bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of B Cell-Activating Factor in Fibrosis Progression in a Murine Model of Non-Alcoholic Steatohepatitis
Authors: Kanemitsu-Okada Kozue , Abe Masanori , Nakamura Yoshiko , Miyake Teruki , Watanabe Takao , Yoshida Osamu , Koizumi Yohei , Hirooka Masashi , Tokumoto Yoshio , Matsuura Bunzo , Koizumi Mitsuhito , Hiasa Yoichi
Published: January 2023

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease all over the world. Therapeutic strategies targeting its multidirectional pathways are required. Particularly, fibrosis is closely associated with its prognosis. We previously found that B cell-activating factor (BAFF) is associated with severity of NAFLD. Here, we determined the direct in vivo role of BAFF in the development of liver fibrosis. Histological and biochemical analyses were performed using wild-type and BAFF-deficient mice. We established a murine model of non-alcoholic steatohepatitis (NASH) using carbon tetrachloride injection accompanied by high-fat/high-cholesterol diet feeding. Additionally, in vitro analysis using mouse macrophage-like cell line RAW264.7 and primary hepatic stellate cells was performed. Hepatic steatosis and inflammation, and most importantly, the progression of liver fibrosis, were ameliorated in BAFF-deficient mice compared to those wild-type mice in our model. Additionally, BAFF deficiency reduced the number of CD11c+ M1-type macrophages in the liver. Moreover, BAFF stimulated RAW264.7 cells to secrete nitric oxide and tumor necrosis factor α, which drove the activation of hepatic stellate cells. This indicates that BAFF plays a crucial role in NASH development and may be a promising therapeutic target for NASH.
A Mini Review of Novel Topoisomerase II Inhibitors as Future Anticancer Agents
Authors: Okoro Cosmas O. , Fatoki Toluwase Hezekiah
Published: January 2023

Several reviews of inhibitors of topoisomerase II have been published, covering research before 2018. Therefore, this review is focused primarily on more recent publications with relevant points from the earlier literature. Topoisomerase II is an established target for anticancer drugs, which are further subdivided into poisons and catalytic inhibitors. While most of the topoisomerase II-based drugs in clinical use are mostly topoisomerase II poisons, their mechanism of action has posed severe concern due to DNA damaging potential, including the development of multi-drug resistance. As a result, we are beginning to see a gradual paradigm shift towards non-DNA damaging agents, such as the lesser studied topoisomerase II catalytic inhibitors. In addition, this review describes some novel selective catalytic topoisomerase II inhibitors. The ultimate goal is to bring researchers up to speed by curating and delineating new scaffolds as the leads for the optimization and development of new potent, safe, and selective agents for the treatment of cancer.
The Role of Alpha-Fetoprotein (AFP) in Contemporary Oncology: The Path from a Diagnostic Biomarker to an Anticancer Drug
Authors: Głowska-Ciemny Joanna , Szymański Marcin , Kuszerska Agata , Malewski Zbyszko , von Kaisenberg Constantin , Kocyłowski Rafał
Published: January 2023

This article presents contemporary opinion on the role of alpha-fetoprotein in oncologic diagnostics and treatment. This role stretches far beyond the already known one—that of the biomarker of hepatocellular carcinoma. The turn of the 20th and 21st centuries saw a significant increase in knowledge about the fundamental role of AFP in the neoplastic processes, and in the induction of features of malignance and drug resistance of hepatocellular carcinoma. The impact of AFP on the creation of an immunosuppressive environment for the developing tumor was identified, giving rise to attempts at immunotherapy. The paper presents current and prospective therapies using AFP and its derivatives and the gene therapy options. We directed our attention to both the benefits and risks associated with the use of AFP in oncologic therapy.
Editorial to Special Issue “Glioblastoma: Recapitulating the Key Breakthroughs and Future Perspective”
Authors: Sharma Amit , Guerrero-Cázares Hugo , Maciaczyk Jarek
Published: January 2023

Glioblastoma (GBM) remains the most common and aggressive malignant primary brain tumor [...]
Insulin Receptor Substrate 1 Signaling Inhibits Foxp3 Expression and Suppressive Functions in Treg Cells through the mTORC1 Pathway
Authors: Lee Woo Ho , Kim Ga Eul , Hong Kyung Jin , Kim Hyeong Su , Lee Gap Ryol
Published: January 2023

Regulatory T (Treg) cells play an important role in immune homeostasis by inhibiting cells within the innate and adaptive immune systems; therefore, the stability and immunosuppressive function of Treg cells need to be maintained. In this study, we found that the expression of insulin receptor substrate 1 (IRS1) by Treg cells was lower than that by conventional CD4 T cells. IRS1-overexpressing Treg cells showed the downregulated expression of FOXP3, as well as Treg signature markers CD25 and CTLA4. IRS1-overexpressing Treg cells also showed diminished immunosuppressive functions in an in vitro suppression assay. Moreover, IRS1-overexpressing Treg cells were unable to suppress the pathogenic effects of conventional T cells in a transfer-induced colitis model. IRS1 activated the mTORC1 signaling pathway, a negative regulator of Treg cells. Moreover, IRS1 destabilized Treg cells by upregulating the expression of IFN-γ and Glut1. Thus, IRS1 acts as a negative regulator of Treg cells by downregulating the expression of FOXP3 and disrupting stability.
Antiproliferative Activity of Antibiotics through DNA Binding Mechanism: Evaluation and Molecular Docking Studies
Authors: Magklaras Alexandros-Dimitrios C. , Banti Christina N. , Hadjikakou Sotiris K.
Published: January 2023

