bluuebunny/crossref_metadata_2025 huggingface dataset:
Reporting Criteria for Clinical Trials on Medication-Related Osteonecrosis of the Jaw (MRONJ): A Review and Recommendations
Authors: Gaudet Camille , Odet Stephane , Meyer Christophe , Chatelain Brice , Weber Elise , Parmentier Anne-Laure , Derruau Stéphane , Laurence Sébastien , Mauprivez Cédric , Brenet Esteban , Kerdjoudj Halima , Fenelon Mathilde , Fricain Jean-Christophe , Zwetyenga Narcisse , Hoarau David , Curien Rémi , Gerard Eric , Louvrier Aurélien , Gindraux Florelle
Published: December 2022

Medication-related osteonecrosis of the jaw (MRONJ) is a complication caused by anti-resorptive agents and anti-angiogenesis drugs. Since we wanted to write a protocol for a randomized clinical trial (RCT), we reviewed the literature for the essential information needed to estimate the size of the active patient population and measure the effects of therapeutics. At the same time, we designed a questionnaire intended for clinicians to collect detailed information about their practices. Twelve essential criteria and seven additional items were identified and compiled from 43 selected articles. Some of these criteria were incorporated in the questionnaire coupled with data on clinical practices. Our review found extensive missing data and a lack of consensus. For example, the success rate often combined MRONJ stages, diseases, and drug treatments. The occurrence date and evaluation methods were not harmonized or quantitative enough. The primary and secondary endpoints, failure definition, and date coupled to bone measurements were not well established. This information is critical for writing a RCT protocol. With this review article, we aim to encourage authors to contribute all their findings in the field to bridge the current knowledge gap and provide a stronger database for the coming years.
The Journey of SCAPs (Stem Cells from Apical Papilla), from Their Native Tissue to Grafting: Impact of Oxygen Concentration
Authors: Mavinga Marine , Palmier Mathilde , Rémy Murielle , Jeannière Caroline , Lenoir Solène , Rey Sylvie , Saint-Marc Martine , Alonso Florian , Génot Elisabeth , Thébaud Noélie , Chevret Edith , Mournetas Virginie , Rousseau Benoit , Boiziau Claudine , Boeuf Helene
Published: December 2022

Tissue engineering strategies aim at characterizing and at optimizing the cellular component that is combined with biomaterials, for improved tissue regeneration. Here, we present the immunoMap of apical papilla, the native tissue from which SCAPs are derived. We characterized stem cell niches that correspond to a minority population of cells expressing Mesenchymal stromal/Stem Cell (CD90, CD105, CD146) and stemness (SSEA4 and CD49f) markers as well as endothelial cell markers (VWF, CD31). Based on the colocalization of TKS5 and cortactin markers, we detected migration-associated organelles, podosomes-like structures, in specific regions and, for the first time, in association with stem cell niches in normal tissue. From six healthy teenager volunteers, each with two teeth, we derived twelve cell banks, isolated and amplified under 21 or 3% O2. We confirmed a proliferative advantage of all banks when cultured under 3% versus 21% O2. Interestingly, telomerase activity was similar to that of the highly proliferative hiPSC cell line, but unrelated to O2 concentration. Finally, SCAPs embedded in a thixotropic hydrogel and implanted subcutaneously in immunodeficient mice were protected from cell death with a slightly greater advantage for cells preconditioned at 3% O2.
Cannabinoid Compounds as a Pharmacotherapeutic Option for the Treatment of Non-Cancer Skin Diseases
Authors: Ramer Robert , Hinz Burkhard
Published: December 2022

The endocannabinoid system has been shown to be involved in various skin functions, such as melanogenesis and the maintenance of redox balance in skin cells exposed to UV radiation, as well as barrier functions, sebaceous gland activity, wound healing and the skin’s immune response. In addition to the potential use of cannabinoids in the treatment and prevention of skin cancer, cannabinoid compounds and derivatives are of interest as potential systemic and topical applications for the treatment of various inflammatory, fibrotic and pruritic skin conditions. In this context, cannabinoid compounds have been successfully tested as a therapeutic option for the treatment of androgenetic alopecia, atopic and seborrhoeic dermatitis, dermatomyositis, asteatotic and atopic eczema, uraemic pruritis, scalp psoriasis, systemic sclerosis and venous leg ulcers. This review provides an insight into the current literature on cannabinoid compounds as potential medicines for the treatment of skin diseases.
Vagus Nerve Stimulation: A Personalized Therapeutic Approach for Crohn’s and Other Inflammatory Bowel Diseases
Authors: Cirillo Giovanni , Negrete-Diaz Flor , Yucuma Daniela , Virtuoso Assunta , Korai Sohaib Ali , De Luca Ciro , Kaniusas Eugenijus , Papa Michele , Panetsos Fivos
Published: December 2022

Inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, are incurable autoimmune diseases characterized by chronic inflammation of the gastrointestinal tract. There is increasing evidence that inappropriate interaction between the enteric nervous system and central nervous system and/or low activity of the vagus nerve, which connects the enteric and central nervous systems, could play a crucial role in their pathogenesis. Therefore, it has been suggested that appropriate neuroprosthetic stimulation of the vagus nerve could lead to the modulation of the inflammation of the gastrointestinal tract and consequent long-term control of these autoimmune diseases. In the present paper, we provide a comprehensive overview of (1) the cellular and molecular bases of the immune system, (2) the way central and enteric nervous systems interact and contribute to the immune responses, (3) the pathogenesis of the inflammatory bowel disease, and (4) the therapeutic use of vagus nerve stimulation, and in particular, the transcutaneous stimulation of the auricular branch of the vagus nerve. Then, we expose the working hypotheses for the modulation of the molecular processes that are responsible for intestinal inflammation in autoimmune diseases and the way we could develop personalized neuroprosthetic therapeutic devices and procedures in favor of the patients.
Tumor Growth Remains Refractory to Myc Ablation in Host Macrophages
Authors: Morrow Riley J. , Allam Amr H. , Konecnik Josh , Baloyan David , Dijkstra Christine , Eissmann Moritz F. , Jacob Saumya P. , O’Brien Megan , Poh Ashleigh R. , Ernst Matthias
Published: December 2022

Aberrant expression of the oncoprotein c-Myc (Myc) is frequently observed in solid tumors and is associated with reduced overall survival. In addition to well-recognized cancer cell-intrinsic roles of Myc, studies have also suggested tumor-promoting roles for Myc in cells of the tumor microenvironment, including macrophages and other myeloid cells. Here, we benchmark Myc inactivation in tumor cells against the contribution of its expression in myeloid cells of murine hosts that harbor endogenous or allograft tumors. Surprisingly, we observe that LysMCre-mediated Myc ablation in host macrophages does not attenuate tumor growth regardless of immunogenicity, the cellular origin of the tumor, the site it develops, or the stage along the tumor progression cascade. Likewise, we find no evidence for Myc ablation to revert or antagonize the polarization of alternatively activated immunosuppressive macrophages. Thus, we surmise that systemic targeting of Myc activity may confer therapeutic benefits primarily through limiting Myc activity in tumor cells rather than reinvigorating the anti-tumor activity of macrophages.
To Be or Not to Be? Are Reactive Oxygen Species, Antioxidants, and Stress Signalling Universal Determinants of Life or Death?
Authors: Szechyńska-Hebda Magdalena , Ghalami Roshanak Zarrin , Kamran Muhammad , Van Breusegem Frank , Karpiński Stanisław
Published: December 2022

In the environmental and organism context, oxidative stress is complex and unavoidable. Organisms simultaneously cope with a various combination of stress factors in natural conditions. For example, excess light stress is accompanied by UV stress, heat shock stress, and/or water stress. Reactive oxygen species (ROS) and antioxidant molecules, coordinated by electrical signalling (ES), are an integral part of the stress signalling network in cells and organisms. They together regulate gene expression to redirect energy to growth, acclimation, or defence, and thereby, determine cellular stress memory and stress crosstalk. In plants, both abiotic and biotic stress increase energy quenching, photorespiration, stomatal closure, and leaf temperature, while toning down photosynthesis and transpiration. Locally applied stress induces ES, ROS, retrograde signalling, cell death, and cellular light memory, then acclimation and defence responses in the local organs, whole plant, or even plant community (systemic acquired acclimation, systemic acquired resistance, network acquired acclimation). A simplified analogy can be found in animals where diseases vs. fitness and prolonged lifespan vs. faster aging, are dependent on mitochondrial ROS production and ES, and body temperature is regulated by sweating, temperature-dependent respiration, and gene regulation. In this review, we discuss the universal features of stress factors, ES, the cellular production of ROS molecules, ROS scavengers, hormones, and other regulators that coordinate life and death.
Multi-Scope Feature Extraction for Intracranial Aneurysm 3D Point Cloud Completion
Authors: Ma Wuwei , Yang Xi , Wang Qiufeng , Huang Kaizhu , Huang Xiaowei
Published: December 2022

3D point clouds are gradually becoming more widely used in the medical field, however, they are rarely used for 3D representation of intracranial vessels and aneurysms due to the time-consuming data reconstruction. In this paper, we simulate the incomplete intracranial vessels (including aneurysms) in the actual collection from different angles, then propose Multi-Scope Feature Extraction Network (MSENet) for Intracranial Aneurysm 3D Point Cloud Completion. MSENet adopts a multi-scope feature extraction encoder to extract the global features from the incomplete point cloud. This encoder utilizes different scopes to fuse the neighborhood information for each point fully. Then a folding-based decoder is applied to obtain the complete 3D shape. To enable the decoder to intuitively match the original geometric structure, we engage the original points coordinates input to perform residual linking. Finally, we merge and sample the complete but coarse point cloud from the decoder to obtain the final refined complete 3D point cloud shape. We conduct extensive experiments on both 3D intracranial aneurysm datasets and general 3D vision PCN datasets. The results demonstrate the effectiveness of the proposed method on three evaluation metrics compared to baseline: our model increases the F-score to 0.379 (+21.1%)/0.320 (+7.7%), reduces Chamfer Distance score to 0.998 (−33.8%)/0.974 (−6.4%), and reduces the Earth Mover’s Distance to 2.750 (17.8%)/2.858 (−0.8%).
Ubiquitination Occurs in the Mitochondrial Matrix by Eclipsed Targeted Components of the Ubiquitination Machinery
Authors: Zhang Yu , Karmon Ofri , Das Koyeli , Wiener Reuven , Lehming Norbert , Pines Ophry
Published: December 2022

