bluuebunny/crossref_metadata_2025 huggingface dataset:
K63 Ubiquitination of P21 Can Facilitate Pellino-1 in the Context of Chronic Obstructive Pulmonary Disease and Lung Cellular Senescence
Authors: Ma Jia-Hui , Zhang Yi-Ting , Wang Lu-Ping , Sun Qing-Yu , Zhang Hao , Li Jian-Jiang , Han Ning-Ning , Zhu Yao-Yao , Xie Xiao-Yu , Li Xia
Published: October 2022

Chronic obstructive pulmonary diseases (COPD) is a kind of age-related, airflow-obstruction disease mostly caused by cigarette smoke. However, the relationship between COPD and lung cellular senescence is still not fully understood. Here, we found silencing Pellino-1 could inhibit the protein level of P21. Then, through constructing cell lines expressed ubiquitin-HA, we found that the E3 ubiquitin ligase Pellino-1 could bind to senescence marker p21 and modify p21 by K63-site ubiquitination by co-IP assays. Furthermore, we found that p21-mediated lung cellular senescence could be inhibited by silencing Pellino-1 in a D-galactose senescence mice model. Moreover, by constructing a COPD mouse model with shPellino-1 adenovirus, we found that silencing Pellino-1 could inhibit COPD and inflammation via reduction of SASPs regulated by p21. Taken together, our study findings elucidated that silencing E3 ligase Pellino-1 exhibits therapeutic potential for treatment to attenuate the progression of lung cellular senescence and COPD.
Characterization of the Aquaporin-9 Inhibitor RG100204 In Vitro and in db/db Mice
Authors: Florio Marilina , Engfors Angelica , Gena Patrizia , Larsson Jessica , Massaro Alessandro , Timpka Stella , Reimer Martina Kvist , Kjellbom Per , Beitz Eric , Johanson Urban , Rützler Michael , Calamita Giuseppe
Published: October 2022

Aquaporin-9 (AQP9) is a facilitator of glycerol and other small neutral solute transmembrane diffusion. Identification of specific inhibitors for aquaporin family proteins has been difficult, due to high sequence similarity between the 13 human isoforms, and due to the limited channel surface areas that permit inhibitor binding. The few AQP9 inhibitor molecules described to date were not suitable for in vivo experiments. We now describe the characterization of a new small molecule AQP9 inhibitor, RG100204 in cell-based calcein-quenching assays, and by stopped-flow light-scattering recordings of AQP9 permeability in proteoliposomes. Moreover, we investigated the effects of RG100204 on glycerol metabolism in mice. In cell-based assays, RG100204 blocked AQP9 water permeability and glycerol permeability with similar, high potency (~5 × 10−8 M). AQP9 channel blocking by RG100204 was confirmed in proteoliposomes. After oral gavage of db/db mice with RG100204, a dose-dependent elevation of plasma glycerol was observed. A blood glucose-lowering effect was not statistically significant. These experiments establish RG100204 as a direct blocker of the AQP9 channel, and suggest its use as an experimental tool for in vivo experiments on AQP9 function.
Platelet-Derived Extracellular Vesicles Stimulate Migration through Partial Remodelling of the Ca2+ Handling Machinery in MDA-MB-231 Breast Cancer Cells
Authors: Vismara Mauro , Negri Sharon , Scolari Francesca , Brunetti Valentina , Trivigno Silvia Maria Grazia , Faris Pawan , Galgano Luca , Soda Teresa , Berra-Romani Roberto , Canobbio Ilaria , Torti Mauro , Guidetti Gianni Francesco , Moccia Francesco
Published: October 2022

Background: Platelets can support cancer progression via the release of microparticles and microvesicles that enhance the migratory behaviour of recipient cancer cells. We recently showed that platelet-derived extracellular vesicles (PEVs) stimulate migration and invasiveness in highly metastatic MDA-MB-231 cells by stimulating the phosphorylation of p38 MAPK and the myosin light chain 2 (MLC2). Herein, we assessed whether the pro-migratory effect of PEVs involves the remodelling of the Ca2+ handling machinery, which drives MDA-MB-231 cell motility. Methods: PEVs were isolated from human blood platelets, and Fura-2/AM Ca2+ imaging, RT-qPCR, and immunoblotting were exploited to assess their effect on intracellular Ca2+ dynamics and Ca2+-dependent migratory processes in MDA-MB-231 cells. Results: Pretreating MDA-MB-231 cells with PEVs for 24 h caused an increase in Ca2+ release from the endoplasmic reticulum (ER) due to the up-regulation of SERCA2B and InsP3R1/InsP3R2 mRNAs and proteins. The consequent enhancement of ER Ca2+ depletion led to a significant increase in store-operated Ca2+ entry. The larger Ca2+ mobilization from the ER was required to potentiate serum-induced migration by recruiting p38 MAPK and MLC2. Conclusions: PEVs stimulate migration in the highly metastatic MDA-MB-231 breast cancer cell line by inducing a partial remodelling of the Ca2+ handling machinery.
COVID-19 Pathology in the Lung, Kidney, Heart and Brain: The Different Roles of T-Cells, Macrophages, and Microthrombosis
Authors: Poloni Tino Emanuele , Moretti Matteo , Medici Valentina , Turturici Elvira , Belli Giacomo , Cavriani Elena , Visonà Silvia Damiana , Rossi Michele , Fantini Valentina , Ferrari Riccardo Rocco , Carlos Arenn Faye , Gagliardi Stella , Tronconi Livio , Guaita Antonio , Ceroni Mauro
Published: October 2022

