bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro Replication Inhibitory Activity of Xanthorrhizol against Severe Acute Respiratory Syndrome Coronavirus 2
Authors: Kim Minwoo , Cho Hee , Ahn Dae-Gyun , Jung Hae-Gwang , Seo Han Young , Kim Ji-Su , Lee Youn-Jung , Choi Jun Yong , Park In Ho , Shin Jeon-Soo , Kim Seong-Jun , Oh Jong-Won
Published: November 2021

In spite of the large number of repositioned drugs and direct-acting antivirals in clinical trials for the management of the ongoing COVID-19 pandemic, there are few cost-effective therapeutic options for severe acute respiratory syndrome (SARS) coronavirus 2 (SCoV2) infection. In this paper, we show that xanthorrhizol (XNT), a bisabolane-type sesquiterpenoid compound isolated from the Curcuma xanthorrhizza Roxb., a ginger-line plant of the family Zingiberaceae, displays a potent antiviral efficacy in vitro against SCoV2 and other related coronaviruses, including SARS-CoV-1 (SCoV1) and a common cold-causing human coronavirus. XNT reduced infectious SCoV2 titer by ~3-log10 at 20 μM and interfered with the replication of the SCoV1 subgenomic replicon, while it had no significant antiviral effects against hepatitis C virus and noroviruses. Further, XNT exerted similar antiviral functions against SCoV2 variants, such as a GH clade strain and a delta strain currently predominant worldwide. Neither SCoV2 entry into cells nor the enzymatic activity of viral RNA polymerase (Nsp12), RNA helicase (Nsp13), or the 3CL main protease (Nsp5) was inhibited by XNT. While its CoV replication inhibitory mechanism remains elusive, our results demonstrate that the traditional folk medicine XNT could be a promising antiviral candidate that inhibits a broad range of SCoV2 variants of concern and other related CoVs.
Cell and Cell Free Therapies in Osteoarthritis
Authors: Peláez Pau , Damiá Elena , Torres-Torrillas Marta , Chicharro Deborah , Cuervo Belén , Miguel Laura , del Romero Ayla , Carrillo Jose Maria , Sopena Joaquín J. , Rubio Mónica
Published: November 2021

Osteoarthritis (OA) is the most common articular disease in adults and has a current prevalence of 12% in the population over 65 years old. This chronic disease causes damage to articular cartilage and synovial joints, causing pain and leading to a negative impact on patients’ function, decreasing quality of life. There are many limitations regarding OA conventional therapies—pharmacological therapy can cause gastrointestinal, renal, and cardiac adverse effects, and some of them could even be a threat to life. On the other hand, surgical options, such as microfracture, have been used for the last 20 years, but hyaline cartilage has a limited regeneration capacity. In recent years, the interest in new therapies, such as cell-based and cell-free therapies, has been considerably increasing. The purpose of this review is to describe and compare bioregenerative therapies’ efficacy for OA, with particular emphasis on the use of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). In OA, these therapies might be an alternative and less invasive treatment than surgery, and a more effective option than conventional therapies.
ZnO Tips Dotted with Au Nanoparticles—Advanced SERS Determination of Trace Nicotine
Authors: Cao Jiaying , Zhai Yan , Tang Wanxin , Guo Xiaoyu , Wen Ying , Yang Haifeng
Published: November 2021

Long-term exposure to nicotine causes a variety of human diseases, such as lung damage/adenocarcinoma, nausea and vomiting, headache, incontinence and heart failure. In this work, as a surface-enhanced Raman scattering (SERS) substrate, zinc oxide (ZnO) tips decorated with gold nanoparticles (AuNPs) are fabricated and designated as ZnO/Au. Taking advantage of the synergistic effect of a ZnO semiconductor with morphology of tips and AuNPs, the ZnO/Au-based SERS assay for nicotine demonstrates high sensitivity and the limit of detection 8.9 × 10−12 mol/L is reached, as well as the corresponding linear dynamic detection range of 10−10–10−6 mol/L. Additionally, the signal reproducibility offered by the SERS substrate could realize the reliable determination of trace nicotine in saliva.
Modulation of Long-Term Potentiation by Gamma Frequency Transcranial Alternating Current Stimulation in Transgenic Mouse Models of Alzheimer’s Disease
Authors: Jeong Won-Hyeong , Kim Wang-In , Lee Jin-Won , Park Hyeng-Kyu , Song Min-Keun , Choi In-Sung , Han Jae-Young
Published: November 2021

Transcranial alternating current stimulation (tACS) is a neuromodulation procedure that is currently studied for the purpose of improving cognitive function in various diseases. A few studies have shown positive effects of tACS in Alzheimer’s disease (AD). However, the mechanism underlying tACS has not been established. The purpose of this study was to investigate the mechanism of tACS in five familial AD mutation (5xFAD) mouse models. We prepared twenty 4-month-old mice and divided them into four groups: wild-type mice without stimulation (WT-NT group), wild-type mice with tACS (WT-T group), 5xFAD mice without stimulation (AD-NT group), and 5xFAD mice with tACS (AD-T group). The protocol implemented was as follows: gamma frequency 200 μA over the bilateral frontal lobe for 20 min over 2 weeks. The following tests were conducted: excitatory postsynaptic potential (EPSP) recording, Western blot analysis (cyclic AMP response element-binding (CREB) proteins, phosphorylated CREB proteins, brain-derived neurotrophic factor, and parvalbumin) to examine the synaptic plasticity. The EPSP was remarkably increased in the AD-T group compared with in the AD-NT group. In the Western blot analysis, the differences among the groups were not significant. Hence, tACS can affect the long-lasting enhancement of synaptic transmission in mice models of AD.
From aMCI to AD: The Role of Visuo-Spatial Memory Span and Executive Functions in Egocentric and Allocentric Spatial Impairments
Authors: Iachini Tina , Ruotolo Francesco , Iavarone Alessandro , Mazzi Michele Carpinelli , Ruggiero Gennaro
Published: November 2021