Ubiquitination is a critical type of post-translational modification in eukaryotic cells. It is involved in regulating nearly all cellular processes in the cytosol and nucleus. Mitochondria, known as the metabolism heart of the cell, are organelles that evolved from bacteria. Using the subcellular compartment-dependent α-complementation, we detect multiple components of ubiquitination machinery as being eclipsed distributed to yeast mitochondria. Ubiquitin conjugates and mono-ubiquitin can be detected in lysates of isolated mitochondria from cells expressing HA-Ub and treated with trypsin. By expressing MTS (mitochondrial targeting sequence) targeted HA-tagged ubiquitin, we demonstrate that certain ubiquitination events specifically occur in yeast mitochondria and are independent of proteasome activity. Importantly, we show that the E2 Rad6 affects the pattern of protein ubiquitination in mitochondria and provides an in vivo assay for its activity in the matrix of the organelle. This study shows that ubiquitination occurs in the mitochondrial matrix by eclipsed targeted components of the ubiquitin machinery, providing a new perspective on mitochondrial and ubiquitination research.
The Association between Maternal Oral Inflammation and Neutrophil Phenotypes and Poly-Unsaturated Fatty Acids Composition in Human Milk: A Prospective Cohort Study
Authors: Badewy Rana , Azarpazhooh Amir , Tenenbaum Howard , Connor Kristin L. , Lai Jim Yuan , Sgro Michael , Bazinet Richard P. , Fine Noah , Watson Erin , Sun Chunxiang , Saha Sourav , Glogauer Michael
Published: December 2022

This prospective cohort study aimed to investigate the impact of maternal oral inflammation on human milk composition including neutrophil counts, activation state (based on cluster of differentiation (CD) markers expression), and fatty acid levels. Fifty mothers were recruited from St. Michael’s hospital, Toronto, and followed up from 2–4 weeks until 4 months postpartum. Oral rinse and human milk samples were collected at both timepoints. Oral polymorphonuclear neutrophils (oPMNs) within the rinses were quantified using flow cytometry and the participants’ oral health state was categorized into three groups (i.e., healthy, moderate, and severe) based on the oPMNs counts. Fatty acids were identified and quantified using a gas chromatography-flame ionization detector (GC-FID). Compared to mothers with a healthy oral health state, mothers with moderate to severe oral inflammation had a statistically significant decrease in the expression of CD64 biomarker, an increase in the expression of CD14 biomarker on human milk neutrophils and a decrease in the levels of eicosapentaenoic acid (C20:5n-3) in their human milk at follow-up compared to baseline. This study demonstrates for the first time that maternal oral inflammation can affect human milk composition. The mechanism by which these alterations can affect infant health outcomes in the long term critically needs to be considered.
Astrocytic MicroRNAs and Transcription Factors in Alzheimer’s Disease and Therapeutic Interventions
Authors: Nassar Ajmal , Kodi Triveni , Satarker Sairaj , Chowdari Gurram Prasada , Upadhya Dinesh , SM Fayaz , Mudgal Jayesh , Nampoothiri Madhavan
Published: December 2022

Astrocytes are important for maintaining cholesterol metabolism, glutamate uptake, and neurotransmission. Indeed, inflammatory processes and neurodegeneration contribute to the altered morphology, gene expression, and function of astrocytes. Astrocytes, in collaboration with numerous microRNAs, regulate brain cholesterol levels as well as glutamatergic and inflammatory signaling, all of which contribute to general brain homeostasis. Neural electrical activity, synaptic plasticity processes, learning, and memory are dependent on the astrocyte–neuron crosstalk. Here, we review the involvement of astrocytic microRNAs that potentially regulate cholesterol metabolism, glutamate uptake, and inflammation in Alzheimer’s disease (AD). The interaction between astrocytic microRNAs and long non-coding RNA and transcription factors specific to astrocytes also contributes to the pathogenesis of AD. Thus, astrocytic microRNAs arise as a promising target, as AD conditions are a worldwide public health problem. This review examines novel therapeutic strategies to target astrocyte dysfunction in AD, such as lipid nanodiscs, engineered G protein-coupled receptors, extracellular vesicles, and nanoparticles.
Synovial Fluid in Knee Osteoarthritis Extends Proinflammatory Niche for Macrophage Polarization
Authors: Kulkarni Priya , Srivastava Vanshika , Tootsi Kaspar , Electricwala Ali , Kharat Avinash , Bhonde Ramesh , Koks Sulev , Martson Aare , Harsulkar Abhay
Published: December 2022