Here, we aim to describe COVID-19 pathology across different tissues to clarify the disease’s pathophysiology. Lungs, kidneys, hearts, and brains from nine COVID-19 autopsies were compared by using antibodies against SARS-CoV-2, macrophages-microglia, T-lymphocytes, B-lymphocytes, and activated platelets. Alzheimer’s Disease pathology was also assessed. PCR techniques were used to verify the presence of viral RNA. COVID-19 cases had a short clinical course (0–32 days) and their mean age was 77.4 y/o. Hypoxic changes and inflammatory infiltrates were present across all tissues. The lymphocytic component in the lungs and kidneys was predominant over that of other tissues (p < 0.001), with a significantly greater presence of T-lymphocytes in the lungs (p = 0.020), which showed the greatest presence of viral antigens. The heart showed scant SARS-CoV-2 traces in the endothelium–endocardium, foci of activated macrophages, and rare lymphocytes. The brain showed scarce SARS-CoV-2 traces, prominent microglial activation, and rare lymphocytes. The pons exhibited the highest microglial activation (p = 0.017). Microthrombosis was significantly higher in COVID-19 lungs (p = 0.023) compared with controls. The most characteristic pathological features of COVID-19 were an abundance of T-lymphocytes and microthrombosis in the lung and relevant microglial hyperactivation in the brainstem. This study suggests that the long-term sequelae of COVID-19 derive from persistent inflammation, rather than persistent viral replication.
HOCI Probe CPP Induces the Differentiation of Human Dermal Fibroblasts into Vascular Endothelial Cells through PHD2/HIF-1α/HEY1 Signaling Pathway
Authors: Cui Xiaoling , Wen Jie , Li Nan , Hao Xuxiao , Zhang Shangli , Zhao Baoxiang , Wu Xunwei , Miao Junying
Published: October 2022

Human dermal fibroblasts (HDFs) have the potential to differentiate into endothelial cells (VECs). In our previous research, we reported that a hypochlorous acid (HOCl) probe CPP efficiently induced the differentiation of HDFs into VECs, however, the mechanism of differentiation was not clear. As an HOCI probe, CPP binds HOCI to modulate its effects. In this study, through Western blotting, qPCR, and PHD2 enzyme activity assay, we found that CPP inhibited the enzyme activity of prolyl-4-hydroxylase 2 (PHD2), thereby stabilizing HIF-1α. To further clarify the mechanism by which CPP inhibits PHD2 enzyme activity, we constructed plasmids, and found that CPP inhibited PHD2 activity to increase the HIF-1α level through the modulation of PHD2 at Cys302 by HOCl in HDFs. Furthermore, RNA-seq experiments showed that CPP could induce the expression of HEY1, which is not only a target gene regulated by HIF1α, but also a key transcription factor for VECs. We used siRNA transfection and in vivo experiments to confirm that CPP could induce HDFs to differentiate into VECs by HEY1. In summary, we identified a new inhibitor of PHD2, demonstrated the new role of HOCl in cell differentiation, and elucidated the mechanism by which HOCl probe CPP induced the differentiation of HDFs into VECs.
FGFR2 Mutation p.Cys342Arg Enhances Mitochondrial Metabolism-Mediated Osteogenesis via FGF/FGFR-AMPK-Erk1/2 Axis in Crouzon Syndrome
Authors: Wang Yidi , Liu Yue , Chen Haotian , Liu Xiaojing , Zhang Yi , Wang Yixiang , Gu Yan
Published: October 2022

Background: Crouzon syndrome ([OMIM] #123500) caused by FGFR2 mutation is an autosomal dominant syndrome with craniosynostosis, the underlying mechanism of which remains obscure. Methods: First, whole exome sequencing was used to screen the possible pathogenic variant in two sporadic patients with Crouzon syndrome. The investigation of primary and secondary structures as well as the conservation analysis of FGFR2 mutation (p.Cys342Arg) was performed. Then, wild-type and mutant overexpression plasmids were constructed and transfected into pre-osteoblastic murine cell line MC3T3-E1 cells. Osteogenesis and mitochondrial metabolism were analyzed by CCK8, ALP staining and ALP activity, alizarin red staining, qRT-PCR, Western blot, seahorse assays and mitochondrial staining. The siRNA targeting FGFR2 and domain negative FGFR2 were designed for verification. Results: First, FGFR2 mutation (p.Cys342Arg) was detected in two sporadic Chinese Crouzon syndrome patients. FGFR2 p.Cys342Arg promoted the osteogenic differentiation of MC3T3-E1 cells through the upregulation of AMP-activated protein kinase (AMPK)-Erk1/2 signal pathway. Furthermore, FGFR2 p.Cys342Arg enhanced oxidative phosphorylation and converted mitochondrial fusion to the fission of MC3T3-E1, promoting osteogenic differentiation and craniosynostosis in Crouzon syndrome. Additionally, AMPK or Erk1/2 inhibitors delayed the cranial suture closure. Conclusion: FGFR2 mutation p.Cys342Arg promotes osteogenesis by enhancing mitochondrial metabolism-mediated via FGF/FGFR-AMPK-Erk1/2 axis, which indicates the potential of therapy targeting AMPK or Erk1/2 for syndromic craniosynostosis treatment.
Intrachromosomal Looping and Histone K27 Methylation Coordinately Regulates the lncRNA H19-Fetal Mitogen IGF2 Imprinting Cluster in the Decidual Microenvironment of Early Pregnancy
Authors: Wen Xue , Zhang Qi , Zhou Lei , Li Zhaozhi , Wei Xue , Yang Wang , Zhang Jiaomei , Li Hui , Xu Zijun , Cui Xueling , Zhang Songling , Wang Yufeng , Li Wei , Hoffman Andrew R. , Liu Zhonghui , Hu Ji-Fan , Cui Jiuwei
Published: October 2022