A difficulty in encoding spatial information in an egocentric (i.e., body-to-object) and especially allocentric (i.e., object-to-object) manner, and impairments in executive function (EF) are typical in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). Since executive functions are involved in spatial encodings, it is important to understand the extent of their reciprocal or selective impairment. To this end, AD patients, aMCI and healthy elderly people had to provide egocentric (What object was closest to you?) and allocentric (What object was closest to object X?) judgments about memorized objects. Participants’ frontal functions, attentional resources and visual-spatial memory were assessed with the Frontal Assessment Battery (FAB), the Trail Making Test (TMT) and the Corsi Block Tapping Test (forward/backward). Results showed that ADs performed worse than all others in all tasks but did not differ from aMCIs in allocentric judgments and Corsi forward. Regression analyses showed, although to different degrees in the three groups, a link between attentional resources, visuo-spatial memory and egocentric performance, and between frontal resources and allocentric performance. Therefore, visuo-spatial memory, especially when it involves allocentric frames and requires demanding active processing, should be carefully assessed to reveal early signs of conversion from aMCI to AD.
Anticancer Effect of Heparin–Taurocholate Conjugate on Orthotopically Induced Exocrine and Endocrine Pancreatic Cancer
Authors: Hwang Hae Hyun , Jeong Hee Jeong , Yun Sangwu , Byun Youngro , Okano Teruo , Kim Sung Wan , Lee Dong Yun
Published: November 2021

Pancreatic cancers are classified based on where they occur, and are grouped into those derived from exocrine and those derived from neuroendocrine tumors, thereby experiencing different anticancer effects under medication. Therefore, it is necessary to develop anticancer drugs that can inhibit both types. To this end, we developed a heparin–taurocholate conjugate, i.e., LHT, to suppress tumor growth via its antiangiogenic activity. Here, we conducted a study to determine the anticancer efficacy of LHT on pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumor (PNET), in an orthotopic animal model. LHT reduced not only proliferation of cancer cells, but also attenuated the production of VEGF through ERK dephosphorylation. LHT effectively reduced the migration, invasion and tube formation of endothelial cells via dephosphorylation of VEGFR, ERK1/2, and FAK protein. Especially, these effects of LHT were much stronger on PNET (RINm cells) than PDAC (PANC1 and MIA PaCa-2 cells). Eventually, LHT reduced ~50% of the tumor weights and tumor volumes of all three cancer cells in the orthotopic model, via antiproliferation of cancer cells and antiangiogenesis of endothelial cells. Interestingly, LHT had a more dominant effect in the PNET-induced tumor model than in PDAC in vivo. Collectively, these findings demonstrated that LHT could be a potential antipancreatic cancer medication, regardless of pancreatic cancer types.
Cancer Survivorship Issues: Dissemination and Translation of Evidence-Based Knowledge
Authors: Duijts Saskia F. A. , Spelten Evelien R.
Published: November 2021

This issue of Cancers is a Special Issue focusing on ‘cancer survivorship’ [...]
FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance
Authors: Szymczyk Jakub , Sluzalska Katarzyna , Materla Izabela , Opalinski Lukasz , Otlewski Jacek , Zakrzewska Malgorzata
Published: November 2021

Increased expression of both FGF proteins and their receptors observed in many cancers is often associated with the development of chemoresistance, limiting the effectiveness of currently used anti-cancer therapies. Malfunctioning of the FGF/FGFR axis in cancer cells generates a number of molecular mechanisms that may affect the sensitivity of tumors to the applied drugs. Of key importance is the deregulation of cell signaling, which can lead to increased cell proliferation, survival, and motility, and ultimately to malignancy. Signaling pathways activated by FGFRs inhibit apoptosis, reducing the cytotoxic effect of some anti-cancer drugs. FGFRs-dependent signaling may also initiate angiogenesis and EMT, which facilitates metastasis and also correlates with drug resistance. Therefore, treatment strategies based on FGF/FGFR inhibition (using receptor inhibitors, ligand traps, monoclonal antibodies, or microRNAs) appear to be extremely promising. However, this approach may lead to further development of resistance through acquisition of specific mutations, metabolism switching, and molecular cross-talks. This review brings together information on the mechanisms underlying the involvement of the FGF/FGFR axis in the generation of drug resistance in cancer and highlights the need for further research to overcome this serious problem with novel therapeutic strategies.
Osteoradionecrosis of the Jaws Due to Teeth Extractions during and after Radiotherapy: A Systematic Review
Authors: Lajolo Carlo , Rupe Cosimo , Gioco Gioele , Troiano Giuseppe , Patini Romeo , Petruzzi Massimo , Micciche’ Francesco , Giuliani Michele
Published: November 2021