Macrophage polarization is a steering factor of osteoarthritis (OA) progression. Synovial fluid (SF) obtained from OA patients with different Kellgren–Lawrence grades (KL grades) holds several proinflammatory factors and was hypothesized to induce macrophage differentiation and polarization by providing the needed microenvironment. U937 cells and peripheral-blood-mononuclear-cell-derived monocytes (PBMC-derived CD14+ cells) were induced with SFs of progressive KL grades for 48 h, and the status of the differentiated cells was evaluated by cell surface markers representing M1 and M2 macrophage phenotypes. Functional viability assessment of the differentiated cells was performed by cytokine estimation. The fraction of macrophages and their phenotypes were estimated by immunophenotyping of SF-isolated cells of different KL grades. A grade-wise proteome analysis of SFs was performed in search of the factors which are influential in macrophage differentiation and polarization. In the assay on U937 cells, induction with SF of KL grade III and IV showed a significant increase in M1 type (CD86+). The percentage of M2 phenotype (CD163+) was significantly higher after the induction with SF of KL grade II. A Significantly higher M1/M2 ratio was estimated in the cells induced with KL grade III and IV. The cell differentiation pattern in the assay on PBMC-derived CD14+ cells showed a grade-wise decline in both M1 (CD11C+, CD86+) and M2 phenotype (CD163+). Cytokine estimation specific to M1 (TNF-α, IL-6, IL-1β, IFN-γ) and M2 (IL-4 and IL-10) macrophages corelated with the differentiation pattern in the U937 cell assay, while it did not reveal any significant changes in the PBMC-derived CD14+ cells assay. SF cells’ immunophenotyping showed the highest percentage of CD14+ macrophages in KL grade II; CD86+ and CD163+ cells were minimal in all KL grades’ SFs. The proteome analysis revealed significantly expressed MIF, CAPG/MCP, osteopontin, and RAS-related RAB proteins in KL grade III and IV samples, which are linked with macrophages’ movement, polarization, and migration-behavior. In conclusion, this study demonstrated that SF in OA joints acts as a niche and facilitates M1 phenotype polarization by providing a proinflammatory microenvironment.
Human PSEN1 Mutant Glia Improve Spatial Learning and Memory in Aged Mice
Authors: Jäntti Henna , Oksanen Minna , Kettunen Pinja , Manta Stella , Mouledous Lionel , Koivisto Hennariikka , Ruuth Johanna , Trontti Kalevi , Dhungana Hiramani , Keuters Meike , Weert Isabelle , Koskuvi Marja , Hovatta Iiris , Linden Anni-Maija , Rampon Claire , Malm Tarja , Tanila Heikki , Koistinaho Jari , Rolova Taisia
Published: December 2022

The PSEN1 ΔE9 mutation causes a familial form of Alzheimer’s disease (AD) by shifting the processing of amyloid precursor protein (APP) towards the generation of highly amyloidogenic Aβ42 peptide. We have previously shown that the PSEN1 ΔE9 mutation in human-induced pluripotent stem cell (iPSC)-derived astrocytes increases Aβ42 production and impairs cellular responses. Here, we injected PSEN1 ΔE9 mutant astrosphere-derived glial progenitors into newborn mice and investigated mouse behavior at the ages of 8, 12, and 16 months. While we did not find significant behavioral changes in younger mice, spatial learning and memory were paradoxically improved in 16-month-old PSEN1 ΔE9 glia-transplanted male mice as compared to age-matched isogenic control-transplanted animals. Memory improvement was associated with lower levels of soluble, but not insoluble, human Aβ42 in the mouse brain. We also found a decreased engraftment of PSEN1 ΔE9 mutant cells in the cingulate cortex and significant transcriptional changes in both human and mouse genes in the hippocampus, including the extracellular matrix-related genes. Overall, the presence of PSEN1 ΔE9 mutant glia exerted a more beneficial effect on aged mouse brain than the isogenic control human cells likely as a combination of several factors.
Hepatic Polarized Differentiation Promoted the Maturity and Liver Function of Human Embryonic Stem Cell-Derived Hepatocytes via Activating Hippo and AMPK Signaling Pathways
Authors: Wang Jue , Situ Ping , Chen Sen , Wu Haibin , Zhang Xueyan , Liu Shoupei , Wang Yiyu , Xie Jinghe , Chen Honglin , Duan Yuyou
Published: December 2022

Hepatocytes exhibit a multi-polarized state under the in vivo physiological environment, however, human embryonic stem cell-derived hepatocytes (hEHs) rarely exhibit polarity features in a two-dimensional (2D) condition. Thus, we hypothesized whether the polarized differentiation might enhance the maturity and liver function of hEHs. In this study, we obtained the polarized hEHs (phEHs) by using 2D differentiation in conjunct with employing transwell-based polarized culture. Our results showed that phEHs directionally secreted albumin, urea and bile acids, and afterward, the apical membrane and blood–bile barrier (BBIB) were identified to form in phEHs. Moreover, phEHs exhibited a higher maturity and capacitity of cellular secretory and drug metabolism than those of non-phEHs. Through transcriptome analysis, it was found that the polarized differentiation induced obvious changes in gene expression profiles of cellular adhesion and membrane transport in hEHs. Our further investigation revealed that the activation of Hippo and AMPK signaling pathways made contributions to the regulation of function and cellular polarity in phEHs, further verifying that the liver function of hEHs was closely related with their polarization state. These results not only demonstrated that the polarized differentiation enhanced the maturity and liver function of hEHs, but also identified the molecular targets that regulated the polarization state of hEHs.
Easy and Affordable: A New Method for the Studying of Bacterial Biofilm Formation
Authors: Toc Dan Alexandru , Csapai Alexandra , Popa Florin , Popa Catalin , Pascalau Violeta , Tosa Nicoleta , Botan Alexandru , Mihaila Razvan Marian , Costache Carmen Anca , Colosi Ioana Alina , Junie Lia Monica
Published: December 2022

Background: Bacterial biofilm formation (BBF) proves itself to be in the spotlight of microbiology research due to the wide variety of infections that it can be associated with, the involvement in food spoilage, industrial biofouling and perhaps sewage treatment. However, BBF remains difficult to study due to the lack of standardization of the existing methods and the expensive equipment needed. We aim to describe a new inexpensive and easy to reproduce protocol for a 3D-printed microfluidic device that can be used to study BBF in a dynamic manner. Methods: We used the SolidWorks 3D CAD Software (EducationEdition 2019–2020, Dassault Systèmes, Vélizy-Villacoublay, France) to design the device and the Creality3D Ender 5 printer (Shenzhen Creality 3D Technology Co., Ltd., Shenzhen, China) for its manufacture. We cultivated strains of Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa. For the biofilm evaluation we used optical coherence tomography (OCT), scanning electron microscopy (SEM), Fourier Transform Infrared (FTIR) spectroscopy and crystal violet staining technique. Results: Based on the analysis, Enterococcus faecalis seems to produce more biofilm in the first hours while Pseudomonas aeruginosa started to take the lead on biofilm production after 24 h. Conclusions: With an estimated cost around €0.1285 for one microfluidic device, a relatively inexpensive and easy alternative for the study of BBF was developed.
AP-2δ Is the Most Relevant Target of AP-2 Family-Focused Cancer Therapy and Affects Genome Organization
Authors: Kołat Damian , Zhao Lin-Yong , Kciuk Mateusz , Płuciennik Elżbieta , Kałuzińska-Kołat Żaneta
Published: December 2022