The antiproliferative activity of three antibiotics clinically use, was studied through DNA inhibition mechanisms, ex vivo, in silico and in vitro. The ex vivo interaction of DNA with ciprofloxacin hydrochloride (CIP·HCl), penicillin G sodium salt (PEN·Na), and tetracycline hydrochloride (TC·HCl) was determined by UV-Vis spectra and viscosity measurements. Furthermore, their binding constants (Kb) toward CT-DNA were calculated (Kb = (2.8 ± 0.6) × 104 (CIP·HCl), (0.4 ± 0.1) × 104 (PEN·Na) and (6.9 ± 0.3) × 104 (TC·HCl) Μ−1). Docking studies on the binding interactions of antibiotics with DNA were performed to rationalize the ex vivo results. The in vitro antiproliferative activity of the antibiotics was evaluated against human breast adenocarcinoma (MCF-7) cells (IC50 values: 417.4 ± 28.2 (CIP·HCl), >2000 (PEN·Na) and 443.1 ± 17.2 (TC·HCl) μΜ). Cell cycle arrest studies confirmed the apoptotic type of MCF-7 cells. The toxicity of the studied agents was in vitro tested against human fetal lung fibroblast cells (MRC-5). The results are compared with the corresponding one for doxorubicin (DOX). Despite their low binding affinity to DNA (Kb) or their different mode of interaction, TC·HCl (anthracycline) or CIP·HCl (quinolones), exhibit notable antiproliferative activity and low toxicity.
NMR Analysis Suggests Synergy between the RRM2 and the Carboxy-Terminal Segment of Human La Protein in the Recognition and Interaction with HCV IRES
Authors: Argyriou Aikaterini I. , Machaliotis Georgios A. , Makrynitsa Garyfallia I. , Kaliatsi Eleni G. , Stathopoulos Constantinos , Spyroulias Georgios A.
Published: January 2023

The La protein (lupus antigen) is a ubiquitous RNA-binding protein found in all human cells. It is mainly localized in the nucleus, associates with all RNA polymerase III (Pol III) transcripts, as the first factor they interact with, and modulates subsequent processing events. Export of La to the cytoplasm has been reported to stimulate the decoding of specific cellular and viral mRNAs through IRES-dependent (Internal ribosome entry site) binding and translation. Using NMR (Nuclear Magnetic Resonance) spectroscopy, we provide atomic-level-resolution structural insights on the dynamical properties of human La (hLa) protein in solution. Moreover, using a combination of NMR spectroscopy and isothermal titration calorimetry (ITC), we provide evidence about the role and ligand specificity of the C-terminal domain of the La protein (RRM2 and C-terminal region) that could mediate the recognition of HCV-IRES.
Active Glycogen Synthase in the Liver Prevents High-Fat Diet-Induced Glucose Intolerance, Decreases Food Intake, and Lowers Body Weight
Authors: López-Soldado Iliana , Guinovart Joan J. , Duran Jordi
Published: January 2023

Many lines of evidence demonstrate a correlation between liver glycogen content and food intake. We previously demonstrated that mice overexpressing protein targeting to glycogen (PTG) specifically in the liver—which have increased glycogen content in this organ—are protected from high-fat diet (HFD)-induced obesity by reduced food intake. However, the use of PTG to increase liver glycogen implies certain limitations. PTG stimulates glycogen synthesis but also inhibits the enzyme responsible for glycogen degradation. Furthermore, as PTG is a regulatory subunit of protein phosphatase 1 (PP1), which regulates many cellular functions, its overexpression could have side effects beyond the regulation of glycogen metabolism. Therefore, it is necessary to determine whether the direct activation of glycogen synthesis, without affecting its degradation or other cellular functions, has the same effects. To this end, we generated mice overexpressing a non-inactivatable form of glycogen synthase (GS) specifically in the liver (9A-MGSAlb mice). Control and 9a-MGSAlb mice were fed a standard diet (SD) or HFD for 16 weeks. Glucose tolerance and feeding behavior were analyzed. 9A-MGSAlb mice showed an increase in hepatic glycogen in fed and fasting conditions. When fed an HFD, these animals preserved their hepatic energy state, had a reduced food intake, and presented a lower body weight and fat mass than control animals, without changes in energy expenditure. Furthermore, 9A-MGSAlb animals showed improved glucose tolerance when fed an SD or HFD. Moreover, liver triacylglycerol levels that were increased after HFD feeding were lower in these mice. These results confirm that increased liver glycogen stores contribute to decreased appetite and improve glucose tolerance in mice fed an HFD. On the basis of our findings, strategies to preserve hepatic glycogen stores emerge as potential treatments for obesity and hyperglycemia.
Weak Ultrasound Contributes to Neuromodulatory Effects in the Rat Motor Cortex
Authors: Chu Po-Chun , Huang Chen-Syuan , Chang Pi-Kai , Chen Rou-Shayn , Chen Ko-Ting , Hsieh Tsung-Hsun , Liu Hao-Li
Published: January 2023