Teeth extractions before or after radiotherapy (RT) could be procedures at high risk for osteoradionecrosis (ORN) onset. This systematic review was performed to investigate the ORN incidence following teeth extractions during and after RT for head and neck (H&N) cancer and to evaluate any other possible risk factor. Methods: This systematic review was conducted according to PRISMA protocol, and the PROSPERO registration number was CRD42018079986. An electronic search was performed on the following search engines: PubMed, Scopus, and Web of Science. A cumulative meta-analysis was performed. Results: Two thousand two hundred and eighty-one records were screened, and nine were finally included. This systematic review revealed an ORN incidence of 5.8% (41 patients out of 462, 95% CI = 2.3–9.4); 3 ORN developed in the maxilla. No other clinical risk factors were detected. Conclusion: Post-RT teeth extractions represent a major risk factor for ORN development, especially in the mandible, with a diminishing trend in the last years. Further research on other possible risk factors might improve this evidence.
Autoimmune Hemolytic Anemia in Chronic Lymphocytic Leukemia: A Comprehensive Review
Authors: Autore Francesco , Pasquale Raffaella , Innocenti Idanna , Fresa Alberto , Sora’ Federica , Laurenti Luca
Published: November 2021

Chronic lymphocytic leukemia (CLL) patients have a greater predisposition to develop autoimmune complications. The most common of them is autoimmune hemolytic anemia (AIHA) with a frequency of 7–10% of cases. Pathogenesis is multifactorial involving humoral, cellular, and innate immunity. CLL B-cells have damaged apoptosis, produce less immunoglobulins, and could be responsible for antigen presentation and releasing inflammatory cytokines. CLL B-cells can act similar to antigen-presenting cells activating self-reactive T helper cells and may induce T-cell subsets imbalance, favoring autoreactive B-cells which produce anti-red blood cells autoantibodies. Treatment is individualized and it depends on the presence and severity of clinical symptoms, disease status, and comorbidities. Corticosteroids are the standardized first-line treatment; second-line treatment comprises rituximab. Patients not responding to corticosteroids and rituximab should be treated with CLL-specific drugs as per current guidelines according to age and comorbidities. New targeted drugs (BTK inhibitors and anti BCL2) are recently used after or together with steroids to manage AIHA. In the case of cold agglutinin disease, rituximab is preferred, because steroids are ineffective. Management must combine supportive therapies, including vitamins; antibiotics and heparin prophylaxis are indicated in order to minimize infectious and thrombotic risk.
Excess Mortality by Multimorbidity, Socioeconomic, and Healthcare Factors, amongst Patients Diagnosed with Diffuse Large B-Cell or Follicular Lymphoma in England
Authors: Smith Matthew James , Belot Aurélien , Quartagno Matteo , Luque Fernandez Miguel Angel , Bonaventure Audrey , Gachau Susan , Benitez Majano Sara , Rachet Bernard , Njagi Edmund Njeru
Published: November 2021

(1) Background: Socioeconomic inequalities of survival in patients with lymphoma persist, which may be explained by patients’ comorbidities. We aimed to assess the association between comorbidities and the survival of patients diagnosed with diffuse large B-cell (DLBCL) or follicular lymphoma (FL) in England accounting for other socio-demographic characteristics. (2) Methods: Population-based cancer registry data were linked to Hospital Episode Statistics. We used a flexible multilevel excess hazard model to estimate excess mortality and net survival by patient’s comorbidity status, adjusted for sociodemographic, economic, and healthcare factors, and accounting for the patient’s area of residence. We used the latent normal joint modelling multiple imputation approach for missing data. (3) Results: Overall, 15,516 and 29,898 patients were diagnosed with FL and DLBCL in England between 2005 and 2013, respectively. Amongst DLBCL and FL patients, respectively, those in the most deprived areas showed 1.22 (95% confidence interval (CI): 1.18–1.27) and 1.45 (95% CI: 1.30–1.62) times higher excess mortality hazard compared to those in the least deprived areas, adjusted for comorbidity status, age at diagnosis, sex, ethnicity, and route to diagnosis. (4) Conclusions: Deprivation is consistently associated with poorer survival among patients diagnosed with DLBCL or FL, after adjusting for co/multimorbidities. Comorbidities and multimorbidities need to be considered when planning public health interventions targeting haematological malignancies in England.
New Insight into the Interplay of Method of Deposition, Chemical State of Pd, Oxygen Storage Capability and Catalytic Activity of Pd-Containing Perovskite Catalysts for Combustion of Methane
Authors: Stanchovska Silva , Ivanov Georgy , Harizanova Sonya , Tenchev Krasimir , Zhecheva Ekaterina , Naydenov Anton , Stoyanova Radostina
Published: November 2021

Elaboration of Pd-supported catalysts for catalytic combustion is, nowadays, considered as an imperative task to reduce the emissions of methane. This study provides new insight into the method of deposition, chemical state of Pd and oxygen storage capability of transition metal ions and their effects on the catalytic reactivity of supported catalysts for the combustion of methane. The catalyst with nominal composition La(Co0.8Ni0.1Fe0.1)0.85Pd0.15O3 was supported on SiO2-modified/γ-alumina using two synthetic procedures: (i) aerosol assisted chemical vapor deposition (U-AACVD) and (ii) wet impregnation (Imp). A comparative analysis shows that a higher catalytic activity is established for supported catalyst obtained by wet impregnation, where the PdO-like phase is well dispersed and the transition metal ions display a high oxygen storage capability. The reaction pathway over both catalysts proceeds most probably through Mars–van Krevelen mechanism. The supported catalysts are thermally stable when they are aged at 505 °C for 120 h in air containing 1.2 vol.% water vapor. Furthermore, the experimentally obtained data on La(Co0.8Ni0.1Fe0.1)0.85Pd0.15O3—based catalyst, supported on monolithic substrate VDM®Aluchrom Y Hf are simulated by using a two-dimensional heterogeneous model for monolithic reactor in order to predict the performance of an industrial catalytic reactor for abatement of methane emissions.
An Effective Strategy to Enhance the Electrocatalytic Activity of Ruddlesden−Popper Oxides Sr3Fe2O7−δ Electrodes for Solid Oxide Fuel Cells
Authors: Peng Longsheng , Li Qiang , Sun Liping , Zhao Hui
Published: November 2021