Formerly hailed as “undruggable” proteins, transcription factors (TFs) are now under investigation for targeted therapy. In cancer, this may alter, inter alia, immune evasion or replicative immortality, which are implicated in genome organization, a process that accompanies multi-step tumorigenesis and which frequently develops in a non-random manner. Still, targeting-related research on some TFs is scarce, e.g., among AP-2 proteins, which are known for their altered functionality in cancer and prognostic importance. Using public repositories, bioinformatics tools, and RNA-seq data, the present study examined the ligandability of all AP-2 members, selecting the best one, which was investigated in terms of mutations, targets, co-activators, correlated genes, and impact on genome organization. AP-2 proteins were found to have the conserved “TF_AP-2” domain, but manifested different binding characteristics and evolution. Among them, AP-2δ has not only the highest number of post-translational modifications and extended strands but also contains a specific histidine-rich region and cleft that can receive a ligand. Uterine, colon, lung, and stomach tumors are most susceptible to AP-2δ mutations, which also co-depend with cancer hallmark genes and drug targets. Considering AP-2δ targets, some of them were located proximally in the spatial genome or served as co-factors of the genes regulated by AP-2δ. Correlation and functional analyses suggested that AP-2δ affects various processes, including genome organization, via its targets; this has been eventually verified in lung adenocarcinoma using expression and immunohistochemistry data of chromosomal conformation-related genes. In conclusion, AP-2δ affects chromosomal conformation and is the most appropriate target for cancer therapy focused on the AP-2 family.
Relative Importance of Different Elements of Mitochondrial Oxidative Phosphorylation in Maintaining the Barrier Integrity of Retinal Endothelial Cells: Implications for Vascular-Associated Retinal Diseases
Authors: Eltanani Shaimaa , Yumnamcha Thangal , Gregory Andrew , Elshal Mahmoud , Shawky Mohamed , Ibrahim Ahmed S.
Published: December 2022

Purpose: Mitochondrial dysfunction is central to breaking the barrier integrity of retinal endothelial cells (RECs) in various blinding eye diseases such as diabetic retinopathy and retinopathy of prematurity. Therefore, we aimed to investigate the role of different mitochondrial constituents, specifically those of oxidative phosphorylation (OxPhos), in maintaining the barrier function of RECs. Methods: Electric cell-substrate impedance sensing (ECIS) technology was used to assess in real time the role of different mitochondrial components in the total impedance (Z) of human RECs (HRECs) and its components: capacitance (C) and the total resistance (R). HRECs were treated with specific mitochondrial inhibitors that target different steps in OxPhos: rotenone for complex I, oligomycin for complex V (ATP synthase), and FCCP for uncoupling OxPhos. Furthermore, data were modeled to investigate the effects of these inhibitors on the three parameters that govern the total resistance of cells: Cell–cell interactions (Rb), cell–matrix interactions (α), and cell membrane permeability (Cm). Results: Rotenone (1 µM) produced the greatest reduction in Z, followed by FCCP (1 µM), whereas no reduction in Z was observed after oligomycin (1 µM) treatment. We then further deconvoluted the effects of these inhibitors on the Rb, α, and Cm parameters. Rotenone (1 µM) completely abolished the resistance contribution of Rb, as the Rb became zero immediately after the treatment. Secondly, FCCP (1 µM) eliminated the resistance contribution of Rb only after 2.5 h and increased Cm without a significant effect on α. Lastly, of all the inhibitors used, oligomycin had the lowest impact on Rb, as evidenced by the fact that this value became similar to that of the control group at the end of the experiment without noticeable effects on Cm or α. Conclusion: Our study demonstrates the differential roles of complex I, complex V, and OxPhos coupling in maintaining the barrier functionality of HRECs. We specifically showed that complex I is the most important component in regulating HREC barrier integrity. These observed differences are significant since they could serve as the basis for future pharmacological and gene expression studies aiming to improve the activity of complex I and thereby provide avenues for therapeutic modalities in endothelial-associated retinal diseases.
Therapeutic Potential of Mesenchymal Stem Cells in the Treatment of Epilepsy and Their Interaction with Antiseizure Medications
Authors: Tesiye Maryam Rahimi , Gol Mohammad , Fadardi Mohammad Rajabi , Kani Seyede Nasim Mousavi , Costa Anna-Maria , Ghasemi-Kasman Maryam , Biagini Giuseppe
Published: December 2022