Recurrent spontaneous abortion (RSA) is a highly heterogeneous complication of pregnancy with the underlying mechanisms remaining uncharacterized. Dysregulated decidualization is a critical contributor to the phenotypic alterations related to pregnancy complications. To understand the molecular factors underlying RSA, we explored the role of longnoncoding RNAs (lncRNAs) in the decidual microenvironment where the crosstalk at the fetal–maternal interface occurs. By exploring RNA-seq data from RSA patients, we identified H19, a noncoding RNA that exhibits maternal monoallelic expression, as one of the most upregulated lncRNAs associated with RSA. The paternally expressed fetal mitogen IGF2, which is reciprocally coregulated with H19 within the same imprinting cluster, was also upregulated. Notably, both genes underwent loss of imprinting, as H19 and IGF2 were actively transcribed from both parental alleles in some decidual tissues. This loss of imprinting in decidual tissues was associated with the loss of the H3K27m3 repressive histone marker in the IGF2 promoter, CpG hypomethylation at the central CTCF binding site in the imprinting control center (ICR), and the loss of CTCF-mediated intrachromosomal looping. These data suggest that dysregulation of the H19/IGF2 imprinting pathway may be an important epigenetic factor in the decidual microenvironment related to poor decidualization.
Understanding Cell Model Characteristics—RNA Expression Profiling in Primary and Immortalized Human Mesothelial Cells, and in Human Vein and Microvascular Endothelial Cells
Authors: Marinovic Iva , Bartosova Maria , Herzog Rebecca , Sacnun Juan Manuel , Zhang Conghui , Hoogenboom Robin , Unterwurzacher Markus , Hackert Thilo , Teleman Aurelio A. , Kratochwill Klaus , Schmitt Claus Peter
Published: October 2022

In vitro studies are essential in pre-clinical research. While choice of cell lines is often driven by handling and cost-effectiveness, in-depth knowledge on specific characteristics is scant. Mesothelial cells, which interact with endothelial cells, are widely used in research, including cancer and drug development, but have not been comprehensively profiled. We therefore performed RNA sequencing of polarized, primary peritoneal (HPMC) and immortalized pleural mesothelial cells (MeT-5A), and compared them to endothelial cells from umbilical vein (HUVEC) and cardiac capillaries (HCMEC). Seventy-seven per cent of 12,760 genes were shared between the 4 cell lines, 1003 were mesothelial and 969 were endothelial cell specific. The transcripts reflected major differences between HPMC and MeT-5A in DNA-related processes, extracellular matrix, migration, proliferation, adhesion, transport, growth factor- and immune response, and between HUVEC and HCMEC in DNA replication, extracellular matrix and adhesion organization. Highly variable shared genes were related to six clusters, cell tissue origin and immortalization, but also cell migration capacity, cell adhesion, regulation of angiogenesis and response to hypoxia. Distinct, cell type specific biological processes were further described by cellular component-, molecular function- and Reactome pathway analyses. We provide crucial information on specific features of the most frequently used mesothelial and endothelial cell lines, essential for appropriate use.
Astrocyte Heterogeneity in Regulation of Synaptic Activity
Authors: Kruyer Anna
Published: October 2022

Our awareness of the number of synapse regulatory functions performed by astroglia is rapidly expanding, raising interesting questions regarding astrocyte heterogeneity and specialization across brain regions. Whether all astrocytes are poised to signal in a multitude of ways, or are instead tuned to surrounding synapses and how astroglial signaling is altered in psychiatric and cognitive disorders are fundamental questions for the field. In recent years, molecular and morphological characterization of astroglial types has broadened our ability to design studies to better analyze and manipulate specific functions of astroglia. Recent data emerging from these studies will be discussed in depth in this review. I also highlight remaining questions emerging from new techniques recently applied toward understanding the roles of astrocytes in synapse regulation in the adult brain.
Systematic Interrogation of the Temperature Perturbation in the Insulin Signaling Pathway for Optogenetic Stimulation
Authors: Dong Qi , Endo Mizuki , Kawamura Genki , Ozawa Takeaki
Published: October 2022

The application of NIR to optogenetic systems is in great demand due to its superior properties enabling in vivo deep tissue penetration. Irradiation of NIR to tissue samples or cells rapidly generates heat locally. The resultant elevation in temperature affects cells at the molecular level because of the activation of the heat shock pathway and ROS generation. Nevertheless, few reports have presented detailed comparisons of the effects of the temperature change rate on signaling pathway biomolecules, especially those of rapid heat changes. Aiming at broadening the understanding of temperature sensitivity, we investigated seven insulin signaling pathway biomolecules (INSR, IRS1, Akt, GSK3β, p70S6K, FoxO1, and ERK1/2) in three cell lines (C2C12, HepG2, and Fao) at temperatures between 25 and 45 °C. The results show that, except for INSR, pAkt(T308), and FoxO1, biomolecules are sensitive to rapid temperature changes at temperatures higher than 42 °C, at which they are significantly phosphorylated. At 25 °C, around a 50% reduction in phosphorylation occurred. Moreover, p70S6K is sensitive over time. It dephosphorylates quickly (5 min) and then phosphorylates over time. Our findings extend the temperature range to 45 °C, while providing additional time course information about the signaling pathway biomolecule response necessary to advance NIR optogenetic research.
Hierarchical Clustering and Trajectory Analyses Reveal Viremia-Independent B-Cell Perturbations in HIV-2 Infection
Authors: Johansson Emil , Kerkman Priscilla F. , Scharf Lydia , Lindman Jacob , Szojka Zsófia I. , Månsson Fredrik , Biague Antonio , Medstrand Patrik , Norrgren Hans , Buggert Marcus , Karlsson Annika C. , Forsell Mattias N. E. , Esbjörnsson Joakim , Jansson Marianne ,   the SWEGUB CORE Group
Published: October 2022

