bluuebunny/crossref_metadata_2025 huggingface dataset:
How to Alleviate Feelings of Crowding in a Working from Home Environment: Lessons Learned from the COVID-19 Pandemic
Authors: Park So Yeon , Newton Caroline , Lee Rachel
Published: January 2023

The sudden adoption of working from home (WFH) during the COVID-19 pandemic has required the reconfiguration of home spaces to fit space for remote work into existing spaces already filled with other domestic functions. This resulted in blurring of home and work boundaries, the potential lack of space for telecommuting from home, and telecommuters’ feelings of crowding. Numerous studies have shown the negative effects of crowding feelings on workers’ responses. This study focused on the issue of crowding in the residential workspace. An online survey was conducted to investigate how features of the home workspace correlate with telecommuters’ feelings of crowding and how these feelings affect satisfaction, health, and productivity. As a result, we found that various environmental features of home workspaces (e.g., house size, purpose of workspace, accessible balcony, lighting, noise, etc.), as well as psychological aspects (e.g., individual control over space use), had significant effects on telecommuters’ feelings of crowdedness. It was also found that feelings of crowding in the WFH environment can directly and indirectly affect teleworkers’ satisfaction with work environments, well-being, and work performance. Based on the results, we offered various potential ways to alleviate overcrowding issues in the WFH context.
Dibenzothiophene Removal from Fuel Oil by Metal-Organic Frameworks: Performance and Kinetics
Authors: Chen Han , Huang Zhipeng , You Juping , Xia Yinfeng , Ye Jiexu , Zhao Jingkai , Zhang Shihan
Published: January 2023

Desulfurization of organic sulfur in the fuel oil is essential to cut down the emission of sulfur dioxide, which is a major precursor of the acid rain and PM2.5. Currently, hydrodesulfurization is regarded as a state-of-art technology for the desulfurization of fuel oil. However, due to the stringent legislation of the fuel oil, the deep desulfurization technology is urgent to be developed. Adsorptive desulfurization method is promising due to the high selectivity and easy operation. The development of efficient adsorbent is important to advance this technology into industrial application. In this work, the five types of metal-organic frameworks (MOFs), including Cu-BTC, UMCM-150, MIL-101(Cr), UIO-66, and Cu-ABTC were synthesized for the adsorption of dibenzothiophene (DBT), a typical organic sulfur compound in the fuel oil. The experimental results revealed that the adsorption capacity of the five MOFs followed the order of Cu-ABTC, UMCM-150, Cu-BTC, MIL-101(Cr), and UIO-66, which adsorption capacities were 46.2, 34.2, 28.3, 26.3, and 22.0 mgS/g, respectively. The three types of Cu-based MOFs such as Cu-ABTC, UMCM-150, and Cu-BTC outperformed the Cr-based MOFs, MIL-101, and Zr-based MOFs, UIO-66. Since the surface area and pore volumes of the Cu-based MOFs were not the greatest among the tested five MOFs, the physical properties of the MOFs were not the only limited factor for the DBT adsorption. The π-complexation between DBT and linkers/metal in the MOFs was also important. Kinetic analysis showed that the DBT adsorption onto the five tested MOFs follows the pseudo-second-order kinetics, confirming that the chemical π-complexation was also contributed to the DBT adsorption. Furthermore, the operation parameters such as oil-adsorbent ratio, initial sulfur concentration and adsorption temperature for the DBT adsorption onto Cu-ABTC were optimized to be 100:1 g/g, 1000 mgS/L and 30 °C, respectively. This work can provide some insights into the development of efficient adsorbent for the organic sulfur adsorption.
Breaking Down the Screen: Italian Psychologists’ and Psychotherapists’ Experiences of the Therapeutic Relationship in Online Interventions during the COVID-19 Pandemic
Authors: Tomaino Silvia Caterina Maria , Manzoni Gian Mauro , Brotto Giada , Cipolletta Sabrina
Published: January 2023

(1) Background: The COVID-19 pandemic posed new challenges to clinical practice and delineated future directions for online interventions in psychological care. The present study aimed to explore Italian psychologists’ and psychotherapists’ experiences of online interventions during the pandemic, focusing on the strategies they used to develop and maintain therapeutic relationships with their patients. (2) Methods: Between February and July 2021, 368 Italian psychologists and/or psychotherapists completed an online survey. A mixed-methods analysis was conducted, using Jamovi to analyze quantitative data and ATLAS.ti 9 to analyze qualitative data. (3) Results: Of the participants, 62% had never delivered online interventions before the pandemic; though 95.4% were delivering online interventions at the time of the survey, many reported facing technical disruptions (77.1%) and having little confidence in the online setting (45.3%). Feeling present in online sessions—facilitated by emotional attunement, active listening, and conversational spontaneity—was reported as “very important” by 93.6%. (4) Conclusions: Overall, the COVID-19 pandemic allowed a great leap forward in the use of online interventions by Italian psychologists and psychotherapists. This period of upheaval generated not only a positive change in their attitudes toward and intention to use online interventions but also revealed associated technical and relational issues that must be properly addressed.
Bayesian Approach to Disease Risk Evaluation Based on Air Pollution and Weather Conditions
Authors: Wang Charlotte , Lin Shu-Ju , Hsiao Chuhsing Kate , Lu Kuo-Chen
Published: January 2023

