bluuebunny/crossref_metadata_2025 huggingface dataset:
TmSpz-like Plays a Fundamental Role in Response to E. coli but Not S. aureus or C. albican Infection in Tenebrio molitor via Regulation of Antimicrobial Peptide Production
Authors: Jang Ho , Patnaik Bharat , Ali Mohammadie Kojour Maryam , Kim Bo , Bae Young , Park Ki , Lee Yong , Jo Yong , Han Yeon
Published: October 2021

The cystine knot protein Spätzle is a Toll receptor ligand that modulates the intracellular signaling cascade involved in the nuclear factor kappa B (NF-κB)-mediated regulation of antimicrobial peptide (AMP)-encoding genes. Spätzle-mediated activation of the Toll pathway is critical for the innate immune responses of insects against Gram-positive bacteria and fungi. In this study, the open reading frame (ORF) sequence of Spätzle-like from T. molitor (TmSpz-like) identified from the RNA sequencing dataset was cloned and sequenced. The 885-bp TmSpz-like ORF encoded a polypeptide of 294 amino acid residues. TmSpz-like comprised a cystine knot domain with six conserved cysteine residues that formed three disulfide bonds. Additionally, TmSpz-like exhibited the highest amino acid sequence similarity with T. castaneum Spätzle (TcSpz). In the phylogenetic tree, TmSpz-like and TcSpz were located within a single cluster. The expression of TmSpz-like was upregulated in the Malpighian tubules and gut tissues of T. molitor. Additionally, the expression of TmSpz-like in the whole body and gut of the larvae was upregulated at 24 h post-E. coli infection. The results of RNA interference experiments revealed that TmSpz-like is critical for the viability of E. coli-infected T. molitor larvae. Eleven AMP-encoding genes were downregulated in the E. coli-infected TmSpz-like knockdown larvae, which suggested that TmSpz-like positively regulated these genes. Additionally, the NF-κB-encoding genes (TmDorX1, TmDorX2, and TmRelish) were downregulated in the E. coli-infected TmSpz-like knockdown larvae. Thus, TmSpz-like plays a critical role in the regulation of AMP production in T. molitor in response to E. coli infection.
Electroencephalography as a Non-Invasive Biomarker of Alzheimer’s Disease: A Forgotten Candidate to Substitute CSF Molecules?
Authors: Monllor Paloma , Cervera-Ferri Ana , Lloret Maria-Angeles , Esteve Daniel , Lopez Begoña , Leon Jose-Luis , Lloret Ana
Published: October 2021

Biomarkers for disease diagnosis and prognosis are crucial in clinical practice. They should be objective and quantifiable and respond to specific therapeutic interventions. Optimal biomarkers should reflect the underlying process (pathological or not), be reproducible, widely available, and allow measurements repeatedly over time. Ideally, biomarkers should also be non-invasive and cost-effective. This review aims to focus on the usefulness and limitations of electroencephalography (EEG) in the search for Alzheimer’s disease (AD) biomarkers. The main aim of this article is to review the evolution of the most used biomarkers in AD and the need for new peripheral and, ideally, non-invasive biomarkers. The characteristics of the EEG as a possible source for biomarkers will be revised, highlighting its advantages compared to the molecular markers available so far.
Sphingosine-1 Phosphate Lyase Regulates Sensitivity of Pancreatic Beta-Cells to Lipotoxicity
Authors: Tang Yadi , Plötz Thomas , Gräler Markus H. , Gurgul-Convey Ewa
Published: October 2021

Elevated levels of free fatty acids (FFAs) have been related to pancreatic beta-cell failure in type 2 diabetes (T2DM), though the underlying mechanisms are not yet fully understood. FFAs have been shown to dysregulate formation of bioactive sphingolipids, such as ceramides and sphingosine-1 phosphate (S1P) in beta-cells. The aim of this study was to analyze the role of sphingosine-1 phosphate lyase (SPL), a key enzyme of the sphingolipid pathway that catalyzes an irreversible degradation of S1P, in the sensitivity of beta-cells to lipotoxicity. To validate the role of SPL in lipotoxicity, we modulated SPL expression in rat INS1E cells and in human EndoC-βH1 beta-cells. SPL overexpression in INS1E cells (INS1E-SPL), which are characterized by a moderate basal expression level of SPL, resulted in an acceleration of palmitate-mediated cell viability loss, proliferation inhibition and induction of oxidative stress. SPL overexpression affected the mRNA expression of ER stress markers and mitochondrial chaperones. In contrast to control cells, in INS1E-SPL cells no protective effect of oleate was detected. Moreover, Plin2 expression and lipid droplet formation were strongly reduced in OA-treated INS1E-SPL cells. Silencing of SPL in human EndoC-βH1 beta-cells, which are characterized by a significantly higher SPL expression as compared to rodent beta-cells, resulted in prevention of FFA-mediated caspase-3/7 activation. Our findings indicate that an adequate control of S1P degradation by SPL might be crucially involved in the susceptibility of pancreatic beta-cells to lipotoxicity.
Structural Alterations of Antigens at the Material Interface: An Early Decision Toolbox Facilitating Safe-by-Design Nanovaccine Development
Authors: Johnson Litty , Aglas Lorenz , Soh Wai Tuck , Geppert Mark , Hofer Sabine , Hofstätter Norbert , Briza Peter , Ferreira Fatima , Weiss Richard , Brandstetter Hans , Duschl Albert , Himly Martin
Published: October 2021