Time to AIDS in HIV-2 infection is approximately twice as long compared to in HIV-1 infection. Despite reduced viremia, HIV-2-infected individuals display signs of chronic immune activation. In HIV-1-infected individuals, B-cell hyperactivation is driven by continuous antigen exposure. However, the contribution of viremia to B-cell perturbations in HIV-2-infected individuals remains largely unexplored. Here, we used polychromatic flow cytometry, consensus hierarchical clustering and pseudotime trajectory inference to characterize B-cells in HIV-1- or HIV-2-infected and in HIV seronegative individuals. We observed increased frequencies of clusters containing hyperactivated T-bethighCD95highCD27int and proliferating T-bet+CD95highCD27+CD71+ memory B-cells in viremic HIV-1 (p < 0.001 and p < 0.001, respectively), viremic HIV-2 (p < 0.001 and p = 0.014, respectively) and in treatment-naïve aviremic HIV-2 (p = 0.004 and p = 0.020, respectively)-infected individuals, compared to seronegative individuals. In contrast, these expansions were not observed in successfully treated HIV-1-infected individuals. Finally, pseudotime trajectory inference showed that T-bet-expressing hyperactivated and proliferating memory B-cell populations were located at the terminal end of two trajectories, in both HIV-1 and HIV-2 infections. As the treatment-naïve aviremic HIV-2-infected individuals, but not the successfully ART-treated HIV-1-infected individuals, showed B-cell perturbations, our data suggest that aviremic HIV-2-infected individuals would also benefit from antiretroviral treatment.
Structural Heterogeneity of the GABAergic Tripartite Synapse
Authors: Brunskine Cindy , Passlick Stefan , Henneberger Christian
Published: October 2022

The concept of the tripartite synapse describes the close interaction of pre- and postsynaptic elements and the surrounding astrocyte processes. For glutamatergic synapses, it is established that the presence of astrocytic processes and their structural arrangements varies considerably between and within brain regions and between synapses of the same neuron. In contrast, less is known about the organization of astrocytic processes at GABAergic synapses although bi-directional signaling is known to exist at these synapses too. Therefore, we established super-resolution expansion microscopy of GABAergic synapses and nearby astrocytic processes in the stratum radiatum of the mouse hippocampal CA1 region. By visualizing the presynaptic vesicular GABA transporter and the postsynaptic clustering protein gephyrin, we documented the subsynaptic heterogeneity of GABAergic synaptic contacts. We then compared the volume distribution of astrocytic processes near GABAergic synapses between individual synapses and with glutamatergic synapses. We made two novel observations. First, astrocytic processes were more abundant at the GABAergic synapses with large postsynaptic gephyrin clusters. Second, astrocytic processes were less abundant in the vicinity of GABAergic synapses compared to glutamatergic, suggesting that the latter may be selectively approached by astrocytes. Because of the GABA transporter distribution, we also speculate that this specific arrangement enables more efficient re-uptake of GABA into presynaptic terminals.
A Novel Homozygous Founder Variant of RTN4IP1 in Two Consanguineous Saudi Families
Authors: Aldosary Mazhor , Alsagob Maysoon , AlQudairy Hanan , González-Álvarez Ana C. , Arold Stefan T. , Dababo Mohammad Anas , Alharbi Omar A. , Almass Rawan , AlBakheet AlBandary , AlSarar Dalia , Qari Alya , Al-Ansari Mysoon M. , Oláhová Monika , Al-Shahrani Saif A. , AlSayed Moeenaldeen , Colak Dilek , Taylor Robert W. , AlOwain Mohammed , Kaya Namik
Published: October 2022

The genetic architecture of mitochondrial disease continues to expand and currently exceeds more than 350 disease-causing genes. Bi-allelic variants in RTN4IP1, also known as Optic Atrophy-10 (OPA10), lead to early-onset recessive optic neuropathy, atrophy, and encephalopathy in the afflicted patients. The gene is known to encode a mitochondrial ubiquinol oxidoreductase that interacts with reticulon 4 and is thought to be a mitochondrial antioxidant NADPH oxidoreductase. Here, we describe two unrelated consanguineous families from the northern region of Saudi Arabia harboring a missense variant (RTN4IP1:NM_032730.5; c.475G<T, p.Val159Phe) in the gene. Clinically affected individuals presented with intellectual disability, encephalopathy, ataxia, optic atrophy, and seizures. Based on whole exome sequencing and confirmatory Sanger sequencing, the variant was fully segregated with the phenotype in the families, absent among large ethnically matching controls as well as numerous in-house exomes, and predicted to be pathogenic by different in silico classifiers. Structural modeling and immunoblot analyses strongly indicated this variant to be pathogenic. Since the families belong to one of the tribal inhabitants of Saudi Arabia, we postulate that the variant is likely to be a founder. We provide the estimated age of the variant and present data confirming the disease-causality of this founder variant.
Influence of Pyrolysis Temperature on Biochar Produced from Lignin–Rich Biorefinery Residue
Authors: Grottola Corinna Maria , Giudicianni Paola , Stanzione Fernando , Ragucci Raffaele
Published: October 2022