Transcranial focused ultrasound (tFUS) is a novel neuromodulating technique. It has been demonstrated that the neuromodulatory effects can be induced by weak ultrasound exposure levels (spatial-peak temporal average intensity, ISPTA < 10 mW/cm2) in vitro. However, fewer studies have examined the use of weak tFUS to potentially induce long-lasting neuromodulatory responses in vivo. The purpose of this study was to determine the lower-bound threshold of tFUS stimulation for inducing neuromodulation in the motor cortex of rats. A total of 94 Sprague–Dawley rats were used. The sonication region aimed at the motor cortex under weak tFUS exposure (ISPTA of 0.338–12.15 mW/cm2). The neuromodulatory effects of tFUS on the motor cortex were evaluated by the changes in motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS). In addition to histology analysis, the in vitro cell culture was used to confirm the neuromodulatory mechanisms following tFUS stimulation. In the results, the dose-dependent inhibitory effects of tFUS were found, showing increased intensities of tFUS suppressed MEPs and lasted for 30 min. Weak tFUS significantly decreased the expression of excitatory neurons and increased the expression of inhibitory GABAergic neurons. The PIEZO-1 proteins of GABAergic neurons were found to involve in the inhibitory neuromodulation. In conclusion, we show the use of weak ultrasound to induce long-lasting neuromodulatory effects and explore the potential use of weak ultrasound for future clinical neuromodulatory applications.
The Intricate Role of Non-Coding RNAs in Sepsis-Associated Disseminated Intravascular Coagulation
Authors: Cánovas-Cervera Irene , Nacher-Sendra Elena , Osca-Verdegal Rebeca , Dolz-Andrés Enric , Beltrán-García Jesús , Rodríguez-Gimillo María , Ferrando-Sánchez Carolina , Carbonell Nieves , García-Giménez José Luis
Published: January 2023

Disseminated Intravascular Coagulation (DIC) is a type of tissue and organ dysregulation in sepsis, due mainly to the effect of the inflammation on the coagulation system. Unfortunately, the underlying molecular mechanisms that lead to this disorder are not fully understood. Moreover, current biomarkers for DIC, including biological and clinical parameters, generally provide a poor diagnosis and prognosis. In recent years, non-coding RNAs have been studied as promising and robust biomarkers for a variety of diseases. Thus, their potential in the diagnosis and prognosis of DIC should be further studied. Specifically, the relationship between the coagulation cascade and non-coding RNAs should be established. In this review, microRNAs, long non-coding RNAs, and circular RNAs are studied in relation to DIC. Specifically, the axis between these non-coding RNAs and the corresponding affected pathway has been identified, including inflammation, alteration of the coagulation cascade, and endothelial damage. The main affected pathway identified is PI3K/AKT/mTOR axis, where several ncRNAs participate in its regulation, including miR-122-5p which is sponged by circ_0005963, ciRS-122, and circPTN, and miR-19a-3p which is modulated by circ_0000096 and circ_0063425. Additionally, both miR-223 and miR-24 were found to affect the PI3K/AKT pathway and were regulated by lncGAS5 and lncKCNQ1OT1, respectively. Thus, this work provides a useful pipeline of inter-connected ncRNAs that future research on their impact on DIC can further explore.
Follicular Fluid Components in Reduced Ovarian Reserve, Endometriosis, and Idiopathic Infertility
Authors: Collodel Giulia , Gambera Laura , Stendardi Anita , Nerucci Fabiola , Signorini Cinzia , Pisani Caterina , Marcheselli Marzia , Vellucci Francesca Letizia , Pizzasegale Silvana Enrica , Micheli Lucia , Moretti Elena
Published: January 2023

Follicular fluid (FF) molecules, and their increase or decrease, can contribute to appropriate follicular growth and oocyte maturation, thus being related to female infertility conditions. In this paper, we studied the changes and the relationships of some biochemical components, hormones, antioxidant enzymes, F2-Isoprostanes (F2-IsoPs), and resolvin (Rv) D1 in the FF of infertile women with different reproductive conditions such as endometriosis, reduced ovarian reserve, and idiopathic infertility during assisted reproductive techniques (ART). In the whole population, positive correlations between albumin (ALB)/iron (Fe), ALB/beta-2-microglobulin (B2MG), and F2-IsoPs/RvD1 were detected in the FF. In FF from aged women, increased levels of follicle stimulating hormone (FSH) and reduced anti-Müllerian hormone (AMH) levels were associated with a worse oocyte quality. The negative ART outcome was influenced by patient age and AMH, B2MG, and FSH levels. Moreover, the reduced ovarian reserve condition was characterised by a significant decrease in oocyte number and quality, AMH amount, and lactate dehydrogenase (LDH) activity, as well as by an increase in age and FSH levels. In the presence of endometriosis, high levels of MDA and RvD1 were detected in FF, with a decrease in luteinising hormone (LH). Finally, among the molecules examined, none characterised the condition of idiopathic infertility. These data could support the identification of new FF markers in different reproductive disorders, suggesting the need for personalised therapeutic approaches and optimised ART outcomes. In particular, the evaluation of resolvins and lipid mediators in FF could be a promising field of investigation with which to understand the entity of oxidative stress and inflammation in some female infertility conditions.
Peripheral Blood Genes Crosstalk between COVID-19 and Sepsis
Authors: Fang Changyin , Ma Yongping
Published: January 2023

