bluuebunny/crossref_metadata_2025 huggingface dataset:
Oleic Acid Protects Endothelial Cells from Silica-Coated Superparamagnetic Iron Oxide Nanoparticles (SPIONs)-Induced Oxidative Stress and Cell Death
Authors: Repar Neža , Jovičić Eva Jarc , Kump Ana , Birarda Giovanni , Vaccari Lisa , Erman Andreja , Kralj Slavko , Nemec Sebastjan , Petan Toni , Drobne Damjana
Published: June 2022

Superparamagnetic iron oxide nanoparticles (SPIONs) have great potential for use in medicine, but they may cause side effects due to oxidative stress. In our study, we investigated the effects of silica-coated SPIONs on endothelial cells and whether oleic acid (OA) can protect the cells from their harmful effects. We used viability assays, flow cytometry, infrared spectroscopy, fluorescence microscopy, and transmission electron microscopy. Our results show that silica-coated SPIONs are internalized by endothelial cells, where they increase the amount of reactive oxygen species (ROS) and cause cell death. Exposure to silica-coated SPIONs induced accumulation of lipid droplets (LD) that was not dependent on diacylglycerol acyltransferase (DGAT)-mediated LD biogenesis, suggesting that silica-coated SPIONs suppress LD degradation. Addition of exogenous OA promoted LD biogenesis and reduced SPION-dependent increases in oxidative stress and cell death. However, exogenous OA protected cells from SPION-induced cell damage even in the presence of DGAT inhibitors, implying that LDs are not required for the protective effect of exogenous OA. The molecular phenotype of the cells determined by Fourier transform infrared spectroscopy confirmed the destructive effect of silica-coated SPIONs and the ameliorative role of OA in the case of oxidative stress. Thus, exogenous OA protects endothelial cells from SPION-induced oxidative stress and cell death independent of its incorporation into triglycerides.
Neuroprotective Effect of Macrophage Migration Inhibitory Factor (MIF) in a Mouse Model of Ischemic Stroke
Authors: Kim Ji Ae , Kim Ye Young , Lee Seung Hak , Jung Chul , Kim Mi Hee , Kim Dae Yul
Published: June 2022

The mechanism of the neuroprotective effect of the macrophage migration inhibitory factor (MIF) in vivo is unclear. We investigated whether the MIF promotes neurological recovery in an in vivo mouse model of ischemic stroke. Transient middle cerebral artery occlusion (MCAO) surgery was performed to make ischemic stroke mouse model. Male mice were allocated to a sham vehicle, a sham MIF, a middle cerebral artery occlusion (MCAO) vehicle, and MCAO+MIF groups. Transient MCAO (tMCAO) was performed in the MCAO groups, and the vehicle and the MIF were administered via the intracerebroventricular route. We evaluated the neurological functional scale, the rotarod test, and T2-weighted magnetic resonance imaging. The expression level of the microtubule-associated protein 2 (MAP2), Bcl2, and the brain-derived neurotrophic factor (BDNF) were further measured by Western blot assay. The Garcia test was significantly higher in the MCAO+MIF group than in the MCAO+vehicle group. The MCAO+MIF group exhibited significantly better performance on the rotarod test than the MCAO+vehicle group, which further had a significantly reduced total infarct volume on T2-weighted MRI imaging than the MCAO vehicle group. Expression levels of BDNF, and MAP2 tended to be higher in the MCAO+MIF group than in the MCAO+vehicle group. The MIF exerts a neuroprotective effect in an in vivo ischemic stroke model. The MIF facilitates neurological recovery and protects brain tissue from ischemic injury, indicating a possibility of future novel therapeutic agents for stroke patients.
Virtual Vibrational Analytics of Reduced Graphene Oxide
Authors: Sheka Elena F. , Popova Nadezhda A.
Published: June 2022

The digital twin concept lays the foundation of the virtual vibrational analytics suggested in the current paper. The latter presents extended virtual experiments aimed at determining the specific features of the optical spectra of the studied molecules that provide reliable express analysis of the body spatial structure and chemical content. Reduced graphene oxide was selected as the virtual experiment goal. A set of nanosize necklaced graphene molecules, based on the same graphene domain but differing by the necklace contents, were selected as the relevant DTs. As shown, the Raman spectra signatures contained information concerning the spatial structure of the graphene domains, while the molecule necklaces were responsible for the IR spectra. Suggested sets of general frequency kits facilitate the detailed chemical analysis. Express analysis of a shungite carbon, composed of rGO basic structural units, revealed the high ability of the approach.
Molecular Allergen-Specific IgE Recognition Profiles and Cumulative Specific IgE Levels Associated with Phenotypes of Cat Allergy
Authors: Riabova Ksenja , Karsonova Antonina V. , van Hage Marianne , Käck Ulrika , Konradsen Jon R. , Grönlund Hans , Fomina Daria , Beltyukov Evgeny , Glazkova Polina A. , Semenov Dmitry Yu. , Valenta Rudolf , Karaulov Alexander , Curin Mirela
Published: June 2022