The biorefinery concept is growing rapidly for bio-based production of fuels and products, and steam explosion is by far the most applied pre-treatment technology allowing the delignification of lignocellulosic biomass. Within the bioethanol production process, pyrolysis of lignin-rich residue (LRR), for producing char to be used in a wide variety of applications, presents a viable way to recover materials and energy, helping to improve the sustainability of the whole production chain. In the present study, it is shown that yields, elemental composition and porosity characteristics of LLR-char are significantly different from those of char produced from alkali lignin. Both products yields and char composition were more similar to the typical values of woody and herbaceous biomasses. The chemical characterization of the chars’ organic matrices as well as the content of the main inorganic species suggest the opportunity to perform pyrolysis at low temperatures for producing high yields of chars suitable to be used as carbon sink or soil fertilizers. The BET values of the chars obtained at final temperatures in the range 500–700 °C seem to be promising for char-application processes involving surface phenomena (e.g., adsorption, catalyst support), thus encouraging further analyses of char-surface chemistry.
Sweet, Sugar-Coated Hierarchical Platinum Nanostructures for Easy Support, Heterogenization and Separation
Authors: Woitassek Dennis , Moya-Cancino José G. , Sun Yangyang , Song Yefan , Woschko Dennis , Roitsch Stefan , Janiak Christoph
Published: October 2022

Metal nanoparticles are increasingly gaining interest in the field of heterogeneous catalysis. Here, we present a novel strategy for synthesizing sugar-coated platinum nanostructures (SC-Pt-NS) from the carbohydrates sucrose and D(-)-fructose. In the synthesis from a mixture of H2PtCl6·6H2O, the carbohydrate in an ionic liquid (IL) yielded primary particles of a homogeneous average size of ~10 nm, which were aggregated to hierarchical Pt nanostructures of ~40–65 nm and surrounded or supported by the carbohydrate. These sugar-coated platinum nanostructures present a facile way to support and heterogenize nanoparticles, avoid leaching and enable easier separation and handling. The catalytic activity of the SC-Pt-NS was shown in the hydrosilylation test reaction of phenylacetylene with triethylsilane, where very high turnover frequency (TOF) values of up to 87,200 h−1 could be achieved, while the platinum metal leaching into the product was very low.
Traditional Uses, Phytochemical Composition, Pharmacological Properties, and the Biodiscovery Potential of the Genus Cirsium
Authors: Aggarwal Gaurav , Kaur Gurpreet , Bhardwaj Garima , Mutreja Vishal , Sohal Harvinder Singh , Nayik Gulzar Ahmad , Bhardwaj Anikesh , Sharma Ajay
Published: October 2022

Medicinal plants are rich in phytochemicals, which have been used as a source of raw material in medicine since ancient times. Presently they are mostly used to treat Henoch–Schonlein purpura, hemoptysis, and bleeding. The manuscript covers the classification, traditional applications, phytochemistry, pharmacology, herbal formulations, and patents of Cirsium. The main goal of this review is to impart recent information to facilitate future comprehensive research and use of Cirsium for the development of therapeutics. We investigated numerous databases PubMed, Google Scholar, Springer, Elsevier, Taylor and Francis imprints, and books on ethnopharmacology. The plants of the genus Cirsium of the family Asteraceae contain 350 species across the world. Phytochemical investigations showed that it contains flavonoids, phenols, polyacetylenes, and triterpenoids. The biological potential of this plant is contributed by these secondary metabolites. Cirsium plants are an excellent and harmless agent for the cure of liver diseases; therefore, they might be a good clinical option for the development of therapeutics for hepatic infections. The phytochemical studies of different Cirsium species and their renowned pharmacological activities could be exploited for pharmaceutic product development. Furthermore, studies are required on less known Cirsium species, particularly on the elucidation of the mode of action of their activities.
New Bi-Nuclear Nickel(II) Complex-Based Salen Schiff Base: Synthesis, Crystal Structure, Spectroscopic, Thermal, and Electrical Investigations
Authors: Es-Sounni Bouchra , Haily El Mehdi , Nakkabi Asmae , Bakhouch Mohamed , Bejaoui Linda , Kaya Savaş , El Yazidi Mohamed , Bih Lahcen , Saadi Mohamed , El Ammari Lahcen , Fahim Mohammed
Published: October 2022

In this study, a new bi-nuclear nickel complex [Ni2HL2(EtOH)2](Cl)(EtOH) of a Schiff base ligand, 2-[3-[2-hydroxybenzylideneamino]propyliminomethyl]phenol, was synthesized and characterized using UV/Vis, IR, HRMS, and TGA/DTA analysis. The molecular structure of the obtained complex was corroborated by the single crystal X-ray diffraction technique. It was found in the complex that two molecules of the ligand coordinate with two nickel atoms through azomethine-N and phenoxy-O, resulting in 6-coordinate distorted octahedral geometry, in which two ethanol molecules occupy the axial positions. The dielectric and electrical properties of the obtained samples were studied by impedance spectroscopy at different frequencies (from 1 Hz to 1 MHz) in the temperature range 298–343 K. It is found that the electrical conductivity of the Ni(II) complex is lower than that of the free ligand H2L, suggesting that the complexation traps the charge carriers contained in the ligand.
Current Trends in Photonic Biosensors: Advances towards Multiplexed Integration
Authors: Ramirez Jhonattan C. , Grajales García Daniel , Maldonado Jesús , Fernández-Gavela Adrián
Published: October 2022