Nanomaterials have found extensive interest in the development of novel vaccines, as adjuvants and/or carriers in vaccination platforms. Conjugation of protein antigens at the particle surface by non-covalent adsorption is the most widely used approach in licensed particulate vaccines. Hence, it is essential to understand proteins’ structural integrity at the material interface in order to develop safe-by-design nanovaccines. In this study, we utilized two model proteins, the wild-type allergen Bet v 1 and its hypoallergenic fold variant (BM4), to compare SiO2 nanoparticles with Alhydrogel® as particulate systems. A set of biophysical and functional assays including circular dichroism spectroscopy and proteolytic degradation was used to examine the antigens’ structural integrity at the material interface. Conjugation of both biomolecules to the particulate systems decreased their proteolytic stability. However, we observed qualitative and quantitative differences in antigen processing concomitant with differences in their fold stability. These changes further led to an alteration in IgE epitope recognition. Here, we propose a toolbox of biophysical and functional in vitro assays for the suitability assessment of nanomaterials in the early stages of vaccine development. These tools will aid in safe-by-design innovations and allow fine-tuning the properties of nanoparticle candidates to shape a specific immune response.
7,8-Dihydroxiflavone Protects Adult Rat Axotomized Retinal Ganglion Cells through MAPK/ERK and PI3K/AKT Activation
Authors: Galindo-Romero Caridad , Vidal-Villegas Beatriz , Asís-Martínez Javier , Lucas-Ruiz Fernando , Gallego-Ortega Alejandro , Vidal-Sanz Manuel
Published: October 2021

We analyze the 7,8-dihydroxyflavone (DHF)/TrkB signaling activation of two main intracellular pathways, mitogen-activated protein kinase (MAPK)/ERK and phosphatidylinositol 3 kinase (PI3K)/AKT, in the neuroprotection of axotomized retinal ganglion cells (RGCs). Methods: Adult albino Sprague-Dawley rats received left intraorbital optic nerve transection (IONT) and were divided in two groups. One group received daily intraperitoneal DHF (5 mg/kg) and another vehicle (1%DMSO in 0.9%NaCl) from one day before IONT until processing. Additional intact rats were employed as control (n = 4). At 1, 3 or 7 days (d) after IONT, phosphorylated (p)AKT, p-MAPK, and non-phosphorylated AKT and MAPK expression levels were analyzed in the retina by Western blotting (n = 4/group). Radial sections were also immunodetected for the above-mentioned proteins, and for Brn3a and vimentin to identify RGCs and Müller cells (MCs), respectively (n = 3/group). Results: IONT induced increased levels of p-MAPK and MAPK at 3d in DHF- or vehicle-treated retinas and at 7d in DHF-treated retinas. IONT induced a fast decrease in AKT in retinas treated with DHF or vehicle, with higher levels of phosphorylation in DHF-treated retinas at 7d. In intact retinas and vehicle-treated groups, no p-MAPK or MAPK expression in RGCs was observed. In DHF- treated retinas p-MAPK and MAPK were expressed in the ganglion cell layer and in the RGC nuclei 3 and 7d after IONT. AKT was observed in intact and axotomized RGCs, but the signal intensity of p-AKT was stronger in DHF-treated retinas. Finally, MCs expressed higher quantities of both MAPK and AKT at 3d in both DHF- and vehicle-treated retinas, and at 7d the phosphorylation of p-MAPK was higher in DHF-treated groups. Conclusions: Phosphorylation and increased levels of AKT and MAPK through MCs and RGCs in retinas after DHF-treatment may be responsible for the increased and long-lasting RGC protection afforded by DHF after IONT.
GreeningDB: A Database of Host–Pathogen Protein–Protein Interactions and Annotation Features of the Bacteria Causing Huanglongbing HLB Disease
Authors: Loaiza Cristian D. , Duhan Naveen , Kaundal Rakesh
Published: October 2021

The Citrus genus comprises some of the most important and commonly cultivated fruit plants. Within the last decade, citrus greening disease (also known as huanglongbing or HLB) has emerged as the biggest threat for the citrus industry. This disease does not have a cure yet and, thus, many efforts have been made to find a solution to this devastating condition. There are challenges in the generation of high-yield resistant cultivars, in part due to the limited and sparse knowledge about the mechanisms that are used by the Liberibacter bacteria to proliferate the infection in Citrus plants. Here, we present GreeningDB, a database implemented to provide the annotation of Liberibacter proteomes, as well as the host–pathogen comparactomics tool, a novel platform to compare the predicted interactomes of two HLB host–pathogen systems. GreeningDB is built to deliver a user-friendly interface, including network visualization and links to other resources. We hope that by providing these characteristics, GreeningDB can become a central resource to retrieve HLB-related protein annotations, and thus, aid the community that is pursuing the development of molecular-based strategies to mitigate this disease’s impact. The database is freely available at http://bioinfo.usu.edu/GreeningDB/ (accessed on 11 August 2021).
Influence of Serratia marcescens and Rhodococcus rhodnii on the Humoral Immunity of Rhodnius prolixus
Authors: Batista Kate K. S. , Vieira Cecília S. , Figueiredo Marcela B. , Costa-Latgé Samara G. , Azambuja Patrícia , Genta Fernando A. , Castro Daniele P.
Published: October 2021