Cat allergy is a major trigger factor for respiratory reactions (asthma and rhinitis) in patients with immunoglobulin E (IgE) sensitization. In this study, we used a comprehensive panel of purified cat allergen molecules (rFel d 1, nFel d 2, rFel d 3, rFel d 4, rFel d 7, and rFel d 8) that were obtained by recombinant expression in Escherichia coli or by purification as natural proteins to study possible associations with different phenotypes of cat allergy (i.e., rhinitis, conjunctivitis, asthma, and dermatitis) by analyzing molecular IgE recognition profiles in a representative cohort of clinically well-characterized adult cat allergic subjects (n = 84). IgE levels specific to each of the allergen molecules and to natural cat allergen extract were quantified by ImmunoCAP measurements. Cumulative IgE levels specific to the cat allergen molecules correlated significantly with IgE levels specific to the cat allergen extract, indicating that the panel of allergen molecules resembled IgE epitopes of the natural allergen source. rFel d 1 represented the major cat allergen, which was recognized by 97.2% of cat allergic patients; however, rFel d 3, rFel d 4, and rFel d 7 each showed IgE reactivity in more than 50% of cat allergic patients, indicating the importance of additional allergens in cat allergy. Patients with cat-related skin symptoms showed a trend toward higher IgE levels and/or frequencies of sensitization to each of the tested allergen molecules compared with patients suffering only from rhinitis or asthma, while there were no such differences between patients with rhinitis and asthma. The IgE levels specific to allergen molecules, the IgE levels specific to cat allergen extract, and the IgE levels specific to rFel d 1 were significantly higher in patients with four different symptoms compared with patients with 1–2 symptoms. This difference was more pronounced for the sum of IgE levels specific to the allergen molecules and to cat extract than for IgE levels specific for rFel d 1 alone. Our study indicates that, in addition to rFel d 1, rFel d 3, rFel d 4, and rFel d 7 must be considered as important cat allergens. Furthermore, the cumulative sum of IgE levels specific to cat allergen molecules seems to be a biomarker for identifying patients with complex phenotypes of cat allergy. These findings are important for the diagnosis of IgE sensitization to cats and for the design of allergen-specific immunotherapies for the treatment and prevention of cat allergy.
Ca2+/Calmodulin-Dependent Protein Kinase II Regulation by Inhibitor of Receptor Interacting Protein Kinase 3 Alleviates Necroptosis in Glycation End Products-Induced Cardiomyocytes Injury
Authors: Hua Yuyun , Qian Jianan , Cao Ji , Wang Xue , Zhang Wei , Zhang Jingjing
Published: June 2022

Necroptosisis a regulatory programmed form of necrosis. Receptor interacting protein kinase 3 (RIPK3) is a robust indicator of necroptosis. RIPK3 mediates myocardial necroptosis through activation of calcium/calmodulin-dependent protein kinase II (CaMKII) in cardiac ischemia-reperfusion (I/R) injury and heart failure. However, the exact mechanism of RIPK3 in advanced glycation end products (AGEs)-induced cardiomyocytes necroptosis is not clear. In this study, cardiomyocytes were subjected to AGEs stimulation for 24 h. RIPK3 expression, CaMKII expression, and necroptosis were determined in cardiomyocytes after AGEs stimulation. Then, cardiomyocytes were transfected with RIPK3 siRNA to downregulate RIPK3 followed by AGEs stimulation for 24 h. CaMKIIδ alternative splicing, CaMKII activity, oxidative stress, necroptosis, and cell damage were detected again. Next, cardiomyocytes were pretreated with GSK′872, a specific RIPK3 inhibitor to assess whether it could protect cardiomyocytes against AGEs stimulation. We found that AGEs increased the expression of RIPK3, aggravated the disorder of CaMKII δ alternative splicing, promoted CaMKII activation, enhanced oxidative stress, induced necroptosis, and damaged cardiomyocytes. RIPK3 downregulation or RIPK3 inhibitor GSK′872 corrected CaMKIIδ alternative splicing disorder, inhibited CaMKII activation, reduced oxidative stress, attenuated necroptosis, and improved cell damage in cardiomyocytes.
Editorial of Special Issue ‘Dissecting Neurological and Neuropsychiatric Diseases: Neurodegeneration and Neuroprotection’
Authors: Tanaka Masaru , Vécsei László
Published: June 2022

This Special Issue has focused on dissecting the neuroprotective and neurodegenerative components of neurological and neuropsychiatric diseases, highlighting the latest advance in understanding the etiology, pathomechanism, biomarkers, imaging techniques, and novel therapeutic targets of neurodegenerative diseases (NDDs) [...]
miR-218-5p/RUNX2 Axis Positively Regulates Proliferation and Is Associated with Poor Prognosis in Cervical Cancer
Authors: Cruz-De la Rosa Merlin Itsel , Jiménez-Wences Hilda , Alarcón-Millán Judit , Romero-López Manuel Joaquín , Castañón-Sánchez Carlos Alberto , Salmerón-Bárcenas Eric Genaro , Fernández-Tilapa Gloria
Published: June 2022

The overexpression of miR-218-5p in cervical cancer (CC) cell lines decreases migration, invasion and proliferation. The objective was to identify target genes of miR-218-5p and the signaling pathways and cellular processes that they regulate. The relationship between the expression of miR-218-5p and RUNX2 and overall survival in CC as well as the effect of the exogenous overexpression of miR-218-5p on the level of RUNX2 were analyzed. The target gene prediction of miR-218-5p was performed in TargetScan, miRTarBase and miRDB. Predicted target genes were subjected to gene ontology (GO) and pathway enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes (KEGG). The miR-218-5p mimetic was transfected into C-33A and CaSki cells, and the miR-218-5p and RUNX2 levels were determined by RT–qPCR. Of the 118 predicted targets for miR-218-5p, 86 are involved in protein binding, and 10, including RUNX2, are involved in the upregulation of proliferation. Low miR-218-5p expression and a high level of RUNX2 are related to poor prognosis in CC. miR-218-5p overexpression is related to decreased RUNX2 expression in C-33A and CaSki cells. miR-218-5p may regulate RUNX2, and both molecules may be prognostic markers in CC.
The Contribution of Wnt Signaling to Vascular Complications in Type 2 Diabetes Mellitus
Authors: Sanabria-de la Torre Raquel , García-Fontana Cristina , González-Salvatierra Sheila , Andújar-Vera Francisco , Martínez-Heredia Luis , García-Fontana Beatriz , Muñoz-Torres Manuel
Published: June 2022

