bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of Ceftriaxone Resistance of Penicillin-Binding Proteins 2 Revealed by Molecular Modeling
Authors: Krivitskaya Alexandra V. , Khrenova Maria G.
Published: December 2022

Penicillin-binding proteins 2 (PBP2) are critically important enzymes in the formation of the bacterial cell wall. Inhibition of PBP2 is utilized in the treatment of various diseases, including gonorrhea. Ceftriaxone is the only drug used to treat gonorrhea currently, and recent growth in PBP2 resistance to this antibiotic is a serious threat to human health. Our study reveals mechanistic aspects of the inhibition reaction of PBP2 from the wild-type FA19 strain and mutant 35/02 and H041 strains of Neisseria Gonorrhoeae by ceftriaxone. QM(PBE0-D3/6-31G**)/MM MD simulations show that the reaction mechanism for the wild-type PBP2 consists of three elementary steps including nucleophilic attack, C–N bond cleavage in the β-lactam ring and elimination of the leaving group in ceftriaxone. In PBP2 from the mutant strains, the second and third steps occur simultaneously. For all considered systems, the acylation rate is determined by the energy barrier of the first step that increases in the order of PBP2 from FA19, 35/02 and H041 strains. Dynamic behavior of ES complexes is analyzed using geometry and electron density features including Fukui electrophilicity index and Laplacian of electron density maps. It reveals that more efficient activation of the carbonyl group of the antibiotic leads to the lower energy barrier of nucleophilic attack and larger stabilization of the first reaction intermediate. Dynamical network analysis of MD trajectories explains the differences in ceftriaxone binding affinity: in PBP2 from the wild-type strain, the β3-β4 loop conformation facilitates substrate binding, whereas in PBP2 from the mutant strains, it exists in the conformation that is unfavorable for complex formation. Thus, we clarify that the experimentally observed decrease in the second-order rate constant of acylation (k2/KS) in PBP2 from the mutant strains is due to both a decrease in the acylation rate constant k2 and an increase in the dissociation constant KS.
G Protein-Coupled Receptor 15 Expression Is Associated with Myocardial Infarction
Authors: Haase Tina , Müller Christian , Stoffers Bastian , Kirn Philipp , Waldenberger Melanie , Kaiser Frank J. , Karakas Mahir , Kim Sangwon V. , Voss Svenja , Wild Philipp S. , Lackner Karl J. , Andersson Jonas , Söderberg Stefan , Lindner Diana , Zeller Tanja
Published: December 2022

Beyond the influence of lifestyle-related risk factors for myocardial infarction (MI), the mechanisms of genetic predispositions for MI remain unclear. We sought to identify and characterize differentially expressed genes in early-onset MI in a translational approach. In an observational case–control study, transcriptomes from 112 early-onset MI individuals showed upregulated G protein-coupled receptor 15 (GPR15) expression in peripheral blood mononuclear cells compared to controls (fold change = 1.4, p = 1.87 × 10−7). GPR15 expression correlated with intima-media thickness (β = 0.8498, p = 0.111), C-reactive protein (β = 0.2238, p = 0.0052), ejection fraction (β = −0.9991, p = 0.0281) and smoking (β = 0.7259, p = 2.79 × 10−10). The relation between smoking and MI was diminished after the inclusion of GPR15 expression as mediator in mediation analysis (from 1.27 (p = 1.9 × 10−5) to 0.46 (p = 0.21)). The DNA methylation of two GPR15 sites was 1%/5% lower in early-onset MI individuals versus controls (p = 2.37 × 10−6/p = 0.0123), with site CpG3.98251219 significantly predicting risk for incident MI (hazard ratio = 0.992, p = 0.0177). The nucleotide polymorphism rs2230344 (C/T) within GPR15 was associated with early-onset MI (odds ratio = 3.61, p = 0.044). Experimental validation showed 6.3-fold increased Gpr15 expression in an ischemic mouse model (p < 0.05) and 4-fold increased Gpr15 expression in cardiomyocytes under ischemic stress (p < 0.001). After the induction of MI, Gpr15gfp/gfp mice showed lower survival (p = 0.042) and deregulated gene expression for response to hypoxia and signaling pathways. Using a translational approach, our data provide evidence that GPR15 is linked to cardiovascular diseases, mediating the adverse effects of smoking.
Foliar Application of dsRNA Targeting Endogenous Potato (Solanum tuberosum) Isoamylase Genes ISA1, ISA2, and ISA3 Confers Transgenic Phenotype
Authors: Simon Ido , Persky Zohar , Avital Aviram , Harat Hila , Schroeder Avi , Shoseyov Oded
Published: December 2022

Isoamylase (ISA) is a debranching enzyme found in many plants, which hydrolyzes (1-6)-α-D glucosidic linkages in starch, amylopectin, and β-dextrins, and is thought to be responsible for starch granule formation (ISA1 and ISA2) and degradation (ISA3). Lipid-modified PEI (lmPEI) was synthesized as a carrier for long double-stranded RNA (dsRNA, 250-bp), which targets the three isoamylase isoforms. The particles were applied to the plant via the foliar spray and were differentially effective in suppressing the expressions of ISA1 and ISA2 in the potato leaves, and ISA3 in the tubers. Plant growth was not significantly impaired, and starch levels in the tubers were not affected as well. Interestingly, the treated plants had significantly smaller starch granule sizes as well as increased sucrose content, which led to an early sprouting phenotype. We confirm the proposal of previous research that an increased number of small starch granules could be responsible for an accelerated turnover of glucan chains and, thus, the rapid synthesis of sucrose, and we propose a new relationship between ISA3 and the starch granule size. The implications of this study are in achieving a transgenic phenotype for endogenous plant genes using a systemic, novel delivery system, and foliar applications of dsRNA for agriculture.
Matched Analyses of Brain Metastases versus Primary Non-Small Cell Lung Cancer Reveal a Unique microRNA Signature
Authors: Tsakonas Georgios , Koulouris Andreas , Kazmierczak Dominika , Botling Johan , Ortiz-Villalon Cristian , Nord Helena , Lindskog Magnus , Sandelin Martin , Micke Patrick , Hydbring Per , Ekman Simon
Published: December 2022