The target of this work is to develop advanced electrode materials with excellent performance compared to conventional cathodes. Cobalt-free Ruddlesden−Popper oxides Sr3Fe2−xCuxO7−δ (SFCx, x = 0, 0.1, 0.2) were successfully synthesized and assessed as cathode materials for solid oxide fuel cells (SOFCs). Herein, a Cu-doping strategy is shown to increase the electrical conductivity and improve the electrochemical performance of the pristine Sr3Fe2O7−δ. Among all the cathode materials, the Sr3Fe1.9Cu0.1O7−δ (SFC10) cathode exhibits the best electrocatalytic activity for oxygen reduction reaction (ORR). The polarization resistance is 0.11 Ω cm2 and the peak power density of the single-cell with an SFC10 cathode reaches 955 mW cm−2 at 700 °C, a measurement comparable to cobalt-based electrodes. The excellent performance is owed to favorable oxygen surface exchange capabilities and larger oxygen vacancy concentrations at elevated temperatures. Moreover, the electrochemical impedance spectra and distribution of relaxation time results indicate that the charge transfer process at the triple-phase boundary is the rate-limiting step for ORR on the electrode. This work provides an effective strategy for designing novel cathode electrocatalysts for SOFCs.
Interplay between Sublethal Aminoglycosides and Quorum Sensing: Consequences on Survival in V. cholerae
Authors: Carvalho André , Krin Evelyne , Korlowski Chloé , Mazel Didier , Baharoglu Zeynep
Published: November 2021

Antibiotics are well known drugs which, when present above certain concentrations, are able to inhibit the growth of certain bacteria. However, a growing body of evidence shows that even when present at lower doses (subMIC, for sub-minimal inhibitory concentration), unable to inhibit or affect microbial growth, antibiotics work as signaling molecules, affect gene expression and trigger important bacterial stress responses. However, how subMIC antibiotic signaling interplays with other well-known signaling networks in bacteria (and the consequences of such interplay) is not well understood. In this work, through transcriptomic and genetic approaches, we have explored how quorum-sensing (QS) proficiency of V. cholerae affects this pathogen’s response to subMIC doses of the aminoglycoside tobramycin (TOB). We show that the transcriptomic signature of V. cholerae in response to subMIC TOB depends highly on the presence of QS master regulator HapR. In parallel, we show that subMIC doses of TOB are able to negatively interfere with the AI-2/LuxS QS network of V. cholerae, which seems critical for survival to aminoglycoside treatment and TOB-mediated induction of SOS response in this species. This interplay between QS and aminoglycosides suggests that targeting QS signaling may be a strategy to enhance aminoglycoside efficacy in V. cholerae.
High Glucose Reduces the Paracellular Permeability of the Submandibular Gland Epithelium via the MiR-22-3p/Sp1/Claudin Pathway
Authors: Huang Yan , Liu Hui-Min , Mao Qian-Ying , Cong Xin , Zhang Yan , Lee Sang-Woo , Park Kyungpyo , Wu Li-Ling , Xiang Ruo-Lan , Yu Guang-Yan
Published: November 2021

Tight junctions (TJs) play an important role in water, ion, and solute transport through the paracellular pathway of epithelial cells; however, their role in diabetes-induced salivary gland dysfunction remains unknown. Here, we found that the TJ proteins claudin-1 and claudin-3 were significantly increased in the submandibular glands (SMGs) of db/db mice and high glucose (HG)-treated human SMGs. HG decreased paracellular permeability and increased claudin-1 and claudin-3 expression in SMG-C6 cells. Knockdown of claudin-1 or claudin-3 reversed the HG-induced decrease in paracellular permeability. MiR-22-3p was significantly downregulated in diabetic SMGs and HG-treated SMG-C6 cells. A miR-22-3p mimic suppressed claudin-1 and claudin-3 expression and abolished the HG-induced increases in claudin-1 and claudin-3 levels in SMG-C6 cells, whereas a miR-22-3p inhibitor produced the opposite effects. Specificity protein-1 (Sp1) was enhanced in diabetic SMGs and HG-treated SMG-C6 cells, which promoted claudin-1 and claudin-3 transcription through binding to the corresponding promoters. A luciferase reporter assay confirmed that miR-22-3p repressed Sp1 by directly targeting the Sp1 mRNA 3′-untranslated region (3′-UTR). Consistently, the miR-22-3p mimic suppressed, whereas the miR-22-3p inhibitor enhanced, the effects of HG on Sp1 expression. Taken together, our results demonstrate a new regulatory pathway through which HG decreases the paracellular permeability of SMG cells by inhibiting miR-22-3p/Sp1-mediated claudin-1 and claudin-3 expression.
Transfer of Cellular Content from the Allogeneic Cell-Based Cancer Vaccine DCP-001 to Host Dendritic Cells Hinges on Phosphatidylserine and Is Enhanced by CD47 Blockade
Authors: Zuo Haoxiao , van Lierop Marie-José C. , Kaspers Jorn , Bos Remco , Reurs Anneke , Sarkar Saheli , Konry Tania , Kamermans Alwin , Kooij Gijs , de Vries Helga E. , de Gruijl Tanja D. , Karlsson-Parra Alex , Manting Erik H. , Kruisbeek Ada M. , Singh Satwinder Kaur
Published: November 2021