Chagas disease is a human infectious disease caused by Trypanosoma cruzi and can be transmitted by triatomine vectors, such as Rhodnius prolixus. One limiting factor for T. cruzi development is the composition of the bacterial gut microbiota in the triatomine. Herein, we analyzed the humoral immune responses of R. prolixus nymphs treated with antibiotics and subsequently recolonized with either Serratia marcescens or Rhodococcus rhodnii. The treatment with antibiotics reduced the bacterial load in the digestive tract, and the recolonization with each bacterium was successfully detected seven days after treatment. The antibiotic-treated insects, recolonized with S. marcescens, presented reduced antibacterial activity against Staphylococcus aureus and phenoloxidase activity in hemolymph, and lower nitric oxide synthase (NOS) and higher defensin C gene (DefC) gene expression in the fat body. These insects also presented a higher expression of DefC, lower prolixicin (Prol), and lower NOS levels in the anterior midgut. However, the antibiotic-treated insects recolonized with R. rhodnii had increased antibacterial activity against Escherichia coli and lower activity against S. aureus, higher phenoloxidase activity in hemolymph, and lower NOS expression in the fat body. In the anterior midgut, these insects presented higher NOS, defensin A (DefA) and DefC expression, and lower Prol expression. The R. prolixus immune modulation by these two bacteria was observed not only in the midgut, but also systemically in the fat body, and may be crucial for the development and transmission of the parasites Trypanosoma cruzi and Trypanosoma rangeli.
Serum miR-373-3p and miR-194-5p Are Associated with Early Tumor Progression during FOLFIRINOX Treatment in Pancreatic Cancer Patients: A Prospective Multicenter Study
Authors: van der Sijde Fleur , Homs Marjolein Y. V. , van Bekkum Marlies L. , van den Bosch Thierry P. P. , Bosscha Koop , Besselink Marc G. , Bonsing Bert A. , de Groot Jan Willem B. , Karsten Thomas M. , Groot Koerkamp Bas , Haberkorn Brigitte C. M. , Luelmo Saskia A. C. , Mekenkamp Leonie J. M. , Mustafa Dana A. M. , Wilmink Johanna W. , van Eijck Casper H. J. , Vietsch Eveline E. ,   on behalf of the Dutch Pancreatic Cancer Group
Published: October 2021

In this study, we explored the predictive value of serum microRNA (miRNA) expression for early tumor progression during FOLFIRINOX chemotherapy and its association with overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). A total of 132 PDAC patients of all disease stages were included in this study, of whom 25% showed progressive disease during FOLFIRINOX according to the RECIST criteria. MiRNA expression was analyzed in serum collected before the start and after one cycle of chemotherapy. In the discovery cohort (n = 12), a 352-miRNA RT-qPCR panel was used. In the validation cohorts (total n = 120), miRNA expression was detected using individual RT-qPCR miRNA primers. Before the start of FOLFIRINOX, serum miR-373-3p expression was higher in patients with progressive disease compared to patients with disease control after FOLFIRINOX (Log2 fold difference (FD) 0.88, p = 0.006). MiR-194-5p expression after one cycle of FOLFIRINOX was lower in patients with progressive disease (Log2 FD −0.29, p = 0.044). Both miRNAs were predictors of early tumor progression in a multivariable model including disease stage and baseline CA19-9 level (miR-373-3p odds ratio (OR) 3.99, 95% CI 1.10–14.49; miR-194-5p OR 0.91, 95% CI 0.83–0.99). MiR-373-3p and miR-194-5p did not show an association with OS after adjustment for disease stage, baseline CA19-9, and chemotherapy response. In conclusion, high serum miR-373-3p before the start and low serum miR-194-5p after one cycle are associated with early tumor progression during FOLFIRINOX.
Modeling Intestinal Stem Cell Function with Organoids
Authors: Takahashi Toshio , Fujishima Kazuto , Kengaku Mineko
Published: October 2021

Intestinal epithelial cells (IECs) are crucial for the digestive process and nutrient absorption. The intestinal epithelium is composed of the different cell types of the small intestine (mainly, enterocytes, goblet cells, Paneth cells, enteroendocrine cells, and tuft cells). The small intestine is characterized by the presence of crypt-villus units that are in a state of homeostatic cell turnover. Organoid technology enables an efficient expansion of intestinal epithelial tissue in vitro. Thus, organoids hold great promise for use in medical research and in the development of new treatments. At present, the cholinergic system involved in IECs and intestinal stem cells (ISCs) are attracting a great deal of attention. Thus, understanding the biological processes triggered by epithelial cholinergic activation by acetylcholine (ACh), which is produced and released from neuronal and/or non-neuronal tissue, is of key importance. Cholinergic signaling via ACh receptors plays a pivotal role in IEC growth and differentiation. Here, we discuss current views on neuronal innervation and non-neuronal control of the small intestinal crypts and their impact on ISC proliferation, differentiation, and maintenance. Since technology using intestinal organoid culture systems is advancing, we also outline an organoid-based organ replacement approach for intestinal diseases.
Photoactivatable nanoCRISPR/Cas9 System Based on crRNA Reversibly Immobilized on Carbon Nanoparticles
Authors: Semikolenova Olga , Sakovina Lubov , Akhmetova Elizaveta , Kim Daria , Vokhtantsev Ivan , Golyshev Victor , Vorobyeva Mariya , Novopashin Sergey , Novopashina Darya
Published: October 2021

Here, we proposed a new approach to engineering a photoactivatable CRISPR/Cas9 gene-editing system. The novel nanoCRISPR/Cas9 system is based on the use of auxiliary photocleavable oligodeoxyribonucleotides (PC-DNAs) complementary to crRNA. PC-DNAs contained up to three UV-sensitive linkers made of 1-(2-nitrophenyl)-1,2-ethanediol inside the oligonucleotide chain. Immobilizing PC-DNAs on the surface of carbon nanoparticles through 3′-terminal pyrene residue provided sufficient blocking of crRNA (and corresponding Cas9 activity) before UV irradiation and allows for crRNA release after UV irradiation at 365 nm, which restores Cas9 activity. We optimized the length of blocking photocleavable oligonucleotide, number of linkers, time of irradiation, and the type of carbon nanoparticles. Based on the results, we consider the nanoCRISPR/Cas9 system involving carbon-encapsulated iron nanoparticles the most promising. It provides the greatest difference of functional activity before/after irradiation and can be used in prospective for magnetic field-controlled delivery of CRISPR system into the target cells or tissues and spatiotemporal gene editing induced by UV irradiation.
K-RAS Acts as a Critical Regulator of CD44 to Promote the Invasiveness and Stemness of GBM in Response to Ionizing Radiation
Authors: Zhao Yi , Kang Jae-Hyeok , Yoo Ki-Chun , Kang Seok-Gu , Lee Hae-June , Lee Su-Jae
Published: October 2021