Distant spreading of tumor cells to the central nervous system in non-small cell lung cancer (NSCLC) occurs frequently and poses major clinical issues due to limited treatment options. RNAs displaying differential expression in brain metastasis versus primary NSCLC may explain distant tumor growth and may potentially be used as therapeutic targets. In this study, we conducted systematic microRNA expression profiling from tissue biopsies of primary NSCLC and brain metastases from 25 patients. RNA analysis was performed using the nCounter Human v3 miRNA Expression Assay, NanoString technologies, followed by differential expression analysis and in silico target gene pathway analysis. We uncovered a panel of 11 microRNAs with differential expression and excellent diagnostic performance in brain metastasis versus primary NSCLC. Five microRNAs were upregulated in brain metastasis (miR-129-2-3p, miR-124-3p, miR-219a-2-3p, miR-219a-5p, and miR-9-5p) and six microRNAs were downregulated in brain metastasis (miR-142-3p, miR-150-5p, miR-199b-5p, miR-199a-3p, miR-199b-5p, and miR-199a-5p). The differentially expressed microRNAs were predicted to converge on distinct target gene networks originating from five to twelve core target genes. In conclusion, we uncovered a unique microRNA profile linked to two target gene networks. Our results highlight the potential of specific microRNAs as biomarkers for brain metastasis in NSCLC and indicate plausible mechanistic connections.
Identification, Characterization and Expression Profiling of the RS Gene Family during the Withering Process of White Tea in the Tea Plant (Camellia sinensis) Reveal the Transcriptional Regulation of CsRS8
Authors: Wang Tao , Wang Yiqing , Zhao Jiamin , Kong Jiumei , Zhang Lingzhi , Qi Siyu , Chen Jiajia , Chen Zhidan , Zeng Wen , Sun Weijiang
Published: December 2022

Raffinose synthetase (RS) is a key enzyme in the process of raffinose (Raf) synthesis and is involved in plant development and stress responses through regulating Raf content. As a sweetener, Raf makes an important contribution to the sweet taste of white tea. However, studies on the identification, analysis and transcriptional regulation of CsRSs (Camellia sinensis RS genes) are still lacking. In this study, nine CsRSs were identified from the tea plant (Camellia sinensis) genome database. The CsRSs were classified into five groups in the phylogenetic tree. Expression level analysis showed that the CsRSs varied in different parts of the tea plant. Transcriptome data showed that CsRSs could respond to persistent drought and cold acclimation. Except for CsRS5 and CsRS9, the expression pattern of all CsRSs increased at 12 h and decreased at 30 h during the withering process of white tea, consistent with the change trend of the Raf content. Furthermore, combining yeast one-hybrid assays with expression analysis, we found that CsDBB could potentially regulate the expression of CsRS8. Our results provide a new perspective for further research into the characterization of CsRS genes and the formation of the white tea flavour.
Leveraging Natural Killer Cell Innate Immunity against Hematologic Malignancies: From Stem Cell Transplant to Adoptive Transfer and Beyond
Authors: Lin Chenyu , Horwitz Mitchell E. , Rein Lindsay A. M.
Published: December 2022

Numerous recent advancements in T-cell based immunotherapies have revolutionized the treatment of hematologic malignancies. In the race towards the first approved allogeneic cellular therapy product, there is growing interest in utilizing natural killer (NK) cells as a platform for off-the-shelf cellular therapies due to their scalable manufacturing potential, potent anti-tumor efficacy, and superior safety profile. Allogeneic NK cell therapies are now being actively explored in the setting of hematopoietic stem cell transplantation and adoptive transfer. Increasingly sophisticated gene editing techniques have permitted the engineering of chimeric antigen receptors, ectopic cytokine expression, and tumor recognition signals to improve the overall cytotoxicity of NK cell therapies. Furthermore, the enhancement of antibody-dependent cellular cytotoxicity has been achieved through the use of NK cell engagers and combination regimens with monoclonal antibodies that act synergistically with CD16-expressing NK cells. Finally, a greater understanding of NK cell biology and the mechanisms of resistance have allowed the preclinical development of NK checkpoint blockade and methods to modulate the tumor microenvironment, which have been evaluated in early phase trials. This review will discuss the recent clinical advancements in NK cell therapies in hematologic malignancies as well as promising avenues of future research.
The Potential Importance of CXCL1 in the Physiological State and in Noncancer Diseases of the Cardiovascular System, Respiratory System and Skin
Authors: Korbecki Jan , Maruszewska Agnieszka , Bosiacki Mateusz , Chlubek Dariusz , Baranowska-Bosiacka Irena
Published: December 2022

