essential for maintaining resident proteins in the endoplasmic reticulum (ER) lumen. ER resident proteins serve a variety of functions, including protein folding and maturation. Perturbations to the lumenal ER microenvironment, such as calcium depletion, can cause protein misfolding and activation of the unfolded protein response (UPR). Additionally, ER resident proteins are secreted from the cell by overwhelming the KDEL receptor retrieval pathway. Recent data show that KDEL receptors are also activated during the UPR through the IRE1/XBP1 signaling pathway as an adaptive response to cellular stress set forth to reduce the loss of ER resident proteins. This review will discuss the emerging connection between UPR activation and KDEL receptors as it pertains to ER proteostasis and disease states.
Cell Proliferation in the Piriform Cortex of Rats with Motor Cortex Ablation Treated with Growth Hormone and Rehabilitation
Authors: Heredia Margarita , Sánchez-Robledo Virginia , Gómez Inés , Criado José María , Fuente Antonio de la , Devesa Jesús , Devesa Pablo , Riolobos Adelaida Sánchez
Published: May 2021

Traumatic brain injury represents one of the main health problems in developed countries. Growth hormone (GH) and rehabilitation have been claimed to significantly contribute to the recovery of lost motor function after acquired brain injury, but the mechanisms by which this occurs are not well understood. In this work, we have investigated cell proliferation in the piriform cortex (PC) of adult rats with ablation of the frontal motor cortex treated with GH and rehabilitation, in order to evaluate if this region of the brain, related to the sense of smell, could be involved in benefits of GH treatment. Male rats were either ablated the frontal motor cortex in the dominant hemisphere or sham-operated and treated with GH or vehicle at 35 days post-injury (dpi) for five days. At 36 dpi, all rats received daily injections of bromodeoxyuridine (BrdU) for four days. We assessed motor function through the paw-reaching-for-food task. GH treatment and rehabilitation at 35 dpi significantly improved the motor deficit caused by the injury and promoted an increase of cell proliferation in the PC ipsilateral to the injury, which could be involved in the improvement observed. Cortical ablation promoted a greater number of BrdU+ cells in the piriform cortex that was maintained long-term, which could be involved in the compensatory mechanisms of the brain after injury.
Design, Radiosynthesis and Preliminary Biological Evaluation in Mice of a Brain-Penetrant 18F-Labelled σ2 Receptor Ligand
Authors: Moldovan Rareş-Petru , Gündel Daniel , Teodoro Rodrigo , Ludwig Friedrich-Alexander , Fischer Steffen , Toussaint Magali , Schepmann Dirk , Wünsch Bernhard , Brust Peter , Deuther-Conrad Winnie
Published: May 2021

The σ2 receptor (transmembrane protein 97), which is involved in cholesterol homeostasis, is of high relevance for neoplastic processes. The upregulated expression of σ2 receptors in cancer cells and tissue in combination with the antiproliferative potency of σ2 receptor ligands motivates the research in the field of σ2 receptors for the diagnosis and therapy of different types of cancer. Starting from the well described 2-(4-(1H-indol-1-yl)butyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline class of compounds, we synthesized a novel series of fluorinated derivatives bearing the F-atom at the aromatic indole/azaindole subunit. RM273 (2-[4-(6-fluoro-1H-pyrrolo[2,3-b]pyridin-1-yl)butyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline) was selected for labelling with 18F and evaluation regarding detection of σ2 receptors in the brain by positron emission tomography. Initial metabolism and biodistribution studies of [18F]RM273 in healthy mice revealed promising penetration of the radioligand into the brain. Preliminary in vitro autoradiography on brain cryosections of an orthotopic rat glioblastoma model proved the potential of the radioligand to detect the upregulation of σ2 receptors in glioblastoma cells compared to healthy brain tissue. The results indicate that the herein developed σ2 receptor ligand [18F]RM273 has potential to assess by non-invasive molecular imaging the correlation between the availability of σ2 receptors and properties of brain tumors such as tumor proliferation or resistance towards particular therapies.
Two Cases of Pancytopenia with Coombs-Negative Hemolytic Anemia after Chimeric Antigen Receptor T-Cell Therapy
Authors: Kiem Dominik , Leisch Michael , Neureiter Daniel , Haslauer Theresa , Egle Alexander , Melchardt Thomas , Topp Max S. , Greil Richard
Published: May 2021