Vascular complications are the leading cause of morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). These vascular abnormalities result in a chronic hyperglycemic state, which influences many signaling molecular pathways that initially lead to increased oxidative stress, increased inflammation, and endothelial dysfunction, leading to both microvascular and macrovascular complications. Endothelial dysfunction represents the initial stage in both types of vascular complications; it represents “mandatory damage” in the development of microvascular complications and only “introductory damage” in the development of macrovascular complications. Increasing scientific evidence has revealed an important role of the Wnt pathway in the pathophysiology of the vascular wall. It is well known that the Wnt pathway is altered in patients with T2DM. This review aims to be an update of the current literature related to the Wnt pathway molecules that are altered in patients with T2DM, which may also be the cause of damage to the vasculature. Both microvascular complications (retinopathy, nephropathy, and neuropathy) and macrovascular complications (coronary artery disease, cerebrovascular disease, and peripheral arterial disease) are analyzed. This review aims to concisely concentrate all the evidence to facilitate the view on the vascular involvement of the Wnt pathway and its components by highlighting the importance of exploring possible therapeutic strategy for patients with T2DM who develop vascular pathologies.
Fibrogenic Pathways in Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD)
Authors: Subramanian Pallavi , Hampe Jochen , Tacke Frank , Chavakis Triantafyllos
Published: June 2022

The prevalence of nonalcoholic fatty liver disease (NAFLD), recently also re-defined as metabolic dysfunction associated fatty liver disease (MAFLD), is rapidly increasing, affecting ~25% of the world population. MALFD/NAFLD represents a spectrum of liver pathologies including the more benign hepatic steatosis and the more advanced non-alcoholic steatohepatitis (NASH). NASH is associated with enhanced risk for liver fibrosis and progression to cirrhosis and hepatocellular carcinoma. Hepatic stellate cells (HSC) activation underlies NASH-related fibrosis. Here, we discuss the profibrogenic pathways, which lead to HSC activation and fibrogenesis, with a particular focus on the intercellular hepatocyte–HSC and macrophage–HSC crosstalk.
TRα2—An Untuned Second Fiddle or Fine-Tuning Thyroid Hormone Action?
Authors: Hönes Georg Sebastian , Härting Nina , Mittag Jens , Kaiser Frank J.
Published: June 2022

Thyroid hormones (THs) control a wide range of physiological functions essential for metabolism, growth, and differentiation. On a molecular level, TH action is exerted by nuclear receptors (TRs), which function as ligand-dependent transcription factors. Among several TR isoforms, the function of TRα2 remains poorly understood as it is a splice variant of TRα with an altered C-terminus that is unable to bind T3. This review highlights the molecular characteristics of TRα2, proposed mechanisms that regulate alternative splicing and indications pointing towards an antagonistic function of this TR isoform in vitro and in vivo. Moreover, remaining knowledge gaps and major challenges that complicate TRα2 characterization, as well as future strategies to fully uncover its physiological relevance, are discussed.
The 2-hydroxy-3-(4-aryl-1-piperazinyl)propyl Phthalimide Derivatives as Prodrugs—Spectroscopic and Theoretical Binding Studies with Plasma Proteins
Authors: Marciniak Aleksandra , Kotynia Aleksandra , Szkatuła Dominika , Krzyżak Edward
Published: June 2022

Many publications in databases deal with the interactions of new drugs with albumin. However, it is not only albumin that is responsible for binding pharmaceutical molecules to proteins in the human body. There are many more proteins in plasma that are important for the study of the ADME pathway. Therefore, in this study, we have shown the results of the interactions between the plasma proteins albumin, orosomucoid, and gamma globulins and non-toxic anti-inflammatory phthalimide analogs, which due to the promising obtained results, may be potential candidates in the group of analgesic and anti-inflammatory drugs. Using spectroscopic methods and molecular modeling, we showed that all four tested compounds form complexes with the analyzed proteins. The formation of a complex with proteins raises the pharmacological efficacy of the drug. Therefore, the obtained results could be a step in the study of the pharmacokinetics and pharmacodynamics of new potential pharmaceuticals.
Experiment-Based Interventions to Diabetic Retinopathy: Present and Advances
Authors: Liu Siwei , Ju Yahan , Gu Ping
Published: June 2022

Diabetic retinopathy is the major blinding disease among working-age populations, which is becoming more significant due to the growth of diabetes. The metabolic-induced oxidative and inflammatory stress leads to the insult of neovascular unit, resulting in the core pathophysiology of diabetic retinopathy. Existing therapies focus on the inflammation, oxidation, and angiogenesis phenomena of diabetic retinopathy, without effect to radically cure the disease. This review also summarizes novel therapeutic attempts for diabetic retinopathy along with their advantages and disadvantages, mainly focusing on those using cellular and genetic techniques to achieve remission on a fundamental level of disease.
Impact of the Histidine-Triazole and Tryptophan-Pyrene Exchange in the WHW Peptide: Cu(II) Binding, DNA/RNA Interactions and Bioactivity
Authors: Krošl Ivona , Košćak Marta , Ribičić Karla , Žinić Biserka , Majhen Dragomira , Božinović Ksenija , Piantanida Ivo
Published: June 2022