DCP-001 is a cell-based cancer vaccine generated by differentiation and maturation of cells from the human DCOne myeloid leukemic cell line. This results in a vaccine comprising a broad array of endogenous tumor antigens combined with a mature dendritic cell (mDC) costimulatory profile, functioning as a local inflammatory adjuvant when injected into an allogeneic recipient. Intradermal DCP-001 vaccination has been shown to be safe and feasible as a post-remission therapy in acute myeloid leukemia. In the current study, the mode of action of DCP-001 was further characterized by static and dynamic analysis of the interaction between labelled DCP-001 and host antigen-presenting cells (APCs). Direct cell–cell interactions and uptake of DCP-001 cellular content by APCs were shown to depend on DCP-001 cell surface expression of calreticulin and phosphatidylserine, while blockade of CD47 enhanced the process. Injection of DCP-001 in an ex vivo human skin model led to its uptake by activated skin-emigrating DCs. These data suggest that, following intradermal DCP-001 vaccination, local and recruited host APCs capture tumor-associated antigens from the vaccine, become activated and migrate to the draining lymph nodes to subsequently (re)activate tumor-reactive T-cells. The improved uptake of DCP-001 by blocking CD47 rationalizes the possible combination of DCP-001 vaccination with CD47 blocking therapies.
Platelets in ITP: Victims in Charge of Their Own Fate?
Authors: Nelson Vivianne S. , Jolink Anne-Tess C. , Amini Sufia N. , Zwaginga Jaap Jan , Netelenbos Tanja , Semple John W. , Porcelijn Leendert , de Haas Masja , Schipperus Martin R. , Kapur Rick
Published: November 2021

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder. The pathophysiological mechanisms leading to low platelet levels in ITP have not been resolved, but at least involve autoantibody-dependent and/or cytotoxic T cell mediated platelet clearance and impaired megakaryopoiesis. In addition, T cell imbalances involving T regulatory cells (Tregs) also appear to play an important role. Intriguingly, over the past years it has become evident that platelets not only mediate hemostasis, but are able to modulate inflammatory and immunological processes upon activation. Platelets, therefore, might play an immuno-modulatory role in the pathogenesis and pathophysiology of ITP. In this respect, we propose several possible pathways in which platelets themselves may participate in the immune response in ITP. First, we will elaborate on how platelets might directly promote inflammation or stimulate immune responses in ITP. Second, we will discuss two ways in which platelet microparticles (PMPs) might contribute to the disrupted immune balance and impaired thrombopoiesis by megakaryocytes in ITP. Importantly, from these insights, new starting points for further research and for the design of potential future therapies for ITP can be envisioned.
Matrix Metalloproteinases Inhibition by Doxycycline Rescues Extracellular Matrix Organization and Partly Reverts Myofibroblast Differentiation in Hypermobile Ehlers-Danlos Syndrome Dermal Fibroblasts: A Potential Therapeutic Target?
Authors: Chiarelli Nicola , Zoppi Nicoletta , Venturini Marina , Capitanio Daniele , Gelfi Cecilia , Ritelli Marco , Colombi Marina
Published: November 2021

Hypermobile Ehlers-Danlos syndrome (hEDS) is the most frequent type of EDS and is characterized by generalized joint hypermobility and musculoskeletal manifestations which are associated with chronic pain, and mild skin involvement along with the presence of more than a few comorbid conditions. Despite numerous research efforts, no causative gene(s) or validated biomarkers have been identified and insights into the disease-causing mechanisms remain scarce. Variability in the spectrum and severity of symptoms and progression of hEDS patients’ phenotype likely depend on a combination of age, gender, lifestyle, and the probable multitude of genes involved in hEDS. However, considering the clinical overlap with other EDS forms, which lead to abnormalities in extracellular matrix (ECM), it is plausible that the mechanisms underlying hEDS pathogenesis also affect the ECM to a certain extent. Herein, we performed a series of in vitro studies on the secretome of hEDS dermal fibroblasts that revealed a matrix metalloproteinases (MMPs) dysfunction as one of the major disease drivers by causing a detrimental feedback loop of excessive ECM degradation coupled with myofibroblast differentiation. We demonstrated that doxycycline-mediated inhibition of MMPs rescues in hEDS cells a control-like ECM organization and induces a partial reversal of their myofibroblast-like features, thus offering encouraging clues for translational studies confirming MMPs as a potential therapeutic target in hEDS with the expectation to improve patients’ quality of life and alleviate their disabilities.
Localization and Functional Roles of Components of the Translation Apparatus in the Eukaryotic Cell Nucleus
Authors: Kachaev Zaur M. , Ivashchenko Sergey D. , Kozlov Eugene N. , Lebedeva Lyubov A. , Shidlovskii Yulii V.
Published: November 2021

Components of the translation apparatus, including ribosomal proteins, have been found in cell nuclei in various organisms. Components of the translation apparatus are involved in various nuclear processes, particularly those associated with genome integrity control and the nuclear stages of gene expression, such as transcription, mRNA processing, and mRNA export. Components of the translation apparatus control intranuclear trafficking; the nuclear import and export of RNA and proteins; and regulate the activity, stability, and functional recruitment of nuclear proteins. The nuclear translocation of these components is often involved in the cell response to stimulation and stress, in addition to playing critical roles in oncogenesis and viral infection. Many components of the translation apparatus are moonlighting proteins, involved in integral cell stress response and coupling of gene expression subprocesses. Thus, this phenomenon represents a significant interest for both basic and applied molecular biology. Here, we provide an overview of the current data regarding the molecular functions of translation factors and ribosomal proteins in the cell nucleus.
Efficient Microwave-Assisted Extraction of Nitrites from Cured Meat and Their Voltammetric Detection at Chemically Modified Electrodes Based on Hexamethyl-p-Terphenyl Poly(methylatedbenzimidazolium) Incorporating Nitrogen-Doped Graphite Nanoplatelets
Authors: Hernandez-Aldave Sandra , Tarat Afshin , Bertoncello Paolo
Published: November 2021