Radiation therapy is a current standard-of-care treatment and is used widely for GBM patients. However, radiation therapy still remains a significant barrier to getting a successful outcome due to the therapeutic resistance and tumor recurrence. Understanding the underlying mechanisms of this resistance and recurrence would provide an efficient approach for improving the therapy for GBM treatment. Here, we identified a regulatory mechanism of CD44 which induces infiltration and mesenchymal shift of GBM. Ionizing radiation (IR)-induced K-RAS/ERK signaling activation elevates CD44 expression through downregulation of miR-202 and miR-185 expression. High expression of CD44 promotes SRC activation to induce cancer stemness and EMT features of GBM cells. In this study, we demonstrate that the K-RAS/ERK/CD44 axis is a key mechanism in regulating mesenchymal shift of GBM cells after irradiation. These findings suggest that blocking the K-RAS activation or CD44 expression could provide an efficient way for GBM treatment.
Cardiac Troponins Metabolism: From Biochemical Mechanisms to Clinical Practice (Literature Review)
Authors: Chaulin Aleksey M.
Published: October 2021

The metabolic processes of endo- and exogenous compounds play an important role in diagnosing and treating patients since many metabolites are laboratory biomarkers and/or targets for therapeutic agents. Cardiac troponins are one of the most critical biomarkers to diagnose cardiovascular diseases, including acute myocardial infarction. The study of troponin metabolism is of great interest as it opens up new possibilities for optimizing laboratory diagnostics. This article discusses in detail the key stages of the cardiac troponins metabolism, in particular the mechanisms of release from a healthy myocardium, mechanisms of circulation in the bloodstream, possible mechanisms of troponin penetration into other biological fluids (oral fluid, cerebrospinal fluid, pericardial and amniotic fluids), mechanisms of elimination of cardiac troponins from the blood, and daily changes in the levels of troponins in the blood. Considering these aspects of cardiac troponin metabolism, attention is focused on the potential value for clinical practice.
Epstein-Barr Virus miR-BART1-3p Regulates the miR-17-92 Cluster by Targeting E2F3
Authors: Park Myung Chan , Kim Hyoji , Choi Hoyun , Chang Mee Soo , Lee Suk Kyeong
Published: October 2021

Epstein-Barr virus (EBV) is associated with several tumors and generates BamHI A rightward transcript (BART) microRNAs (miRNAs) from BART transcript introns. These BART miRNAs are expressed at higher levels in EBV-associated epithelial malignancies than in EBV-infected B lymphomas. To test the effects of EBV miRNA on the cell cycle and cell growth, we transfected miR-BART1-3p, a highly expressed EBV-associated miRNA, into gastric carcinoma cells. We found that miR-BART1-3p induced G0/G1 arrest and suppressed cell growth in gastric carcinoma cells. As our microarray analyses showed that E2F3, a cell cycle regulator, was inhibited by EBV infection, we hypothesized that miR-BART1-3p regulates E2F3. Luciferase assays revealed that miR-BART1-3p directly targeted the 3′-UTR of E2F3 mRNA. Both E2F3 mRNA and encoded protein levels were reduced following miR-BART1-3p transfection. In contrast, E2F3 expression in AGS-EBV cells transfected with a miR-BART1-3p inhibitor was enhanced. As E2F3 has been shown to regulate the expression of highly conserved miR-17-92 clusters in vertebrates, we examined whether this expression is affected by miR-BART1-3p, which can downregulate E2F3. The expression of E2F3, miR-17-92a-1 cluster host gene (MIR17HG), and miR-17-92 cluster miRNAs was significantly reduced in EBV-associated gastric carcinoma (EBVaGC) patients compared with EBV-negative gastric carcinoma (EBVnGC) patients. Further, miR-BART1-3p as well as the siRNA specific to E2F3 inhibited the expression of the miR-17-92 cluster, while inhibition of miR-BART1-3p enhanced the expression of the miR-17-92 cluster in cultured GC cells. Our results suggest a possible role of miR-BART1-3p in cell cycle regulation and in regulation of the miR-17-92 cluster through E2F3 suppression.
Ampelopsin Confers Endurance and Rehabilitation Mechanisms in Glycine max cv. Sowonkong under Multiple Abiotic Stresses
Authors: Kazerooni Elham Ahmed , Al-Sadi Abdullah Mohammed , Kim Il-Doo , Imran Muhammad , Lee In-Jung
Published: October 2021

The present investigation aims to perceive the effect of exogenous ampelopsin treatment on salinity and heavy metal damaged soybean seedlings (Glycine max L.) in terms of physiochemical and molecular responses. Screening of numerous ampelopsin concentrations (0, 0.1, 1, 5, 10 and 25 μM) on soybean seedling growth indicated that the 1 μM concentration displayed an increase in agronomic traits. The study also determined how ampelopsin application could recover salinity and heavy metal damaged plants. Soybean seedlings were irrigated with water, 1.5% NaCl or 3 mM chosen heavy metals for 12 days. Our results showed that the application of ampelopsin raised survival of the 45-day old salinity and heavy metal stressed soybean plants. The ampelopsin treated plants sustained high chlorophyll, protein, amino acid, fatty acid, salicylic acid, sugar, antioxidant activities and proline contents, and displayed low hydrogen peroxide, lipid metabolism, and abscisic acid contents under unfavorable status. A gene expression survey revealed that ampelopsin application led to the improved expression of GmNAC109, GmFDL19, GmFAD3, GmAPX, GmWRKY12, GmWRKY142, and GmSAP16 genes, and reduced the expression of the GmERF75 gene. This study suggests irrigation with ampelopsin can alleviate plant damage and improve plant yield under stress conditions, especially those including salinity and heavy metals.
Redox Homeostasis and Regulation in Pluripotent Stem Cells: Uniqueness or Versatility?
Authors: Ivanova Julia S. , Lyublinskaya Olga G.
Published: October 2021