In this review, we present the current trends in photonic biosensors, focusing on devices based on lab-on-a-chip (LOC) systems capable of simultaneously detecting multiple real-life diseases on a single platform. The first section lists the advantages and challenges of building LOC platforms based on integrated optics. Some of the most popular materials for the fabrication of microfluidic cells are also shown. Then, a review of the latest developments in biosensors using the evanescent wave detection principle is provided; this includes interferometric biosensors, ring resonators, and photonic crystals, including a brief description of commercial solutions, if available. Then, a review of the latest advances in surface plasmon resonance (SPR) biosensors is presented, including localized-SPRs (LSPRs). A brief comparison between the benefits and required improvements on each kind of biosensor is discussed at the end of each section. Finally, prospects in the field of LOC biosensors based on integrated optics are glimpsed.
Recent Developments in Rhodamine-Based Chemosensors: A Review of the Years 2018–2022
Authors: Wang Yujiao , Wang Xiaojun , Ma Wenyu , Lu Runhua , Zhou Wenfeng , Gao Haixiang
Published: October 2022

Chemosensors based on traditional fluorescent dyes have always contributed to the development of chemical sensor areas. In this review, the rhodamine-based chemosensors’ improvements and applications from 2018 to 2022 are discussed, mainly focusing on cations (metal ions and H+), anions (CN−, F−, etc.), and small bio-functional molecules’ (thiols, amino acids, etc.) detection. Specifically, this review highlights the detection target, detection limit, detection solution system, detection mechanism, and performance of the rhodamine-based sensors. Although these rhodamine-based sensors are well developed, their repeatability and sensitivity still need significant improvement. This review is expected to bring new clues and bright ideas to researchers for further advances in rhodamine-based chemosensors in the future.
A Novel Electrochemical Sensing Platform for the Detection of the Antidepressant Drug, Venlafaxine, in Water and Biological Specimens
Authors: Sultan Sundas , Shah Afzal , Firdous Naveeda , Nisar Jan , Ashiq Muhammad Naeem , Shah Iltaf
Published: October 2022

A stable bimetallic catalyst composed of Co–Pd@Al2O3 was synthesized using a wet impregnation method, followed by calcination and H2 reduction. The synthesized catalyst was thoroughly characterized using XRD, BET, SEM, EDX, and TPR techniques. The catalyst was then drop-casted on a glassy carbon electrode (Co–Pd@Al2O3/GCE) and applied for the sensitive and selective electrochemical determination of a common antidepressant drug, venlafaxine (VEN). The proposed sensor (Co–Pd@Al2O3/GCE) demonstrated a remarkable catalytic activity for the electro-oxidation of VEN, with a decent repeatability and reproducibility. The pH dependent responsiveness of the electro-oxidation of VEN helped in proposing the redox mechanism. A linear relationship between the peak current and concentration of VEN was observed in the range of 1.95 nM to 0.5 µM, with LOD and LOQ of 1.86 pM and 6.20 pM, respectively. The designed sensor demonstrated an adequate selectivity and significant stability. Moreover, the sensor was found to be quite promising for determining the VEN in biological specimens.
A Review of Patient-Reported Outcome Measures in Childhood Cancer
Authors: Horan Madeline R. , Sim Jin-ah , Krull Kevin R. , Baker Justin N. , Huang I-Chan
Published: October 2022

Patient-reported outcomes (PROs) are used in clinical work and research to capture the subjective experiences of childhood cancer patients and survivors. PROs encompass content domains relevant and important to this population, including health-related quality-of-life (HRQOL), symptoms, and functional status. To inform future efforts in the application of PRO measures, this review describes the existing generic and cancer-specific PRO measures for pediatric cancer populations and summarizes their characteristics, available language translations, content coverage, and measurement properties into tables for clinicians and researchers to reference before choosing a PRO measure that suits their purpose. We have identified often unreported measurement properties that could provide evidence about the clinical utility of the PRO measures. Routine PRO assessment in pediatric cancer care offers opportunities to facilitate clinical decision-making and improve quality of care for these patients. However, we suggest that before implementing PRO measures into research or clinical care, the psychometric properties and content coverage of the PRO measures must be considered to ensure that PRO measures are appropriately assessing the intended construct in childhood cancer patients.
Exploring the Possible Impact of Echocardiographic Diastolic Function Parameters on Outcome in Paediatric Dilated Cardiomyopathy
Authors: Bressieux-Degueldre Sabrina , Fenton Matthew , Dominguez Troy , Burch Michael
Published: October 2022

Diastolic dysfunction is an important determinant for prognosis and survival in several paediatric heart diseases. We aimed to explore its possible impact on outcome in children with dilated cardiomyopathy. From 2006 to 2016, children less than 18 years old with dilated cardiomyopathy were retrospectively enrolled. Echocardiographic diastolic function parameters and child outcomes were analysed. Of 43 children aged 0.2 to 16.1 years old referred with dilated cardiomyopathy, 8 patients required cardiac transplant or mechanical assist devices (18%), 24 had persistently abnormal left ventricular function and/or dilatation (56%) and 11 patients recovered (26%). There was no significant difference in mitral velocities on Tissue Doppler Imaging, mitral valve inflow velocities, isovolumic relaxation time, left atrial area z-score and mitral lateral E/e’ ratios between patients with recovery and patients with disease progression or persistently abnormal ventricular function and/or dilation. This is the first study on childhood dilated cardiomyopathy to address individual echocardiographic diastolic function parameters and their association to recovery. In this study, echocardiographic parameters for diastolic function did not predict recovery.
New Resident Training Strategy Based on Gamification Techniques: An Escape Room on Sepsis in Children
Authors: Alejandre Carme , Corniero Patricia , Claret Gemma , Alaez Carlos , Esteban Elisabeth , Jordan Iolanda
Published: October 2022