Severe coronavirus disease 2019 (COVID-19) has led to a rapid increase in death rates all over the world. Sepsis is a life-threatening disease associated with a dysregulated host immune response. It has been shown that COVID-19 shares many similarities with sepsis in many aspects. However, the molecular mechanisms underlying sepsis and COVID-19 are not well understood. The aim of this study was to identify common transcriptional signatures, regulators, and pathways between COVID-19 and sepsis, which may provide a new direction for the treatment of COVID-19 and sepsis. First, COVID-19 blood gene expression profile (GSE179850) data and sepsis blood expression profile (GSE134347) data were obtained from GEO. Then, we intersected the differentially expressed genes (DEG) from these two datasets to obtain common DEGs. Finally, the common DEGs were used for functional enrichment analysis, transcription factor and miRNA prediction, pathway analysis, and candidate drug analysis. A total of 307 common DEGs were identified between the sepsis and COVID-19 datasets. Protein–protein interactions (PPIs) were constructed using the STRING database. Subsequently, hub genes were identified based on PPI networks. In addition, we performed GO functional analysis and KEGG pathway analysis of common DEGs, and found a common association between sepsis and COVID-19. Finally, we identified transcription factor–gene interaction, DEGs-miRNA co-regulatory networks, and protein–drug interaction, respectively. Through ROC analysis, we identified 10 central hub genes as potential biomarkers. In this study, we identified SARS-CoV-2 infection as a high risk factor for sepsis. Our study may provide a potential therapeutic direction for the treatment of COVID-19 patients suffering from sepsis.
An Insight into the Impact of Serum Tellurium, Thallium, Osmium and Antimony on the Antioxidant/Redox Status of PCOS Patients: A Comprehensive Study
Authors: Abudawood Manal , Alnuaim Lulu , Tabassum Hajera , Ghneim Hazem K. , Alfhili Mohammad A. , Alanazi Samyah T. , Alenzi Naif D. , Alsobaie Sarah
Published: January 2023

Humans exploit heavy metals for various industrial and economic reasons. Although some heavy metals are essential for normal physiology, others such as Tellurium (Te), Thallium (TI), antimony (Sb), and Osmium (Os) are highly toxic and can lead to Polycystic Ovarian Syndrome (PCOS), a common female factor of infertility. The current study was undertaken to determine levels of the heavy metals TI, Te, Sb and Os in serum of PCOS females (n = 50) compared to healthy non-PCOS controls (n = 56), and to relate such levels with Total Antioxidant Capacity (TAC), activity of key antioxidant enzymes, oxidative stress marker levels and redox status. PCOS serum samples demonstrated significantly higher levels of TI, Te, Sb and Os and diminished TAC compared to control (p < 0.001). Furthermore, there was significant inhibition of SOD, CAT and several glutathione-related enzyme activities in sera of PCOS patients with concurrent elevations in superoxide anions, hydrogen and lipid peroxides, and protein carbonyls, along with disrupted glutathione homeostasis compared to those of controls (p < 0.001 for all parameters). Additionally, a significant negative correlation was found between the elevated levels of heavy metals and TAC, indicative of the role of metal-induced oxidative stress as a prominent phenomenon associated with the pathophysiology of the underlying PCOS. Data obtained in the study suggest toxic metals as risk factors causing PCOS, and thus protective measures should be considered to minimize exposure to prevent such reproductive anomalies.
The Potential Role of Connexins in the Pathogenesis of Atherosclerosis
Authors: Kiełbowski Kajetan , Bakinowska Estera , Pawlik Andrzej
Published: January 2023

Connexins (Cx) are members of a protein family which enable extracellular and intercellular communication through hemichannels and gap junctions (GJ), respectively. Cx take part in transporting important cell–cell messengers such as 3′,5′-cyclic adenosine monophosphate (cAMP), adenosine triphosphate (ATP), and inositol 1,4,5-trisphosphate (IP3), among others. Therefore, they play a significant role in regulating cell homeostasis, proliferation, and differentiation. Alterations in Cx distribution, degradation, and post-translational modifications have been correlated with cancers, as well as cardiovascular and neurological diseases. Depending on the isoform, Cx have been shown either to promote or suppress the development of atherosclerosis, a progressive inflammatory disease affecting large and medium-sized arteries. Cx might contribute to the progression of the disease by enhancing endothelial dysfunction, monocyte recruitment, vascular smooth muscle cell (VSMC) activation, or by inhibiting VSMC autophagy. Inhibition or modulation of the expression of specific isoforms could suppress atherosclerotic plaque formation and diminish pro-inflammatory conditions. A better understanding of the complexity of atherosclerosis pathophysiology linked with Cx could result in developing novel therapeutic strategies. This review aims to present the role of Cx in the pathogenesis of atherosclerosis and discusses whether they can become novel therapeutic targets.
CD47-Dependent Regulation of Immune Checkpoint Gene Expression and MYCN mRNA Splicing in Murine CD8 and Jurkat T Cells
Authors: Kaur Sukhbir , Awad Duha , Finney Richard P. , Meyer Thomas J. , Singh Satya P. , Cam Margaret C. , Karim Baktiar O. , Warner Andrew C. , Roberts David D.
Published: January 2023

Elevated expression of CD47 in some cancers is associated with poor survival related to its function as an innate immune checkpoint when expressed on tumor cells. In contrast, elevated CD47 expression in cutaneous melanomas is associated with improved survival. Previous studies implicated protective functions of CD47 expressed by immune cells in the melanoma tumor microenvironment. RNA sequencing analysis of responses induced by CD3 and CD28 engagement on wild type and CD47-deficient Jurkat T lymphoblast cells identified additional regulators of T cell function that were also CD47-dependent in mouse CD8 T cells. MYCN mRNA expression was upregulated in CD47-deficient cells but downregulated in CD47-deficient cells following activation. CD47 also regulated alternative splicing that produces two N-MYC isoforms. The CD47 ligand thrombospondin-1 inhibited expression of these MYCN mRNA isoforms, as well as induction of the oncogenic decoy MYCN opposite strand (MYCNOS) RNA during T cell activation. Analysis of mRNA expression data for melanomas in The Cancer Genome Atlas identified a significant coexpression of MYCN with CD47 and known regulators of CD8 T cell function. Thrombospondin-1 inhibited the induction of TIGIT, CD40LG, and MCL1 mRNAs following T cell activation in vitro. Increased mRNA expression of these T cell transcripts and MYCN in melanomas was associated with improved overall survival.
Regulatory Role of Ribonucleotide Reductase Subunit M2 in Hepatocyte Growth and Pathogenesis of Hepatitis C Virus
Authors: Kitab Bouchra , Tsukiyama-Kohara Kyoko
Published: January 2023