Background: Chimeric antigen receptor (CAR) T-cells are changing the therapeutic landscape of hematologic malignancies. Severe side effects include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), but prolonged cytopenia has also been reported. The underlying mechanism for prolonged cytopenia is poorly understood so far. Cases: Severe pancytopenia with grade 2-3 anemia was marked 2–3 months after treatment. Laboratory evaluation revealed undetectable levels of haptoglobin with increased reticulocyte counts. Coomb’s tests were negative, no schistocytes were detected on blood smear, and infectious causes were ruled out. Increased erythropoiesis without lymphoma infiltration was noted on bone marrow biopsy. A spontaneous increase in haptoglobin and hemoglobin levels was observed after several weeks. For one patient, peripheral CAR-T levels were monitored over time. We observed a decline at the same time as hemoglobin levels began to rise, implying a potential causality. Conclusion: To our knowledge, we describe the first two cases of Coombs-negative hemolytic anemia after CAR-T treatment for B-cell lymphoma. We encourage routine monitoring for hemolytic anemia after CAR-T treatment and also encourage further investigations on the underlying mechanism.
Lemur Tyrosine Kinases and Prostate Cancer: A Literature Review
Authors: Ferrari Elena , Naponelli Valeria , Bettuzzi Saverio
Published: May 2021

The members of the Lemur Tyrosine Kinases (LMTK1-3) subfamily constitute a group of three membrane-anchored kinases. They are known to influence a wide variety of key cellular events, often affecting cell proliferation and apoptosis. They have been discovered to be involved in cancer, in that they impact various signalling pathways that influence cell proliferation, migration, and invasiveness. Notably, in the context of genome-wide association studies, one member of the LMTK family has been identified as a candidate gene which could contribute to the development of prostate cancer. In this review, of published literature, we present evidence on the role of LMTKs in human prostate cancer and model systems, focusing on the complex network of interacting partners involved in signalling cascades that are frequently activated in prostate cancer malignancy. We speculate that the modulators of LMTK enzyme expression and activity would be of high clinical relevance for the design of innovative prostate cancer treatment.
Involvement of Chaperone Sigma1R in the Anxiolytic Effect of Fabomotizole
Authors: Voronin Mikhail V. , Vakhitova Yulia V. , Tsypysheva Inna P. , Tsypyshev Dmitry O. , Rybina Inna V. , Kurbanov Rustam D. , Abramova Elena V. , Seredenin Sergei B.
Published: May 2021

Sigma-1 receptor (chaperone Sigma1R) is an intracellular protein with chaperone functions, which is expressed in various organs, including the brain. Sigma1R participates in the regulation of physiological mechanisms of anxiety (Su, T. P. et al., 2016) and reactions to emotional stress (Hayashi, T., 2015). In 2006, fabomotizole (ethoxy-2-[2-(morpholino)-ethylthio]benzimidazole dihydrochloride) was registered in Russia as an anxiolytic (Seredenin S. and Voronin M., 2009). The molecular targets of fabomotizole are Sigma1R, NRH: quinone reductase 2 (NQO2), and monoamine oxidase A (MAO-A) (Seredenin S. and Voronin M., 2009). The current study aimed to clarify the dependence of fabomotizole anxiolytic action on its interaction with Sigma1R and perform a docking analysis of fabomotizole interaction with Sigma1R. An elevated plus maze (EPM) test revealed that the anxiolytic-like effect of fabomotizole (2.5 mg/kg i.p.) administered to male BALB/c mice 30 min prior EPM exposition was blocked by Sigma1R antagonists BD-1047 (1.0 mg/kg i.p.) and NE-100 (1.0 mg/kg i.p.) pretreatment. Results of initial in silico study showed that fabomotizole locates in the active center of Sigma1R, reproducing the interactions with the site’s amino acids common for established Sigma1R ligands, with the ΔGbind value closer to that of agonist (+)-pentazocine in the 6DK1 binding site.
miRNAs and Genes Involved in the Interplay between Ocular Hypertension and Primary Open-Angle Glaucoma. Oxidative Stress, Inflammation, and Apoptosis Networks
Authors: Raga-Cervera Jorge , Bolarin Jose M. , Millan Jose M. , Garcia-Medina Jose J. , Pedrola Laia , Abellán-Abenza Javier , Valero-Vello Mar , Sanz-González Silvia M. , O’Connor José E. , Galarreta-Mira David , Bendala-Tufanisco Elena , Mayordomo-Febrer Aloma , Pinazo-Durán Maria D. , Zanón-Moreno Vicente
Published: May 2021