Aim: Adapting “escape rooms” for educational purposes is an innovative teaching method. The aim of this study was to ascertain the degree of learning of the residents. A secondary objective was to determine their degree of satisfaction. Methods: A prospective, observational study took place in October 2019. A sepsis-based escape room was designed and carried out. A mix of paediatric medical residents and paediatric nursing residents were enrolled. A prior knowledge test was carried out, which was repeated right at the end of the escape room and then again three months later. Furthermore, all participants completed an anonymous post-study survey. Results: We enrolled 48 residents, 79.2% of whom were women. The mean score for the pre-escape room exam was 7.85/9 (SD 1.65), that for the post-escape room exam was 8.75/9 (SD 0.53), and for the exam three months later, it was 8.30/9 (SD 0.94). Among the participants, 18.8% did not manage to leave before the established 60 min time limit. The results of the satisfaction survey showed high participant satisfaction. Conclusions: The escape room proved to be a valuable educational game that increased students’ knowledge of sepsis management and showed a positive overall perceived value among the participants.
Effectiveness of Botulinum Neurotoxin in Treatment of Scoliosis among Children and Adolescents: A Systematic Review and Meta-Analysis
Authors: Su Yu-Chi , Lin Yu-Ching , Hsieh Pei-Chun , Liao Chung-Lun , Guo Yao-Hong
Published: October 2022

Scoliosis refers to a three-dimensional deviation in the axis of the spine. Muscle imbalance is believed to play a role in scoliosis. Botulinum neurotoxin (BoNT) can reduce muscle overactivity and may have the potential to ameliorate spinal scoliosis. This study investigated the effectiveness of intramuscular BoNT injection in vertebral curve correction and reviewed the possible influencing factors. PubMed, Medline, Cochrane Central Register of Controlled Trials, Web of Science, Airiti Library, and Index of the Taiwan Periodical Literature System databases were searched from inception until 7 September 2022 for eligible studies. The main outcome was the change in Cobb angle after BoNT application. Subgroup analysis was conducted according to differences in study designs, etiology of scoliosis, and methods used for target muscle selection. We enrolled three studies including 31 participants aged between 2 and 18 years. The meta-analysis revealed no significant reduction in the Cobb angle after BoNT injection (standardized mean difference, −0.783, 95% CI, −2.142 to 0.576). Study designs (p = 0.011) and methods used for target muscle selection (p = 0.017) but not etiology of scoliosis (p = 0.997) reached statistical significance between subgroups. In conclusion, the current meta-analysis does not support the application of BoNT in children and adolescents with scoliosis. However, a decisive conclusion could not be made due to high between-study heterogeneity and small sample size. More randomized controlled trials with appropriate target muscle selection and standard outcome measurement should be conducted to examine the efficacy of botulinum neurotoxin in treating scoliosis. INPLASY ID: INPLASY202290031.
Psychometric Performance of a Condition-Specific Quality-of-Life Instrument for Dutch Children Born with Esophageal Atresia
Authors: ten Kate Chantal A. , IJsselstijn Hanneke , Dellenmark-Blom Michaela , van Tuyll van Serooskerken E. Sofie , Joosten Maja , Wijnen René M. H. , van Wijk Michiel P. ,   on behalf of the DCEA Study Group
Published: October 2022

A condition-specific instrument (EA-QOL©) to assess quality of life of children born with esophageal atresia (EA) was developed in Sweden and Germany. Before implementing this in the Netherlands, we evaluated its psychometric performance in Dutch children. After Swedish–Dutch translation, cognitive debriefing was conducted with a subset of EA patients and their parents. Next, feasibility, reliability, and validity were evaluated in a nationwide field test. Cognitive debriefing confirmed the predefined concepts, although some questions were not generally applicable. Feasibility was poor to moderate. In 2-to-7-year-old children, 8/17 items had >5% missing values. In 8-to-17-year-old children, this concerned 3/24 items of the proxy-report and 5/14 items of the self-report. The internal reliability was good. The retest reliability showed good correlation. The comparison reliability between self-reports and proxy-reports was strong. The construct validity was discriminative. The convergent validity was strong for the 2-to-7-year-old proxy-report, and weak to moderate for the 8-to-17-year-old proxy-report and self-report. In conclusion, the Dutch-translated EA-QOL questionnaires showed good reliability and validity. Feasibility was likely affected by items not deemed applicable to an individual child’s situation. Computer adaptive testing could be a potential solution to customizing the questionnaire to the individual patient. Furthermore, cross-cultural validation studies and implementation-evaluation studies in different countries are needed.
Characteristics, Diagnosis and Treatment of Compound Odontoma Associated with Impacted Teeth
Authors: Mazur Marta , Di Giorgio Gianni , Ndokaj Artnora , Jedliński Maciej , Corridore Denise , Marasca Beatrice , Salucci Alessandro , Polimeni Antonella , Ottolenghi Livia , Bossù Maurizio , Guerra Fabrizio
Published: October 2022

Compound odontoma is a malformation typical of young adults below the age of 20, with a slight preference for the male gender and the anterior region of the maxilla. Clinically asymptomatic, it can be detected during a radiological investigation in connection with the persistence of deciduous dental elements and the impaction of definitive ones. The treatment of choice is excisional surgery and recurrence is a rare event. The need for orthodontic therapy for impacted elements is usually not necessary because in most cases, odontomas are small, circumscribed lesions the size of a permanent tooth. In this article, the diagnostic and therapeutic surgical excision procedure is presented in three patients at developmental age with large compound odontomas associated with at least one retained canine, and in two of the cases, with serious transmigration to the impacted tooth elements.
Frequency of Candida spp. in the Oral Cavity of Asymptomatic Preschool Mexican Children and Its Association with Nutritional Status
Authors: Pinto-Almazán Rodolfo , Frías-De-León María Guadalupe , Fuentes-Venado Claudia Erika , Arenas Roberto , González-Gutiérrez Leopoldo , Chávez-Gutiérrez Edwin , Torres-Paez Oscar Uriel , Martínez-Herrera Erick
Published: October 2022