Epilepsy is a life-threatening neurological disease that affects approximately 70 million people worldwide. Although the vast majority of patients may be successfully managed with currently used antiseizure medication (ASM), the search for alternative therapies is still necessary due to pharmacoresistance in about 30% of patients with epilepsy. Here, we review the effects of ASMs on stem cell treatment when they could be, as expected, co-administered. Indeed, it has been reported that ASMs produce significant effects on the differentiation and determination of stem cell fate. In addition, we discuss more recent findings on mesenchymal stem cells (MSCs) in pre-clinical and clinical investigations. In this regard, their ability to differentiate into various cell types, reach damaged tissues and produce and release biologically active molecules with immunomodulatory/anti-inflammatory and regenerative properties make them a high-potential therapeutic tool to address neuroinflammation in different neurological disorders, including epilepsy. Overall, the characteristics of MSCs to be genetically engineered, in order to replace dysfunctional elements with the aim of restoring normal tissue functioning, suggested that these cells could be good candidates for the treatment of epilepsy refractory to ASMs. Further research is required to understand the potential of stem cell treatment in epileptic patients and its interaction with ASMs.
Lactobacillus salivarius SNK-6 Regulates Liver Lipid Metabolism Partly via the miR-130a-5p/MBOAT2 Pathway in a NAFLD Model of Laying Hens
Authors: Zhu Lihui , Liao Rongrong , Huang Jiwen , Xiao Changfeng , Yang Yunzhou , Wang Huiying , He Daqian , Yan Huaxiang , Yang Changsuo
Published: December 2022

Lactobacillus spp., as probiotics, have shown efficacy in alleviating nonalcoholic fatty liver disease (NAFLD). Here, we screened a new probiotic strain, Lactobacillus salivarius SNK-6 (L. salivarius SNK-6), which was isolated from the ileum of healthy Xinyang black-feather laying hens in China. We investigated the beneficial activity of L. salivarius SNK-6 in a NAFLD model in laying hens and found that L. salivarius SNK-6 inhibited liver fat deposition and decreased serum triglyceride levels and activity of aspartate transaminase and alanine transaminase. MBOAT2 (membrane-bound O-acyltransferase domain containing 2) was directly targeted by miR-130a-5p, which was downregulated in the liver of NAFLD laying hens but reversed after L. salivarius SNK-6 treatment. Downregulation of MBOAT2, L. salivarius SNK-6 supplementation in vivo, and L. salivarius SNK-6 cell culture treatment in vitro suppressed the mRNA expression of genes involved in the PPAR/SREBP pathway. In addition, 250 metabolites were identified in the supernatants of L. salivarius SNK-6 culture media, and most of them participated in metabolic pathways, including amino acid, carbohydrate, and lipid metabolism. Targeted metabolomic analysis revealed that acetate, butyrate, and propionate were the most abundant short-chain fatty acids, while cholic acid, ursodeoxycholic acid, chenodeoxycholic acid, and tauroursodeoxycholic acid were the four most-enriched bile acids among L. salivarius SNK-6 metabolites. This may have contributed to the reparative effect of L. salivarius SNK-6 in the NAFLD chicken model. Our study suggested that L. salivarius SNK-6 alleviated liver damage partly via the miR-130a-5p/MBOAT2 signaling pathway.
Therapeutic Potential of VEGF-B in Coronary Heart Disease and Heart Failure: Dream or Vision?
Authors: Mallick Rahul , Ylä-Herttuala Seppo
Published: December 2022

Coronary heart disease (CHD) is the leading cause of death around the world. Based on the roles of vascular endothelial growth factor (VEGF) family members to regulate blood and lymphatic vessels and metabolic functions, several therapeutic approaches have been attempted during the last decade. However proangiogenic therapies based on classical VEGF-A have been disappointing. Therefore, it has become important to focus on other VEGFs such as VEGF-B, which is a novel member of the VEGF family. Recent studies have shown the very promising potential of the VEGF-B to treat CHD and heart failure. The aim of this review article is to present the role of VEGF-B in endothelial biology and as a potential therapeutic agent for CHD and heart failure. In addition, key differences between the VEGF-A and VEGF-B effects on endothelial functions are demonstrated.
Comparative Analysis of the Chemical Composition and Antimicrobial Activity of Four Moroccan North Middle Atlas Medicinal Plants’ Essential Oils: Rosmarinus officinalis L., Mentha pulegium L., Salvia officinalis L., and Thymus zygis subsp. gracilis (Boiss.) R. Morales
Authors: Gourich Aman Allah , Bencheikh Noureddine , Bouhrim Mohamed , Regragui Mohamed , Rhafouri Rachid , Drioiche Aziz , Asbabou Ayoub , Remok Firdaous , Mouradi Aicha , Addi Mohamed , Hano Christophe , Zair Touriya
Published: December 2022