We describe a fast and reliable procedure for the efficient extraction of nitrites in cured meat using microwave-assisted heat and report their in situ determination via voltammetry using an anion-exchanger ionene, hexamethyl-p-terphenyl poly(benzimidazolium) (HMT-PMBI), and nitrogen-doped graphite nanoplatelets (NGNPs). Cyclic voltammetry and chronoamperometry were utilized to evaluate the concentration of the redox mediator within the film and apparent diffusion coefficient. To investigate the suitability of the composite material for sensing applications, HMT-PMBI/NGNPs were tested for their detection of nitrite in bacon samples without the need of any pretreatments or dilutions. HMT-PMBI/NGNP coated electrodes showed enhanced sensitivity in the detection of nitrite ions in bacon with a limit of detection (LoD) of 0.64 µM, sensitivity 0.52 µA µM−1 cm−2, and operating in a linear range between 1–300 μM. The results highlight that the determination of nitrites in cured meat using microwave extraction is in good agreement with standard procedures such as the ISO 2918 and the AOAC International 973.31 methods.
Lamotrigine Induced DRESS Syndrome in a Child: A Case Report and Literature Review
Authors: Lin Chien-Heng , Lin Sheng-Shing , Hong Syuan-Yu , Chen Chieh-Ho , Chou I-Ching
Published: November 2021

Lamotrigine is an important anticonvulsant drug. Its use, however, has been limited by the risk of potentially life-threatening dermatological reactions, such as a drug reaction with eosinophilia and systemic symptoms (DRESS). Here, we report the case of a 7-year-6-month-old girl with a history of epilepsy who developed a skin rash with dyspnoea after 2 weeks of lamotrigine treatment, with DRESS ultimately being diagnosed. After discontinuation of the offending drug and the initiation of systemic glucocorticosteroids, the DRESS symptoms were relieved and the patient was discharged in a stable condition. Anticonvulsant drugs such as lamotrigine are among the factors that induce DRESS in children. When a patient displays skin rash and systemic organ involvement following the initiation of an anticonvulsant drug, DRESS should not be overlooked as a diagnosis, and immunosuppressant drugs should be considered as an option for treating DRESS patients.
Evaluating the Functional Outcomes and the Quality of Life for Pediatric Patients with Osteogenesis Imperfecta after Fracture Treatment with Intramedullary Rodding
Authors: Herdea Alexandru , Ulici Alexandru , Qirjako Dimitra , Toma Alexandra , Derihaci Răzvan Petru , Lungu Claudiu N. , Charkaoui Adham
Published: November 2021

Background and Objectives: Osteogenesis imperfecta is a rare pathology involving the bones and the connective tissues, generating alterations that lead to frequent fractures during childhood. When fractures occur at birth, they are associated with an impairment of walking and the quality of life. Although surgical techniques have significantly improved in recent years, functional outcomes and the quality of life for pediatric patients that benefited from surgical management with telescopic rods have been less evaluated. This study aimed to measure functional results and determine the factors that influence the quality of life for the pediatric population diagnosed with Osteogenesis imperfecta and surgically treated using the telescopic rod approach after suffering a fracture or severe deformity. Materials and Methods: We conducted a cohort study that consisted of 15 patients diagnosed with Osteogenesis imperfecta (average age of 11.6 years). All individuals possessed at least one intramedullary telescopic rod as a result of the surgical treatment. Results: We observed that the pain, both acute and chronic, impairs the quality of life and interferes with daily living activities, for instance, self-care tasks. Conclusions: Osteogenesis imperfecta is associated with a severely damaged level of walking. All of the aspects of the pediatric patient’s daily life activity seem to be affected. Furthermore, these patients, especially those residing in rural areas, have a poor quality of life.
Simulation of Cold Atmospheric Plasma Generated by Floating-Electrode Dielectric Barrier Pulsed Discharge Used for the Cancer Cell Necrosis
Authors: Elaissi Samira , Charrada Kamel
Published: November 2021

A numerical simulation of a pulsed floating electrode dielectric barrier discharge (FE-DBD) at atmospheric pressure, used for melanoma cancer cell therapy, is performed using a plasma model in COMSOL Multiphysics software. Distributions of electron density, space charge, and electric field are presented at different instants of the pulsed argon discharge. Significant results related to the characteristics of the plasma device used, the inter-electrodes distance, and the power supply are obtained to improve the efficiency of FE-DBD apparatus for melanoma cancer cell treatment. The FE-DBD presents a higher sensitivity to short pulse durations, related to the accumulated charge over the dielectric barrier around the powered electrode. At higher applied voltage, more energy is injected into the discharge channel and an increase in electron density and electric consumed power is noted. Anticancer activity provided by the FE-DBD plasma is improved using a small interelectrode distance with a high electron emission coefficient and a high dielectric constant with a small dielectric thickness, allowing higher electron density, generating reactive species responsible for the apoptosis of tumor cells.
Validation of Antibacterial Systems for Sustainable Ceramic Tiles
Authors: La Torre Valeria , Rambaldi Elisa , Masi Giulia , Nici Silvia , Ghezzi Daniele , Cappelletti Martina , Bignozzi Maria Chiara
Published: November 2021