In three novel peptidoids based on the tryptophan—histidine—tryptophan (WHW) peptide, the central histidine was replaced by Ala-(triazole), and two derivatives also had one tryptophan replaced with pyrene-alkyls of different lengths and flexibility. Pyrene analogues show strong fluorescence at 480–500 nm, attributed to intramolecular exciplex formation with tryptophan. All three peptidoids bind Cu2+ cation in water with strong affinity, with Trp- Ala-(triazole)-Trp binding comparably to the parent WHW, and the pyrene analogues even stronger, demonstrating that replacement of histidine with triazole in peptides does not hamper Cu2+ coordination. The studied peptidoids strongly bind to ds-DNA and ds-RNA, whereby their complexes with Cu2+ exhibit distinctively different interactions in comparison to metal-free analogues, particularly in the stabilization of ds-DNA against thermal denaturation. The pyrene peptidoids efficiently enter living cells with no apparent cytotoxic effect, whereby their red-shifted emission compared to the parent pyrene allows intracellular confocal microscopy imaging, showing accumulation in cytoplasmic organelles. However, irradiation with 350 nm light resulted in evident antiproliferative effect on cells treated with micromolar concentrations of the pyrene analogues, presumably attributed to pyrene-induced production of singlet oxygen and consecutive cellular damage.
Pb-Induced Eryptosis May Provoke Thrombosis Prior to Hemolysis
Authors: Jin Qiushuo , Yao Chunyang , Bian Yiying , Pi Jingbo
Published: June 2022

Lead (Pb) is a common metal, which can be toxic to the human body via the pollution of water or food, and can cause anemia and other diseases. However, what happens before hemolysis and anemia caused by Pb poisoning is unclear. Here, we demonstrated Pb can cause procoagulant activity of erythroid cells leading to thrombosis before hemolysis. In freshly isolated human erythroid cells, we observed that Pb resulted in hemolysis in both concentration- and time-dependent manners, but that no lysis occurred in Pb-exposed erythroid cells (≤20 μM for 1 h). Pb treatment did not cause shape changes at up to 0.5 h incubation but at 1 h incubation echinocyte and echino-spherocyte shape changes were observed, indicating that Pb can exaggerate a concentration- and time-dependent trend of shape changes in erythroid cells. After Pb treatment, ROS-independent eryptosis was shown with no increase of reactive oxygen species (ROS), but with an increase of [Ca2+]i and caspase 3 activity. With a thrombosis mouse model, we observed increased thrombus by Pb treatment (0 or 25 mg/kg). In brief, prior to hemolysis, we demonstrated Pb can cause ROS-independent but [Ca2+]i-dependent eryptosis, which might provoke thrombosis.
Travel-Time Estimation by Cubic Hermite Curve
Authors: Tamin Owen , Ikram Badrul , Amri Ramli Ahmad Lutfi , Moung Ervin Gubin , Chin Pei Yee Christie
Published: June 2022

Travel time is a measure of time taken to travel from one place to another. Global Positioning System (GPS) navigation applications such as Waze and Google Maps are easily accessible presently and allow users to plan a route based on travel time from one place to another. However, these applications can only estimate general travel time based on a vehicle’s total distance and average safe speed without considering route curvature. A parametric cubic curve has shown a potential result in travel-time estimation through geometric properties. In this paper, travel time has been estimated using the curvature value obtained from the Hermite Interpolation curve fitted to each section of the selected road. Design speed is determined from the curvature value, and thus an algorithm for travel-time estimation incorporating initial driving information is developed. The proposed method’s accuracy was compared to the existing method’s accuracy using a real-life driving test. This comparison demonstrated that the proposed method estimates travel time more accurately than Google Maps and Waze. Future study can further improve the estimation by embedding traffic data into the algorithm.
Adverse Impact of Earthquake Seismic Loading on Angular Offset Tunnels and Effects of Isolation Grout
Authors: Elgamal Ahmed , Elfaris Nissreen
Published: June 2022

This paper investigates the effects of seismic loads on tunnels in an attempt to provide better protection from earthquake shaking. Dynamic analysis of angular offset tunnels was performed, and the tunnels’ behavior under earthquake shaking and their response when using seismic isolation were analyzed in detail. The time history analysis was used to compute the stresses and deformation that develop in the tunnels during seismic events. Earthquake records with different frequency spectra were applied as seismic excitation to the twin tunnels. The excitation was applied normally to the tunnel axis, with peak ground accelerations of 0.10 g–0.30 g. The seismic event lasted 15 s, with a time step of 0.02 s utilized in the numerical analysis. Finite element modeling was employed to simulate the soil–tunnel interaction. Numerical models simulated twin tunnels passing through soft clay or stiff clay, with various earthquake records applied as seismic inputs. The effects of a silicon-based isolation material composed of silicon oil and fly-ash were compared with the use of traditional grout. The numerical model results show how seismic isolation affects the stresses and deformations that happen in tunnel bodies during earthquakes.
Expression of MRJP3 and HSP70 mRNA Levels in Apis mellifera L. Workers after Dietary Supplementation with Proteins, Prebiotics, and Probiotics
Authors: Oliveira Maria Carolina Paleari Varjão , Pereira Eloisa Magalhaes , Sereia Maria Josiane , Lima Érica Gomes , Silva Breno Gabriel , Toledo Vagner Alencar Arnaut , Ruvolo-Takasusuki Maria Claudia Colla
Published: June 2022