Background: Environmental factors such as meteorological conditions and air pollutants are recognized as important for human health, where mortality and morbidity of certain diseases may be related to abrupt climate change or air pollutant concentration. In the literature, environmental factors have been identified as risk factors for chronic diseases such as ischemic heart disease. However, the likelihood evaluation of the disease occurrence probability due to environmental factors is missing. Method: We defined people aged 51–90 years who were free from ischemic heart disease (ICD9: 410–414) in 1996–2002 as the susceptible group. A Bayesian conditional logistic regression model based on a case-crossover design was utilized to construct a risk information system and applied to data from three databases in Taiwan: air quality variables from the Environmental Protection Administration (EPA), meteorological parameters from the Central Weather Bureau (CWB), and subject information from the National Health Insurance Research Database (NHIRD). Results: People living in different geographic regions in Taiwan were found to have different risk factors; thus, disease risk alert intervals varied in the three regions. Conclusions: Disease risk alert intervals can be a reference for weather bureaus to issue health warnings. With early warnings, susceptible groups can take measures to avoid exacerbation of disease when meteorological conditions and air pollution become hazardous to their health.
Do CAR-T and Allogeneic Stem Cell Transplant Both Have a Place in Lymphoid Neoplasms?
Authors: Martino Massimo , Canale Filippo Antonio , Naso Virginia , Porto Gaetana , Gerace Demetrio , Allegra Alessandro
Published: January 2023

Allogeneic stem cell transplantation (allo-SCT) represented the first immunotherapy to treat hematologic malignancies: it has been considered as a cure for the disease and never as an approach to extend the life of patients. The success of allo-SCT derives both from the ability to treat patients with intensive chemoradiotherapy and from the potent graft-versus-leukemia effects mediated by donor immunity. Although considerable progress has been made in the last years, significant barriers still remain in the form of disease relapse, graft-versus-host disease, infectious complications, and regimen-related toxicities. Moreover, the treatment of hematologic malignancies, particularly acute lymphoblastic leukemia and certain forms of lymphomas, has been revolutionized by the commercial introduction of genetically modified autologous T-lymphocyte therapy (CAR-T). Our review discusses current standards and the shifting paradigms in the indications for allo-SCT and the role of CAR-T cell therapy for lymphoid neoplasms.
Opioid-Modulated Receptor Localization and Erk1/2 Phosphorylation in Cells Coexpressing μ-Opioid and Nociceptin Receptors
Authors: Zhuo Guan-Yu , Chen Ming-Chi , Lin Tzu-Yu , Lin Shih-Ting , Chen Daniel Tzu-Li , Lee Cynthia Wei-Sheng
Published: January 2023

We attempted to examine the alterations elicited by opioids via coexpressed μ-opioid (MOP) and nociceptin/orphanin FQ (NOP) receptors for receptor localization and Erk1/2 (p44/42 MAPK) in human embryonic kidney (HEK) 293 cells. Through two-photon microscopy, the proximity of MOP and NOP receptors was verified by fluorescence resonance energy transfer (FRET), and morphine but not buprenorphine facilitated the process of MOP-NOP heterodimerization. Single-particle tracking (SPT) further revealed that morphine or buprenorphine hindered the movement of the MOP-NOP heterodimers. After exposure to morphine or buprenorphine, receptor localization on lipid rafts was detected by immunocytochemistry, and phosphorylation of Erk1/2 was determined by immunoblotting in HEK 293 cells expressing MOP, NOP, or MOP+NOP receptors. Colocalization of MOP and NOP on lipid rafts was enhanced by morphine but not buprenorphine. Morphine stimulated the phosphorylation of Erk1/2 with a similar potency in HEK 293 cells expressing MOP and MOP+NOP receptors, but buprenorphine appeared to activate Erk1/2 solely through NOP receptors. Our results suggest that opioids can fine-tune the cellular localization of opioid receptors and phosphorylation of Erk1/2 in MOP+NOP-expressing cells.
New DNA Plasmid Model for Studying DNA Mismatch Repair Response to the G4 Structure
Authors: Pavlova Anzhela V. , Dolinnaya Nina G. , Zvereva Maria I. , Kubareva Elena A. , Monakhova Mayya V.
Published: January 2023

G-quadruplexes (G4s), the most widely studied alternative DNA structures, are implicated in the regulation of the key cellular processes. In recent years, their involvement in DNA repair machinery has become the subject of intense research. Here, we evaluated the effect of G4 on the prokaryotic DNA mismatch repair (MMR) pathway from two bacterial sources with different mismatch repair mechanisms. The G4 folding, which competes with the maintenance of double-stranded DNA, is known to be controlled by numerous opposing factors. To overcome the kinetic barrier of G4 formation, we stabilized a parallel G4 formed by the d(GGGT)4 sequence in a DNA plasmid lacking a fragment complementary to the G4 motif. Unlike commonly used isolated G4 structures, our plasmid with an embedded stable G4 structure contained elements, such as a MutH cleavage site, required to initiate the repair process. G4 formation in the designed construct was confirmed by Taq polymerase stop assay and dimethyl sulfate probing. The G4-carrying plasmid, together with control ones (lacking a looped area or containing unstructured d(GT)8 insert instead of the G4 motif), were used as new type models to answer the question of whether G4 formation interferes with DNA cleavage as a basic function of MMR.
Discovery and Functional Analysis of Secondary Hair Follicle miRNAs during Annual Cashmere Growth
Authors: Wang Minglin , Dai Han , Sheng Shengda , Liu Yanlei , Zhang Shuyi , Bai Wenlin , Xue Huiling
Published: January 2023