Glaucoma has no cure and is a sight-threatening neurodegenerative disease affecting more than 100 million people worldwide, with primary open angle glaucoma (POAG) being the most globally prevalent glaucoma clinical type. Regulation of gene expression and gene networks, and its multifactorial pathways involved in glaucoma disease are landmarks for ophthalmic research. MicroRNAs (miRNAs/miRs) are small endogenous non-coding, single-stranded RNA molecules (18–22 nucleotides) that regulate gene expression. An analytical, observational, case-control study was performed in 42 patients of both sexes, aged 50 to 80 years, which were classified according to: (1) suffering from ocular hypertension (OHT) but no glaucomatous neurodegeneration (ND) such as the OHT group, or (2) have been diagnosed of POAG such as the POAG group. Participants were interviewed for obtaining sociodemographic and personal/familial records, clinically examined, and their tear samples were collected and frozen at 80 °C until processing for molecular-genetic assays. Tear RNA extraction, libraries construction, and next generation sequencing were performed. Here, we demonstrated, for the first time, the differential expression profiling of eight miRNAs when comparing tears from the OHT versus the POAG groups: the miR-26b-5p, miR-152-3p, miR-30e-5p, miR-125b-2-5p, miR-224-5p, miR-151a-3p, miR-1307-3p, and the miR-27a-3p. Gene information was set up from the DIANA-TarBase v7, DIANA-microT-CDS, and TargetScan v7.1 databases. To build a network of metabolic pathways, only genes appearing in at least four of the following databases: DisGeNet, GeneDistiller, MalaCards, OMIM PCAN, UniProt, and GO were considered. We propose miRNAs and their target genes/signaling pathways as candidates for a better understanding of the molecular-genetic bases of glaucoma and, in this way, to gain knowledge to achieve optimal diagnosis strategies for properly identifying HTO at higher risk of glaucoma ND. Further research is needed to validate these miRNAs to discern the potential role as biomarkers involved in oxidative stress, immune response, and apoptosis for the diagnosis and/or prognosis of OHT and the prevention of glaucoma ND.
Cardiovascular Implications of Sleep Bruxism—A Systematic Review with Narrative Summary and Future Perspectives
Authors: Michalek-Zrabkowska Monika , Martynowicz Helena , Wieckiewicz Mieszko , Smardz Joanna , Poreba Rafal , Mazur Grzegorz
Published: May 2021

Sleep bruxism is a common sleep-related behavior characterized as repetitive masticatory muscle activity. Genetic vulnerability to stress and anxiety is considered a basal component in the pathogenesis of bruxism events. Dysfunction of the autonomic nervous system related with an arousal during sleep is considered an underlying cause of the cardiovascular implications of sleep bruxism. Increased cardiovascular risk was previously linked with sleep conditions: for example, obstructive sleep apnea and insomnia, and sleep bruxism. The aim of present systematic review was to evaluate the current arguments on the relationship between sleep bruxism and cardiovascular diseases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We have reviewed the Embase, PubMed (Medline) and Scopus databases to identify applicable articles (1994–2021). A total of 127 records in English language were identified, then after screening and exclusion of nonrelevant records, 19 full-text articles were evaluated. Finally, we included 12 studies for synthesis. Due to the heterogeneity of the compared studies, only a qualitative comparison and narrative summary were performed. In the majority of studies, increased sympathetic activity was successfully established to escalate heart rate variability, the inflammatory process, oxidative stress, endothelial remodeling and hormonal disturbances, leading to hypertension and other cardiovascular complications.
Application of a Lifestyle-Based Score to Predict Cardiovascular Risk in African Americans: The Jackson Heart Study
Authors: Sotos-Prieto Mercedes , Zhao Songzhu , Kline David , Brock Guy , Gooding Holly , Mattei Josiemer , Rodriguez-Artalejo Fernando , Min Yuan-I , Rimm Eric B. , Tucker Katherine L. , Joseph Joshua J.
Published: May 2021