Royal jelly is an essential substance for the development of bees from larval to adult stages. Studies have identified a group of key proteins in royal jelly, denominated major royal jelly proteins (MRJPs). The group currently consists of nine proteins (MRJP1–MRJP9), with MRJP1 being the most abundant and MRJP3 being used as a microsatellite marker for the selection of queens with a greater production of royal jelly. The diet of bees is mostly composed of proteins, and supplementing this intake to encourage a higher production of their primary product is important for producers. It is estimated that, by adding probiotic and prebiotic organisms to their diets, the benefits to bees will be even greater, both for their immune systems and primary responses to stress. Circumstances that are adverse compared to those of the natural habitat of bees eventually substantially interfere with bee behavior. Stress situations are modulated by proteins termed heat shock proteins (HSPs). Among these, HSP70 has been shown to exhibit abundance changes whenever bees experience unusual situations of stress. Thus, we sought to supplement A. mellifera bee colony diets with proteins and prebiotic and probiotic components, and to evaluate the expression levels of MRJP3 and HSP70 mRNAs using qRT-PCR. The results revealed that differences in the expression of MRJP3 can be attributed to the different types of feed offered. Significant differences were evident when comparing the expression levels of MRJP3 and HSP70, suggesting that protein supplementation with pre/probiotics promotes positive results in royal jelly synthesis carried out by honey bee nurses.
Calculation and Experimental Study of Low-Cycle Fatigue of Gas Turbine Engines Booster Drum
Authors: Arkhipov Alexander , Ravikovich Yury , Kholobtsev Dmitry , Shakhov Alexander
Published: June 2022

A calculation-experimental study of durability of titanium booster drum of gas turbine engine (GTE) was carried out. A methodology of experimental estimation of titanium component life of GTE using structurally similar elements (SSE) has been proposed. A series of three-dimensional calculations by the finite element method of SSE cut out of the finished part was carried out to estimate the strength of the booster drum. A methodology for testing the durability of SSE in the low-cycle fatigue (LCF) area was developed, and statistical processing of the test results was performed. Tests of SSE allowed carrying out advanced-edge assessment of the durability of a full-size drum, taking into account the manufacturing technology.
Current Treatment Options for COVID-19 Associated Mucormycosis: Present Status and Future Perspectives
Authors: Madhavan Yasasve , Sai Kadambari Vijay , Shanmugam Dilip Kumar , Manimaran Aashabharathi , Guruviah Karthigadevi , Mohanta Yugal Kishore , Venugopal Divyambika Catakapatri , Mohanta Tapan Kumar , Sharma Nanaocha , Muthupandian Saravanan
Published: June 2022

Mucormycosis has become increasingly associated with COVID-19, leading to the use of the term “COVID-19 associated mucormycosis (CAM)”. Treatment of CAM is challenging due to factors such as resistance to many antifungals and underlying co-morbidities. India is particularly at risk for this disease due to the large number of patients with COVID-19 carrying comorbidities that predispose them to the development of mucormycosis. Additionally, mucormycosis treatment is complicated due to the atypical symptoms and delayed presentation after the resolution of COVID-19. Since this disease is associated with increased morbidity and mortality, early identification and diagnosis are desirable to initiate a suitable combination of therapies and control the disease. At present, the first-line treatment involves Amphotericin B and surgical debridement. To overcome limitations associated with surgery (invasive, multiple procedures required) and amphotericin B (toxicity, extended duration and limited clinical success), additional therapies can be utilized as adjuncts or alternatives to reduce treatment duration and improve prognosis. This review discusses the challenges associated with treating CAM and the critical aspects for controlling this invasive fungal infection—early diagnosis and initiation of therapy, reversal of risk factors, and adoption of a multipronged treatment strategy. It also details the various therapeutic options (in vitro, in vivo and human case reports) that have been used for the treatment of CAM.
Retinal Microvascular Changes in COVID-19 Bilateral Pneumonia Based on Optical Coherence Tomography Angiography
Authors: Kal Magdalena , Winiarczyk Mateusz , Cieśla Elżbieta , Płatkowska-Adamska Bernadetta , Walczyk Anna , Biskup Michał , Pabjan Paweł , Głuszek Stanisław , Odrobina Dominik , Mackiewicz Jerzy , Zarębska-Michaluk Dorota
Published: June 2022

The purpose of this study was to evaluate retinal and choroidal microvascular alterations with optical coherence tomography angiography (OCTA) in COVID-19 patients hospitalized because of bilateral pneumonia caused by SARS-CoV-2. The vessel density (VD) and foveal avascular zone (FAZ) of 63 patients with SARS-CoV-2 pneumonia who had positive polymerase chain reaction (PCR) tests and who recovered after receiving treatment and 45 healthy age- and gender-matched controls were evaluated and compared using OCTA in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). The VD was also estimated in both groups in the choriocapillaris (CC). In COVID-19 patients, there was a statistically significant difference between the patients and a control group in both superficial (FAZs) and deep (FAZd) avascular zone (p = 0.000). The VD was significantly lower in the foveal area in choriocapillaris (p = 0.046). There were no statistically significant changes in the VD in the superior, inferior, nasal, and temporal quadrants in superficial and deep plexus, or in the choriocapillaris. The VD was not significantly lower in the foveal area in superficial or deep plexus. COVID-19 may affect the retinal vasculature, causing ischemia, enlargement of the FAZ, and lowering of the VD in the choriocapillaris area. Routine ophthalmic examination after SARS-CoV-2 infection should be considered in the course of post-infectious rehabilitation.
Identification of Genetic Variations in the NAD-Related Pathways for Patients with Major Depressive Disorder: A Case-Control Study in Taiwan
Authors: Chen Daniel Tzu-Li , Cheng Szu-Wei , Chen Tiffany , Chang Jane Pei-Chen , Hwang Bing-Fang , Chang Hen-Hong , Chuang Eric Y. , Chen Che-Hong , Su Kuan-Pin
Published: June 2022