Hepatitis C virus (HCV) frequently causes chronic infection in the human liver, which may progress to advanced hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. HCV primarily infects highly differentiated quiescent hepatocytes and can modulate cell cycle-regulatory genes and proliferation pathways, which ultimately contribute to persistent infection and pathogenesis. On the other hand, several studies have shown differential regulation of HCV RNA and viral protein expression levels, depending on the proliferation state of hepatocytes and the phase of the cell cycle. HCV typically requires factors provided by host cells for efficient and persistent viral replication. Previously, we found that HCV infection upregulates the expression of ribonucleotide reductase subunit M2 (RRM2) in quiescent hepatocytes. RRM2 is a rate-limiting protein that catalyzes de novo synthesis of deoxyribonucleotide triphosphates, and its expression is highly regulated during various phases of the cell cycle. RRM2 functions as a pro-viral factor essential for HCV RNA synthesis, but its functional role in HCV-induced liver diseases remains unknown. Here, we present a comprehensive review of the role of the hepatocyte cell cycle, in correlation with RRM2 expression, in the regulation of HCV replication. We also discuss the potential relevance of this protein in the pathogenesis of HCV, particularly in the development of hepatocellular carcinoma.
Roles of Tryptophan and Charged Residues on the Polymorphisms of Amyloids Formed by K-Peptides of Hen Egg White Lysozyme Investigated through Molecular Dynamics Simulations
Authors: Zein Husnul Fuad , Sutthibutpong Thana
Published: January 2023

Atomistic molecular dynamics simulations of amyloid models, consisting of the previously reported STDY-K-peptides and K-peptides from the hen egg white lysozyme (HEWL), were performed to address the effects of charged residues and pH observed in an in vitro study. Simulation results showed that amyloid models with antiparallel configurations possessed greater stability and compactness than those with parallel configurations. Then, peptide chain stretching and ordering were measured through the end-to-end distance and the order parameter, for which the amyloid models consisting of K-peptides and the STDY-K-peptides at pH 2 displayed a higher level of chain stretching and ordering. After that, the molecular mechanics energy decomposition and the radial distribution function (RDF) clearly displayed the importance of Trp62 to the K-peptide and the STDY-K-peptide models at pH 2. Moreover, the results also displayed how the negatively charged Asp52 disrupted the interaction networks and prevented the amyloid formation from STDY-K-peptide at pH 7. Finally, this study provided an insight into the interplay between pH conditions and molecular interactions underlying the formation of amyloid fibrils from short peptides contained within the HEWL. This served as a basis of understanding towards the design of other amyloids for biomaterial applications.
Prevention of Metabolic Syndrome by Phytochemicals and Vitamin D
Authors: Santa Kazuki , Kumazawa Yoshio , Nagaoka Isao
Published: January 2023

In recent years, attention has focused on the roles of phytochemicals in fruits and vegetables in maintaining and improving the intestinal environment and preventing metabolic syndrome. A high-fat and high-sugar diet, lack of exercise, and excess energy accumulation in the body can cause metabolic syndrome and induce obesity, diabetes, and disorders of the circulatory system and liver. Therefore, the prevention of metabolic syndrome is important. The current review shows that the simultaneous intake of phytochemicals contained in citruses and grapes together with vitamin D improves the state of gut microbiota and immunity, preventing metabolic syndrome and related diseases. Phytochemicals contained in citruses include polyphenols such as hesperidin, rutin, and naringin; those in grapes include quercetin, procyanidin, and oleanolic acid. The intake of these phytochemicals and vitamin D, along with prebiotics and probiotics, nurture good gut microbiota. In general, Firmicutes are obese-prone gut microbiota and Bacteroidetes are lean-prone gut microbiota; good gut microbiota nurture regulatory T cells, which suppress inflammatory responses and upregulate immunity. Maintaining good gut microbiota suppresses TNF-α, an inflammatory cytokine that is also considered to be a pathogenic contributor adipokine, and prevents chronic inflammation, thereby helping to prevent metabolic syndrome. Maintaining good gut microbiota also enhances adiponectin, a protector adipokine that prevents metabolic syndrome. For the prevention of metabolic syndrome and the reduction of various disease risks, the intake of phytochemicals and vitamin D will be important for human health in the future.
Modulation of NBAS-Related Functions in the Early Response to SARS-CoV-2 Infection
Authors: Granata Valentina , Pagani Isabel , Morenghi Emanuela , Schiavone Maria Lucia , Lezzi Alessandra , Ghezzi Silvia , Vicenzi Elisa , Poli Guido , Sobacchi Cristina
Published: January 2023