Cardiovascular disease (CVD) primordial prevention tools applicable to diverse populations are scarce. Our aim was to assess the performance of a lifestyle-based tool to estimate CVD risk in an African American population. The Jackson Heart Study is a prospective cohort including 5306 African American participants in Jackson, Mississippi (2000–2004), with a mean follow up of 12 years. The Healthy Heart Score is a lifestyle-based CVD risk prediction model based on nine components: body mass index (BMI), physical activity, smoking, and a 5-component diet score. Gender-specific beta coefficients from its derivation cohorts were used to assess the performance of the Healthy Heart Score. Model discrimination was assessed using Harrell’s C-Index for survival data and time dependent Area Under the Curve. Model calibration was evaluated through calibration plots. A total of 189 CVD events occurred. The Healthy Heart Score showed high-moderate discrimination for CVD events (C-statistic 0.75 [95% CI, 0.71–0.78]) but with little improvement over the age-only model. Both the age-only and Healthy Heart Score models had better performance in participants without diabetes at baseline and showed good calibration. In African Americans, the Healthy Heart Score does not improve prediction of mid-life CVD events beyond what is obtained by age alone.
An Update on Pituitary Neuroendocrine Tumors Leading to Acromegaly and Gigantism
Authors: Asa Sylvia L. , Ezzat Shereen
Published: May 2021

An excess of growth hormone (GH) results in accelerated growth and in childhood, the clinical manifestation is gigantism. When GH excess has its onset after epiphyseal fusion at puberty, the overgrowth of soft tissue and bone results in acromegaly. Persistent GH excess in gigantism also causes acromegalic features that become evident in the adult years. The causes of GH excess are primarily lesions in the pituitary, which is the main source of GH. In this review, we provide an update on the clinical, radiological and pathologic features of the various types of pituitary neuroendocrine tumors (PitNETs) that produce GH. These tumors are all derived from PIT1-lineage cells. Those composed of somatotrophs may be densely granulated, resembling normal somatotrophs, or sparsely granulated with unusual fibrous bodies. Those composed of mammosomatotrophs also produce prolactin; rare plurihormonal tumors composed of cells that resemble mammosomatotrophs also produce TSH. Some PitNETs are composed of immature PIT1-lineage cells that do not resemble differentiated somatotrophs, mammosomatotrophs, lactotroph or thyrotrophs; these tumors may cause GH excess. An unusual oncocytic PIT1-lineage tumor known as the acidophil stem cell tumor is predominantly a lactotroph tumor but may express GH. Immature PIT1-lineage cells that express variable amounts of hormones alone or in combination can sometimes cause GH excess. Unusual tumors that do not follow normal lineage differentiation may also secrete GH. Exceptional examples of acromegaly/gigantism are caused by sellar tumors composed of hypothalamic GHRH-producing neurons, alone or associated with a sparsely granulated somatotroph tumor. Each of these various tumors has distinct clinical, biochemical and radiological features. Data from careful studies based on morphologic subtyping indicate that morphologic classification has both prognostic and predictive value.
Association between MANBA Gene Variants and Chronic Kidney Disease in a Korean Population
Authors: Kim Hye-Rim , Jin Hyun-Seok , Eom Yong-Bin
Published: May 2021

Chronic kidney disease (CKD), a damaged condition of the kidneys, is a global public health problem that can be caused by diabetes, hypertension, and other disorders. Recently, the MANBA gene was identified in CKD by integrating CKD-related variants and kidney expression quantitative trait loci (eQTL) data. This study evaluated the effects of MANBA gene variants on CKD and kidney function-related traits using a Korean cohort. We also analyzed the association of MANBA gene variants with kidney-related traits such as the estimated glomerular filtration rate (eGFR), and blood urea nitrogen (BUN), creatinine, and uric acid levels using linear regression analysis. As a result, 14 single nucleotide polymorphisms (SNPs) were replicated in CKD (p < 0.05), consistent with previous studies. Among them, rs4496586, which was the most significant for CKD and kidney function-related traits, was associated with a decreased CKD risk in participants with the homozygous minor allele (CC), increased eGFR, and decreased creatinine and uric acid concentrations. Furthermore, the association analysis between the rs4496586 genotype and MANBA gene expression in human tubules and glomeruli showed high MANBA gene expression in the minor allele carriers. In conclusion, this study demonstrated that MANBA gene variants were associated with CKD and kidney function-related traits in a Korean cohort.
Learning from Embryogenesis—A Comparative Expression Analysis in Melanoblast Differentiation and Tumorigenesis Reveals miRNAs Driving Melanoma Development
Authors: Linck-Paulus Lisa , Lämmerhirt Lisa , Völler Daniel , Meyer Katharina , Engelmann Julia C. , Spang Rainer , Eichner Norbert , Meister Gunter , Kuphal Silke , Bosserhoff Anja Katrin
Published: May 2021