Ceramic tiles are bacteriostatic materials; however, the COVID-19 emergency has pushed tile producers to improve surfaces’ antibacterial properties. The aim of this work was to validate a silver-based antibacterial treatment applied to porcelain stoneware tiles based on natural and waste materials, thus correlating surface functionalization to tile composition and relevant physical, microstructural, and textural parameters. The treatment was applied before firing, with and without a polymeric primer. Antibacterial activity tests, stain resistance tests, and contact angle measurements were carried out on fired tiles. Further investigations were made by SEM and optical profilometry in order to study the morphological–structural profile of tile surfaces. Results showed strong antibacterial activities for all the functionalized tiles, which were mainly correlated to the morphological and textural parameters of ceramic surfaces, as well as the presence of the polymeric primer.
Influence of Different Acid on the Interfacial Compatibility between Rusted Steel and Water-Based Coating
Authors: Li Wenbo , Jiang Yue , Liu Dingguo , Zhu Jiran , Xie Yi , Liu Lanlan
Published: November 2021

We aimed to improve the corrosion resistance of transmission network cabinet equipment in high temperature and humidity environment. In this paper, using acid modified acrylic acid as the main component, the composite conversion agent was obtained by adding phosphoric acid phytic acid and other components. Through the surface morphology, electrochemical test and adhesion force test of rust conversion coating, the versatility and corrosion resistance of rust conversion coating on the substrates were analyzed. Combined with zinc phosphate primer, the effect of rust conversion agent on the adhesion and salt spray corrosion resistance of the commercial primers was studied. The composite conversion agent has good effect on atmospheric corrosion rust layer. The corrosion resistance and adhesion force of the atmospheric corrosion rust layer treated with rust conversion agent were significantly increased. The adhesion of zinc phosphate primer on atmospheric corrosion rust coating with rust conversion was three times higher than that of atmospheric corrosion rust coating without rust conversion, respectively. Composite rust conversion agent has broad versatility, which can be used for rust conversion of atmospheric corrosion rust layer. At the same time, it has a good corrosion resistance, that can obviously improve the corrosion potential of the corroded surface and reduce the corrosion current density. In addition, the composite rust conversion agent can significantly improve the adhesion and corrosion resistance of the primer coating.
Self-Adaptive Acceptance Rate-Driven Markov Chain Monte Carlo Method Applied to the Study of Magnetic Nanoparticles
Authors: Zapata Juan Camilo , Restrepo Johans
Published: November 2021

A standard canonical Markov Chain Monte Carlo method implemented with a single-macrospin movement Metropolis dynamics was conducted to study the hysteretic properties of an ensemble of independent and non-interacting magnetic nanoparticles with uniaxial magneto-crystalline anisotropy randomly distributed. In our model, the acceptance-rate algorithm allows accepting new updates at a constant rate by means of a self-adaptive mechanism of the amplitude of Néel rotation of magnetic moments. The influence of this proposal upon the magnetic properties of our system is explored by analyzing the behavior of the magnetization versus field isotherms for a wide range of acceptance rates. Our results allows reproduction of the occurrence of both blocked and superparamagnetic states for high and low acceptance-rate values respectively, from which a link with the measurement time is inferred. Finally, the interplay between acceptance rate with temperature in hysteresis curves and the time evolution of the saturation processes is also presented and discussed.
Valorization of Wine-Making By-Products’ Extracts in Cosmetics
Authors: Hoss Israa , Rajha Hiba N. , El Khoury Rindala , Youssef Sahar , Manca Maria Letizia , Manconi Maria , Louka Nicolas , Maroun Richard G.
Published: November 2021

The increased demand for conscious, sustainable and beneficial products by the consumers has pushed researchers from both industries and universities worldwide to search for smart strategies capable of reducing the environmental footprint, especially the ones connected with industrial wastes. Among various by-products, generally considered as waste, those obtained by winemaking industries have attracted the attention of a wide variety of companies, other than the vineries. In particular, grape pomaces are considered of interest due to their high content in bioactive molecules, especially phenolic compounds. The latter can be recovered from grape pomace and used as active ingredients in easily marketable cosmetic products. Indeed, phenolic compounds are well known for their remarkable beneficial properties at the skin level, such as antioxidant, antiaging, anti-hyperpigmentation and photoprotective effects. The exploitation of the bioactives contained in grape pomaces to obtain high value cosmetics may support the growing of innovative start-ups and expand the value chain of grapes. This review aims to describe the strategies for recovery of polyphenols from grape pomace, to highlight the beneficial potential of these extracts, both in vitro and in vivo, and their potential utilization as active ingredients in cosmetic products.
Analysis of Rational Proportion of Raw Materials Based on Biomass
Authors: Kang Yue , Liu Chao , Zhang Yuzhu , Xing Hongwei , Wang Hui
Published: November 2021