Background and Objectives: Nicotinamide adenine dinucleotide (NAD) is an important coenzyme in various physiological processes, including sirtuins (SIRTs) and kynurenine pathway (KP). Previous studies have shown that lower NAD levels can be indicative of increased risks of cancer and psychiatric disorders. However, there has been no prior study exploring the link between NAD homeostasis and psychiatric disorders from a genetic perspective. Therefore, we aimed to investigate the association of genetic polymorphism in the pathways of NAD biosynthesis with major depressive disorder (MDD). Methods: A total of 317 patients were included in the case group and were compared with sex-matched control group of 1268 participants (1:4 ratio) from Taiwan Biobank (TWB). All subjects in the control group were over 65 years old, which is well past the average age of onset of MDD. Genomic DNA extracted from patients’ blood buffy coat was analyzed using the Affymetrix TWB array. Full-model tests were conducted for the analysis of single nucleotide polymorphism (SNPs) in all candidate genes. We focused on genes within the NAD-related candidate pathways, including 15 in KP, 12 in nicotinate metabolism, 7 in SIRTs, and 19 in aldehyde dehydrogenases (ALDHs). A total of 508 SNPs were analyzed in this study. After significant SNPs were determined, 5000 genome-wide max(T) permutations were performed in Plink. Finally, we built a predictive model with logistic regression and assessed the interactions of SNPs with the haplotype association tests. Results: We found three SNPs that were significantly associated with MDD in our NAD-related candidate pathways, one within the KP (rs12622574 in ACMSD) and two within the nicotinate metabolism (rs28532698 in BST1 and rs3733593 in CD38). The observed association with MDD was significant in the dominant model of inheritance with marital status, education level, and body mass index (BMI) adjusted as covariates. Lastly, in haplotype analysis, the three associated SNPs consisted of one haploblock in ACMSD, four haploblocks in BST1, and two haploblocks in CD38. Conclusions: This study provides the first evidence that genetic variations involved in NAD homeostasis in the KP and nicotinate metabolism may be associated with the occurrence of MDD.
PCSK9 and Other Metabolic Targets to Counteract Ischemia/Reperfusion Injury in Acute Myocardial Infarction and Visceral Vascular Surgery
Authors: Ortona Silvia , Barisione Chiara , Ferrari Pier Francesco , Palombo Domenico , Pratesi Giovanni
Published: June 2022

Ischemia/reperfusion (I/R) injury complicates both unpredictable events (myocardial infarction and stroke) as well as surgically-induced ones when transient clampage of major vessels is needed. Although the main cause of damage is attributed to mitochondrial dysfunction and oxidative stress, the use of antioxidant compounds for protection gave poor results when challenged in clinics. More recently, there is an assumption that, in humans, profound metabolic changes may prevail in driving I/R injury. In the present work, we narrowed the field of search to I/R injury in the heart/brain/kidney axis in acute myocardial infarction, major vascular surgery, and to the current practice of protection in both settings; then, to help the definition of novel strategies to be translated clinically, the most promising metabolic targets with their modulatory compounds—when available—and new preclinical strategies against I/R injury are described. The consideration arisen from the broad range of studies we have reviewed will help to define novel therapeutic approaches to ensure mitochondrial protection, when I/R events are predictable, and to cope with I/R injury, when it occurs unexpectedly.
Performance Estimation of High-Level Dataflow Program on Heterogeneous Platforms by Dynamic Network Execution
Authors: Bloch Aurelien , Casale-Brunet Simone , Mattavelli Marco
Published: June 2022

The performance of programs executed on heterogeneous parallel platforms largely depends on the design choices regarding how to partition the processing on the various different processing units. In other words, it depends on the assumptions and parameters that define the partitioning, mapping, scheduling, and allocation of data exchanges among the various processing elements of the platform executing the program. The advantage of programs written in languages using the dataflow model of computation (MoC) is that executing the program with different configurations and parameter settings does not require rewriting the application software for each configuration setting, but only requires generating a new synthesis of the execution code corresponding to different parameters. The synthesis stage of dataflow programs is usually supported by automatic code generation tools. Another competitive advantage of dataflow software methodologies is that they are well-suited to support designs on heterogeneous parallel systems as they are inherently free of memory access contention issues and naturally expose the available intrinsic parallelism. So as to fully exploit these advantages and to be able to efficiently search the configuration space to find the design points that better satisfy the desired design constraints, it is necessary to develop tools and associated methodologies capable of evaluating the performance of different configurations and to drive the search for good design configurations, according to the desired performance criteria. The number of possible design assumptions and associated parameter settings is usually so large (i.e., the dimensions and size of the design space) that intuition as well as trial and error are clearly unfeasible, inefficient approaches. This paper describes a method for the clock-accurate profiling of software applications developed using the dataflow programming paradigm such as the formal RVL-CAL language. The profiling can be applied when the application program has been compiled and executed on GPU/CPU heterogeneous hardware platforms utilizing two main methodologies, denoted as static and dynamic. This paper also describes how a method for the qualitative evaluation of the performance of such programs as a function of the supplied configuration parameters can be successfully applied to heterogeneous platforms. The technique was illustrated using two different application software examples and several design points.
Processability and Physical Properties of Compatibilized Recycled HDPE/Rice Husk Biocomposites
Authors: Rigail-Cedeño Andrés , Lazo Miriam , Gaona Julio , Delgado Joshua , Tapia-Bastidas Clotario V. , Rivas Ana L. , Adrián Estephany , Perugachi Rodrigo
Published: June 2022