Secondary hair follicles (SHFs) produce the thermoregulatory cashmere of goats. MicroRNAs (miRNAs) play indispensable roles in hair follicle formation and growth. However, most studies examining miRNAs related to cashmere have been performed on goat skin. It remains unclear which miRNAs are highly expressed in SHFs or how miRNAs affect cashmere growth. In the present study, we isolated the SHFs under a dissecting microscope and analyzed the miRNA signatures during annual cashmere growth. Small-RNA sequencing followed by genome-wide expression analysis revealed that early anagen is a crucial phase for miRNA regulation of the cashmere growth, as revealed by two predominant groups of miRNAs. Although they exhibited opposite expression patterns, both groups demonstrated sharp changes of expression when in transit from early anagen to mid-anagen. In addition, we identified 96 miRNA signatures that were differentially expressed between different phases among 376 miRNAs. Functional analysis of the predicted target genes of highly expressed or differentially expressed miRNAs indicated that these miRNAs were involved in signal pathways associated with SHF development, regeneration, and regression. Furthermore, miR-143-3p was preferentially expressed in SHFs and Itga6 was identified as one of targets. The dual-luciferase and in situ hybridization assay demonstrated that miR-143-3p directly repressed the expression of Itga6, suggesting a possible novel role for miR-143-3p in cashmere growth.
Choroidal Neovascular Membranes in Retinal and Choroidal Tumors: Origins, Mechanisms, and Effects
Authors: Di Staso Federico , Di Pippo Mariachiara , Abdolrahimzadeh Solmaz
Published: January 2023

Choroidal neovascularizations are historically associated with exudative macular degeneration, nonetheless, they have been observed in nevus, melanoma, osteoma, and hemangioma involving the choroid and retina. This review aimed to elucidate the possible origins of neovascular membranes by examining in vivo and in vitro models compared to real clinical cases. Among the several potential mechanisms examined, particular attention was paid to histologic alterations and molecular cascades. Physical or biochemical resistance to vascular invasion from the choroid offered by Bruch’s membrane, the role of fibroblast growth factor 2 and vascular endothelial growth factor, resident or recruited stem-like/progenitor cells, and other angiogenic promoters were taken into account. Even if the exact mechanisms are still partially obscure, experimental models are progressively enhancing our understanding of neovascularization etiology. Choroidal neovascularization (CNV) over melanoma, osteoma, and other tumors is not rare and is not contraindicative of malignancy as previously believed. In addition, CNV may represent a late complication of either benign or malignant choroidal tumors, stressing the importance of a long follow-up.
Antibacterial Effect of Acoustic Cavitation Promoted by Mesoporous Silicon Nanoparticles
Authors: Sviridov Andrey , Mazina Svetlana , Ostapenko Anna , Nikolaev Alexander , Timoshenko Victor
Published: January 2023

As-prepared mesoporous silicon nanoparticles, which were synthesized by electrochemical etching of crystalline silicon wafers followed by high-energy milling in water, were explored as a sonosensitizer in aqueous media under irradiation with low-intensity ultrasound at 0.88 MHz. Due to the mixed oxide-hydride coating of the nanoparticles’ surfaces, they showed both acceptable colloidal stability and sonosensitization of the acoustic cavitation. The latter was directly measured and quantified as a cavitation energy index, i.e., time integral of the magnitude of ultrasound subharmonics. The index turned out to be several times greater for nanoparticle suspensions as compared to pure water, and it depended nonmonotonically on nanoparticle concentration. In vitro tests with Lactobacillus casei revealed a dramatic drop of the bacterial viability and damage of the cells after ultrasonic irradiation with intensity of about 1 W/cm2 in the presence of nanoparticles, which themselves are almost non-toxic at the studied concentrations of about 1 mg/mL. The experimental results prove that nanoparticle-sensitized cavitation bubbles nearby bacteria can cause bacterial lysis and death. The sonosensitizing properties of freshly prepared mesoporous silicon nanoparticles are beneficial for their application in mild antibacterial therapy and treatment of liquid media.
Lipid Structure Determines the Differential Impact of Single Metal Additions and Binary Mixtures of Manganese, Calcium and Magnesium on Membrane Fluidity and Liposome Size
Authors: Sule Kevin , Anikovskiy Max , Prenner Elmar J.
Published: January 2023

Unilamellar vesicles of the biologically relevant lipids phosphatidic acid (PA) and phosphatidylserine (PS) with fully saturated (DM-) or partly unsaturated (PO-) acyl side chains were exposed to Ca, Mn and Mg in single metal additions; in equimolar mixtures or by sequential additions of one metal at a time. Laurdan generalized polarization measured the membrane fluidity, while dynamic light scattering reported liposome size changes complemented by zeta potential. All metals induced membrane rigidity and increased liposome sizes across all systems. Mn had the strongest effect overall, but Mg was comparable for DMPS. Lipid side chain architecture was important as GP values for binary mixtures were higher than expected from the sum of values for single additions added to POPS but smaller for DMPS. Sequential additions were predominantly different for Ca:Mg mixtures. Mn induced the strongest increase of liposome size in saturated lipids whereas Ca effects dominated unsaturated matrices. Binary additions induced larger sizes than the sum of single additions for POPS, but much lower changes in DMPA. The order of addition was relevant for PS systems. Thus, lipid structure determines metal effects, but their impact is modulated by other ions. Thus, metal effects may differ with the local lipid architecture and metal concentrations within cells.
Red Blood Cells: A Newly Described Partner in Central Retinal Vein Occlusion Pathophysiology?
Authors: Laurance Sandrine , Marin Mickaël , Colin Yves
Published: January 2023

Central retinal vein occlusion (CRVO) is a frequent retinal disorder inducing blindness due to the occlusion of the central vein of the retina. The primary cause of the occlusion remains to be identified leading to the lack of treatment. To date, current treatments mainly target the complications of the disease and do not target the primary dysfunctions. CRVO pathophysiology seems to be a multifactorial disorder; several studies did attempt to decipher the cellular and molecular mechanisms underlying the vessel obstruction, but no consensual mechanism has been found. The aim of the current review is to give an overview of CRVO pathophysiology and more precisely the role of the erythroid lineage. The review presents emerging data on red blood cell (RBC) functions besides their role as an oxygen transporter and how disturbance of RBC function could impact the whole vascular system. We also aim to gather new evidence of RBC involvement in CRVO occurrence.
Can Our Blood Help Ensure Antimicrobial and Anti-Inflammatory Properties in Oral and Maxillofacial Surgery?
Authors: Micko Lana , Salma Ilze , Skadins Ingus , Egle Karina , Salms Girts , Dubnika Arita
Published: January 2023