Pluripotent stem cells (PSCs) hold great potential both in studies on developmental biology and clinical practice. Mitochondrial metabolism that encompasses pathways that generate ATP and produce ROS significantly differs between PSCs and somatic cells. Correspondingly, for quite a long time it was believed that the redox homeostasis in PSCs is also highly specific due to the hypoxic niche of their origin—within the pre-implantation blastocyst. However, recent research showed that redox parameters of cultivated PSCs have much in common with that of their differentiated progeny cells. Moreover, it has been proven that, similar to somatic cells, maintaining the physiological ROS level is critical for the regulation of PSC identity, proliferation, differentiation, and de-differentiation. In this review, we aimed to summarize the studies of redox metabolism and signaling in PSCs to compare the redox profiles of pluripotent and differentiated somatic cells. We collected evidence that PSCs possess metabolic plasticity and are able to adapt to both hypoxia and normoxia, that pluripotency is not strictly associated with anaerobic conditions, and that cellular redox homeostasis is similar in PSCs and many other somatic cells under in vitro conditions that may be explained by the high conservatism of the redox regulation system.
Genome-Wide Identification of CYP72A Gene Family and Expression Patterns Related to Jasmonic Acid Treatment and Steroidal Saponin Accumulation in Dioscorea zingiberensis
Authors: Hou Lixiu , Yuan Xincheng , Li Song , Li Yi , Li Zihao , Li Jiaru
Published: October 2021

Dioscorea zingiberensis is a medicinal herb containing a large amount of steroidal saponins, which are the major bioactive compounds and the primary storage form of diosgenin. The CYP72A gene family, belonging to cytochromes P450, exerts indispensable effects on the biosynthesis of numerous bioactive compounds. In this work, a total of 25 CYP72A genes were identified in D. zingiberensis and categorized into two groups according to the homology of protein sequences. The characteristics of their phylogenetic relationship, intron–exon organization, conserved motifs and cis-regulatory elements were performed by bioinformatics methods. The transcriptome data demonstrated that expression patterns of DzCYP72As varied by tissues. Moreover, qRT-PCR results displayed diverse expression profiles of DzCYP72As under different concentrations of jasmonic acid (JA). Likewise, eight metabolites in the biosynthesis pathway of steroidal saponins (four phytosterols, diosgenin, parvifloside, protodeltonin and dioscin) exhibited different contents under different concentrations of JA, and the content of total steroidal saponin was largest at the dose of 100 μmol/L of JA. The redundant analysis showed that 12 DzCYP72As had a strong correlation with specialized metabolites. Those genes were negatively correlated with stigmasterol and cholesterol but positively correlated with six other specialized metabolites. Among all DzCYP72As evaluated, DzCYP72A6, DzCYP72A16 and DzCYP72A17 contributed the most to the variation of specialized metabolites in the biosynthesis pathway of steroidal saponins. This study provides valuable information for further research on the biological functions related to steroidal saponin biosynthesis.
RNA Editing: A New Therapeutic Target in Amyotrophic Lateral Sclerosis and Other Neurological Diseases
Authors: Hosaka Takashi , Tsuji Hiroshi , Kwak Shin
Published: October 2021

The conversion of adenosine to inosine in RNA editing (A-to-I RNA editing) is recognized as a critical post-transcriptional modification of RNA by adenosine deaminases acting on RNAs (ADARs). A-to-I RNA editing occurs predominantly in mammalian and human central nervous systems and can alter the function of translated proteins, including neurotransmitter receptors and ion channels; therefore, the role of dysregulated RNA editing in the pathogenesis of neurological diseases has been speculated. Specifically, the failure of A-to-I RNA editing at the glutamine/arginine (Q/R) site of the GluA2 subunit causes excessive permeability of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors to Ca2+, inducing fatal status epilepticus and the neurodegeneration of motor neurons in mice. Therefore, an RNA editing deficiency at the Q/R site in GluA2 due to the downregulation of ADAR2 in the motor neurons of sporadic amyotrophic lateral sclerosis (ALS) patients suggests that Ca2+-permeable AMPA receptors and the dysregulation of RNA editing are suitable therapeutic targets for ALS. Gene therapy has recently emerged as a new therapeutic opportunity for many heretofore incurable diseases, and RNA editing dysregulation can be a target for gene therapy; therefore, we reviewed neurological diseases associated with dysregulated RNA editing and a new therapeutic approach targeting dysregulated RNA editing, especially one that is effective in ALS.
Polycyclic Aromatic Hydrocarbons Detected in Processed Meats Cause Genetic Changes in Colorectal Cancers
Authors: Cheng Tracie , Chaousis Stephanie , Kodagoda Gamage Sujani Madhurika , Lam Alfred King-yin , Gopalan Vinod
Published: October 2021

