bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Evaluation of Biological Effects of Pentathiepins on Various Human Cancer Cell Lines and Insights into Their Mode of Action
Authors: Wolff Lisa , Bandaru Siva Sankar Murthy , Eger Elias , Lam Hoai-Nhi , Napierkowski Martin , Baecker Daniel , Schulzke Carola , Bednarski Patrick J.
Published: July 2021

Pentathiepins are polysulfur-containing compounds that exert antiproliferative and cytotoxic activity in cancer cells, induce oxidative stress and apoptosis, and inhibit glutathione peroxidase (GPx1). This renders them promising candidates for anticancer drug development. However, the biological effects and how they intertwine have not yet been systematically assessed in diverse cancer cell lines. In this study, six novel pentathiepins were synthesized to suit particular requirements such as fluorescent properties or improved water solubility. Structural elucidation by X-ray crystallography was successful for three derivatives. All six underwent extensive biological evaluation in 14 human cancer cell lines. These studies included investigating the inhibition of GPx1 and cell proliferation, cytotoxicity, and the induction of ROS and DNA strand breaks. Furthermore, selected hallmarks of apoptosis and the impact on cell cycle progression were studied. All six pentathiepins exerted high cytotoxic and antiproliferative activity, while five also strongly inhibited GPx1. There is a clear connection between the potential to provoke oxidative stress and damage to DNA in the form of single- and double-strand breaks. Additionally, these studies support apoptosis but not ferroptosis as the mechanism of cell death in some of the cell lines. As the various pentathiepins give rise to different biological responses, modulation of the biological effects depends on the distinct chemical structures fused to the sulfur ring. This may allow for an optimization of the anticancer activity of pentathiepins in the future.
Specific Increase in Joint Neutrophil Extracellular Traps and Its Relation to Interleukin 6 in Autoimmune Arthritis
Authors: Ohyama Ayako , Osada Atsumu , Kawaguchi Hoshimi , Kurata Izumi , Nishiyama Taihei , Iwai Tamaki , Ishigami Akihito , Kondo Yuya , Tsuboi Hiroto , Sumida Takayuki , Matsumoto Isao
Published: July 2021

Neutrophils and their extracellular traps have been shown to play an important role in the pathogenesis of rheumatoid arthritis (RA), but the detailed mechanisms in joints are still unclear, and their regulation remains to be solved. Here, we explored neutrophil extracellular trap (NET)osis in experimental models of arthritis and further investigated the effects of interleukin-6 (IL-6) inhibition in neutrophils and NETosis. In skins of peptide GPI-induced arthritis (pGIA), citrullinated protein was detected as well as citrullinated histone expression in immunized skin but this was not specific to pGIA. Citrullinated histone expression in pGIA joints was specific to pGIA and was merged with neutrophil elastase, suggesting NETosis. Neutrophils in joints tend to upregulate IL-6 receptors when compared with bone marrow neutrophils. Administration of mouse anti-IL-6 receptor antibodies in pGIA suppressed arthritis in association with a decrease in neutrophil infiltration and NETosis in joints. In the plasma of RA patients, citrullinated protein was significantly reduced after tocilizumab treatment. Our results suggest that IL-6 enhances neutrophil chemotaxis and NETosis in inflammatory joints and could be the source of citrullinated proteins.
Computational Design of Radical Recognition Assay with the Possible Application of Cyclopropyl Vinyl Sulfides as Tunable Sensors
Authors: Sahharova Liliya T. , Gordeev Evgeniy G. , Eremin Dmitry B. , Ananikov Valentine P.
Published: July 2021

The processes involving the capture of free radicals were explored by performing DFT molecular dynamics simulations and modeling of reaction energy profiles. We describe the idea of a radical recognition assay, where not only the presence of a radical but also the nature/reactivity of a radical may be assessed. The idea is to utilize a set of radical-sensitive molecules as tunable sensors, followed by insight into the studied radical species based on the observed reactivity/selectivity. We utilize this approach for selective recognition of common radicals—alkyl, phenyl, and iodine. By matching quantum chemical calculations with experimental data, we show that components of a system react differently with the studied radicals. Possible radical generation processes were studied involving model reactions under UV light and metal-catalyzed conditions.
Rhodamine 6G-Ligand Influencing G-Quadruplex Stability and Topology
Authors: Trizna Lukáš , Janovec Ladislav , Halaganová Andrea , Víglaský Viktor
Published: July 2021

The involvement of G-quadruplex (G4) structures in nucleic acids in various molecular processes in cells such as replication, gene-pausing, the expression of crucial cancer-related genes and DNA damage repair is well known. The compounds targeting G4 usually bind directly to the G4 structure, but some ligands can also facilitate the G4 folding of unfolded G-rich sequences and stabilize them even without the presence of monovalent ions such as sodium or potassium. Interestingly, some G4-ligand complexes can show a clear induced CD signal, a feature which is indirect proof of the ligand interaction. Based on the dichroic spectral profile it is not only possible to confirm the presence of a G4 structure but also to determine its topology. In this study we examine the potential of the commercially available Rhodamine 6G (RhG) as a G4 ligand. RhG tends to convert antiparallel G4 structures to parallel forms in a manner similar to that of Thiazole Orange. Our results confirm the very high selectivity of this ligand to the G4 structure. Moreover, the parallel topology of G4 can be verified unambiguously based on the specific induced CD profile of the G4-RhG complex. This feature has been verified on more than 50 different DNA sequences forming various non-canonical structural motifs.
Anti-Cancer Immune Reaction and Lymph Node Macrophage; A Review from Human and Animal Studies
Authors: Komohara Yoshihiro , Anami Toshiki , Asano Kenichi , Fujiwara Yukio , Yatsuda Junji , Kamba Tomomi
Published: July 2021