In recent decades, the potential of PRF has been extensively studied. The number of studies about PRF has increased three times since the year 2012, but the full spectrum of its fundamental properties, such as antimicrobial and anti-inflammatory activity, is not clearly described. In oral and maxillofacial surgery, PRF is described in alveolar ridge preservation, orthognathic surgery, cleft lip and palate surgery, maxillary sinus augmentation, and dental implant placement as demonstrating favorable results and its clinical advantages. The structural complexity, inhomogeneous nature, and clotting ability of PRF make its antimicrobial effect evaluation complicated. Nevertheless, most of the used antimicrobial testing methods are based on antibacterial agent diffusion ability in culture media. Because the oral and maxillofacial region is the most frequent area of PRF application, its antimicrobial activity evaluation also prevails in the oral microbiome. PRF’s biological potential is highly dependent on the specific preparation protocol and methodology used; it should be carefully prepared and kept under proper conditions to keep cellular content alive. PRF’s influence on living cells demonstrates a stimulating effect on bone regeneration, and an angiogenetic effect, and it provides anti-inflammatory activity. According to analyzed studies, PRF demonstrated success in oral and maxillofacial surgery in various methods of application. Antibacterial and anti-inflammatory properties were proven by antibacterial activity against different bacterial species, sustained growth factor, sustained release, and cell activity on the material application. Accurately and correctly prepared PRF can ensure antibacterial and anti-inflammatory properties, and it can be a beneficial clinical tool in oral and maxillofacial surgery.
ArtinM Cytotoxicity in B Cells Derived from Non-Hodgkin’s Lymphoma Depends on Syk and Src Family Kinases
Authors: Barboza Bruno Rafael , Thomaz Sandra Maria de Oliveira , Junior Airton de Carvalho , Espreafico Enilza Maria , Miyamoto Jackson Gabriel , Tashima Alexandre Keiji , Camacho Maurício Frota , Zelanis André , Roque-Barreira Maria Cristina , da Silva Thiago Aparecido
Published: January 2023

Receptors on the immune cell surface have a variety of glycans that may account for the immunomodulation induced by lectins, which have a carbohydrate recognition domain (CRD) that binds to monosaccharides or oligosaccharides in a specific manner. ArtinM, a D-mannose-binding lectin obtained from Artocarpus heterophyllus, has affinity for the N-glycans core. Immunomodulation by ArtinM toward the Th1 phenotype occurs via its interaction with TLR2/CD14 N-glycans on antigen-presenting cells, as well as recognition of CD3γ N-glycans on murine CD4+ and CD8+ T cells. ArtinM exerts a cytotoxic effect on Jurkat human leukemic T-cell line and human myeloid leukemia cell line (NB4). The current study evaluated the effects of ArtinM on murine and human B cells derived from non-Hodgkin’s lymphoma. We found that murine B cells are recognized by ArtinM via the CRD, and the ArtinM stimulus did not augment the proliferation rate or production of IL-2. However, murine B cell incubation with ArtinM augmented the rate of apoptosis, and this cytotoxic effect of ArtinM was also seen in human B cell-lines sourced from non-Hodgkin’s lymphoma Raji cell line. This cytotoxic effect was inhibited by the phosphatase activity of CD45 on Lck, and the protein kinases of the Src family contribute to cell death triggered by ArtinM.
Skin Cancer Pathobiology at a Glance: A Focus on Imaging Techniques and Their Potential for Improved Diagnosis and Surveillance in Clinical Cohorts
Authors: Dobre Elena-Georgiana , Surcel Mihaela , Constantin Carolina , Ilie Mihaela Adriana , Caruntu Ana , Caruntu Constantin , Neagu Monica
Published: January 2023

Early diagnosis is essential for completely eradicating skin cancer and maximizing patients’ clinical benefits. Emerging optical imaging modalities such as reflectance confocal microscopy (RCM), optical coherence tomography (OCT), magnetic resonance imaging (MRI), near-infrared (NIR) bioimaging, positron emission tomography (PET), and their combinations provide non-invasive imaging data that may help in the early detection of cutaneous tumors and surgical planning. Hence, they seem appropriate for observing dynamic processes such as blood flow, immune cell activation, and tumor energy metabolism, which may be relevant for disease evolution. This review discusses the latest technological and methodological advances in imaging techniques that may be applied for skin cancer detection and monitoring. In the first instance, we will describe the principle and prospective clinical applications of the most commonly used imaging techniques, highlighting the challenges and opportunities of their implementation in the clinical setting. We will also highlight how imaging techniques may complement the molecular and histological approaches in sharpening the non-invasive skin characterization, laying the ground for more personalized approaches in skin cancer patients.
Proteomic Analysis of Dupuytren’s Contracture-Derived Sweat Glands Revealed the Synthesis of Connective Tissue Growth Factor and Initiation of Epithelial-Mesenchymal Transition as Major Pathogenetic Events
Authors: Cárdenas-León Claudia Griselda , Mäemets-Allas Kristina , Klaas Mariliis , Maasalu Katre , Jaks Viljar
Published: January 2023