Upon infection, severe acute respiratory syndrome—coronavirus 2 (SARS-CoV-2) is predicted to interact with diverse cellular functions, such as the nonsense-mediated decay (NMD) pathway, as suggested by the identification of the core NMD factor upframeshift-1 (UPF1) in the SARS-CoV-2 interactome, and the retrograde transport from the Golgi to the endoplasmic reticulum (ER) through the endoplasmic reticulum–Golgi intermediate compartment (ERGIC), where coronavirus assembly occurs. Here, we investigated the expression and localization of the neuroblastoma-amplified sequence (NBAS) protein, a UPF1 partner for the NMD at the ER, participating also in retrograde transport, and of its functional partners, at early time points after SARS-CoV-2 infection of the human lung epithelial cell line Calu3. We found a significant decrease of DExH-Box Helicase 34 (DHX34), suppressor with morphogenetic effect on genitalia 5 (SMG5), and SMG7 expression at 6 h post-infection, followed by a significant increase of these genes and also UPF1 and UPF2 at 9 h post-infection. Conversely, NBAS and other genes coding for NMD factors were not modulated. Known NMD substrates related to cell stress (Growth Arrest Specific 5, GAS5; transducin beta-like 2, TBL2; and DNA damage-inducible transcript 3, DDIT3) were increased in infected cells, possibly as a result of alterations in the NMD pathway and of a direct effect of the infection. We also found that the expression of unconventional SNARE in the ER 1, USE1 (p31) and Zeste White 10 homolog, ZW10, partners of NBAS in the retrograde transport function, significantly increased over time in infected cells. Co-localization of NBAS and UPF1 proteins did not change within 24 h of infection nor did it differ in infected versus non-infected cells at 1 and 24 h after infection; similarly, the co-localization of NBAS and p31 proteins was not altered by infection in this short time frame. Finally, both NBAS and UPF1 were found to co-localize with SARS-CoV-2 S and N proteins. Overall, these data are preliminary evidence of an interaction between NBAS and NBAS-related functions and SARS-CoV-2 in infected cells, deserving further investigation.
Non-Coding RNAs Regulating Mitochondrial Functions and the Oxidative Stress Response as Putative Targets against Age-Related Macular Degeneration (AMD)
Authors: Hyttinen Juha M. T. , Blasiak Janusz , Kaarniranta Kai
Published: January 2023

Age-related macular degeneration (AMD) is an ever-increasing, insidious disease which reduces the quality of life of millions of elderly people around the world. AMD is characterised by damage to the retinal pigment epithelium (RPE) in the macula region of the retina. The origins of this multi-factorial disease are complex and still not fully understood. Oxidative stress and mitochondrial imbalance in the RPE are believed to be important factors in the development of AMD. In this review, the regulation of the mitochondrial function and antioxidant stress response by non-coding RNAs (ncRNAs), newly emerged epigenetic factors, is discussed. These molecules include microRNAs, long non-coding RNAs, and circular non-coding RNAs. They act mainly as mRNA suppressors, controllers of other ncRNAs, or by interacting with proteins. We include here examples of these RNA molecules which affect various mitochondrial processes and antioxidant signaling of the cell. As a future prospect, the possibility to manipulate these ncRNAs to strengthen mitochondrial and antioxidant response functions is discussed. Non-coding RNAs could be used as potential diagnostic markers for AMD, and in the future, also as therapeutic targets, either by suppressing or increasing their expression. In addition to AMD, it is possible that non-coding RNAs could be regulators in other oxidative stress-related degenerative diseases.
Acknowledgment to the Reviewers of IJTM in 2022
Authors:   IJTM Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
Multilingual Speech Recognition for Turkic Languages
Authors: Mussakhojayeva Saida , Dauletbek Kaisar , Yeshpanov Rustem , Varol Huseyin Atakan
Published: January 2023

The primary aim of this study was to contribute to the development of multilingual automatic speech recognition for lower-resourced Turkic languages. Ten languages—Azerbaijani, Bashkir, Chuvash, Kazakh, Kyrgyz, Sakha, Tatar, Turkish, Uyghur, and Uzbek—were considered. A total of 22 models were developed (13 monolingual and 9 multilingual). The multilingual models that were trained using joint speech data performed more robustly than the baseline monolingual models, with the best model achieving an average character and word error rate reduction of 56.7%/54.3%, respectively. The results of the experiment showed that character and word error rate reduction was more likely when multilingual models were trained with data from related Turkic languages than when they were developed using data from unrelated, non-Turkic languages, such as English and Russian. The study also presented an open-source Turkish speech corpus. The corpus contains 218.2 h of transcribed speech with 186,171 utterances and is the largest publicly available Turkish dataset of its kind. The datasets and codes used to train the models are available for download from our GitHub page.
LiST: A Lightweight Framework for Continuous Indian Sign Language Translation
Authors: K Amrutha , P Prabu , Poonia Ramesh Chandra
Published: January 2023

Sign language is a natural, structured, and complete form of communication to exchange information. Non-verbal communicators, also referred to as hearing impaired and hard of hearing (HI&HH), consider sign language an elemental mode of communication to convey information. As this language is less familiar among a large percentage of the human population, an automatic sign language translator that can act as an interpreter and remove the language barrier is mandatory. The advent of deep learning has resulted in the availability of several sign language translation (SLT) models. However, SLT models are complex, resulting in increased latency in language translation. Furthermore, SLT models consider only hand gestures for further processing, which might lead to the misinterpretation of ambiguous sign language words. In this paper, we propose a lightweight SLT framework, LiST (Lightweight Sign language Translation), that simultaneously considers multiple modalities, such as hand gestures, facial expressions, and hand orientation, from an Indian sign video. The Inception V3 architecture handles the features associated with different signer modalities, resulting in the generation of a feature map, which is processed by a two-layered (long short-term memory) (LSTM) architecture. This sequence helps in sentence-by-sentence recognition and in the translation of sign language into text and audio. The model was tested with continuous Indian Sign Language (ISL) sentences taken from the INCLUDE dataset. The experimental results show that the LiST framework achieved a high translation accuracy of 91.2% and a prediction accuracy of 95.9% while maintaining a low word-level translation error compared to other existing models.
Insecticide Resistance of Cimex lectularius L. Populations and the Performance of Selected Neonicotinoid-Pyrethroid Mixture Sprays and an Inorganic Dust
Authors: Yu Jin-Jia , Ranabhat Sabita , Wang Changlu
Published: January 2023