In this paper, we present a literature review of the role of CXC motif chemokine ligand 1 (CXCL1) in physiology, and in selected major non-cancer diseases of the cardiovascular system, respiratory system and skin. CXCL1, a cytokine belonging to the CXC sub-family of chemokines with CXC motif chemokine receptor 2 (CXCR2) as its main receptor, causes the migration and infiltration of neutrophils to the sites of high expression. This implicates CXCL1 in many adverse conditions associated with inflammation and the accumulation of neutrophils. The aim of this study was to describe the significance of CXCL1 in selected diseases of the cardiovascular system (atherosclerosis, atrial fibrillation, chronic ischemic heart disease, hypertension, sepsis including sepsis-associated encephalopathy and sepsis-associated acute kidney injury), the respiratory system (asthma, chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis, coronavirus disease 2019 (COVID-19), influenza, lung transplantation and ischemic-reperfusion injury and tuberculosis) and the skin (wound healing, psoriasis, sunburn and xeroderma pigmentosum). Additionally, the significance of CXCL1 is described in vascular physiology, such as the effects of CXCL1 on angiogenesis and arteriogenesis.
Posterior Polymorphous Corneal Dystrophy in a Patient with a Novel ZEB1 Gene Mutation
Authors: Fernández-Gutiérrez Eva , Fernández-Pérez Pedro , Boto-De-Los-Bueis Ana , García-Fernández Laura , Rodríguez-Solana Patricia , Solís Mario , Vallespín Elena
Published: December 2022

Posterior polymorphous corneal dystrophy (PPCD), a rare, bilateral, autosomal-dominant, inherited corneal dystrophy, affects the Descemet membrane and corneal endothelium. We describe an unusual presentation of PPCD associated with a previously unknown genetic alteration in the ZEB1 gene. The proband is a 64-year-old woman diagnosed with keratoconus referred for a corneal endothelium study who presented endothelial lesions in both eyes suggestive of PPCD, corectopia and iridocorneal endothelial synechiae in the right eye and intrastromal segments in the left eye. The endothelial count was 825 in the right eye and 1361 in the left eye, with typical PPCD lesions visible under specular and confocal microscopy. In the next generation sequencing genetic analysis, a heterozygous c.1A > C (p.Met1Leu) mutation was found in the ZEB1 gene (TCF8). The PPCD3 subtype is associated with corneal ectasia, and both can appear due to a pathogenic mutation in the ZEB1 gene (OMIM #189909). However, our patient had a previously unreported mutation in the ZEB1 gene, which mediates the transition between cell lines and provides a pathogenic explanation for the epithelialisation of the corneal endothelium, a characteristic of PPCD.
Silver Nanoparticles and Glycyrrhiza glabra (Licorice) Root Extract as Modifying Agents of Hydrogels Designed as Innovative Dressings
Authors: Kędzierska Magdalena , Bańkosz Magdalena , Drabczyk Anna , Kudłacik-Kramarczyk Sonia , Jamroży Mateusz , Potemski Piotr
Published: December 2022

The interest in the application of plant extracts as modifiers of polymers intended for biomedical purposes is constantly increasing. The therapeutical properties of the licorice root, including its anti-inflammatory and antibacterial activity, make this plant particularly promising. The same applies to silver nanoparticles showing antibacterial properties. Thus the main purpose of the research was to design hydrogel dressings containing both licorice root extract and nanosilver so as to obtain a system promoting wound regeneration processes by preventing infection and inflammation within the wound. The first step included the preparation of the plant extract via the solid-liquid extraction using the Soxhlet extractor and the synthesis of silver nanoparticles by the chemical reduction of silver ions using a sodium borohydride as a reducing agent. Subsequently, hydrogels were synthesized via photopolymerization and subjected to studies aiming at characterizing their sorption properties, surface morphology via scanning electron microscopy, and their impact on simulated physiological liquids supported by defining these liquids’ influence on hydrogels’ structures by FT-IR spectroscopy. Next, the tensile strength of hydrogels and their percentage elongation were determined. Performed studies also allowed for determining the hydrogels’ wettability and free surface energies. Finally, the cytotoxicity of hydrogels towards L929 murine fibroblasts via the MTT reduction assay was also verified. It was demonstrated that developed materials showed stability in simulated physiological liquids. Moreover, hydrogels were characterized by high elasticity (percentage elongation within the range of 24–29%), and their surfaces were hydrophilic (wetting angles below 90°). Hydrogels containing both licorice extract and nanosilver showed smooth and homogeneous surfaces. Importantly, cytotoxic properties towards L929 murine fibroblasts were excluded; thus, developed materials seem to have great potential for application as innovative dressings.
Mice Lacking Gpr179 with Complete Congenital Stationary Night Blindness Are a Good Model for Myopia
Authors: Wilmet Baptiste , Callebert Jacques , Duvoisin Robert , Goulet Ruben , Tourain Christophe , Michiels Christelle , Frederiksen Helen , Schaeffel Frank , Marre Olivier , Sahel José Alain , Audo Isabelle , Picaud Serge , Zeitz Christina
Published: December 2022

Mutations in GPR179 are one of the most common causes of autosomal recessive complete congenital stationary night blindness (cCSNB). This retinal disease is characterized in patients by impaired dim and night vision, associated with other ocular symptoms, including high myopia. cCSNB is caused by a complete loss of signal transmission from photoreceptors to ON-bipolar cells. In this study, we hypothesized that the lack of Gpr179 and the subsequent impaired ON-pathway could lead to myopic features in a mouse model of cCSNB. Using ultra performance liquid chromatography, we show that adult Gpr179−/− mice have a significant decrease in both retinal dopamine and 3,4-dihydroxyphenylacetic acid, compared to Gpr179+/+ mice. This alteration of the dopaminergic system is thought to be correlated with an increased susceptibility to lens-induced myopia but does not affect the natural refractive development. Altogether, our data added a novel myopia model, which could be used to identify therapeutic interventions.
About the Transient Effects of Synthetic Amorphous Silica: An In Vitro Study on Macrophages
Authors: Torres Anaëlle , Collin-Faure Véronique , Fenel Daphna , Sergent Jacques-Aurélien , Rabilloud Thierry
Published: December 2022