Lymph nodes are secondary lymphoid organs that appear as bean-like nodules usually <1 cm in size, and they are localized throughout the body. Many antigen-presenting cells such as dendritic cells and macrophages reside in lymph nodes, where they mediate host defense responses against pathogens such as viruses and bacteria. In cancers, antigen-presenting cells induce cytotoxic T lymphocytes (CTLs) to react to cancer cell-derived antigens. Macrophages located in the lymph node sinus are of particular interest in relation to anti-cancer immune responses because many studies using both human specimens and animal models have suggested that lymph node macrophages expressing CD169 play a key role in activating anti-cancer CTLs. The regulation of lymph node macrophages therefore represents a potentially promising novel approach in anti-cancer therapy.
Looking Back to Move Forward: How Review Articles Could Boost Forensic Entomology
Authors: Charabidze Damien , Martín-Vega Daniel
Published: July 2021

The Locard′s exchange principle (1930) holds that the perpetrator of a crime leaves traces behind that can later be sampled and used as forensic evidence [...]
Persistent Atrial Fibrillation: The Role of Left Atrial Posterior Wall Isolation and Ablation Strategies
Authors: Kaba Riyaz A. , Momin Aziz , Camm John
Published: July 2021

Atrial fibrillation (AF) is a global disease with rapidly rising incidence and prevalence. It is associated with a higher risk of stroke, dementia, cognitive decline, sudden and cardiovascular death, heart failure and impairment in quality of life. The disease is a major burden on the healthcare system. Paroxysmal AF is typically managed with medications or endocardial catheter ablation to good effect. However, a large proportion of patients with AF have persistent or long-standing persistent AF, which are more complex forms of the condition and thus more difficult to treat. This is in part due to the progressive electro-anatomical changes that occur with AF persistence and the spread of arrhythmogenic triggers and substrates outside of the pulmonary veins. The posterior wall of the left atrium is a common site for these changes and has become a target of ablation strategies to treat these more resistant forms of AF. In this review, we discuss the role of the posterior left atrial wall in persistent and long-standing persistent AF, the limitations of current endocardial-focused treatment strategies, and future perspectives on hybrid epicardial–endocardial approaches to posterior wall isolation or ablation.
Interstitial Lung Abnormalities Detected by CT in Asbestos-Exposed Subjects Are More Likely Associated to Age
Authors: Laurent François , Benlala Ilyes , Dournes Gael , Gramond Celine , Thaon Isabelle , Clin Bénédicte , Brochard Patrick , Gislard Antoine , Andujar Pascal , Chammings Soizick , Gallet Justine , Lacourt Aude , Delva Fleur , Paris Christophe , Ferretti Gilbert , Pairon Jean-Claude
Published: July 2021

Objective: the aim of this study was to evaluate the association between interstitial lung abnormalities, asbestos exposure and age in a population of retired workers previously occupationally exposed to asbestos. Methods: previously occupationally exposed former workers to asbestos eligible for a survey conducted between 2003 and 2005 in four regions of France, underwent chest CT examinations and pulmonary function testing. Industrial hygienists evaluated asbestos exposure and calculated for each subject a cumulative exposure index (CEI) to asbestos. Smoking status information was also collected in this second round of screening. Expert radiologists performed blinded independent double reading of chest CT-scans and classified interstitial lung abnormalities into: no abnormality, minor interstitial findings, interstitial findings inconsistent with UIP, possible or definite UIP. In addition, emphysema was assessed visually (none, minor: emphysema <25%, moderate: between 25 and 50% and severe: >50% of the lung). Logistic regression models adjusted for age and smoking were used to assess the relationship between interstitial lung abnormalities and occupational asbestos exposure. Results: the study population consisted of 2157 male subjects. Interstitial lung abnormalities were present in 365 (16.7%) and emphysema in 444 (20.4%). Significant positive association was found between definite or possible UIP pattern and age (OR adjusted =1.08 (95% CI: 1.02–1.13)). No association was found between interstitial abnormalities and CEI or the level of asbestos exposure. Conclusion: presence of interstitial abnormalities at HRCT was associated to aging but not to cumulative exposure index in this cohort of former workers previously occupationally exposed to asbestos.
Prevalence of High-Risk Human Papillomavirus Infections before and after Cervical Lesion Treatment, among Women Living with HIV
Authors: Dub Timothée , Le Cœur Sophie , Ngo-Giang-Huong Nicole , Matanasarawut Wanmanee , Suriyachai Pornnapa , Saisawat Kannikar , Putiyanun Chaiwat , Buranabanjasatean Sudanee , Leenasirimakul Prattana , Randaeng Samreung , Delory Tristan
Published: July 2021