Malnutrition is a public health problem in developing countries, affecting the child population, which favors the appearance of infections such as oral candidiasis. In Mexico, information on the presence of oral colonization by Candida spp. in asymptomatic children is scarce. The present study aimed to determine the presence of Candida spp. in the oral cavity of asymptomatic preschool Mexican children and its association with their nutritional status. A sample of oral mucosa was obtained using a sterile swab and then inoculated in Sabouraud dextrose agar with antibiotics, and the yeast growth was phenotypically identified. The anthropometric profile of children was performed based on the guidelines of the International Society for the Advancement of Kinanthropometry. In addition, eating habits were investigated. The possible associations between the variables were determined through the chi-square test (IC95%, p < 0.05) (GraphPad Prism 8.0). Among the 743 assessed children (403 boys and 340 girls), the average age was 4.6 years, and the average nutritional status was normal (53.7%), followed by undernutrition (28.4%), overweight (12.4%) and obesity (5.5%). In 52 children, Candida was isolated, and the identified species were C. albicans (87.8%), C. glabrata (11.5%), C. krusei (5.8%) and C. parapsilosis (1.9%). The frequency of colonization was greater in males of six years (69.23%). There was no significant association between the colonization by Candida spp. and the nutritional status; however, a relation was observed with a high intake of simple carbohydrates.
Retrospective Analysis of FED Method Treatment Results in 11–17-Year-Old Children with Idiopathic Scoliosis
Authors: Trzcińska Sandra , Koszela Kamil
Published: October 2022

(1) Background: Idiopathic scoliosis is a major treatment problem due to its unknown origin and its three-dimensional nature. Attempts to cure it and search for new methods of physiotherapeutic treatment that would lead to its correction are one of the key issues of modern medicine. One of them is the fixation, elongation, de-rotation method (FED), used in the conservative treatment of idiopathic scoliosis. The aim of the study was evaluation of the short-term effectiveness of the FED method in the treatment of patients with idiopathic scoliosis. (2) Methods: Each patient underwent therapy based on the guidelines of the FED method. Patients were tested with the Bunnell scoliometer and the Zebris computer system. The treatment period was three weeks, after which the examinations were repeated. (3) Results: The results appeared to be statistically significant for all tested variables. (4) Conclusions: The examinations showed that the FED method had a statistically significant effect on the improvement of all parameters of posture examination, regardless of the size of the scoliotic deformation angle and bone maturity.
The Quality, Reliability, and Accuracy of Videos Regarding Exercises and Management for Dysphagia in Pediatric Populations Uploaded on YouTube
Authors: Chang Min Cheol , Lee Byung Joo , Park Donghwi
Published: October 2022

Objectives: YouTube is well known for providing easy access to various kinds of video content. In this study, we investigated the quality and reliability of videos on YouTube addressing exercise or dysphagia management in the pediatric population. Methods: Video quality and reliability were assessed by using the Global Quality Scale (GQS) and a modified DISCERN tool, respectively. The accuracy of the information in each video was also evaluated. Other information, including the video source, length, date of upload, as well as the number of views, likes, dislikes, and comments were investigated, and statistical significance was determined. Results: In total, 22 videos on exercises and dysphagia management in pediatric populations were evaluated; 36.4% and 72.7% of these videos did not have high quality or reliability, respectively. Moreover, half of the videos did not contain accurate information. Even when videos were created by medical specialists, many of these YouTube videos were of low quality, reliability, and accuracy. Conclusions: The reliability, quality, and accuracy of many videos on exercise or dysphagia management in the pediatric population were low. Video creators, especially medical specialists, should strive to create videos with high quality, reliability, and accuracy.
Taking a Closer Look at Social Performance in Childhood Social Anxiety Disorder: Biopsychosocial Context Considerations and Effects of Cognitive Behavior Therapy
Authors: Asbrand Julia , Tuschen-Caffier Brunna
Published: October 2022

Models of social anxiety disorder (SAD) describe shortfalls in child social performance, whereas empirically, children often show a deficit only in subjective and not objective performance. We examined social performance in relation to possible changes (before and after cognitive behavior therapy [CBT] including social skills training) and to an objective parameter (vocal arousal). Children with SAD were expected to subjectively judge their behavior as less competent than healthy control (HC) children despite a lack of objective differences. Children receiving CBT were expected to show a change in subjective and objective social performance in comparison to children waiting for treatment. Exploratory correlation analyses were used to disentangle the relation between social performance and vocal arousal. One hundred and nineteen children (64 with and 55 without SAD; aged 9–13 years) completed a Trier Social Stress Test (TSST). Children with SAD participated in a second TSST after CBT or waiting. Performance was assessed by self-report and by blinded observers. Vocal arousal was analyzed by audio recording. Children with SAD were objectively assessed as more socially competent than HC children; subjectively, children with SAD showed lower social performance. CBT showed no effect on subjective or objective performance ratings. Vocal arousal did not correlate with social performance. Results need to be considered carefully, as psychometric problems appeared that had not been considered in previous studies. The surprising lack of CBT effects suggests a need to focus on cognitions surrounding social performance. Further, social skills training should not be a standard SAD treatment component but used only if necessary.