Insecticide resistance is one of the factors contributing to the resurgence of the common bed bug, Cimex lectularius L. This study aimed to profile the resistance levels of field-collected C. lectularius populations to two neonicotinoids and one pyrethroid insecticide and the performance of selected insecticide sprays and an inorganic dust. The susceptibility of 13 field-collected C. lectularius populations from the United States to acetamiprid, imidacloprid, and deltamethrin was assessed by topical application using a discriminating dose (10 × LD90 of the respective chemical against a laboratory strain). The RR50 based on KT50 values for acetamiprid and imidacloprid ranged from 1.0–4.7 except for the Linden 2019 population which had RR50 of ≥ 76.9. Seven populations had RR50 values of > 160 for deltamethrin. The performance of three insecticide mixture sprays and an inorganic dust were evaluated against three C. lectularius field populations. The performance ratio of Transport GHP (acetamiprid + bifenthrin), Temprid SC (imidacloprid + β-cyfluthrin), and Tandem (thiamethoxam + λ-cyhalothrin) based on LC90 were 900–2017, 55–129, and 100–196, respectively. Five minute exposure to CimeXa (92.1% amorphous silica) caused > 95% mortality to all populations at 72 h post-treatment.
Progress in Brain Magnetic Resonance Imaging of Individuals with Prader–Willi Syndrome
Authors: Huang Zhongxin , Cai Jinhua
Published: January 2023

Prader–Willi syndrome (PWS), a rare epigenetic disease mapping the imprinted chromosomal domain of 15q11.2-q13.3, manifests a regular neurodevelopmental trajectory in different phases. The current multimodal magnetic resonance imaging (MRI) approach for PWS focues on morphological MRI (mMRI), diffusion MRI (dMRI) and functional MRI (fMRI) to uncover brain alterations. This technique offers another perspective to understand potential neurodevelopmental and neuropathological processes of PWS, in addition to specific molecular gene expression patterns, various clinical manifestations and metabolic phenotypes. Multimodal MRI studies of PWS patients demonstrated common brain changes in the volume of gray matter, the integrity of the fiber tracts and the activation and connectivity of some networks. These findings mainly showed that brain alterations in the frontal reward circuit and limbic system were related to molecular genetics and clinical manifestations (e.g., overwhelming eating, obsessive compulsive behaviors and skin picking). Further exploration using a large sample size and advanced MRI technologies, combined with artificial intelligence algorithms, will be the main research direction to study the structural and functional changes and potential pathogenesis of PWS.
Chitosan/Phenolic Compounds Scaffolds for Connective Tissue Regeneration
Authors: Kaczmarek-Szczepańska Beata , Polkowska Izabela , Paździor-Czapula Katarzyna , Nowicka Beata , Gierszewska Magdalena , Michalska-Sionkowska Marta , Otrocka-Domagała Iwona
Published: January 2023

Chitosan-based scaffolds modified by gallic acid, ferulic acid, and tannic acid were fabricated. The aim of the experiment was to compare the compatibility of scaffolds based on chitosan with gallic acid, ferulic acid, or tannic acid using the in vivo method. For this purpose, materials were implanted into rabbits in the middle of the latissimus dorsi muscle length. A scaffold based on unmodified chitosan was implanted by the same method as a control. Moreover, the Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR) spectra and scanning electron microscope (SEM) observations were made to study the interactions between chitosan and phenolic acids. Additionally, antioxidant properties and blood compatibility were investigated. The results showed that all studied materials were safe and non-toxic. However, chitosan scaffolds modified by gallic acid and tannic acid were resorbed faster and, as a result, tissues were organized faster than those modified by ferulic acid or unmodified.
Effect of Sterilization Methods on Electrospun Scaffolds Produced from Blend of Polyurethane with Gelatin
Authors: Chernonosova Vera S. , Kuzmin Ilya E. , Shundrina Inna K. , Korobeynikov Mikhail V. , Golyshev Victor M. , Chelobanov Boris P. , Laktionov Pavel P.
Published: January 2023

Fibrous polyurethane-based scaffolds have proven to be promising materials for the tissue engineering of implanted medical devices. Sterilization of such materials and medical devices is an absolutely essential step toward their medical application. In the presented work, we studied the effects of two sterilization methods (ethylene oxide treatment and electron beam irradiation) on the fibrous scaffolds produced from a polyurethane-gelatin blend. Scaffold structure and properties were studied by scanning electron microscopy (SEM), atomic force microscopy (AFM), infrared spectroscopy (FTIR), a stress-loading test, and a cell viability test with human fibroblasts. Treatment of fibrous polyurethane-based materials with ethylene oxide caused significant changes in their structure (formation of glued-like structures, increase in fiber diameter, and decrease in pore size) and mechanical properties (20% growth of the tensile strength, 30% decline of the maximal elongation). All sterilization procedures did not induce any cytotoxic effects or impede the biocompatibility of scaffolds. The obtained data determined electron beam irradiation to be a recommended sterilization method for electrospun medical devices made from polyurethane-gelatin blends.
Magnetic Response of Nano/Microparticles into Elastomeric Electrospun Fibers
Authors: Iannotti Vincenzo , Ausanio Giovanni , Ferretti Anna M. , Babar Zaheer Ud Din , Guarino Vincenzo , Ambrosio Luigi , Lanotte Luciano
Published: January 2023