Even when receiving combination antiretroviral therapy, women living with HIV are at high risk of human papillomavirus (HPV) infection and/or cervical lesions, including cancer. Using data from the PapilloV prospective cohort, we evaluated the prevalence of high-risk HPV (HR-HPV) infections after cervical lesion treatment and investigated factors associated with their carriage. Women were followed up for three years with annual Pap smear and HPV genotyping. We offered treatment to women presenting either a Pap smear with high-grade squamous intraepithelial lesion or higher, and/or a biopsy showing cervical intraepithelial neoplasia II or III. We compared the prevalence of HR-HPV infection at the time of first treatment indication and at the end of follow-up among women who received treatment and those who did not. Overall, 46 women had treatment indication. HR-HPV prevalence significantly decreased from 67% to 27% (p value = 0.001) in the 30 women who received treatment, while it did not significantly decrease (from 56% to 38%) in the 16 women who did not (p value = 0.257). Due to lack of statistical power, the 40% relative difference in HR-HPV carriage between treated and untreated women was not significant. In women living with HIV, the treatment of a cervical lesion may be beneficial for clearing HR-HPV infections.
Neurological Injuries after Calcaneal Osteotomies Are Underdiagnosed
Authors: González-Martín David , Herrera-Pérez Mario , Ojeda-Jiménez Jorge , Rendón-Díaz Diego , Valderrabano Victor , Pais-Brito José Luis
Published: July 2021

The incidence of peripheral neurological injuries related to calcaneal osteotomies reported in the literature is low and often described as occasional. The main objective of this study is to determine the incidence of neurological injuries after calcaneal osteotomies and identify which nerve structures are most affected. This retrospective work included 69 patients. Medical records, surgical protocols, and radiographs were analyzed. All patients were summoned to perform current functional tests (EFAS score and SF-12), and a thorough physical examination was performed systematically and bilaterally. The total incidence of neurological injuries was 43.5% (30/69). The percentage of neurapraxias (transient injuries) was 8.7%, while 34.8% of patients presented neurological sequelae (permanent injuries). The most injured nerve or branch was, in decreasing order: sural nerve, medial plantar branch, lateral plantar branch and medial calcaneal branch. Following the so-called “safe zone” clearly decreases the incidence of sural nerve injury (p = 0.035). No significant differences were found between osteotomy site, number of screws, and type of closure and increased neurological injuries. No significant differences were found in the functional tests between the different techniques, nor between patients who presented neurological injuries and those who did not. Neurological injuries after calcaneal osteotomies are underdiagnosed and the incidence is higher than previously reported (43.5%). Such injuries mostly go unnoticed and have no implications in the functional results and patients’ satisfaction.
Restoration of Osteogenesis by CRISPR/Cas9 Genome Editing of the Mutated COL1A1 Gene in Osteogenesis Imperfecta
Authors: Jung Hyerin , Rim Yeri Alice , Park Narae , Nam Yoojun , Ju Ji Hyeon
Published: July 2021

Osteogenesis imperfecta (OI) is a genetic disease characterized by bone fragility and repeated fractures. The bone fragility associated with OI is caused by a defect in collagen formation due to mutation of COL1A1 or COL1A2. Current strategies for treating OI are not curative. In this study, we generated induced pluripotent stem cells (iPSCs) from OI patient-derived blood cells harboring a mutation in the COL1A1 gene. Osteoblast (OB) differentiated from OI-iPSCs showed abnormally decreased levels of type I collagen and osteogenic differentiation ability. Gene correction of the COL1A1 gene using CRISPR/Cas9 recovered the decreased type I collagen expression in OBs differentiated from OI-iPSCs. The osteogenic potential of OI-iPSCs was also recovered by the gene correction. This study suggests a new possibility of treatment and in vitro disease modeling using patient-derived iPSCs and gene editing with CRISPR/Cas9.
History of IgA Nephropathy Mouse Models
Authors: Wehbi Batoul , Pascal Virginie , Zawil Lina , Cogné Michel , Aldigier Jean-Claude
Published: July 2021

IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. It was first described in 1968 by Jean Berger and Nicole Hinglais as the presence of intercapillary deposits of IgA. Despite this simple description, patients with IgAN may present very broad clinical features ranging from the isolated presence of IgA in the mesangium without clinical or biological manifestations to rapidly progressive kidney failure. These features are associated with a variety of histological lesions, from the discrete thickening of the mesangial matrix to diffuse cell proliferation. Immunofluorescence on IgAN kidney specimens shows the isolated presence of IgA or its inconsistent association with IgG and complement components. This clinical heterogeneity of IgAN clearly echoes its complex and multifactorial pathophysiology in humans, inviting further analyses of its various aspects through the use of experimental models. Small-animal models of IgAN provide the most pertinent strategies for studying the multifactorial aspects of IgAN pathogenesis and progression. Although only primates have the IgA1 subclass, several murine models have been developed in which various aspects of immune responses are deregulated and which are useful in the understanding of IgAN physiopathology as well as in the assessment of IgAN therapeutic approaches. In this manuscript, we review all murine IgAN models developed since 1968 and discuss their remarkable contribution to understanding the disease.
Pharmacological Effects of Methotrexate and Infliximab in a Rats Model of Diet-Induced Dyslipidemia and Beta-3 Overexpression on Endothelial Cells
Authors: Zălar Denisa-Mădălina , Pop Cristina , Buzdugan Elena , Kiss Bela , Ştefan Maria-Georgia , Ghibu Steliana , Bâlteanu Valentin-Adrian , Crişan Doiniţa , Buruiană-Simic Alexandra , Grozav Adriana , Mogoșan Cristina Ionela
Published: July 2021