Silica (either crystalline or amorphous) is widely used for different applications and its toxicological assessment depends on its characteristics and intended use. As sustained inflammation induced by crystalline silica is at the root of silicosis, investigating the inflammatory effects induced by amorphous silicas and their persistence is needed. For the development of new grades of synthetic amorphous silicas, it is also desirable to be able to understand better the factors underlying potential adverse effects. Therefore, we used an optimized in vitro macrophage system to investigate the effects of amorphous silicas, and their persistence. By using different amorphous silicas, we demonstrated that the main driver for the adverse effects is a low size of the overall particle/agglomerate; the second driver being a low size of the primary particle. We also demonstrated that the effects were transient. By using silicon dosage in cells, we showed that the transient effects are coupled with a decrease of intracellular silicon levels over time after exposure. To further investigate this phenomenon, a mild enzymatic cell lysis allowed us to show that amorphous silicas are degraded in macrophages over time, explaining the decrease in silicon content and thus the transiency of the effects of amorphous silicas on macrophages.
Near-Infrared 810 nm Light Affects Porifera Chondrosia reniformis (Nardo, 1847) Regeneration: Molecular Implications and Evolutionary Considerations of Photobiomodulation–Animal Cell Interaction
Authors: Amaroli Andrea , Tassara Eleonora , Ferrando Sara , Aicardi Stefano , Pasquale Claudio , Giovine Marco , Bertolino Marco , Zekiy Angelina , Pozzolini Marina
Published: December 2022

Chemotrophic choice as a metabolic source of energy has characterised animal cell evolution. However, light interactions with animal cell photoacceptors that are able to increase energetic metabolism (photo-biomodulation (PBM)) have been previously described. In the present study, we cut three specimens of Chondrosia reniformis into four equal parts (12 fragments), and we irradiated the regenerating edge of six fragments with the previously characterised 810 nm near-infrared light, delivered at 1 W, 60 J/cm2, 1 W/cm2, and 60 J in a continuous-wave mode for 60 s through a flat-top hand-piece with a rounded spot-size area of 1 cm2. Six fragments were irradiated with 0 W for 60 s as the controls. We performed irradiation at the time 0 h and every 24 h for a total of five administrations. We monitored the regeneration process for five days (120 h) in aquaria by examining the macroscopic and histological changes. We analysed the gene expression profile of the inflammatory processes, apoptosis, heat stress, growth factors, and collagen production and determined oxidative stress enzyme activity and the total prokaryotic symbiont content. PBM sped up C. reniformis regeneration when compared to the controls. Particularly, transforming growth factor TGF3 and TGF6 upregulation during the early phase of regeneration and TGF5 upregulation 120 h postinjury in the irradiated samples supports the positive effect of PBM in sponge tissue recovery. Conversely, the expression of TGF4, a sponge fibroblast growth factor homologue, was not affected by irradiation, indicating that multiple, independent pathways regulate the TGF genes. The results are consistent with our previous data on a wide range of organisms and humans, suggesting that PBM interaction with primary and secondary cell targets has been conserved through the evolution of life forms.
Asprosin Exerts Pro-Inflammatory Effects in THP-1 Macrophages Mediated via the Toll-like Receptor 4 (TLR4) Pathway
Authors: Shabir Kiran , Gharanei Seley , Orton Sophie , Patel Vanlata , Chauhan Parbata , Karteris Emmanouil , Randeva Harpal S. , Brown James E. , Kyrou Ioannis
Published: December 2022

Adipose tissue is a dynamic endocrine organ, secreting a plethora of adipokines which play a key role in regulating metabolic homeostasis and other physiological processes. An altered adipokine secretion profile from adipose tissue depots has been associated with obesity and related cardio-metabolic diseases. Asprosin is a recently described adipokine that is released in response to fasting and can elicit orexigenic and glucogenic effects. Circulating asprosin levels are elevated in a number of cardio-metabolic diseases, including obesity and type 2 diabetes. In vitro studies have reported pro-inflammatory effects of asprosin in a variety of tissues. The present study aimed to further elucidate the role of asprosin in inflammation by exploring its potential effect(s) in THP-1 macrophages. THP-1 monocytes were differentiated to macrophages by 48 h treatment with dihydroxyvitamin D3. Macrophages were treated with 100 nM recombinant human asprosin, 100 ng/mL lipopolysaccharide (LPS), and 10 μM caffeic acid phenethyl ester (CAPE; an inhibitor of NFκB activation) or 1 µM TAK-242 (a Toll-like receptor 4, TLR4, inhibitor). The expression and secretion of pertinent pro-inflammatory mediators were measured by qPCR, Western blot, ELISA and Bioplex. Asprosin stimulation significantly upregulated the expression and secretion of the pro-inflammatory cytokines: tumour necrosis factor α (TNFα), interleukin-1β (IL-1β), IL-8 and IL-12 in vitro. This pro-inflammatory response in THP-1 macrophages was partly attenuated by the treatments with CAPE and was significantly inhibited by TAK-242 treatment. Asprosin-induced inflammation is significantly counteracted by TLR4 inhibition in THP-1 macrophages, suggesting that asprosin exerts its pro-inflammatory effects, at least in part, via the TLR4 signalling pathway.
Extracellular Vesicles’ Role in the Pathophysiology and as Biomarkers in Cystic Fibrosis and COPD
Authors: Di Gioia Sante , Daniello Valeria , Conese Massimo
Published: December 2022