Medicinal plants represent an inexhaustible source of traditional and effective remedies thanks to the various active ingredients they contain. Secondary metabolites present in plant extracts, such as essential oils (EO), have remarkable pharmacological properties, including antimicrobial effects. Here, the chemical composition and antimicrobial effects of four Moroccan medicinal plants, Rosmarinus officinalis L. (R. officinalis), Mentha pulegium L. (M. pulegium), Salvia officinalis L. (S. officinalis), and Thymus zygis subsp. gracilis (Boiss.) R. Morales (T. zygis), traditionally used in Morocco to treat microbial infections, were addressed. EO were extracted using the hydrodistillation method, and analyzed by gas chromatography coupled with mass spectrometry (GC/MS). EO yields were of 3.64 ± 0.12, 3.53 ± 0.06, 2.48 ± 0.06, and 2.34 ± 0.08%, respectively, for M. pulegium, R. officinalis, S. officinalis, and T. zygis. The main bioactive components present in these EO were piperitenone (32.9%) and pulegone (32.8%) for M. pulegium, 1,8-cineol (43.8%) and camphor (18.7%) for R. officinalis, 1,8-cineole (16.8%) and trans-thujone (15.9%) for S. officinalis, and thymol (36.4%), carvacrol (24.1%) and cymene (23.5%) for T. zygis. These EO showed, according to the results of their antimicrobial activities, good effectiveness against bacteria and fungi. Moreover, the T. zygis EO showed the most potent activity against all bacteria studied, while that of R. officinalis, M. pulegium, and S. officinalis showed moderate activity against the Enterobacter cloacae of Streptococcus agalactiae and Escherichia coli. The antifungal activity tests revealed a strong antifungal activity for the T. zygis EO and a moderate activity for the S. officinalis EO. On the other hand, the EO of R. officinalis, and M. pulegium were found to be inactive at the doses used against the selected strains. In conclusion, our results show that the medicinal plants studied contain biologically active molecules with antimicrobial effects. They can replace synthesized molecules, especially in the formulation of additives, and for therapeutic, cosmetic, and food-processing purposes.
Red Blood Cell Donor Sex Associated Effects on Morbidity and Mortality in the Extremely Preterm Newborn
Authors: Crawford Tara M. , Andersen Chad C. , Stark Michael J.
Published: December 2022

Transfusion exposure increases the risk of death in critically ill patients of all ages. This was thought to relate to co-morbidities in the transfusion recipient. However, donor characteristics are increasingly recognised as critical to transfusion recipient outcome with systematic reviews suggesting blood donor sex influences transfusion recipient health. Originally focusing on plasma and platelet transfusions, retrospective studies report greater risks of adverse outcomes such as transfusion related acute lung injury in those receiving products from female donors. There is increasing awareness that exposure to red blood cells (RBCs) poses a similar risk. Recent studies focusing on transfusion related outcomes in extremely preterm newborns report conflicting data on the association between blood donor sex and outcomes. Despite a renewed focus on lower versus higher transfusion thresholds in neonatal clinical practice, this group remain a heavily transfused population, receiving on average 3–5 RBC transfusions during their primary hospital admission. Therefore, evidence supporting a role for better donor selection could have a significant impact on clinical outcomes in this high-risk population. Here, we review the emerging evidence for an association between blood donor sex and clinical outcomes in extremely preterm newborns receiving one or more transfusions.
The Mental Well-Being of Italian Adolescents in the Last Decade through the Lens of the Dual Factor Model
Authors: Bersia Michela , Charrier Lorena , Berchialla Paola , Cosma Alina , Comoretto Rosanna Irene , Dalmasso Paola
Published: December 2022

(1) Background: In Italy, the components of adolescents’ mental well-being (psychological symptomatology and cognitive perception of life satisfaction) showed different temporal trends, suggesting the adoption of a multidimensional conceptualization. We aimed to assess temporal patterns and provide additional insights into Italian adolescents’ mental well-being in the last decade by adopting the Dual Factor Model; (2) Methods: We used nationally representative samples of Italian students (n = 165,000) aged 11, 13, and 15 years across the three more recent Italian Health Behaviour in School-aged Children (HBSC) surveys. Two measures of mental well-being were used: life satisfaction (LS, indicator of positive subjective well-being) and psychological health complaints (PHC, indicator of mental illness); (3) Results: Our study showed that the overall sample has been moving from a Complete Mental Health (Flourishing) to an Incomplete Mental Illness (Struggling) condition. Among 13- and 15-year-old girls, a jump from one to the other mental condition was observed in the 2014–2018 and 2010–2014 time periods, respectively; (4) Conclusions: Our findings suggest that Italian adolescents, especially older girls, have been shifting from Complete Mental Health to Incomplete Mental Illness in the last decade. Further research is needed to investigate this breaking up of the connection between psychological symptomatology and cognitive perception of life satisfaction.
Post-Traumatic Play in Child Victims of Adverse Childhood Experiences: A Pilot Study with the MCAST—Manchester Child Attachment Story Task and the Coding of PTCP Markers
Authors: D’Elia Daniela , Carpinelli Luna , Savarese Giulia
Published: December 2022

Background: Play is among the most frequently observed distorted behaviors in victims of Adverse Childhood Experiences (ACEs). Terr’s (1981) studies helped to describe this behavioral distortion as post-traumatic child’s play (PTCP). This study aimed to evaluate whether child victims of Adverse Childhood Experiences (ACEs) engaging in semi-structured play present the markers of post-traumatic child’s play (PTCP) during the administration of the Manchester Child Attachment Story Task (MCAST), whose playful stories activate the attachment system. Methods: The sample comprised 17 child victims of ACEs (mean age = 6.76). Children were evaluated using the Manchester Child Attachment Story Task. Results: The analysis of the play clearly revealed the presence of markers associated with the characteristics of the post-traumatic play described by Terr (1981), namely, repetition, revisiting, hyperarousal, and danger. In particular, the intrusiveness dimension was observed, which can be identified in the post-traumatic play by the presence of recurrent memories, dreams, and dissociative symptoms. Conclusions: Post-traumatic play is characterized by repetition, containing aspects, scenes, or sequences of the traumatic event, expressed explicitly or symbolically.
Intraoperative Neuromonitoring for Thyroid Surgery in Children and Adolescents: A Single Center Experience
Authors: Martucci Cristina , Madafferi Silvia , Crocoli Alessandro , Randi Franco , Malara Erika , Ponzo Viviana , De Pasquale Maria Debora , Inserra Alessandro
Published: December 2022

Intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN) has been shown in adults to minimize nerve palsy after thyroid surgery, but only few studies on its efficacy in a pediatric population have been reported. We conducted a retrospective study on patients operated for thyroid lesions from 2016 to 2022. The analyzed population was divided in two groups: patients treated from 2016 to 2020, when the identification of the RLN was performed without IONM (Group A); and patients treated since 2021, when IONM was implemented in every surgical procedure on the thyroid (Group B). Intraoperative Neurophysiological Monitoring was performed by using corticobulbar motor-evoked potentials and continuous electromyography. Twentyfive children underwent thyroid resection, 19 (76%) of which due to thyroid carcinoma. Each patient’s recurrent nerve was identified; IONM was used in 13 patients. In Group A, one temporary nerve palsy was identified postoperatively (8.3%), while in group B one nerve dysfunction occurred (7.7%). No statistically significant difference was found between the two groups in terms of post-operative RLN palsy. No surgical complication due to the use of IONM was reported. In children and teenagers, intraoperative neuromonitoring of the recurrent laryngeal nerve is a safe and accurate method, minimizing the risk of nerve damage.
Comprehensive Analysis of Glutamate Receptor-like Genes in Rice (Oryza sativa L.): Genome-Wide Identification, Characteristics, Evolution, Chromatin Accessibility, gcHap Diversity, Population Variation and Expression Analysis
Authors: Shi Yingyao , Zeng Wei , Xu Minhui , Li Hua , Zhang Fanlin , Chen Zulong , Anicet Gatera , Huang Shiji , Huang Yuheng , Wang Xiyu , Li Junhao , Zhang Xinyu , Zheng Yuxing , Rehman Shamsur
Published: December 2022

Glutamate receptors (GLR) are widely present in animals and plants, playing essential roles in regulating plant growth, development and stress response. At present, most studies of GLRs in plants are focused on Arabidopsis thaliana, while there have been few studies on rice. In this study, we identified 26 OsGLR genes in rice (Oryza sativa L.). Then, we analyzed the chromosomal location, physical and chemical properties, subcellular location, transmembrane (TM) helices, signal peptides, three-dimensional (3D) structure, cis-acting elements, evolution, chromatin accessibility, population variation, gene-coding sequence haplotype (gcHap) and gene expression under multiple abiotic stress and hormone treatments. The results showed that out of the 26 OsGLR genes, ten genes had the TM domain, signal peptides and similar 3D structures. Most OsGLRs exhibited high tissue specificity in expression under drought stress. In addition, several OsGLR genes were specifically responsive to certain hormones. The favorable gcHap of many OsGLR genes in modern varieties showed obvious differentiation between Xian/indica and Geng/japonica subspecies. This study, for the first time, comprehensively analyzes the OsGLR genes in rice, and provides an important reference for further research on their molecular function.
Viscoelastic Simulation of Stress and Warpage for Memory Chip 3D-Stacked Package
Authors: Wang Xiyou , Cao Sicheng , Lu Guangsheng , Yang Daoguo
Published: December 2022

Three-dimensional-stacked packaging technology is widely used in memory chip packaging, which can greatly increase the utilization ratio of the packaging area. However, problems with the reliability of 3D-stacked packaging are also becoming more and more serious. In this paper, first, a dynamic mechanical analyzer is used to obtain the EMC viscoelasticity parameters. Then, the influence trend of different factors, such as EMC, die bond material and chip, on the performance of the memory chip 3D-stacked packaging under a fixed temperature cyclic loading condition is explored by the FE method.
Study on Parameter Correlation of Thickness and Performance of Anodizing Film on 6061 Aluminum Alloy Frame in High Energy Laser System
Authors: Wang Kaijie , Cao Yongzhi , Cui Yaowen , Ye Aiying , Yi Shaofan , Hu Zhenjiang
Published: December 2022

As stray laser light is difficult to avoid in high-energy laser systems, it is of great significance to improve the laser damage resistance of the aluminum alloy frame anodizing film system. In this paper, the effects of anodic oxidation parameters on the thickness and performance of 6061 aluminium alloy anodic oxide composite film systems are investigated combining experiments and simulations. The thickness of the oxide film is calculated theoretically, and the simulation model is established. Then the effects of anodizing parameters and the reasons are analyzed. After characterizing the surface quality and laser damage resistance of the oxide film, the influence of anodizing parameters is summarized. This paper enables advance calculations of film thickness within a certain range, combined with the film properties, to provide a reference for the laboratory preparation of 6061 anodizing films and the preparation of structure-specific composite film systems based on the film.
Buckling Behavior of Few-Layer Graphene on Soft Substrate
Authors: Meng Yancheng , Li Baowen , Li Luxian , Zhang Jianqiang
Published: December 2022

The buckling behavior of graphene on soft films has been extensively studied. However, to avoid graphene fracture, most studies focus only on the primary buckling behavior induced by tiny compression. Here, the buckling behavior of monolayer, three-layer, and four-layer graphene on soft films is systematically studied in the experiment under large compression. The cross-sections of buckling patterns in these few-layer graphenes are provided, which depend on focused ion beam (FIB) technology. More significantly, the moduli of few-layer graphene are calculated based on the buckling behavior. We demonstrate that the modulus, 1.12621 TPa, is independent of the number of graphene layers if the number is less than four. Our investigations are crucial for the application of two-dimensional (2D) materials into flexible hybrid electronics, bionics, and various other stiff/soft bilayer systems.