Background: Hyperlipidemia and inflammation are critical components in the pathophysiology of endothelial disorder, which can lead to vascular complications. Our study aimed to evaluate the effects of immunomodulatory therapy (methotrexate and infliximab) in a diet-induced hyperlipidemia rat model. Methods: Sprague-Dawley (wild type (WT), male, n = 32) rats were divided into four groups: one group fed with standard diet (SD), one group fed with high lipid diet (HLD), and two groups that received HLD and drug treatment (methotrexate (Mtx) or infliximab (Ifx)). In order to evaluate if modifications to the endothelial cells may influence the risk of vascular complications following hyperlipidemia or treatment reactivity, each group was doubled by a rats group that overexpressed beta-3 receptors on the endothelial cells (transgenic (TG-beta 3), male, n = 32). Serum lipid profile, liver enzymes, oxidative stress, and inflammation markers were determined. Histopathologic analysis of the liver and aorta was performed. Results: After 9 weeks of HLD, rats exhibited significant pathologic serum lipid profiles, elevated oxidative stress, and pro-inflammatory markers. Additionally, the aortic histopathological analysis revealed aorta media-intima thickening (p < 0.05) in the transgenic group. Methotrexate and infliximab significantly decreased inflammation and oxidative stress parameters, but presented opposing effects on lipid profiles (methotrexate decreased, whereas infliximab increased the atherosclerosis index). Drug treatment decreased the aorta media-intima thickness (p < 0.05) only in transgenic rats. Conclusions: HLD was associated with hyperlipidemia, inflammation and oxidative stress. The overexpression of beta-3 receptors on endothelial cells increased aortic thickening in response to the HLD. Methotrexate and infliximab reduced oxidative stress and inflammation in all groups, but led to favorable histopathologic vascular results only in the transgenic groups.
Administration of Low-Dose Dexmedetomidine Did Not Affect Acute Inflammatory Response after Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Chemotherapy: A Double-Blind Randomized Controlled Trial
Authors: Moon Jiae , Yoo Young Chul , Kim Myoung Hwa , Jeon Soyoung , Joo Hye Ji , Chun Duk-Hee , Kim Na Young
Published: July 2021

During cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), attenuation of inflammatory responses that increase susceptibility to postoperative complications, morbidity, and mortality is important. We aimed to evaluate whether intraoperative dexmedetomidine infusion impacted inflammatory response in patients undergoing CRS with HIPEC. Fifty-six patients scheduled for CRS with HIPEC were randomly assigned to the control (n = 28) and dexmedetomidine (n = 28) groups. The primary endpoint was the effect of dexmedetomidine on the interleukin-6 (IL-6) level measured at pre-operation (Pre-OP), before HIPEC initiation (Pre-HIPEC), immediately after HIPEC; after the end of the operation; and on postoperative day (POD) 1. In both groups, the IL-6 levels from Pre-HIPEC until POD 1 and the C-reactive protein (CRP) levels on PODs 1, 2, and 3 were significantly higher than the Pre-OP values (all Bonferroni corrected, p < 0.001). However, total differences in IL-6 and CRP levels, based on the mean area under the curve, were not detected between the two groups. The continuous intraoperative infusion of dexmedetomidine (0.4 μg/kg/h) in patients undergoing CRS with HIPEC did not significantly lower the inflammatory indices. Further dose investigative studies are needed to find the dexmedetomidine dose that provides anti-inflammatory and sympatholytic effects during HIPEC.
Impact of BCR-ABL1 Transcript Type on Response, Treatment-Free Remission Rate and Survival in Chronic Myeloid Leukemia Patients Treated with Imatinib
Authors: Marcé Sílvia , Xicoy Blanca , García Olga , Cabezón Marta , Estrada Natalia , Vélez Patricia , Boqué Concepción , Sagüés Miguel , Angona Anna , Teruel-Montoya Raúl , Ferrer-Marín Francisca , Amat Paula , Hernández-Boluda Juan , Ibarra Mariana , Anguita Eduardo , Cortés Montserrat , Fernández-Ruiz Andrés , Fontanals Sandra , Zamora Lurdes ,   on behalf of the Grupo Español de Leucemia Mieloide Crónica (GELMC)
Published: July 2021

The most frequent BCR-ABL1-p210 transcripts in chronic myeloid leukemia (CML) are e14a2 and e13a2. Imatinib (IM) is the most common first-line tyrosine–kinase inhibitor (TKI) used to treat CML. Some studies suggest that BCR-ABL1 transcript types confer different responses to IM. The objective of this study was to correlate the expression of e14a2 or e13a2 to clinical characteristics, cumulative cytogenetic and molecular responses to IM, acquisition of deep molecular response (DMR) and its duration (sDMR), progression rate (CIP), overall survival (OS), and treatment-free remission (TFR) rate. We studied 202 CML patients, 76 expressing the e13a2 and 126 the e14a2, and correlated the differential transcript expression with the above-mentioned parameters. There were no differences in the cumulative incidence of cytogenetic responses nor in the acquisition of DMR and sDMR between the two groups, but the e14a2 transcript had a positive impact on molecular response during the first 6 months, whereas the e13a2 was associated with improved long-term OS. No correlation was observed between the transcript type and TFR rate.
Impact of Chronic RAAS Use in Elderly COVID-19 Patients: A Retrospective Analysis
Authors: Oliveira João , Gameiro Joana , Bernardo João , Marques Filipe , Costa Cláudia , Branco Carolina , Duarte Inês , Fonseca José , Carreiro Carolina , Braz Sandra , Lopes José António
Published: July 2021