In keeping with the extraordinary interest and advancement of extracellular vesicles (EVs) in pathogenesis and diagnosis fields, we herein present an update to the knowledge about their role in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Although CF and COPD stem from a different origin, one genetic and the other acquired, they share a similar pathophysiology, being the CF transmembrane conductance regulator (CFTR) protein implied in both disorders. Various subsets of EVs, comprised mainly of microvesicles (MVs) and exosomes (EXOs), are secreted by various cell types that are either resident or attracted in the airways during the onset and progression of CF and COPD lung disease, representing a vehicle for metabolites, proteins and RNAs (especially microRNAs), that in turn lead to events as such neutrophil influx, the overwhelming of proteases (elastase, metalloproteases), oxidative stress, myofibroblast activation and collagen deposition. Eventually, all of these pathomechanisms lead to chronic inflammation, mucus overproduction, remodeling of the airways, and fibrosis, thus operating a complex interplay among cells and tissues. The detection of MVs and EXOs in blood and biological fluids coming from the airways (bronchoalveolar lavage fluid and sputum) allows the consideration of EVs and their cargoes as promising biomarkers for CF and COPD, although clinical expectations have yet to be fulfilled.
Urine-Derived Epithelial Cells as a New Model to Study Renal Metabolic Phenotypes of Patients with Glycogen Storage Disease 1a
Authors: Lenzini Livia , Iori Elisabetta , Scannapieco Federico , Carraro Gianni , Avogaro Angelo , Vitturi Nicola
Published: December 2022

Glycogen storage diseases (GSDs) represent a model of pathological accumulation of glycogen disease in the kidney that, in animal models, results in nephropathy due to abnormal autophagy and mitochondrial function. Patients with Glycogen Storage Disease 1a (GSD1a) accumulate glycogen in the kidneys and suffer a disease resembling diabetic nephropathy that can progress to renal failure. In this study, we addressed whether urine-derived epithelial cells (URECs) from patients with GSD1a maintain their biological features, and whether they can be used as a model to study the renal and metabolic phenotypes of this genetic condition. Studies were performed on cells extracted from urine samples of GSD1a and healthy subjects. URECs were characterized after the fourth passage by transmission electron microscopy and immunofluorescence. Reactive oxygen species (ROS), at different glucose concentrations, were measured by fluorescent staining. We cultured URECs from three patients with GSD1a and three healthy controls. At the fourth passage, URECs from GSD1a patients maintained their massive glycogen content. GSD1a and control cells showed the ciliary structures of renal tubular epithelium and the expression of epithelial (E-cadherin) and renal tubular cells (aquaporin 1 and 2) markers. Moreover, URECs from both groups responded to changes in glucose concentrations by modulating ROS levels. GSD1a cells were featured by a specific response to the low glucose stimulus, which is the condition that more resembles the metabolic derangement of patients with GSD1a. Through this study, we demonstrated that URECs might represent a promising experimental model to study the molecular mechanisms leading to renal damage in GSD1a, due to pathological glycogen storage.
Transcriptomic Analysis Provides Insight into the ROS Scavenging System and Regulatory Mechanisms in Atriplex canescens Response to Salinity
Authors: Feng Shan , Wang Beibei , Li Chan , Guo Huan , Bao Ai-Ke
Published: December 2022

Atriplex canescens is a representative halophyte with excellent tolerance to salt. Previous studies have revealed certain physiological mechanisms and detected functional genes associated with salt tolerance. However, knowledge on the ROS scavenging system and regulatory mechanisms in this species when adapting to salinity is limited. Therefore, this study further analyzed the transcriptional changes in genes related to the ROS scavenging system and important regulatory mechanisms in A. canescens under saline conditions using our previous RNA sequencing data. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation revealed that the differentially expressed genes (DEGs) were highly enriched in signal transduction- and reactive oxygen species-related biological processes, including “response to oxidative stress”, “oxidoreductase activity”, “protein kinase activity”, “transcription factor activity”, and “plant hormone signal transduction”. Further analyses suggested that the transcription abundance of many genes involved in SOD, the AsA-GSH cycle, the GPX pathway, PrxR/Trx, and the flavonoid biosynthesis pathway were obviously enhanced. These pathways are favorable for scavenging excessive ROS induced by salt and maintaining the integrity of the cell membrane. Meanwhile, many vital transcription factor genes (WRKY, MYB, ZF, HSF, DREB, and NAC) exhibited increased transcripts, which is conducive to dealing with saline conditions by regulating downstream salt-responsive genes. Furthermore, a larger number of genes encoding protein kinases (RLK, CDPK, MAPK, and CTR1) were significantly induced by saline conditions, which is beneficial to the reception/transduction of salt-related signals. This study describes the abundant genetic resources for enhancing the salt tolerance in salt-sensitive plants, especially in forages and crops.
The Adaptability of Chromosomal Instability in Cancer Therapy and Resistance
Authors: Carloni Vinicio , Morganti Elisa , Galli Andrea , Mazzocca Antonio
Published: December 2022

Variation in chromosome structure is a central source of DNA damage and DNA damage response, together representinga major hallmark of chromosomal instability. Cancer cells under selective pressure of therapy use DNA damage and DNA damage response to produce newfunctional assets as an evolutionary mechanism. Recent efforts to understand DNA damage/chromosomal instability and elucidate its role in initiation or progression of cancer have also disclosed its vulnerabilities represented by inappropriate DNA damage response, chromatin changes, andinflammation. Understanding these vulnerabilities can provide important clues for predicting treatment response and for the development of novel strategies that prevent the emergence of therapy resistant tumors.
Molecular Mechanisms of Flavonoids against Tumor Gamma-Herpesviruses and Their Correlated Cancers—A Focus on EBV and KSHV Life Cycles and Carcinogenesis
Authors: Hassan Sherif T. S. , Šudomová Miroslava
Published: December 2022