The circular economy promotes plastic recycling, waste minimization, and sustainable materials. Hence, the use of agricultural waste and recycled plastics is an eco-friendly and economic outlook for developing eco-designed products. Moreover, new alternatives to reinforce recycled polyolefins and add value to agroindustrial byproducts are emerging to develop processable materials with reliable performance for industrial applications. In this study, post-consumer recycled high-density polyethylene (rHDPE) and ground rice husk (RH) of 20% w/w were blended in a torque rheometer with or without the following coupling agents: (i) maleic anhydride grafted polymer (MAEO) 5% w/w, (ii) neoalkoxy titanate (NAT) 1.5% w/w, and (iii) ethylene–glycidyl methacrylate copolymer (EGMA) 5% w/w. In terms of processability, the addition of RH decreased the specific energy consumption in the torque experiments with or without additives compared to neat rHDPE. Furthermore, the time to reach thermal stability in the extrusion process was improved with EGMA and MAEO compatibilizers. Tensile and impact test results showed that using coupling agents enhanced the properties of the RH composites. On the other hand, thermal properties analyzed through differential scanning calorimetry and thermogravimetric analysis showed no significant variation for all composites. The morphology of the tensile fracture surfaces was observed via scanning electron microscopy. The results show that these recycled composites are feasible for manufacturing products when an appropriate compatibilizer is used.
Effect of Aquaculture Reclamation on Sediment Nitrates Reduction Processes in Mangrove Wetland
Authors: Hao Lin , Huang Jiafang
Published: June 2022

Sediment denitrification, anaerobic ammonium oxidation (anammox), and nitrate dissimilation to ammonium (DNRA) play an important role in controlling the dynamics of nitrates (NOx−) and their fate in estuarine and coastal ecosystems. However, the effects of land-use change on NOx− reduction processes in mangrove sediments are still unclear. Here, we used a mud experiment method combined with a 15N stable isotope tracer method to study the mechanism and ecological environment of the change of land use pattern on the sediment NOx− reduction processes in mangrove wetlands. Our study showed that most physicochemical parameters, NOx− reduction rates, and their gene abundances varied considerably. The denitrification, anammox, and DNRA rates in mangrove sediment cores were in a range of 1.04–4.24 nmol g−1 h−1, 0.14–0.36 nmol g−1 h−1, and 0–2.72 nmol g−1 h−1, respectively. The denitrification, anammox, and DNRA rates in aquaculture sediment cores were in a range of 1.06–10.96 nmol g−1 h−1, 0.13–0.37 nmol g−1 h−1, and 0–1.96 nmol g−1 h−1, respectively. The highest values of denitrification, anammox, DNRA, the contribution of denitrification and DNRA to total NOx− reduction (DEN% and DNRA%), gene abundances (nirS, Amx 16S rRNA, and nrfA), total organic carbon (TOC), total nitrogen (TN), and TOC/TN in sediments were generally found in the top layer (0–5 cm) and then decreased with depth, while the contribution of anammox to total NOx− reduction (ANA%), Fe2+, and Fe2+/Fe3+ were generally increased with sediment depth in both mangrove and aquaculture ecosystems. When mangrove wetlands are transformed into pools, some properties (including TOC, TN, and Fe3+), DNRA rates, DRNA%, and nrfA gene abundances were decreased, while some properties (including NH4+, TOC/TN, Fe2+, and Fe2+/Fe3+), denitrification rates, DEN%, nirS, and ANAMMOX 16S gene abundances were increased. Sediment organic matter (TOC and TN) content and Fe2+ both affected NO3− reduction rates, with organic matter the most prominent factor. Thus, aquaculture reclamation enhances N loss while reducing N retention in sediments of mangrove wetlands, which plays an important role in regulating the source and fate of reactive N in mangrove ecosystems.
Marine Pollution by Microplastics in the Mediterranean Sea
Authors: Cantasano Nicola
Published: June 2022

Worldwide, plastic debris is becoming a great environmental problem, with potentially negative effects also on human health, although currently the topic is highly debated in the scientific community. In the basin, microplastics come mainly from three coastal regions, namely Egypt, Turkey and Italy, in decreasing order. Today, the knowledge about the possible interactions of microplastics in the biotic system is unclear and huge efforts are required to discover their effects on human health. Therefore, it is necessary to reduce the production and use of plastics by investing money in research planning and strengthening any kind of human efforts to solve this new kind of marine pollution.
Interferon-Inducible Protein-10 as a Marker to Detect Latent Tuberculosis Infection in Patients with Inflammatory Rheumatic Diseases
Authors: Ortakoylu Mediha Gonenc , Bahadir Ayse , Iliaz Sinem , Soy Bugdayci Derya , Uysal Mehmet Atilla , PAKER Nurdan , Tural Onur Seda
Published: June 2022