Combining magnetic nanoparticles (MNPs) with high-voltage processes to produce ultra-thin magnetic nanofibers (MNFs) fosters the development of next-generation technologies. In this study, polycarbonate urethane nanofibers incorporating magnetic particles were produced via the electrospinning technique. Two distinct types of magnetic payload were used: (a) iron oxide nanoparticles (IONPs) with an average size and polydispersity index of 7.2 nm and 3.3%, respectively; (b) nickel particles (NiPs) exhibiting a bimodal size distribution with average sizes of 129 nanometers and 600 nanometers, respectively, and corresponding polydispersity indexes of 27.8% and 3.9%. Due to varying particle sizes, significant differences were observed in their aggregation and distribution within the nanofibers. Further, the magnetic response of the IONP and/or NiP-loaded fiber mats was consistent with their morphology and polydispersity index. In the case of IONPs, the remanence ratio (Mr/Ms) and the coercive field (Hc) were found to be zero, which agrees with their superparamagnetic behavior when the average size is smaller than 20–30 nm. However, the NiPs show Mr/Ms = 22% with a coercive field of 0.2kOe as expected for particles in a single or pseudo-single domain state interacting with each other via dipolar interaction. We conclude that magnetic properties can be modulated by controlling the average size and polydispersity index of the magnetic particles embedded in fiber mats to design magneto-active systems suitable for different applications (i.e., wound healing and drug delivery).
Effects of Modulation of the Hedgehog and Notch Signaling Pathways on Osteoblast Differentiation Induced by Titanium with Nanotopography
Authors: Souza Paola Gomes , Adolpho Leticia Faustino , Lopes Helena Bacha , Weffort Denise , Souza Alann Thaffarell Portilho , Oliveira Fabiola Singaretti , Rosa Adalberto Luiz , Beloti Marcio Mateus
Published: January 2023

Background: The events of bone formation and osteoblast/titanium (Ti) interactions may be affected by Hedgehog and Notch signalling pathways. Herein, we investigated the effects of modulation of these signalling pathways on osteoblast differentiation caused by the nanostructured Ti (Ti-Nano) generated by H2SO4/H2O2. Methods: Osteoblasts from newborn rat calvariae were cultured on Ti-Control and Ti-Nano in the presence of the Hedgehog agonist purmorphamine or antagonist cyclopamine and of the Notch antagonist N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) or agonist bexarotene. Osteoblast differentiation was evaluated by alkaline phosphatase activity and mineralization, and the expression of Hedgehog and Notch receptors was also evaluated. Results: In general, purmorphamine and DAPT increased while cyclopamine and bexarotene decreased osteoblast differentiation and regulated the receptor expression on both Ti surfaces, with more prominent effects on Ti-Nano. The purmorphamine and DAPT combination exhibited synergistic effects on osteoblast differentiation that was more intense on Ti-Nano. Conclusion: Our results indicated that the Hedgehog and Notch signalling pathways drive osteoblast/Ti interactions more intensely on nanotopography. We also demonstrated that combining Hedgehog activation with Notch inhibition exhibits synergistic effects on osteoblast differentiation, especially on Ti-Nano. The uncovering of these cellular mechanisms contributes to create strategies to control the process of osseointegration based on the development of nanostructured surfaces.
Local Journalism: How the War in Ukraine Imposed Itself on the Production Routine of the Local Press
Authors: Midões Miguel , Martins Joana
Published: January 2023

The local press finds its vocation in the community it addresses and in its territory of deployment, taking proximity as the main news value in the choice of events. The war in Ukraine, as an international theme, has imposed itself on the national media agenda, and, as such, we have proposed to evaluate its presence in the regional media agenda. For this case study, we have selected the local daily newspapers Diário As Beiras and Diário de Viseu (located in the center region of Portugal) and analyzed twelve consecutive editions of each newspaper, starting on the first day of the conflict, 24 February 2022. The results point to an appreciation of the event, either from an international perspective or through a regional lens, essentially evident in the coverage of solidarity actions and tributes. The sources used by the newspapers are mostly institutional, which leads us to a “seated journalism” in line with previous studies specific to the local press. This analysis also highlights the emphasis on the information obtained from the prism of sources on the Ukrainian side of the conflict, which, in the case of Diário de Viseu, is underlined by biased discourse and some marks of subjectivity.
Omega-3 Fatty Acids Supplementation in the Treatment of Depression: An Observational Study
Authors: Mehdi Seema , Manohar Kishor , Shariff Atiqulla , Kinattingal Nabeel , Wani Shahid Ud Din , Alshehri Sultan , Imam Mohammad T. , Shakeel Faiyaz , Krishna Kamsagara L.
Published: January 2023

Depression is a common mood disorder characterized by persistent sadness and loss of interest. Research suggests an association between the inclusion of omega-3 fatty acids in the diet and a reduced risk for depression. The present study evaluated the effectiveness of omega-3 fatty acid supplements in alleviating depressive symptoms in patients with mild to moderate depression. A total of 165 patients suffering from mild to moderated depression were randomized to receive omega-3 fatty acid supplementation, an antidepressant (single agent), or a combination of an antidepressant and omega-3 fatty acid supplementation. The clinical features of depression were assessed using the Hamilton Depression Rating Scale (HDRS) during the follow-up period. A statistically significant improvement in depressive symptoms was observed from baseline to first, second and third follow-ups within each treatment arm as measured by HRDS scores (p = 0.00001). Further, the HDRS scores at the third follow-up were significantly lower in patients on combination therapy of omega-3 fatty acid supplement and antidepressants (arm-3) than the patients on the omega-3 fatty acid supplement alone (arm-1) [Q = 5.89; p = 0.0001] or the patients taking an antidepressant alone (arm 2) [Q = 4.36; p = 0.0068]. The combination of an omega-3 fatty acid supplement and an antidepressant elicited significantly higher improvement in depressive symptoms than the supplement or the antidepressant alone.