Epstein–Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) are cancer-causing viruses that belong to human gamma-herpesviruses. They are DNA viruses known to establish lifelong infections in humans, with the ability to develop various types of cancer. Drug resistance remains the main barrier to achieving effective therapies for viral infections and cancer. Thus, new medications with dual antiviral and anticancer actions are highly needed. Flavonoids are secondary metabolites biosynthesized by plants with diverse therapeutic effects on human health. In this review, we feature the potential role of flavonoids (flavones, protoflavones, isoflavones, flavanones, flavonols, dihydroflavonols, catechins, chalcones, anthocyanins, and other flavonoid-type compounds) in controlling gamma-herpesvirus-associated cancers by blocking EBV and KSHV infections and inhibiting the formation and growth of the correlated tumors, such as nasopharyngeal carcinoma, Burkitt’s lymphoma, gastric cancer, extranodal NK/T-cell lymphoma, squamous cell carcinoma, Kaposi sarcoma, and primary effusion lymphoma. The underlying mechanisms via targeting EBV and KSHV life cycles and carcinogenesis are highlighted. Moreover, the effective concentrations or doses are emphasized.
Remembering the Legacy of Judi Tuerck
Authors: Morris Amy , Hermerath Cheryl , Ojodu Jelili , Buist Neil
Published: December 2022

Judith “Judi” Tuerck, RN, MS, one of the true pioneers in the development of newborn screening (NBS), passed away on Saturday, 18 June 2022 (Figure 1) [...]
Characterization of Fruit Quality Traits and Biochemical Properties in Different Myanmar Mango Cultivars during Ripening Stages
Authors: Kyaing May Sandar , Thandar San , Myint Moe Moe , Wai Khaing Phyo , Htwe Honey Thet Paing , Nyein Chan Myae , Han Jeung-Sul , Naing Aung Htay
Published: December 2022

Here, we characterized the changes in fruit quality and biochemical parameters in four Myanmar mango cultivars from ripening stage 1 to 4 at ambient temperature. Total soluble solids, total sugars, and reducing and non-reducing sugar content increased, whereas titratable acidity decreased with increasing storage time in all cultivars. ‘Sein Ta Lone’ showed the highest consumer acceptability, with maximum sensory quality scores owing to its unique characteristics. ‘Hin Thar’ and ‘Ma Chit Su’ also had better quality and sensory attributes than ‘Yin Kwae’. Sugar/acid ratios in all cultivars ranged from 23 to 50, the standard sugar/acid ratios in high-quality mango fruits. The total phenolic content (TPC) and antioxidant activity among cultivars ranged from 8.20 to 14.96 mg gallic acid equivalents and 19.52 to 26.79 mg vitamin C equivalents antioxidant capacity, respectively, per 100 g of fruit extract throughout the storage. ‘Hin Thar’ was the richest in phytochemical compounds. A significant positive correlation was found between total phenolic activity and 2,2-diphenyl-1-picryl-hydrazyl free radical scavenging activity of fruits, showing that TPC exhibited linear relationships with the antioxidant activities of each mango variety during the different stages of ripening.
Higher Frequencies of T-Cells Expressing NK-Cell Markers and Chemokine Receptors in Parkinson’s Disease
Authors: Goldeck David , Schulte Claudia , Teixeira dos Santos Marcia Cristina , Scheller Dieter , Öttinger Lilly , Pawelec Graham , Deuschle Christian , Berg Daniela , Nogueira da Costa Andre , Maetzler Walter
Published: December 2022

Immune cells are thought to be involved in a destructive cycle of sterile cerebral inflammatory responses in neurodegenerative diseases such as Parkinson’s Disease (PD). Despite their peripheral origin, immune cells may enter the CNS due to impaired blood–brain barrier function and may potentially contribute to neuronal damage. Hence, specific characteristics of peripherally activated immune cells could help in understanding neurodegeneration in PD and could potentially serve as accessible disease markers. To investigate immune cell activation status, the expression of receptors for cell surface molecules CD161, NKG2A, NKG2C and NKG2D as well as chemokine receptors CCR6, CXCR2, CXCR3 and CCR5 associated with neurodegenerative diseases was investigated. The frequencies of peripheral CD8+ T-cells expressing the inhibitory and activating receptors NKG2A and NKG2C, and the activating receptor NKG2D were higher in PD patients than in healthy matched controls. The frequencies of NKG2C+CD8− cells were also higher, whereas the frequencies of CD161+ cells were not significantly different. Of the chemokine receptor-expressing cells, only the proportion of CD4−CD56+CCR5+ T-cells was higher in PD patients than in the controls. These observations support the hypothesis that an imbalance in the activation state of T-cells plays a role in the pathological processes of PD and suggest that peripheral blood immune cell phenotypes could be specific early markers for inflammation in PD.
High-Sensitivity Cardiac Troponin Publications during the COVID-19 Pandemic (2020–2022)
Authors: Kavsak Peter A.
Published: December 2022

The first publications detailing the clinical utility of high-sensitivity cardiac troponin (hs-cTn) in patients with possible acute coronary syndrome (ACS) are traceable to 2009 [...]
The Impact of b/tsDMARD Dose Reduction on Chronic Hepatitis B in Rheumatoid Arthritis Patients: A Two-Center Long-Term Safety Analysis
Authors: Chen Der-Yuan , Chen Hsin-Hua , Chang Shih-Hsin , Chen Yi-Ming , Huang Po-Hao , Hsieh Chia-Wei , Lan Joung-Liang , Tang Kuo-Tung
Published: December 2022