Polycyclic aromatic hydrocarbons (PAHs) are commonly ingested via meat and are produced from high-temperature cooking of meat. Some of these PAHs have potential roles in carcinogenesis of colorectal cancer (CRC). We aimed to investigate PAH concentrations in eight types of commonly consumed ready-to-eat meat samples and their potential effects on gene expressions related to CRC. Extraction and clean-up of meat samples were performed using QuEChERS method, and PAHs were detected using GC-MS. Nine different PAHs were found in meat samples. Interestingly, roast turkey contained the highest total PAH content, followed by salami meat. Hams of varying levels of smokedness showed a proportional increase of phenanthrene (PHEN), anthracene (ANTH), and fluorene (FLU). Triple-smoked ham samples showed significantly higher levels of these PAHs compared to single-smoked ham. These three PAHs plus benzo[a]pyrene (B[a]P), being detected in three meat samples, were chosen as treatments to investigate in vitro gene expression changes in human colon cells. After PAH treatment, total RNA was extracted and rtPCR was performed, investigating gene expression related to CRC. B[a]P decreased mRNA expression of TP53. In addition, at high concentrations, B[a]P significantly increased KRAS expression. Treatments with 1 µM PHEN, 25 µM, and 10 µM FLU significantly increased KRAS mRNA expression in vitro, implying the potential basis for PAH-induced colorectal carcinogenesis. Opposingly, the ANTH treatment led to increased TP53 and APC expression and decreased KRAS expression, suggesting an anti-carcinogenic effect. To conclude, PAHs are common in ready-to-eat meat samples and are capable of significantly modifying the expression of key genes related to CRC.
Developmental Exposure to Low Concentrations of Methylmercury Causes Increase in Anxiety-Related Behaviour and Locomotor Impairments in Zebrafish
Authors: Glazer Lilah , Brennan Caroline H.
Published: October 2021

Methylmercury (MeHg) is a ubiquitous pollutant shown to cause developmental neurotoxicity, even at low levels. However, there is still a large gap in our understanding of the mechanisms linking early-life exposure to life-long behavioural impairments. Our aim was to characterise the short- and long-term effects of developmental exposure to low doses of MeHg on anxiety-related behaviours in zebrafish, and to test the involvement of neurological pathways related to stress-response. Zebrafish embryos were exposed to sub-acute doses of MeHg (0, 5, 10, 15, 30 nM) throughout embryo-development, and tested for anxiety-related behaviours and locomotor activity at larval (light/dark locomotor activity) and adult (novel tank and tap assays) life-stages. Exposure to all doses of MeHg caused increased anxiety-related responses; heightened response to the transition from light to dark in larvae, and a stronger dive response in adults. In addition, impairment in locomotor activity was observed in the higher doses in both larvae and adults. Finally, the expressions of several neural stress-response genes from the HPI-axis and dopaminergic system were found to be disrupted in both life-stages. Our results provide important insights into dose-dependent differences in exposure outcomes, the development of delayed effects over the life-time of exposed individuals and the potential mechanisms underlying these effects.
Fungicidal Activity and Mechanism of Action of Glabridin from Glycyrrhiza glabra L.
Authors: Li Anping , Zhao Zhongmin , Zhang Shaoyong , Zhang Zhijun , Shi Yanping
Published: October 2021

Glycyrrhiza glabra (Licorice) belongs to the Fabaceae family and its extracts have exhibited significant fungicidal activity against phytopathogenic fungi, which has mainly been attributed to the presence of phenolic compounds such as flavonoids, isoflavonoids and chalcones. In this study, a series of licorice flavonoids, isoflavonoids and chalcones were evaluated for their fungicidal activity against phytopathogenic fungi. Among them, glabridin exhibited significant fungicidal activity against ten kinds of phytopathogenic fungi. Notably, glabridin displayed the most active against Sclerotinia sclerotiorum with an EC50 value of 6.78 µg/mL and was 8-fold more potent than azoxystrobin (EC50, 57.39 µg/mL). Moreover, the in vivo bioassay also demonstrated that glabridin could effectively control S. sclerotiorum. The mechanism studies revealed that glabridin could induce reactive oxygen species accumulation, the loss of mitochondrial membrane potential and cell membrane destruction through effecting the expression levels of phosphatidylserine decarboxylase that exerted its fungicidal activity. These findings indicated that glabridin exhibited pronounced fungicidal activities against S. sclerotiorum and could be served as a potential fungicidal candidate.
Thermal Requirements of Ooencyrtus submetallicus (Hym.: Encyrtidae) and Telenomus podisi (Hym.: Platygastridae) Parasitizing Euschistus heros Eggs (Hem.: Pentatomidae)
Authors: Chaves Valeria Freitas , Pereira Fabricio Fagundes , Torres Jorge Braz , da Silva Ivana Fernandes , Pastori Patrik Luiz , de Oliveira Harley Nonato , Costa Valmir Antônio , Cardoso Carlos Reinier Garcia
Published: October 2021

Temperature is one of the abiotic factors that strongly influences the biology and behavior of insects. In this study, we assessed the development of egg parasitoids Ooencyrtus submetallicus and Telenomus podisi parasitizing Euschistus heros eggs at different temperatures, and estimated the average number of generations for seven representative soybean-producing regions in Brazil. A comparative biology study was conducted, where the percentage of parasitism and emergence, life cycle duration (egg–adult), and longevity were found to be similar between O. submetallicus and T. podisi. The sex ratio and the number of individuals emerged from parasitized egg were higher in O. submetallicus in all regions. In the study of thermal requirements, temperatures of 16, 19, 22, 25, 28, 31, and 33 °C were tested. O. submetallicus and T. podisi developed at temperatures between 16 and 31 °C. The base temperature (Tb) for O. submetallicus and T. podisi was 9.3 and 6.7 °C, respectively; the thermal constant (K) was 336.9 and 272.7 degree-days, respectively. The estimated average number of annual generations of both parasitoids was higher than the host. O. submetallicus and T. podisi have the same ability to parasitize and develop in eggs of E. heros under the conditions studied. Both parasitoids exhibited satisfactory development and parasitism at temperatures between 19 and 31 °C. The development of both parasitoids was faster than their host, and the number of generations was higher for the seven studied localities.
Long-Term SARS-CoV-2 Specific Immunity Is Affected by the Severity of Initial COVID-19 and Patient Age
Authors: Konik Margarethe , Lindemann Monika , Zettler Markus , Meller Lara , Dolff Sebastian , Rebmann Vera , Horn Peter A. , Dittmer Ulf , Krawczyk Adalbert , Schipper Leonie , Trilling Mirko , Anastasiou Olympia Evdoxia , Schwarzkopf Sina , Thümmler Laura , Taube Christian , Schöbel Christoph , Brenner Thorsten , Skoda Eva-Maria , Wilde Benjamin , Gäckler Anja , Witzke Oliver , Rohn Hana
Published: October 2021