Malignant melanoma is one of the most dangerous tumor types due to its high metastasis rates and a steadily increasing incidence. During tumorigenesis, the molecular processes of embryonic development, exemplified by epithelial–mesenchymal transition (EMT), are often reactivated. For melanoma development, the exact molecular differences between melanoblasts, melanocytes, and melanoma cells are not completely understood. In this study, we aimed to identify microRNAs (miRNAs) that promote melanoma tumorigenesis and progression, based on an in vitro model of normal human epidermal melanocyte (NHEM) de-differentiation into melanoblast-like cells (MBrCs). Using miRNA-sequencing and differential expression analysis, we demonstrated in this study that a majority of miRNAs have an almost equal expression level in NHEMs and MBrCs but are significantly differentially regulated in primary tumor- and metastasis-derived melanoma cell lines. Further, a target gene analysis of strongly regulated but functionally unknown miRNAs yielded the implication of those miRNAs in many important cellular pathways driving malignancy. We hypothesize that many of the miRNAs discovered in our study are key drivers of melanoma development as they account for the tumorigenic potential that differentiates melanoma cells from proliferating or migrating embryonic cells.
Analysis of Plantar Pressure Pattern after Metatarsal Head Resection. Can Plantar Pressure Predict Diabetic Foot Reulceration?
Authors: García-Madrid Marta , García-Álvarez Yolanda , Álvaro-Afonso Francisco Javier , García-Morales Esther , Tardáguila-García Aroa , Lázaro-Martínez José Luis
Published: May 2021

To evaluate the metatarsal head that was associated with the highest plantar pressure after metatarsal head resection (MHR) and the relations with reulceration at one year, a prospective was conducted with a total of sixty-five patients with diabetes who suffered from the first MHR and with an inactive ulcer at the moment of inclusion. Peak plantar pressure and pressure time integral were recorded at five specific locations in the forefoot: first, second, third, fourth, and fifth metatarsal heads. The highest value of the four remaining metatarsals was selected. After resection of the first metatarsal head, there is a displacement of the pressure beneath the second metatarsal head (p < 0.001). Following the resection of the minor metatarsal bones, there was a medial displacement of the plantar pressure. In this way, plantar pressure was displaced under the first metatarsal head following resection of the second or third head (p = 0.001) and under the central heads after resection of the fourth or fifth metatarsal head (p < 0.009 and p < 0.001 respectively). During the one-year follow-up, patients who underwent a metatarsal head resection in the first and second metatarsal heads suffered transfer lesion in the location with the highest pressure. Patients who underwent a minor metatarsal head resection (second–fifth metatarsal heads) showed a medial transference of pressure. Additionally, following the resection of the first metatarsal head there was a transference of pressure beneath the second metatarsal head. Increase of pressure was found to be a predictor of reulceration in cases of resection of the first and second metatarsal heads.
Gene Expression as a Guide to the Development of Novel Therapies in Primary Glomerular Diseases
Authors: Garantziotis Panagiotis , Doumas Stavros A. P. , Boletis Ioannis , Frangou Eleni
Published: May 2021