Background: We aimed to investigate the change of hepatitis B virus (HBV) viral loads and HBV reactivation (HBVr) in rheumatoid arthritis (RA) patients after tapering the dose of biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Methods: This two-center analysis retrospectively investigated the virological and biochemical evidence of HBVr in RA patients who underwent b/tsDMARD dose reduction. Serum levels of viral loads were determined using real-time PCR. Serum levels of alanine transaminase (ALT) were determined using spectrophotometry. Results: Among a total of 40 HBsAg+ RA patients who tapered b/tsDMARDs, 14 (35%) used tocilizumab; 12 (30%) used tumor necrosis factor (TNF)-α inhibitors; and the rest used either abatacept or tofacitinib. We found that patients who had detectable HBV DNA before tapering achieved a one-log reduction in HBV DNA levels, in contrast to the findings in the other 12 patients who did not taper b/tsDMARDs (no change in HBV DNA levels with time). The incidence of HBVr (increased viral loads with hepatitis) was 4.62 (95%CI: 2.08, 10.28) and 2.26 (95%CI: 0.56, 9.02) events per 100 person-years before and after b/tsDMARD tapering, respectively. Conclusions: The HBV viral load decreased after the tapering of b/tsDMARDs in RA patients with detectable HBV DNA. Dose reduction in b/tsDMARDs might be beneficial.
Whether Renal Pathology Is an Independent Predictor for End-Stage Renal Disease in Diabetic Kidney Disease Patients with Nephrotic Range Proteinuria: A Biopsy-Based Study
Authors: Wang Tingli , Zhang Junlin , Wang Yiting , Zhao Lijun , Wu Yucheng , Ren Honghong , Zou Yutong , Zhang Rui , Xu Huan , Chai Zhonglin , Cooper Mark , Zhang Jie , Liu Fang
Published: December 2022

Aims: To investigate whether renal pathology is an independent predictor for end-stage renal disease (ESRD) in diabetic kidney diseases (DKD) with nephrotic range proteinuria. Methods: A total of 199 DKD patients with nephrotic range proteinuria underwent renal biopsy and were divided into an ESRD group and a non-ESRD group. A Kaplan–Meier analysis was used to compare renal survival rate, and univariate and multivariate Cox proportional hazard analyses were used to determine the predictors of the ESRD. Results: The mean age of included patients was 51.49 ± 9.12 years and 113 patients (56.8%) progressed to ESRD. The median follow-up period was 16 (12–28) months. The glomerular pathology class III is the most common type (54.3%). In the Kaplan–Meier analysis, compared with patients without ESRD, patients with ESRD had a longer duration of diabetes (≥6 years), lower eGFR (<60 mL/min/1.73 m2), lower albumin (<30 g/L), lower hemoglobin (<120 g/L), and a higher grade of glomerular stage (class III + IV vs. class I + II) (p < 0.05). The hemoglobin and e-GFR, but not the histopathological damage, were significantly associated with a higher risk of ESRD in both the univariate and multivariate Cox analyses. Conclusions: In patients with diabetic kidney disease characterized by nephrotic range proteinuria, histopathological damage (glomerular alterations, interstitial fibrosis and tubular atrophy (IFTA), interstitial inflammation, and arteriolar hyalinosis) is not associated with poor renal outcomes, but hemoglobin and e-GFR could predict poor renal outcomes.
The Usefulness of Optical Coherence Tomography in Disease Progression Monitoring in Younger Patients with Relapsing-Remitting Multiple Sclerosis: A Single-Centre Study
Authors: Torbus Magdalena , Niewiadomska Ewa , Dobrakowski Paweł , Papuć Ewa , Rybus-Kalinowska Barbara , Szlacheta Patryk , Korzonek-Szlacheta Ilona , Kubicka-Bączyk Katarzyna , Łabuz-Roszak Beata
Published: December 2022

The purpose of the study was to assess the usefulness of optical coherence tomography (OCT) in the detection of the neurodegenerative process in younger patients with multiple sclerosis (MS). The study group consisted of 61 patients with a relapsing remitting course of MS (mean age 36.4 ± 6.7 years) divided into two groups: short (≤5 years) and long (>10 years) disease duration. OCT, P300 evoked potential, Montreal Cognitive Assessment, and performance subtests (Picture Completion and Digit Symbol) of the Wechsler Adult Intelligence Scale were performed in all patients. Mean values of most parameters assessed in OCT (pRNFL Total, pRNFL Inferior, pRNFL Superior, pRNFL Temporalis, mRNFL, GCIPL, mRNFL+GCIPL) were significantly lower in MS patients in comparison to controls. And in patients with longer disease duration in comparison to those with shorter. Most OCT parameters negatively correlated with the EDSS score (p < 0.05). No significant correlation was found between OCT results and both P300 latency and the results of psychometric tests. OCT, as a simple, non-invasive, quick, and inexpensive method, could be useful for monitoring the progression of disease in MS patients.
The Utility of Pre-Treatment Inflammation Markers as Associative Factors to the Adverse Outcomes of Vulvar Cancer: A Study on Staging, Nodal Involvement, and Metastasis Models
Authors: Winarto Hariyono , Habiburrahman Muhammad , Anggraeni Tricia Dewi , Nuryanto Kartiwa Hadi , Julianti Renny Anggia , Purwoto Gatot , Andrijono Andrijono
Published: December 2022