Dupuytren’s contracture (DC) is a chronic and progressive fibroproliferative disorder restricted to the palmar fascia of the hands. Previously, we discovered the presence of high levels of connective tissue growth factor in sweat glands in the vicinity of DC nodules and hypothesized that sweat glands have an important role in the formation of DC lesions. Here, we shed light on the role of sweat glands in the DC pathogenesis by proteomic analysis and immunofluorescence microscopy. We demonstrated that a fraction of sweat gland epithelium underwent epithelial-mesenchymal transition illustrated by negative regulation of E-cadherin. We hypothesized that the increase in connective tissue growth factor expression in DC sweat glands has both autocrine and paracrine effects in sustaining the DC formation and inducing pathological changes in DC-associated sweat glands.
α-Crystallin Domains of Five Human Small Heat Shock Proteins (sHsps) Differ in Dimer Stabilities and Ability to Incorporate Themselves into Oligomers of Full-Length sHsps
Authors: Shatov Vladislav M. , Muranova Lydia K. , Zamotina Maria A. , Sluchanko Nikolai N. , Gusev Nikolai B.
Published: January 2023

The α-crystallin domain (ACD) is the hallmark of a diverse family of small heat shock proteins (sHsps). We investigated some of the ACD properties of five human sHsps as well as their interactions with different full-length sHsps. According to size-exclusion chromatography, at high concentrations, the ACDs of HspB1 (B1ACD), HspB5 (B5ACD) and HspB6 (B6ACD) formed dimers of different stabilities, which, upon dilution, dissociated to monomers to different degrees. Upon dilution, the B1ACD dimers possessed the highest stabilities, and those of B6ACD had the lowest. In striking contrast, the ACDs of HspB7 (B7ACD) and HspB8 (B8ACD) formed monomers in the same concentration range, which indicated the compromised stabilities of their dimer interfaces. B1ACD, B5ACD and B6ACD transiently interacted with full-length HspB1 and HspB5, which are known to form large oligomers, and modulated their oligomerization behavior. The small oligomers formed by the 3D mutant of HspB1 (mimicking phosphorylation at Ser15, Ser78 and Ser82) effectively interacted with B1ACD, B5ACD and B6ACD, incorporating these α-crystallin domains into their structures. The inherently dimeric full-length HspB6 readily formed heterooligomeric complexes with B1ACD and B5ACD. In sharp contrast to the abovementioned ACDs, B7ACD and B8ACD were unable to interact with full-length HspB1, the 3D mutant of HspB1, HspB5 or HspB6. Thus, their high sequence homology notwithstanding, B7ACD and B8ACD differ from the other three ACDs in their inability to form dimers and interact with the full-length small heat shock proteins. Having conservative primary structures and being apparently similar, the ACDs of the different sHsps differ in terms of their dimer stabilities, which can influence the heterooligomerization preferences of sHsps.
Mitochondrial Dysfunction: The Hidden Player in the Pathogenesis of Atherosclerosis?
Authors: Ciccarelli Giovanni , Conte Stefano , Cimmino Giovanni , Maiorano Patrizia , Morrione Andrea , Giordano Antonio
Published: January 2023

Atherosclerosis is a multifactorial inflammatory pathology that involves metabolic processes. Improvements in therapy have drastically reduced the prognosis of cardiovascular disease. Nevertheless, a significant residual risk is still relevant, and is related to unmet therapeutic targets. Endothelial dysfunction and lipid infiltration are the primary causes of atherosclerotic plaque progression. In this contest, mitochondrial dysfunction can affect arterial wall cells, in particular macrophages, smooth muscle cells, lymphocytes, and endothelial cells, causing an increase in reactive oxygen species (ROS), leading to oxidative stress, chronic inflammation, and intracellular lipid deposition. The detection and characterization of mitochondrial DNA (mtDNA) is crucial for assessing mitochondrial defects and should be considered the goal for new future therapeutic interventions. In this review, we will focus on a new idea, based on the analysis of data from many research groups, namely the link between mitochondrial impairment and endothelial dysfunction and, in particular, its effect on atherosclerosis and aging. Therefore, we discuss known and novel mitochondria-targeting therapies in the contest of atherosclerosis.
Potential Neuroprotective Role of Calretinin-N18 and Calbindin-D28k in the Retina of Adult Zebrafish Exposed to Different Wavelength Lights
Authors: Porcino Caterina , Briglia Marilena , Aragona Marialuisa , Mhalhel Kamel , Laurà Rosaria , Levanti Maria , Abbate Francesco , Montalbano Giuseppe , Germanà Germana , Lauriano Eugenia Rita , Meduri Alessandro , Vega Josè Antonio , Germanà Antonino , Guerrera Maria Cristina
Published: January 2023

The incidence rates of light-induced retinopathies have increased significantly in the last decades because of continuous exposure to light from different electronic devices. Recent studies showed that exposure to blue light had been related to the pathogenesis of light-induced retinopathies. However, the pathophysiological mechanisms underlying changes induced by light exposure are not fully known yet. In the present study, the effects of exposure to light at different wavelengths with emission peaks in the blue light range (400–500 nm) on the localization of Calretinin-N18 (CaR-N18) and Calbindin-D28K (CaB-D28K) in adult zebrafish retina are studied using double immunofluorescence with confocal laser microscopy. CaB-D28K and CaR-N18 are two homologous cytosolic calcium-binding proteins (CaBPs) implicated in essential process regulation in central and peripheral nervous systems. CaB-D28K and CaR-N18 distributions are investigated to elucidate their potential role in maintaining retinal homeostasis under distinct light conditions and darkness. The results showed that light influences CaB-D28K and CaR-N18 distribution in the retina of adult zebrafish, suggesting that these CaBPs could be involved in the pathophysiology of retinal damage induced by the short-wavelength visible light spectrum.
PLVAP as an Early Marker of Glomerular Endothelial Damage in Mice with Diabetic Kidney Disease
Authors: Wolf Elena E. , Steglich Anne , Kessel Friederike , Kröger Hannah , Sradnick Jan , Reichelt-Wurm Simone , Eidenschink Kathrin , Banas Miriam C. , Wolf Eckhard , Wanke Rüdiger , Gembardt Florian , Todorov Vladimir T.
Published: January 2023