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the greatest medical challenge. Although crucial to the future management of the pandemic, the factors affecting the persistence of long-term SARS-CoV-2 immunity are not well understood. Therefore, we determined the extent of important correlates of SARS-CoV-2 specific protection in 200 unvaccinated convalescents after COVID-19. To investigate the effective memory response against the virus, SARS-CoV-2 specific T cell and humoral immunity (including virus-neutralizing antibodies) was determined over a period of one to eleven months. SARS-CoV-2 specific immune responses were present in 90% of individual patients. Notably, immunosuppressed patients did not have long-term SARS-CoV-2 specific T cell immunity. In our cohort, the severity of the initial illness influenced SARS-CoV-2 specific T cell immune responses and patients’ humoral immune responses to Spike (S) protein over the long-term, whereas the patients’ age influenced Membrane (M) protein-specific T cell responses. Thus, our study not only demonstrated the long-term persistence of SARS-CoV-2 specific immunity, it also determined COVID-19 severity and patient age as significant factors affecting long-term immunity.
Diagnostic Yield of Transabdominal Ultrasonography for Evaluation of Pancreatic Cystic Lesions Compared with Endoscopic Ultrasonography
Authors: Li Yu Ji , Lee Gil Ho , Yang Min Jae , Hwang Jae Chul , Yoo Byung Moo , Kim Soon Sun , Lim Sun Gyo , Kim Jin Hong
Published: October 2021

Detection rates of pancreatic cystic lesions (PCLs) have increased, resulting in greater requirements for regular monitoring using imaging modalities. We aimed to evaluate the capability of ultrasonography (US) for morphological characterization of PCLs as a reference standard using endoscopic ultrasonography (EUS). A retrospective analysis was conducted of 102 PCLs from 92 patients who underwent US immediately prior to EUS between January 2014 and May 2017. The intermodality reliability and agreement of the PCL morphologic findings of the two techniques were analyzed and compared using the intraclass correlation coefficient and κ values. The success rates of US for delineating PCLs in the head, body, and tail of the pancreas were 77.8%, 91.8%, and 70.6%, respectively. The intraclass correlation coefficient for US and the corresponding EUS lesion size showed very good reliability (0.978; p < 0.001). The κ value between modalities was 0.882 for pancreatic duct dilation, indicating good agreement. The κ values for solid components and cystic wall and septal thickening were 0.481 and 0.395, respectively, indicating moderate agreement. US may be useful for monitoring PCL growth and changes in pancreatic duct dilation, but it has limited use in the diagnosis and surveillance of mural nodules or cystic wall thickness changes.
Dysphoria and Irritability—Diagnostic Pitfalls in the Assessment of Interictal Dysphoric Disorder in Epilepsy
Authors: Grzegorzewska Agata M. , Wiglusz Mariusz S. , Cubała Wiesław J. , Jakuszkowiak-Wojten Katarzyna , Włodarczyk Adam , Szarmach Joanna
Published: October 2021

This article aims to review the concept of epilepsy-specific psychiatric disturbance, Interictal Dysphoric Disorder (IDD), focusing on issues related to its core symptoms and methodological pitfalls. In the psychiatric literature, an epilepsy-specific pleomorphic mood disorder has been long recognized and described as IDD, a condition characterized by eight symptoms, which are grouped into four labile depressive symptoms, two labile affective symptoms, and two specific symptoms. The existence of IDD is still a matter of debate because of several methodological issues. The main features of IDD, such as dysphoria and irritability, lack precise and clear definition. This review article explores the different definitions and approaches towards both terms described in the psychiatric literature and the rationale for modifying the diagnostic process of IDD.
The Effects of Previous Asthma and COPD on the Susceptibility to and Severity of COVID-19: A Nationwide Cohort Study in South Korea
Authors: Jung Younghee , Wee Jee Hye , Kim Joo-Hee , Choi Hyo Geun
Published: October 2021

Background: There is controversial evidence of the associations of asthma and chronic obstructive pulmonary disease (COPD) with the risk and outcomes of Coronavirus Disease 2019 (COVID-19). We aimed to evaluate the effects of asthma and COPD on the susceptibility to and severity of COVID-19. Methods: Data from a nationwide COVID-19 cohort database by the Korea National Health Insurance Corporation were utilized. A total of 4066 COVID-19 patients (1 January 2020 through 4 June 2020) were 1:4 matched with 16,264 controls with regard to age, sex, and income. Asthma and COPD were defined as diagnostic codes (ICD-10) and medication claim codes. Conditional and unconditional multivariate logistic regression were applied to analyze the susceptibility to and severity of COVID-19 associated with asthma and COPD. Results: The prevalence of mild and severe asthma/COPD did not differ between the COVID-19 and control patients in the multivariate analyses. Among the total 4066 COVID-19 patients, 343 (8.4%) had severe COVID-19, of whom 132 (3.2% of the total COVID-19 patients) died. Regarding the outcomes of COVID-19, neither mild nor severe asthma were associated with the severity or mortality of COVID-19 after adjusting for other variables. However, severe COPD was a significant risk factor for severe COVID-19 (odds ratio (OR) = 2.23, 95% confidence intervals (CI): 1.08–4.60, p = 0.030) and the mortality of COVID-19 in the multivariate analyses (OR = 3.06, 95% CI: 1.14–8.2, p = 0.026). Conclusions: In a Korean nationwide cohort, neither asthma nor COPD were associated with COVID-19, but severe COPD was associated with the severity and mortality of COVID-19.
Ultrasound-Guided Anterior Quadratus Lumborum Block Reduces Postoperative Opioid Consumption and Related Side Effects in Patients Undergoing Total Hip Replacement Arthroplasty: A Propensity Score-Matched Cohort Study
Authors: Kim Yeon-Ju , Kim Hyung-Tae , Kim Ha-Jung , Yoon Pil-Whan , Park Ji-In , Lee Sun-Hyung , Ro Young-Jin , Koh Won-Uk
Published: October 2021