Background: Given the role of inflammation in carcinogenesis, this study investigated the utility of pre-treatment inflammatory markers as associative indicators for advanced-stage disease, lymph node metastasis (LNM), and distant metastasis (DM) in vulvar cancer (VC). Methods: A cross-sectional study was conducted on 86 women with VC in a single centre in Jakarta, Indonesia. The laboratory data was based on C-reactive protein (CRP), procalcitonin, the erythrocyte sedimentation rate (ESR) and fourteen derived, recorded and calculated ratios: leukocyte-to-platelet (LPR), neutrophil-to-lymphocyte (NLR), derived neutrophil-to-lymphocyte (dNLR), neutrophil-to-monocyte (NMR), platelet-to-monocyte (PLR), lymphocyte-to-monocyte (LMR), basophil-to-monocyte (BLR), systemic immune-inflammation index (SII), body mass index, albumin, and NLR (BAN) score, haemoglobin-to-platelet (HPR), prognostic nutritional index (PNI), modified Glasgow Prognostic Score (mGPS), CRP-to-albumin, and CRP-to-procalcitonin. The optimal cut-off for each marker was determined using receiver operating characteristic (ROC) curve analysis, and their diagnostic indicator performances were assessed. The utility of these ratios as associative factors for three endpoints was further evaluated in multivariate regression models. Results: Investigated inflammatory markers exhibited specific performances for individual adverse outcomes, proving a fair to excellent ability in case finding and screening. After adjustment, the BAN score ≤ 334.89 (OR 9.20, p = 0.001) and ESR ≥ 104 (OR 4.18, p = 0.048) become two advanced-stage associative factors with AUC: 0.769. LNM was solely determined by higher NLR ≥ 2.83 (OR 4.15, p = 0.014) with AUC: 0.615. Meanwhile, BLR ≥ 0.035 (OR 5.67, p = 0.001) and ESR ≥ 84 (OR 6.01, p = 0.003) were contributing factors for DM, with AUC: 0.765. Conclusions: Inflammatory markers are crucial for identifying the deleterious outcomes of VC. Accordingly, yielded models require external validation.
The Effect of Negative Pressure on Wound Healing and Regeneration in Closed Incisions under High Tension: Evidence from Animal Studies and Clinical Experience
Authors: Hsiao Hui-Yi , Hsieh Wei-Chuan , Chang Frank Chun-Shin , Liu Jia-Wei , Kuo Wen-Ling , Cheong David Chon-Fok , Huang Jung-Ju
Published: December 2022

Closed-incision negative-pressure wound therapy (iNPWT) is known to enhance wound healing and tissue regeneration. The main aim of the present study is to investigate its effectiveness on enhancing wound healing under tension. An animal study was designed using a swine model by removing a skin flap to create a wound that could be closed primarily under tension, and iNPWT was applied. The enhancement of angiogenesis, lymphangiogenesis, collagen deposition, and tissue proliferation with reduced inflammation by iNPWT was confirmed by histology. The effect of iNPWT was further verified in patients receiving a profunda artery perforator (PAP) free flap for breast reconstruction. iNPWT was applied on the transversely designed donor site in continuous mode for 7 days, in which the wound was always closed under tension. A significant improvement in off-bed time was noted with the application of iNPWT (4.6 ± 1.1st and 5.5 ± 0.8th postoperative days in the iNPWT and control groups, respectively, p = 0.028). The control group (without iNPWT treatment) presented more cases of poor wound healing in the acute (23.1% vs. 0%) and wound breakdown in the late (23.1% vs. 8.3%) stages. The treatment of closed incisions under tension with iNPWT clinically enhances wound healing and tissue regeneration and with histological evidence.
Bilateral Fungal Endophthalmitis: A Multidisciplinary Challenge
Authors: Ecsedy Monika , Dohán Judit , Peskó Gergely , Ludwig Endre , Mohammadpour Behnam , Nagy Zoltán Zsolt , Récsán Zsuzsa
Published: December 2022

Endophthalmitis is a serious ophthalmologic condition involving purulent inflammation of the intraocular spaces. Fungal endophthalmitis is a highly sight-threatening condition that can be complicated by difficulties in diagnosis and therapeutic delay. We report herein a rare case of bilateral endogenous Candida albicans endophthalmitis with favorable outcome. High suspicion of fungal origin is essential since the diagnosis for fungal endophthalmitis is usually based on the ophthalmological exhibition in combination with the presence of fungemia or predisposing factors. Only prompt initiation of systemic, intravitreal and surgical treatment may reduce ocular morbidity or even mortality.
Chito-Oligosaccharide and Propolis Extract of Stingless Bees Reduce the Infection Load of Nosema ceranae in Apis dorsata (Hymenoptera: Apidae)
Authors: Ponkit Rujira , Naree Sanchai , Pichayangkura Rath , Beaurepaire Alexis , Paxton Robert J. , Mayack Christopher L. , Suwannapong Guntima
Published: December 2022

Nosema ceranae is a microsporidian that infects Apis species. Recently, natural compounds have been proposed to control nosemosis and reduce its transmission among honey bees. We investigated how ethanolic extract of Tetrigona apicalis’s propolis and chito-oligosaccharide (COS) impact the health of N. ceranae-infected Apis dorsata workers. Nosema ceranae spores were extracted from the guts of A. florea workers and fed 106 spores dissolved in 2 µL 50% (w/v) sucrose solution to A. dorsata individually. These bees were then fed a treatment consisting either of 0% or 50% propolis extracts or 0 ppm to 0.5 ppm COS. We found that propolis and COS significantly increased the number of surviving bees and lowered the infection ratio and spore loads of N. ceranae-infected bees 14 days post-infection. Our results suggest that propolis extract and COS could be possible alternative treatments to reduce N. ceranae infection in A. dorsata. Moreover, N. ceranae isolated from A. florea can damage the ventricular cells of A. dorsata, thereby lowering its survival. Our findings highlight the importance of considering N. ceranae infections and using alternative treatments at the community level where other honey bee species can act as a reservoir and readily transmit the pathogen among the honey bee species.