Plasmalemma vesicle-associated protein (PLVAP) is the main component of endothelial diaphragms in fenestrae, caveolae, and transendothelial channels. PLVAP is expressed in the adult kidney glomerulus upon injury. Glomerular endothelial injury is associated with progressive loss of kidney function in diabetic kidney disease (DKD). This study aimed to investigate whether PLVAP could serve as a marker for glomerular endothelial damage in DKD. Glomerular PLVAP expression was analyzed in different mouse models of DKD and their respective healthy control animals using automatic digital quantification of histological whole kidney sections. Transgenic mice expressing a dominant-negative GIP receptor (GIPRdn) in pancreatic beta-cells as a model for diabetes mellitus (DM) type 1 and black and tan brachyuric (BTBR) ob/ob mice, as a model for DM type 2, were used. Distinct PLVAP induction was observed in all diabetic models studied. Traces of glomerular PLVAP expression could be identified in the healthy control kidneys using automated quantification. Stainings for other endothelial injury markers such as CD31 or the erythroblast transformation-specific related gene (ERG) displayed no differences between diabetic and healthy groups at the time points when PLVAP was induced. The same was also true for the mesangial cells marker α8Integrin, while the podocyte marker nephrin appeared to be diminished only in BTBR ob/ob mice. Glomerular hypertrophy, which is one of the initial morphological signs of diabetic kidney damage, was observed in both diabetic models. These findings suggest that PLVAP is an early marker of glomerular endothelial injury in diabetes-induced kidney damage in mice.
Identification of Novel Pathways Regulated by APE1/Ref-1 in Human Retinal Endothelial Cells
Authors: Mijit Mahmut , Liu Sheng , Sishtla Kamakshi , Hartman Gabriella D. , Wan Jun , Corson Timothy W. , Kelley Mark R.
Published: January 2023

APE1/Ref-1 (apurinic/apyrimidinic endonuclease 1, APE1 or APEX1; redox factor-1, Ref-1) is a dual-functional enzyme with crucial roles in DNA repair, reduction/oxidation (redox) signaling, and RNA processing and metabolism. The redox function of Ref-1 regulates several transcription factors, such as NF-κB, STAT3, HIF-1α, and others, which have been implicated in multiple human diseases, including ocular angiogenesis, inflammation, and multiple cancers. To better understand how APE1 influences these disease processes, we investigated the effects of APEX1 knockdown (KD) on gene expression in human retinal endothelial cells. This abolishes both DNA repair and redox signaling functions, as well as RNA interactions. Using RNA-seq analysis, we identified the crucial signaling pathways affected following APEX1 KD, with subsequent validation by qRT-PCR. Gene expression data revealed that multiple genes involved in DNA base excision repair, other DNA repair pathways, purine or pyrimidine metabolism signaling, and histidine/one carbon metabolism pathways were downregulated by APEX1 KD. This is in contrast with the alteration of pathways by APEX1 KD in human cancer lines, such as pancreatic ductal adenocarcinoma, lung, HeLa, and malignant peripheral nerve sheath tumors. These results highlight the unique role of APE1/Ref-1 and the clinical therapeutic potential of targeting APE1 and pathways regulated by APE1 in the eye. These findings provide novel avenues for ocular neovascularization treatment.
Self-Prepared Hyaluronic Acid/Alkaline Gelatin Composite with Nano-Hydroxyapatite and Bone Morphogenetic Protein for Cranial Bone Formation
Authors: Hachinohe Yuki , Taira Masayuki , Hoshi Miki , Yoshida Daichi , Hatakeyama Wataru , Sawada Tomofumi , Kondo Hisatomo
Published: January 2023

New bone-forming substitute materials are highly useful in dental implantology. The purpose of this study was to prepare cross-linked hyaluronic acid (cHLA)/cross-linked alkaline gelatin (cAG)/nano-hydroxyapatite (nHAp)/bone morphogenic protein (BMP) constructs; and evaluate their bone-forming capabilities in rat cranial bone defects. The cHLA and cAG liquids processed with an epoxy cross-linker were blended with a 3:1 volume ratio, followed by freeze-drying. The dry composites were further infiltrated with water containing nHAp only (BMP (−)) or with water containing nHAp and BMP (BMP (+)). Prepared wet constructs (BMP (−) and BMP (+)) were implanted in rat cranial bone defects, while defects only were also made, and animals were fed for 8 weeks, followed by subsequent soft X-ray measurements and histological observations. The X-ray results showed that BMP (+) constructs disappeared, though caused inward extension of peripherical bone from defect edges with an increase in length of approximately 24%, larger than those of BMP (−) constructs and defect only with approximately 17% and 8% increments, respectively (p < 0.05). Histological observations of BMP (+) construct samples clearly indicated active bone extension consisting of an array of island-like bones. It was concluded that cHLA/cAG/nHAp/BMP could be used as novel bone-substitute materials.
Hydrogel Formulations of Antibacterial Pyrazoles Using a Synthesized Polystyrene-Based Cationic Resin as a Gelling Agent
Authors: Alfei Silvana , Zuccari Guendalina , Russo Eleonora , Villa Carla , Brullo Chiara
Published: January 2023