Corona Virus Disease-19 (COVID-19) recently emerged as a global pandemic. Advanced age is the most important risk factor for increased virus susceptibility and worse outcomes. Many older adults are currently treated with renin–angiotensin–aldosterone system (RAAS) inhibitors and there is concern that these medications might increase the risk of mortality by COVID-19. This is a retrospective cohort of 346 patients older than 65 years with COVID-19, at the Department of Medicine of the Centro Hospitalar Universitário Lisboa Norte, in Portugal, hospitalized between March 2020 and August 2020. Mean age was 80.9 ± 8.7 years old. Most patients had arterial hypertension (n = 279, 80.6%), almost half (n = 161, 46.5%) had cardiovascular disease and approximately one-third of patients had heart failure (n = 127, 36.7%) or diabetes Mellitus (n = 113, 32.7%). Ninety-eight patients (28.3%) had chronic kidney disease and almost half of the patients (49.4%) were chronically under renin–angiotensin–aldosterone system (RAAS) inhibitors. Twenty percent of patients died during hospitalization. In a multivariate analysis, older age (OR 1.11, 95% CI 1.04, 1.18, p = 0.002), absence of baseline medication with RAAS inhibitors (OR 0.27, 95% CI 0.10, 0.75, p = 0.011), higher serum ferritin (OR 1.00, 95% CI 1.00, 1.00, p = 0.003) and higher lactate levels (OR 1.08, 95% CI 1.02, 1.14, p = 0.006) were independent predictors of mortality. Older age, higher serum ferritin and lactate levels at admission were found to be independent predictors of mortality and might act as early predictors of worsening disease in clinical practice. Chronic treatment with RAAS inhibitors appeared to be protective, supporting guidelines in not discontinuing such drugs.
Superparamagnetic Iron Oxide for Identifying Sentinel Lymph Node in Breast Cancer after Neoadjuvant Chemotherapy: Feasibility Study
Authors: Kurylcio Andrzej , Pelc Zuzanna , Skórzewska Magdalena , Rawicz-Pruszyński Karol , Mlak Radosław , Gęca Katarzyna , Sędłak Katarzyna , Kurylcio Piotr , Małecka-Massalska Teresa , Polkowski Wojciech
Published: July 2021

Sentinel lymph node biopsy (SLNB) is a well-established procedure for staging clinically node-negative early breast cancer (BC). Superparamagnetic iron oxide (SPIO) demonstrated efficacy for nodal identification using a magnetic probe after local retroaeroal interstitial injection. Its benefits lie in its flexibility, which is an essential property in the global setting, where access to the isotope is difficult. To the best of our knowledge, this is the first study to evaluate the feasibility and safety of the SPIO for SLNB in BC patients treated with neoadjuvant chemotherapy (NAC). Seventy-four female patients were included. The median time of lymph node retrieval was 20 min. The median number of resected sentinel nodes (SNs) was 4. SN was detected in all patients. No serious adverse event was observed. SPIO in identifying SN in BC patients after NAC is feasible and oncologically safe.
High-Throughput Mechanistic Screening of Epigenetic Compounds for the Potential Treatment of Meningiomas
Authors: Tatman Philip , Wroblewski Tadeusz , Fringuello Anthony , Scherer Samuel , Foreman William , Damek Denise , Lillehei Kevin , Youssef A. , Jensen Randy , Graner Michael , Ormond D.
Published: July 2021

Background: Meningiomas are the most common primary central nervous system tumors. 20–30% of these tumors are considered high-grade and associated with poor prognosis and high recurrence rates. Despite the high occurrence of meningiomas, there are no FDA-approved compounds for the treatment of these tumors. Methods: In this study, we screened patient-cultured meningiomas with an epigenetic compound library to identify targetable mechanisms for the potential treatment of these tumors. Meningioma cell cultures were generated directly from surgically resected patient tumors and were cultured on a neural matrix. Cells were treated with a library of compounds meant to target epigenetic functions. Results: Although each tumor displayed a unique compound sensitivity profile, Panobinostat, LAQ824, and HC toxin were broadly effective across most tumors. These three compounds are broad-spectrum Histone Deacetylase (HDAC) inhibitors which target class I, IIa, and IIb HDACs. Panobinostat was identified as the most broadly effective compound, capable of significantly decreasing the average cell viability of the sample cohort, regardless of tumor grade, recurrence, radiation, and patient gender. Conclusions: These findings strongly suggest an important role of HDACs in meningioma biology and as a targetable mechanism. Additional validation studies are necessary to confirm these promising findings, as well to identify an ideal HDAC inhibitor candidate to develop for clinical use.
The Culturable Mycobiome of Mesophotic Agelas oroides: Constituents and Changes Following Sponge Transplantation to Shallow Water
Authors: Ben-Dor Cohen Eyal , Ilan Micha , Yarden Oded
Published: July 2021