Most of the air pollutants in the steel industry come from the sintering process, and the air pollutants produced by the sintering process mainly come from the sinter fuel (coke breeze). The S and N content of biomass fuel is low; therefore, biomass fuel is used instead of coke breeze for sintering to reduce the emission of the sinter flue gas pollutants. However, the use of biomass fuel reduces the sintering layer temperature, which results in the deterioration of the sinter properties. In order to ensure the quality of sintering base on biomass fuel, the thermodynamic calculation and related experiments were carried out, the effects of different basicity, MgO and Al2O3 content on the formation of low melting point minerals in sintered mixture were studied, and the suitable composition of sintered mixture was determined in this paper, so as to reduce the liquid phase formation temperature of sinter and increase in biomass fuel addition, which provided theoretical support for the application of biomass fuel in sintering. Experimental results indicate that the suitable conditions for the low-temperature sintering were a basicity of 2.0, and MgO and Al2O3 contents of 1.0% and 1.8%, respectively. Under this condition, more biomass fuel can be used to replace coke breeze, and the emission of flue gas pollutants can be greatly reduced.
Substrate Effects on the Electrical Properties in GaN-Based High Electron Mobility Transistors
Authors: Chang Sung-Jae , Cho Kyu-Jun , Lee Sang-Youl , Jeong Hwan-Hee , Lee Jae-Hoon , Jung Hyun-Wook , Bae Sung-Bum , Choi Il-Gyu , Kim Hae-Cheon , Ahn Ho-Kyun , Lim Jong-Won
Published: November 2021

We report the electrical characteristics of GaN-based high electron mobility transistors (HEMTs) operated on various substrates/films. For the detailed investigation and comparison of the electrical properties of GaN-based HEMTs according to the substrates/films, GaN-based HEMTs were processed using 4-inch sapphire substrates and separated from their original substrates through the laser lift-off technique. The separated AlGaN/GaN films including processed GaN-based HEMTs were bonded to AlN substrate or plated with a 100 µm-thick Cu at the back-side of the devices since AlN substrate and Cu film exhibit higher thermal conductivity than the sapphire substrate. Compared to the sapphire substrate, DC and RF properties such as drain current, transconductance, cut-off frequency and maximum oscillation frequency were improved, when GaN-based HEMTs were operated on AlN substrate or Cu film. Our systematic study has revealed that the device property improvement results from the diminishment of the self-heating effect, increase in carrier mobility under the gated region, and amelioration of sheet resistance at the access region. C(V) and pulse-mode stress measurements have confirmed that the back-side processing for the device transfer from sapphire substrate onto AlN substrate or Cu film did not induce the critical defects close to the AlGaN/GaN hetero-interface.
Perceptions of Local Inhabitants towards Land Management Systems Used in the Rainforest Area of Ecuador: An Evaluation Based on Visual Rating of the Main Land Use Types
Authors: Gavilanes Montoya Alex Vinicio , Castillo Vizuete Danny Daniel , Borz Stelian Alexandru
Published: November 2021

Land management policy and practice affects a wide segment of stakeholders, including the general population of a given area. This study evaluates the perceptions of local inhabitants towards the land management systems used in the rainforest area of Ecuador—namely, unmanaged (natural) forest, managed forest, croplands, and pasturelands. Data collected as ratings on 12 pictures were used to check the aggregated perceptions by developing the relative frequencies of ratings, in order to see how the perception rating data were associated with the types of land management systems depicted by the pictures, and to see whether the four types of land management could be mathematically represented by a clustering solution. A distinctive result was that the natural forests were the most positively rated, while the managed forests were the least positively rated among the respondents. It seems, however, that human intervention was not the landscape-related factor affecting this perception, since croplands and pasturelands also received high ratings. The ratings generated a clear clustering solution only in the case of forest management, indicating three groups: natural forests, managed forests, and the rest of the land management systems. Based on the results of this study, a combination of the four land use systems would balance the expectations of different stakeholders from the area, while also being consistent to some extent with the current diversity in land management systems. However, a more developed system of information propagation would be beneficial to educate the local population with regards to the benefits and drawbacks of different types of land management systems and their distribution.
Multidisciplinary In-Depth Investigation in a Young Athlete Suffering from Syncope Caused by Myocardial Bridge
Authors: Brancaccio Mariarita , Mennitti Cristina , Cesaro Arturo , Monda Emanuele , D’Argenio Valeria , Casaburi Giorgio , Mazzaccara Cristina , Ranieri Annaluisa , Fimiani Fabio , Barretta Ferdinando , Uomo Fabiana , Caiazza Martina , Lioncino Michele , D’Alicandro Giovanni , Limongelli Giuseppe , Calabrò Paolo , Terracciano Daniela , Lombardo Barbara , Frisso Giulia , Scudiero Olga
Published: November 2021

Laboratory medicine, along with genetic investigations in sports medicine, is taking on an increasingly important role in monitoring athletes’ health conditions. Acute or intense exercise can result in metabolic imbalances, muscle injuries or reveal cardiovascular disorders. This study aimed to monitor the health status of a basketball player with an integrated approach, including biochemical and genetic investigations and advanced imaging techniques, to shed light on the causes of recurrent syncope he experienced during exercise. Biochemical analyses showed that the athlete had abnormal iron, ferritin and bilirubin levels. Coronary Computed Tomographic Angiography highlighted the presence of an intramyocardial bridge, suggesting this may be the cause of the observed syncopes. The athlete was excluded from competitive activity. In order to understand if this cardiac malformation could be caused by an inherited genetic condition, both array-CGH and whole exome sequencing were performed. Array-CGH showed two intronic deletions involving MACROD2 and COMMD10 genes, which could be related to a congenital heart defect; whole exome sequencing highlighted the genotype compatible with Gilbert syndrome. However, no clear pathogenic mutations related to the patient’s cardiological phenotype were detected, even after applying machine learning methods. This case report highlights the importance and the need to provide exhaustive personalized diagnostic work up for the athletes in order to cover the cause of their malaise and for safeguarding their health. This multidisciplinary approach can be useful to create ad personam training and treatments, thus avoiding the appearance of diseases and injuries which, if underestimated, can become irreversible disorders and sometimes can result in the death of the athlete.