Here, to develop new topical antibacterial formulations to treat staphylococcal infections, two pyrazoles (3c and 4b) previously reported as antibacterial agents, especially against staphylococci, were formulated as hydrogels (R1-HG-3c and R1HG-4b) using a cationic polystyrene-based resin (R1) and here synthetized and characterized as gelling agents. Thanks to the high hydrophilicity, high-level porosity, and excellent swelling capabilities of R1, R1HG-3c and R1HG-4b were achieved with an equilibrium degree of swelling (EDS) of 765% (R1HG-3c) and 675% (R1HG-4b) and equilibrium water content (EWC) of 88% and 87%, respectively. The chemical structure of soaked and dried gels was investigated by PCA-assisted attenuated total reflectance (ATR) Fourier transform infrared (FTIR) spectroscopy, while their morphology was investigated by optical microscopy. Weight loss studies were carried out with R1HG-3c and R1HG-4b to investigate their water release profiles and the related kinetics, while their stability was evaluated over time both by monitoring their inversion properties to detect possible impairments of the 3D network and by PCA-assisted ATR-FTIR spectroscopy to detect possible structural changes. The flow and dynamic rheological characterization of the gels was assessed by determining their viscosity vs. shear rate, applying the Cross rheological equation to achieve the curves of shear stress vs. shear rate, and carrying out amplitude and frequency sweep experiments. Finally, their content in NH3+ groups was determined by potentiometric titrations. Due to their favorable physicochemical characteristic and the antibacterial effects of 3c and 4b possibly improved by the cationic R1, the pyrazole-enriched gels reported here could represent new weapons to treat severe skin and wound infections sustained by MDR bacteria of staphylococcal species.
Unexpected Crosslinking Effects of a Human Thyroid Stimulating Monoclonal Autoantibody, M22, with IGF1 on Adipogenesis in 3T3L-1 Cells
Authors: Umetsu Araya , Sato Tatsuya , Watanabe Megumi , Ida Yosuke , Furuhashi Masato , Tsugeno Yuri , Ohguro Hiroshi
Published: January 2023

To study the effects of the crosslinking of IGF1 and/or the human thyroid-stimulating monoclonal autoantibody (TSmAb), M22 on mouse adipocytes, two- and three-dimensional (2D or 3D) cultures of 3T3-L1 cells were prepared. Each sample was then subjected to the following analyses: (1) lipid staining, (2) a real-time cellular metabolic analysis, (3) analysis of the mRNA expression of adipogenesis-related genes and extracellular matrix (ECM) molecules including collagen (Col) 1, 4 and 6, and fibronectin (Fn), and (4) measurement of the size and physical properties of the 3D spheroids with a micro-squeezer. Upon adipogenic differentiation (DIF+), lipid staining and the mRNA expression of adipogenesis-related genes in the 2D- or 3D-cultured 3T3-L1 cells substantially increased. On adding IGF1 but not M22 to DIF+ cells, a significant enhancement in lipid staining and gene expressions of adipogenesis-related genes was detected in the 2D-cultured 3T3-L1 cells, although some simultaneous suppression or enhancement effects by IGF1 and M22 against lipid staining or Fabp4 expression, respectively, were detected in the 3D 3T3-L1 spheroids. Real-time metabolic analyses indicated that monotherapy with IGF1 or M22 shifted cellular metabolism toward energetic states in the 2D 3T3-L1 cells upon DIF+, although no significant metabolic changes were induced by DIF+ alone in 2D cultures. In addition, some synergistical effects on cellular metabolism by IGF1 and M22 were also observed in the 2D 3T3-L1 cells as well as in cultured non-Graves’ orbitopathy-related human orbital fibroblasts (n-HOFs), but not in Graves’ orbitopathy-related HOFs (GHOFs). In terms of the physical properties of the 3D 3T3-L1 spheroids, (1) their sizes significantly increased upon DIF+, and this increase was significantly enhanced by the presence of both IGF1 and M22 despite downsizing by monotreatment, and (2) their stiffness increased substantially, and no significant effects by IGF-1 and/or M22 were observed. Regarding the expression of ECM molecules, (1) upon DIF+, significant downregulation or upregulation of Col1 and Fn (3D), or Col4 and 6 (2D and 3D) were observed, and (2) in the presence of IGF-1 and/or M22, the mRNA expression of Col4 was significantly downregulated by M22 (2D and 3D), but the expression of Col1 was modulated in different manners by monotreatment (upregulation) or the combined treatment (downregulation) (3D). These collective data suggest that the human-specific TSmAb M22 induced some unexpected simultaneous crosslinking effects with IGF-1 with respect to the adipogenesis of 2D-cultured 3T3-L1 cells and the physical properties of 3D 3T3-L1 spheroids.
Differential Effects of Oligosaccharides, Antioxidants, Amino Acids and PUFAs on Heat/Hypoxia-Induced Epithelial Injury in a Caco-2/HT-29 Co-Culture Model
Authors: Lian Puqiao , Henricks Paul A. J. , Wichers Harry J. , Folkerts Gert , Braber Saskia
Published: January 2023