Quadratus lumborum block (QLB) has been shown to be effective for pain relief after hip surgery. This study evaluated the efficacy of ultrasound-guided anterior QLB in pain control after total replacement hip arthroplasty (TRHA). A total of 115 patients receiving anterior QLB were propensity score-matched with 115 patients who did not receive the block. The primary outcome was opioid consumption at 24, 24–48, and 48 postoperative hours. Secondary outcomes included pain scores at the post-anesthesia care unit (PACU), 8, 16, 24, 32, 40, and 48 h length of hospital stay, time to first ambulation, and the incidence of opioid-related side effects. Postoperative opioid consumption 48 h after surgery was significantly lower in the QLB group. Resting, mean, worst, and the difference of resting pain scores compared with preoperative values were significantly lower in the QLB group during the 48 postoperative hours. The length of hospital stay was shorter in the QLB group. The incidence of postoperative nausea and vomiting was significantly lower in the QLB group during the 48 postoperative hours, except at the PACU. This study suggests that anterior QLB provides effective postoperative analgesia for patients undergoing THRA performed using the posterolateral approach.
Association of the KDIGO Risk Classification with the Prevalence of Heart Failure in Patients with Type 2 Diabetes
Authors: Gimeno-Orna José Antonio , Rodríguez-Padial Luis , Anguita-Sánchez Manuel , Barrios Vivencio , Muñiz Javier , Pérez Antonio
Published: October 2021

The objectives of this study were to determine the main characteristics associated with the presence of heart failure (HF) in patients with type 2 diabetes (T2DM), and specifically to assess the association of the risk classification proposed by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines with HF. The DIABET-IC study is a multicentre, observational, prospective and analytical study in T2DM patients recruited in Spanish hospitals. This work, which features a cross-sectional design, has been conducted with the data obtained at the inclusion visit. The main dependent variable analysed was the presence of HF. The predictive variables evaluated were the demography, clinic, laboratory testing (including natriuretic peptides) and echocardiography. Patients were classified according to the number of vascular territories with atherosclerotic involvement and the KDIGO risk category. Multivariate logistic regression models were performed to determine the risk posed by the various baseline variables to present HF at the time of study inclusion. The study included 1517 patients from 58 hospitals, with a mean age of 67.3 (standard deviation (SD): 10) years, out of which 33% were women. The mean DM duration was 14 (SD: 11) years. The prevalence of HF was 37%. In a multivariate analysis, the independent predictors of HF were increased age (odds ratio (OR) per 1 year = 1.02; p = 0.006), decreased systolic blood pressure (OR per 1 mmHg = 0.98; p < 0.001), decreased haemoglobin (OR per 1 g/dL = 0.86; p < 0.001), the presence of obstructive sleep apnoea (OR = 1.61; p = 0.006), the absence of hepatic steatosis (OR = 0.59; p = 0.016), the severity of atherosclerotic involvement (OR 1 territory = 1.38 and OR > 1 territory = 2.39; p = 0.02 and p < 0.001 respectively) and the KDIGO risk classification (high-risk OR = 2.46 and very high-risk OR = 3.39; p < 0.001 for both). The KDIGO risk classification is useful to screen for the presence of HF in T2DM patients. Therefore, we believe that it is necessary to carry out a systematic screening for HF in the high- and very high-risk KDIGO categories.
Single-Nucleotide Polymorphisms in MICA and MICB Genes Could Play a Role in the Outcome in AML Patients after HSCT
Authors: Machuldova Alena , Houdova Lucie , Kratochvilova Katerina , Leba Martin , Jindra Pavel , Ostasov Pavel , Maceckova Diana , Klieber Robin , Gmucova Hana , Sramek Jiri , Holubova Monika
Published: October 2021

NKG2D and its ligands, MICA and MICB, are known as the key regulators of NK cells. NK cells are the first reconstituted cells after the allogeneic hematopoietic stem cell transplantation (HSCT); therefore, it is crucial to understand their role in HSCT outcome. In the presented study, we investigated the single amino acid changes across the exons 2–4 of MICA and MICB genes, and point mutations within the NKG2D gene, which defines the type of NKG2D haploblock (HNK/LNK) in the donors (n = 124), as well as in patients with acute myeloid leukemia (n = 78). In our cohort, we found that graft from a donor with at least one MICA allele containing glycine at position 14 (MICA-14Gly) is significantly associated with deterioration of a patient’s overall survival (OS) (p < 0.05). We also observed a negative effect of MICB-58 (Lys → Glu) polymorphism on relapse-free survival (RFS), although it was not statistically significant in multivariate analysis (p = 0.069). To our knowledge, this is the first work describing the role of MICA-14 and MICB-58 polymorphisms on HSCT outcome.