It is important to identify cases of latent tuberculosis infection (LTBI) who are at risk for tuberculosis (TB) reactivation. We aimed to evaluate the performance of interferon (IFN)-gamma-inducible protein 10 (IP-10) as a marker to detect LTBI in patients with inflammatory rheumatic diseases (IRD). This study comprised 76 consecutive subjects with IRD. Patients with a history of TB or having active TB were excluded. In all patients, IP-10 level was measured and tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube test (QFT-GIT) were performed. Seventy patients with complete test results were analyzed. Twenty-one (30%) QFT-GIT-positive patients were defined as having LTBI. IP-10 yielded 2197 pg/mL cut-off point. At this cut-off point, IP-10 showed 89% specificity with a sensitivity of 91% (AUC: 0.950, 95% CI 0.906–0.994). TST, QFT-GIT, and IP-10 were positive in 77.1%, 30%, and 44.3% of the patients, respectively. Concordance among the results of TST, QFT-GIT, and IP-10 tests was evaluated. Agreement was poor between IP-10 and TST (58.6%, κ = 0.19), whereas it was good between QFT-GIT and IP-10 (84.3%, κ = 0.65). The results of the present study demonstrated that sensitivity and specificity of released IP-10 were as high as those of QFT-GIT in indicating LTBI in IRD patient group.
“No Ink on Tumor” in Breast-Conserving Surgery after Neoadjuvant Chemotherapy
Authors: Atzori Giulia , Gipponi Marco , Cornacchia Chiara , Diaz Raquel , Sparavigna Marco , Gallo Maurizio , Ruelle Tommaso , Murelli Federica , Franchelli Simonetta , Depaoli Francesca , Friedman Daniele , Fregatti Piero
Published: June 2022

Background/Aim: Patients with Stage I-II breast cancer undergoing breast-conserving surgery after neoadjuvant chemotherapy (BCS-NAC) were retrospectively assessed in order to evaluate the extent of a safe excision margin. Materials and Methods: Between 2003 and 2020, 151 patients underwent risk-adapted BCS-NAC; margin involvement was always assessed at definitive histology. Patients with complete pathological response (pCR) were classified as the RX group, whereas those with residual disease and negative margins were stratified as R0 < 1 mm (margin < 1 mm) and R0 > 1 mm (margin > 1 mm). Results: Totals of 29 (19.2%), 64 (42.4%), and 58 patients (38.4%) were included in the R0 < 1 mm, R0 > 1 mm, and RX groups, respectively, and 2 patients with margin involvement had a mastectomy. Ten instances of local recurrence (6.6%) occurred, with no statistically significant difference in local recurrence-free survival (LRFS) between the three groups. A statistically significant advantage of disease-free survival (p = 0.002) and overall survival (p = 0.010) was observed in patients with pCR. Conclusions: BCS-NAC was increased, especially in HER-2-positive and triple-negative tumors; risk-adapted BCS should be preferably pursued to highlight the cosmetic benefit of NAC. The similar rate of LRFS in the three groups of patients suggests a shift toward the “no ink on tumor” paradigm for patients undergoing BCS-NAC.
Relationship between Advertising Disclosure, Influencer Credibility and Purchase Intention
Authors: Sesar Vesna , Martinčević Ivana , Boguszewicz-Kreft Monika
Published: June 2022

Understanding influencer credibility and online advertising and explaining its implications is the basis for analyzing customer purchase behavior. Novelties in digital marketing are visible in the growth of advertising through digital platforms using micro-influencers, compared to the former trend of using celebrities in creating brand awareness with the purpose to reach many customers and influence their buying decisions. The aim of this study is to examine how advertising disclosure (displayed/not displayed) affects influencer credibility, while analyzing influencer type (celebrity/micro-influencer) as a moderator variable underlying this relationship. Further, this paper investigates whether brand awareness mediates the relationship between influencer credibility and purchase intention. The questionnaire was designed and data were collected from 364 respondents using the convenience sampling method on the student population from one Croatian university. Regression analysis was performed to test the set hypothesis in SPSS using the PROCESS approach and independent sample t-test. The findings show: (1) displayed advertising status increases influencers’ credibility, and (2) this relationship is not moderated by influencer type. Moreover, (3) influencer credibility has a positive and significant relationship with purchase intention, and (4) this relationship is mediated through brand awareness. Research results indicate the importance of advertising disclosure and influencer credibility in influencer marketing, since brand awareness created through influencers’ credibility increased by displayed advertising disclosure significantly affects purchase intention of participants.
Decellularized Wharton Jelly Implants Do Not Trigger Collagen and Cartilaginous Tissue Production in Tracheal Injury in Rabbits
Authors: Foltz Katia Martins , Neto Aloysio Enck , Francisco Júlio César , Simeoni Rossana Baggio , Miggiolaro Anna Flávia Ribeiro dos Santos , do Nascimento Thatyanne Gradowski , Mogharbel Bassam Felipe , de Carvalho Katherine Athayde Teixeira , Faria-Neto José Rocha , de Noronha Lúcia , Guarita-Souza Luiz César
Published: June 2022

Background: Tracheal lesions are pathologies derived from the most diverse insults that can result in a fatal outcome. Despite the number of techniques designed for the treatment, a limiting factor is the extent of the extraction. Therefore, strategies with biomaterials can restructure tissues and maintain the organ’s functionality, like decellularized Wharton’s jelly (WJ) as a scaffold. The aim is to analyze the capacity of tracheal tissue regeneration after the implantation of decellularized WJ in rabbits submitted to a tracheal defect. Methods: An in vivo experimental study was undertaken using twenty rabbits separated into two groups (n = 10). Group 1 submitted to a tracheal defect, group 2 tracheal defect, and implantation of decellularized WJ. The analyses were performed 30 days after surgery through immunohistochemistry. Results: Inner tracheal area diameter (p = 0.643) didn’t show significance. Collagen type I, III, and Aggrecan highlighted no significant difference between the groups (both collagens with p = 0.445 and the Aggrecan p = 0.4). Conclusion: The scaffold appears to fit as a heterologous implant and did not trigger reactions such as rejection or extrusion of the material into the recipient. However, these results suggested that although the WJ matrix presents several characteristics as a biomaterial for tissue regeneration, it did not display histopathological benefits in trachea tissue regeneration.