Marine sponges harbor a diverse array of microorganisms and the composition of the microbial community has been suggested to be linked to holo-biont health. Most of the attention concerning sponge mycobiomes has been given to sponges present in shallow depths. Here, we describe the presence of 146 culturable mycobiome taxa isolated from mesophotic niche (100 m depth)-inhabiting samples of Agelas oroides, in the Mediterranean Sea. We identify some potential in vitro interactions between several A. oroides-associated fungi and show that sponge meso-hyl extract, but not its predominantly collagen-rich part, is sufficient to support hyphal growth. We demonstrate that changes in the diversity of culturable mycobiome constituents occur following sponge transplantation from its original mesophotic habitat to shallow (10 m) waters, where historically (60 years ago) this species was found. We conclude that among the 30 fungal genera identified as associated with A. oroides, Aspergillus, Penicillium and Trichoderma constitute the core mycobiome of A. oroides, and that they persist even when the sponge is transplanted to a suboptimal environment, indicative of the presence of constant, as well as dynamic, components of the sponge mycobiome. Other genera seemed more depth-related and appeared or disappeared upon host’s transfer from 100 to 10 m.
Q-Switched 1064/532 nm Laser with Nanosecond Pulse in Tattoo Treatment: A Double-Center Retrospective Study
Authors: Cannarozzo Giovanni , Nisticò Steven Paul , Zappia Elena , Del Duca Ester , Provenzano Eugenio , Patruno Cataldo , Negosanti Francesca , Sannino Mario , Bennardo Luigi
Published: July 2021

Tattoo removal is a well-established procedure in dermatology. Lasers represent the gold standard in the management of this condition nowadays. In this study, we report our experience on the use of a Q-switched nanosecond source. A total of 52 patients were consecutively enrolled in performing tattoo removal at Magna Graecia University of Catanzaro and Tor Vergata University of Rome. Black and blue tattoos were treated with a 1064 nm laser, with a pulse duration of 6 ns and a fluence up to 10 J/cm2, while colored tattoos were treated with sessions of 532 nm laser, with a pulse duration of 6 ns and a fluence up to 5 J/cm2. Up to nine treatments with a minimum interval of 8 weeks between each session were performed. A six-month follow-up visit assessed patient satisfaction (Visual Analogue Scale). Overall clinical result was assessed with a clinical evaluation by two blinded dermatologists using a 5-point scale, comparing pictures before treatment and at follow up. A total of 52 patients were included and analyzed: 30 females (57.7%) and 22 males (42.3%). Mean age was 43.7 ± 12.7 years. According to Fitzpatrick’s skin classification, 16 individuals (30.8%) were type II, 15 (28.8%) were type III, and 21 (40.4%) were type IV. Most of the treated tattoos were carried out by professionals. The mean number of sessions required to obtain a result was 4.6 ± 2.5, and the final tattoo removal rate was 60% or higher, with 51.9% of the patients reporting highest satisfaction scores Q-Switched 1064/532 nm laser may be considered today as the gold-standard treatment for tattoo removal. Our results confirm literature findings of the safety and effectiveness of these devices.
Lytic Release of Cellular ATP: Physiological Relevance and Therapeutic Applications
Authors: Grygorczyk Ryszard , Boudreault Francis , Ponomarchuk Olga , Tan Ju , Furuya Kishio , Goldgewicht Joseph , Kenfack Falonne , Yu François
Published: July 2021

The lytic release of ATP due to cell and tissue injury constitutes an important source of extracellular nucleotides and may have physiological and pathophysiological roles by triggering purinergic signalling pathways. In the lungs, extracellular ATP can have protective effects by stimulating surfactant and mucus secretion. However, excessive extracellular ATP levels, such as observed in ventilator-induced lung injury, act as a danger-associated signal that activates NLRP3 inflammasome contributing to lung damage. Here, we discuss examples of lytic release that we have identified in our studies using real-time luciferin-luciferase luminescence imaging of extracellular ATP. In alveolar A549 cells, hypotonic shock-induced ATP release shows rapid lytic and slow-rising non-lytic components. Lytic release originates from the lysis of single fragile cells that could be seen as distinct spikes of ATP-dependent luminescence, but under physiological conditions, its contribution is minimal <1% of total release. By contrast, ATP release from red blood cells results primarily from hemolysis, a physiological mechanism contributing to the regulation of local blood flow in response to tissue hypoxia, mechanical stimulation and temperature changes. Lytic release of cellular ATP may have therapeutic applications, as exemplified by the use of ultrasound and microbubble-stimulated release for enhancing cancer immunotherapy in vivo.
Calcium Silicate-Based Root Canal Sealers: A Narrative Review and Clinical Perspectives
Authors: Sfeir Germain , Zogheib Carla , Patel Shanon , Giraud Thomas , Nagendrababu Venkateshbabu , Bukiet Frédéric
Published: July 2021

Over the last two decades, calcium silicate-based materials have grown in popularity. As root canal sealers, these formulations have been extensively investigated and compared with conventional sealers, such as zinc oxide–eugenol and epoxy resin-based sealers, in in vitro studies that showed their promising properties, especially their biocompatibility, antimicrobial properties, and certain bioactivity. However, the consequence of their higher solubility is a matter of debate and still needs to be clarified, because it may affect their long-term sealing ability. Unlike conventional sealers, those sealers are hydraulic, and their setting is conditioned by the presence of humidity. Current evidence reveals that the properties of calcium silicate-based sealers vary depending on their formulation. To date, only a few short-term investigations addressed the clinical outcome of calcium silicate-based root canal sealers. Their use has been showed to be mainly based on practitioners’ clinical habits rather than manufacturers’ recommendations or available evidence. However, their particular behavior implies modifications of the clinical protocol used for conventional sealers. This narrative review aimed to discuss the properties of calcium silicate-based sealers and their clinical implications, and to propose rational indications for these sealers based on the current knowledge.
The Use of Ion Milling for Surface Preparation for EBSD Analysis
Authors: Nowak Wojciech J.
Published: July 2021