(1) Exposure of intestinal epithelial cells to heat and hypoxia causes a (heat) stress response, resulting in the breakdown of epithelial integrity. There are indications that several categories of nutritional components have beneficial effects on maintaining the intestinal epithelial integrity under stress conditions. This study evaluated the effect of nine nutritional components, including non-digestible oligosaccharides (galacto-oligosaccharides (GOS), fructo-oligosaccharides (FOS), chitosan oligosaccharides (COS)), antioxidants (α-lipoic acid (ALA), resveratrol (RES)), amino acids (l-glutamine (Glu), l-arginine (Arg)) and polyunsaturated fatty acids (PUFAs) (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)), on heat/hypoxia-induced epithelial injury. (2) Two human colonic cell lines, Caco-2 and HT-29, were co-cultured and pre-treated with the nutritional components for 48 h. After pre-treatment, the cells were exposed to heat/hypoxia (42 °C, 5% O2) for 2 h. Epithelial integrity was evaluated by measuring trans-epithelial electrical resistance (TEER), paracellular Lucifer Yellow (LY) permeability, and tight junction (TJ) protein expression. Heat stress and oxidative stress levels were evaluated by determining heat-shock protein-70 (HSP-70) expression and the concentration of the lipid peroxidation product malondialdehyde (MDA). (3) GOS, FOS, COS, ALA, RES, Arg, and EPA presented protective effects on epithelial damage in heat/hypoxia-exposed Caco-2/HT-29 cells by preventing the decrease in TEER, the increase in LY permeability, and/or decrease in TJ proteins zonula occludens-1 (ZO-1) and claudin-3 expression. COS, RES, and EPA demonstrated anti-oxidative stress effects by suppressing the heat/hypoxia-induced MDA production, while Arg further elevated the heat/hypoxia-induced increase in HSP-70 expression. (4) This study indicates that various nutritional components have the potential to counteract heat/hypoxia-induced intestinal injury and might be interesting candidates for future in vivo studies and clinical trials in gastrointestinal disorders related to heat stress and hypoxia.
Lunaemycins, New Cyclic Hexapeptide Antibiotics from the Cave Moonmilk-Dweller Streptomyces lunaelactis MM109T
Authors: Martinet Loïc , Naômé Aymeric , Rezende Lucas C. D. , Tellatin Déborah , Pignon Bernard , Docquier Jean-Denis , Sannio Filomena , Baiwir Dominique , Mazzucchelli Gabriel , Frédérich Michel , Rigali Sébastien
Published: January 2023

Streptomyces lunaelactis strains have been isolated from moonmilk deposits, which are calcium carbonate speleothems used for centuries in traditional medicine for their antimicrobial properties. Genome mining revealed that these strains are a remarkable example of a Streptomyces species with huge heterogeneity regarding their content in biosynthetic gene clusters (BGCs) for specialized metabolite production. BGC 28a is one of the cryptic BGCs that is only carried by a subgroup of S. lunaelactis strains for which in silico analysis predicted the production of nonribosomal peptide antibiotics containing the non-proteogenic amino acid piperazic acid (Piz). Comparative metabolomics of culture extracts of S. lunaelactis strains either holding or not holding BGC 28a combined with MS/MS-guided peptidogenomics and 1H/13C NMR allowed us to identify the cyclic hexapeptide with the amino acid sequence (D-Phe)-(L-HO-Ile)-(D-Piz)-(L-Piz)-(D-Piz)-(L-Piz), called lunaemycin A, as the main compound synthesized by BGC 28a. Molecular networking further identified 18 additional lunaemycins, with 14 of them having their structure elucidated by HRMS/MS. Antimicrobial assays demonstrated a significant bactericidal activity of lunaemycins against Gram-positive bacteria, including multi-drug resistant clinical isolates. Our work demonstrates how an accurate in silico analysis of a cryptic BGC can highly facilitate the identification, the structural elucidation, and the bioactivity of its associated specialized metabolites.
Genetic Risk Factors for Neurological Disorders in Children with Adverse Events Following Immunization: A Descriptive Study of a Polish Case Series
Authors: Charzewska Agnieszka , Terczyńska Iwona , Lipiec Agata , Mazurczak Tomasz , Górka-Skoczylas Paulina , Szlendak Róża , Kanabus Karolina , Tataj Renata , Dawidziuk Mateusz , Wojtaś Bartosz , Gielniewski Bartłomiej , Bal Jerzy , Stawicka Elżbieta , Hoffman-Zacharska Dorota
Published: January 2023

Studies conducted on large populations show a lack of connection between vaccination and serious neurological symptoms. However, there are isolated cases that indicate such a relationship. These reports on adverse effects following immunization (AEFI) reduce social confidence in vaccination; however, their background may be rare genetic defects. The aim of the presented study was to examine if neurological AEFI in children may be associated with variants in genes related to neurodevelopment. To identify such possible associations, a descriptive study of the Polish case series was conducted. We performed next-generation sequencing in patients who, up to 4 weeks of injection of any vaccine, manifested neurological AEFI. We included 23 previously normally developing children with first seizures that occurred after vaccination. We identified pathogenic/likely pathogenic variants in genes engaged in neurodevelopment in nine patients and variants of uncertain significance in another nine patients. The mutated genes belonged to the group of genes related to epilepsy syndromes/epileptic encephalopathy. We showed that AEFI might have a genetic background. We hypothesized that in some AEFI patients, the vaccine might only trigger neurological symptoms that would have been manifested anyway as a result of a pathogenic variant in a gene engaged in neurodevelopment.
Models and Methods of Designing Data-Centric Microservice Architectures of Digital Enterprises
Authors: Deryabin Sergey , Temkin Igor , Rzazade Ulvi , Kondratev Egor
Published: January 2023

The article is devoted to methods and models of designing systems for the digital transformation of industrial enterprises within the framework of the Industry 4.0 concept. The purpose of this work is to formalize a new notation for graphical modeling of the architecture of complex large-scale systems with data-centric microservice architectures and to present a variant of the reference model of such an architecture for creating an autonomously functioning industrial enterprise. The paper provides a list and justification for the use of functional components of a data-centric microservice architecture based on the analysis of modern approaches to building systems and the authors’ own results obtained during the implementation of a number of projects. The problems of using traditional graphical modeling notations to represent a data-centric microservice architecture are considered. Examples of designing a model of such an architecture for a mining enterprise are given.