Despite improvements in understanding the pathogenic mechanisms of primary glomerular diseases, therapy still remains nonspecific. We sought to identify novel therapies targeting kidney-intrinsic injury of distinct primary glomerulonephritides through computational systems biology approaches. We defined the unique transcriptional landscape within kidneys from patients with focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), immunoglobulin A nephropathy (IgAN), membranous nephropathy (MN) and thin basement membrane nephropathy (TBMN). Differentially expressed genes were functionally annotated with enrichment analysis, and distinct biological processes and pathways implicated in each primary glomerular disease were uncovered. Finally, we identified novel drugs and small-molecule compounds that may reverse each glomerulonephritis phenotype, suggesting they should be further tested as precise therapy in primary glomerular diseases.
Classification of Monocytes, Promonocytes and Monoblasts Using Deep Neural Network Models: An Area of Unmet Need in Diagnostic Hematopathology
Authors: Osman Mazen , Akkus Zeynettin , Jevremovic Dragan , Nguyen Phuong L. , Roh Dana , Al-Kali Aref , Patnaik Mrinal M. , Nanaa Ahmad , Rizk Samia , Salama Mohamed E.
Published: May 2021

The accurate diagnosis of chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) subtypes with monocytic differentiation relies on the proper identification and quantitation of blast cells and blast-equivalent cells, including promonocytes. This distinction can be quite challenging given the cytomorphologic and immunophenotypic similarities among the monocytic cell precursors. The aim of this study was to assess the performance of convolutional neural networks (CNN) in separating monocytes from their precursors (i.e., promonocytes and monoblasts). We collected digital images of 935 monocytic cells that were blindly reviewed by five experienced morphologists and assigned into three subtypes: monocyte, promonocyte, and blast. The consensus between reviewers was considered as a ground truth reference label for each cell. In order to assess the performance of CNN models, we divided our data into training (70%), validation (10%), and test (20%) datasets, as well as applied fivefold cross validation. The CNN models did not perform well for predicting three monocytic subtypes, but their performance was significantly improved for two subtypes (monocyte vs. promonocytes + blasts). Our findings (1) support the concept that morphologic distinction between monocytic cells of various differentiation level is difficult; (2) suggest that combining blasts and promonocytes into a single category is desirable for improved accuracy; and (3) show that CNN models can reach accuracy comparable to human reviewers (0.78 ± 0.10 vs. 0.86 ± 0.05). As far as we know, this is the first study to separate monocytes from their precursors using CNN.
Accelerated Corneal Endothelial Cell Loss after Phacoemulsification in Patients with Mildly Low Endothelial Cell Density
Authors: Chen Hung-Chi , Huang Chen-Wei , Yeh Lung-Kun , Hsiao Fang-Chi , Hsueh Yi-Jen , Meir Yaa-Jyuhn James , Chen Kuan-Jen , Cheng Chao-Min , Wu Wei-Chi
Published: May 2021

By evaluating preoperative endothelial cell density (ECD), ECD loss after phacoemulsification can be predicted. In this retrospective cross-sectional study, we compared outcomes of phacoemulsification with different levels of preoperative ECD. Three-hundred-and-fifty-three patients aged between 18 and 90 years received phacoemulsification at Chang Gung Memorial Hospital. Age (p = 0.003), preoperative logMAR (p = 0.048), cataract grade (p = 0.005), preoperative ECD (p < 0.001), operation time (p = 0.043), phacoemulsification time (p = 0.001), and phacoemulsification energy (p < 0.001) were significantly associated with postoperative ECD change (%). Patients were divided into three groups according to preoperative ECD levels. Level of ECD, coefficient of variation (CV), cell hexagonality (HEX), central corneal thickness (CCT), visual acuity, underlying diseases, and complications were analyzed. With regard to groups, 29, 71, and 252 patients were respectively allocated into the markedly low (group A; ECD below 1000 cells/mm2), mildly low (group B; ECD between 1000 to 2000 cells/mm2), and normal (group C; ECD above 2000 cells/mm2) ECD level groups. The highest CV (40.8 ± 13.9%; p < 0.001) and lowest HEX (58.4 ± 14.6%; p < 0.001) were found in group A. Significant ECD loss was found in group B (28.9 ± 9.2%) as compared to group A (19.9 ± 5.4%) and C (15.0 ± 12.0%) (p < 0.001). No significant differences were found with regard to changes in CV (p = 0.941), HEX (p = 0.937), CCT (p = 0.346), and logMAR (p = 0.557) among the three groups. In conclusion, preoperative ECD level could be a novel predictive value for postoperative cell loss, which was the most prominent in mildly low ECD level group. Less phacoemulsification energy, earlier surgical intervention, or novel topical medications could be suggested for patients with an ECD range from 1000 to 2000 cells/mm2.