An electron backscattered diffraction (EBSD) method provides information about the crystallographic structure of materials. However, a surface subjected to analysis needs to be well-prepared. This usually requires following a time-consuming procedure of mechanical polishing. The alternative methods of surface preparation for EBSD are performed via electropolishing or focus ion beam (FIB). In the present study, plasma etching using a glow discharge optical emission spectrometer (GD-OES) was applied for surface preparation for EBSD analysis. The obtained results revealed that plasma etching through GD-OES can be successfully used for surface preparation for EBSD analysis. However, it was also found that the plasma etching is sensitive for the alloy microstructure, i.e., the presence of intermetallic phases and precipitates such as carbides possess a different sputtering rate, resulting in non-uniform plasma etching. Preparation of the cross-section of oxidized CM247 revealed a similar problem with non-uniformity of plasma etching. The carbides and oxide scale possess a lower sputtering rate than the metallic matrix, which caused formation of relief. Based on obtained results, possible resolutions to suppress the effect of different sputtering rates are proposed.
Recent Advancements in 3D Printing of Polysaccharide Hydrogels in Cartilage Tissue Engineering
Authors: Naranda Jakob , Bračič Matej , Vogrin Matjaž , Maver Uroš
Published: July 2021

The application of hydrogels coupled with 3-dimensional (3D) printing technologies represents a modern concept in scaffold development in cartilage tissue engineering (CTE). Hydrogels based on natural biomaterials are extensively used for this purpose. This is mainly due to their excellent biocompatibility, inherent bioactivity, and special microstructure that supports tissue regeneration. The use of natural biomaterials, especially polysaccharides and proteins, represents an attractive strategy towards scaffold formation as they mimic the structure of extracellular matrix (ECM) and guide cell growth, proliferation, and phenotype preservation. Polysaccharide-based hydrogels, such as alginate, agarose, chitosan, cellulose, hyaluronan, and dextran, are distinctive scaffold materials with advantageous properties, low cytotoxicity, and tunable functionality. These superior properties can be further complemented with various proteins (e.g., collagen, gelatin, fibroin), forming novel base formulations termed “proteo-saccharides” to improve the scaffold’s physiological signaling and mechanical strength. This review highlights the significance of 3D bioprinted scaffolds of natural-based hydrogels used in CTE. Further, the printability and bioink formation of the proteo-saccharides-based hydrogels have also been discussed, including the possible clinical translation of such materials.
Effect of Transition Elements on the Thermal Stability of Glassy Alloys 82Al–16Fe–2TM (TM: Ti, Ni, Cu) Prepared by Mechanical Alloying
Authors: Oanh Nguyen Thi Hoang , Binh Do Nam , Dang Duc Dung , Hoang Thi Ngoc Quyen , Viet Nguyen Hoang
Published: July 2021

In the present study, the thermal stability and crystallization behavior of mechanical alloyed metallic glassy Al82Fe16Ti2, Al82Fe16Ni2, and Al82Fe16Cu2 were investigated. The microstructure of the milled powders was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). The results showed remarkable distinction in thermal stability of the alloys by varying only two atomic percentages of transition elements. Among them, Al82Fe16Ti2 alloy shows the highest thermal stability compared to the others. In the crystallization process, exothermal peaks corresponding to precipitation of fcc-Al and intermetallic phases from amorphous matrix were observed.
Shrinkage Mitigation of an Ultra-High Performance Concrete Submitted to Various Mixing and Curing Conditions
Authors: Androuët Cédric , Charron Jean-Philippe
Published: July 2021

Ultra-High Performance Concretes (UHPC) are cement-based materials with a very low water-to-binder ratio that present a very-high compressive strength, high tensile strength and ductility as well as excellent durability, making them very interesting for various civil engineering applications. However, one drawback of UHPC is their pretty high autogenous shrinkage stemming from their very low water-to-binder ratio. There are several options to reduce UHPC shrinkage, such as the use of fibers (steel fibers, polypropylene fibers, wollastonite microfibers), shrinkage-reducing admixtures (SRA), expansive admixtures (EA), saturated lightweight aggregates (SLWA) and superabsorbent polymers (SAP). Other factors related to curing conditions, such as humidity and temperature, also affect the shrinkage of UHPC. The aim of this paper is to investigate the impact of various SRA, different mixing and curing conditions (low to moderate mixing temperatures, moderate to high relative humidity and water immersion) as well as different curing starting times and durations on the shrinkage of UHPC. The major importance of the initial mixing and curing conditions has been clearly demonstrated. It was shown that the shrinkage of the UHPC was reduced by more than 20% at early-age and long-term when the fresh UHPC temperature was closer to 20 °C. In addition, curing by water immersion led to drastic reductions in shrinkage of up to 65% and 30% at early-age and long-term, respectively, in comparison to a 20% reduction for fog curing at early-age. Finally, utilization of a liquid polyol-based SRA allowed for reductions of 69% and 63% of early-age and long-term shrinkages, respectively, while a powder polyol-based SRA provided a decrease of 47% and 35%, respectively.
A Critical Review of Carbon Quantum Dots: From Synthesis toward Applications in Electrochemical Biosensors for the Determination of a Depression-Related Neurotransmitter
Authors: Xu Jingying , Tao Jiangang , Su Lili , Wang Jidong , Jiao Tifeng
Published: July 2021

Depression has become the leading cause of disability worldwide and is a global health burden. Quantitative assessment of depression-related neurotransmitter concentrations in human fluids is highly desirable for diagnosis, monitoring disease, and therapeutic interventions of depression. In this review, we focused on the latest strategies of CD-based electrochemical biosensors for detecting a depression-related neurotransmitter. We began this review with an overview of the microstructure, optical properties and cytotoxicity of CDs. Next, we introduced the development of synthetic methods of CDs, including the “Top-down” route and “Bottom-up” route. Finally, we highlighted detecting an application of CD-based electrochemical sensors in a depression-related neurotransmitter. Moreover, challenges and future perspectives on the recent progress of CD-based electrochemical sensors in depression-related neurotransmitter detection were discussed.
SBR Vulcanizates Filled with Modified Ground Tire Rubber
Authors: Klajn Katarzyna , Gozdek Tomasz , Bieliński Dariusz M. , Siciński Mariusz , Zarzecka-Napierała Magdalena , Pędzich Zbigniew
Published: July 2021

Ground tire rubber (GTR) is used to decrease the cost of vulcanizates. However, insufficient interactions between GTR particles and rubber matrices make mechanical properties of vulcanizates containing GTR deteriorate. This paper compares original methods of GTR modification. The effects of surface activation of GTR by sulfuric acid (A), its modification by (3-mercaptopropyl)trimethoxy silane (M), or the hybrid treatment—combining both approaches (H), were analyzed in terms of surface energy, specific surface area and morphology of GTR particles. Vulcanizates containing virgin GTR were compared to the rubber filled with the modified GTR particles keeping the same amount of CB in the rubber mix, according to their crosslink density, mechanical and tribological properties. Contrary to the virgin GTR, the addition of modified GTR increases the stiffness of the vulcanizates. The highest changes have been observed for the samples filled with ca. 12 phr of the GTR modified with silane and ca. 25 phr of the GTR subjected to the hybrid treatment, representing the highest crosslink density of rubber vulcanizates filled with GTR. Furthermore, the addition of modified GTR, especially in the case of the samples where 10 phr of rubber was replaced, results in the significant lowering of friction but higher abrasive wear.
Phase Formation, Microstructure, and Magnetic Properties of Nd14.5Fe79.3B6.2 Melt-Spun Ribbons with Different Ce and Y Substitutions
Authors: Ke Qingjin , Dai Feilong , Li Shengxi , Rong Maohua , Yao Qingrong , Wang Jiang
Published: July 2021

Phase formation and microstructure of (Nd1-2xCexYx)14.5Fe79.3B6.2 (x = 0.05, 0.10, 0.15, 0.20, 0.25) alloys were studied experimentally. The results reveal that (Nd1-2xCexYx)14.5Fe79.3B6.2 annealed alloys show (NdCeY)2Fe14B phase with the tetragonal Nd2Fe14B-typed structure (space group P42/mnm) and rich-RE (α-Nd) phase, while (Nd1-2xCexYx)14.5Fe79.3B6.2 ribbons prepared by melt-spun technology are composed of (NdCeY)2Fe14B phase, α-Nd phase and α-Fe phase, except for the ribbon with x = 0.25, which consists of additional CeFe2 phase. On the other hand, magnetic properties of (Nd1-2xCexYx)14.5Fe79.3B6.2 melt-spun ribbons were measured by a vibrating sample magnetometer (VSM). The measured results show that the remanence (Br) and the coercivity (Hcj) of the melt-spun ribbons decrease with the increase of Ce and Y substitutions, while the maximum magnetic energy product ((BH)max) of the ribbons decreases and then increases. The tendency of magnetic properties of the ribbons could result from the co-substitution of Ce and Y for Nd in Nd2Fe14B phase and different phase constitutions. It was found that the Hcj of the ribbon with x = 0.20 is relatively high to be 9.01 kOe, while the (BH)max of the ribbon with x = 0.25 still reaches to be 9.06 MGOe. It suggests that magnetic properties of Nd-Fe-B ribbons with Ce and Y co-substitution could be tunable through alloy composition and phase formation to fabricate novel Nd-Fe-B magnets with low costs and high performance.
Effect of Tool Geometry Parameters on the Formability of a Camera Cover in the Deep Drawing Process
Authors: Do Thanh Trung , Minh Pham Son , Le Nhan
Published: July 2021

The formability of the drawn part in the deep drawing process depends not only on the material properties, but also on the equipment used, metal flow control and tool parameters. The most common defects can be the thickening, stretching and splitting. However, the optimization of tools including the die and punch parameters leads to a reduction of the defects and improves the quality of the products. In this paper, the formability of the camera cover by aluminum alloy A1050 in the deep drawing process was examined relating to the tool geometry parameters based on numerical and experimental analyses. The results showed that the thickness was the smallest and the stress was the highest at one of the bottom corners where the biaxial stretching was the predominant mode of deformation. The problems of the thickening at the flange area, the stretching at the side wall and the splitting at the bottom corners could be prevented when the tool parameters were optimized that related to the thickness and stress. It was clear that the optimal thickness distribution of the camera cover was obtained by the design of tools with the best values—with the die edge radius 10 times, the pocket radius on the bottom of the die 5 times, and the punch nose radius 2.5 times the sheet thickness. Additionally, the quality of the camera cover was improved with a maximum thinning of 25% experimentally, and it was within the suggested maximum allowable thickness reduction of 45% for various industrial applications after optimizing the tool geometry parameters in the deep drawing process.