bluuebunny/crossref_metadata_2025 huggingface dataset:
Copepods as Indicators of Different Water Masses during the Northeast Monsoon Prevailing Period in the Northeast Taiwan
Authors: Wang Yan-Guo , Tseng Li-Chun , Sun Rou-Xin , Chen Xiao-Yin , Xiang Peng , Wang Chun-Guang , Xing Bing-Peng , Hwang Jiang-Shiou
Published: September 2022

During this research, the average surface temperature, salinity, dissolved oxygen, and pH were 24.65 ± 1.53 (°C), 34.21 ± 0.07 (PSU), 6.85 ± 0.18 (mg/L), and 8.36 ± 0.03, respectively. Based on these environmental parameters, stations were arranged into three groups. Group A represents stations located around Keelung Island with the relative highest average dissolved oxygen, lowest average temperature, and pH values. Instead, the lowest average dissolved oxygen and highest average temperature, salinity, and pH values were recorded at the offshore stations. Keelung Island area was charged by cold water masses, which were driven by the Northeast monsoon, and stations in group C were affected by the Kuroshio Current. Kueishan Island area was mainly affected by mixed water masses resulting from the Kuroshio intrusion and monsoon-derived cold water. In this study, a total of 108 copepod species were identified, with an average abundance of 774.24 ± 289.42 (inds. m−3). Most species belong to the orders Calanoida and Poecilostomatoida, with an average relative abundance (RA) of 62.96% and 30.56%, respectively. Calanoid copepodites were the most dominant group, with a RA of 28.06%. This was followed by Paracalanus aculeatus, with a RA of 18.44%. The RA of Clausocalanus furcatus and Canthocalanus pauper was 4.80% and 3.59%, respectively. The dominant species P. aculeatus, C. pauper, Paracalanus parvus, and Temora turbinata were positively correlated with dissolved oxygen and negatively correlated with temperature in the surface waters. pH showed a negative correlation with P. parvus and T. turbinata, while the temperature was negatively correlated with these two dominant species. Indicator species were selected by an indicator value higher than 50%. Temora turbinata, Calanopia elliptica, C. pauper, Euchaeta concinna, Temora discaudata, Acartia pacifica, Macrosetella gracilis, Corycaeus speciosus, and P. parvus were considered as monsoonal cold water indicator species in Group A. Indicator copepod species for the Kuroshio Current were Farranula concinna, Copilia mirabilis, Candacia aethiopica, Corycaeus agilis, Farranula gibbula and Acrocalanus monachus in the study area. Paracandacia truncata, Oncaea clevei, P. aculeatus, and Centropages furcatus were considered suitable indicators for mixed water masses.
Simulation and Techno-Economical Evaluation of a Microalgal Biofertilizer Production Process
Authors: Romero-García Juan Miguel , González-López Cynthia Victoria , Brindley Celeste , Fernández-Sevilla José María , Acién-Fernández Francisco Gabriel
Published: September 2022

Due to population growth in the coming years, an increase in agricultural production will soon be mandatory, thus requiring fertilizers that are more environmentally sustainable than the currently most-consumed fertilizers since these are important contributors to climate change and water pollution. The objective of this work is the techno-economic evaluation of the production of biofertilizer concentrated in free amino acids from microalgal biomass produced in a wastewater treatment plant, to determine its economic viability. A process proposal has been made in six stages that have been modelled and simulated with the ASPEN Plus simulator. A profitability analysis has been carried out using a Box–Behnken-type response surface statistical design with three factors—the cost of the biomass sludge, the cost of the enzymes, and the sale price of the biofertilizer. It was found that the most influential factor in profitability is the sale price of the biofertilizer. According to a proposed representative base case, in which the cost of the biomass sludge is set to 0.5 EUR/kg, the cost of the enzymes to 20.0 EUR/kg, and the sale price of the biofertilizer to 3.5 EUR/kg, which are reasonable costs, it is concluded that the production of the biofertilizer would be economically viable.
Neurogenesis during Brittle Star Arm Regeneration Is Characterised by a Conserved Set of Key Developmental Genes
Authors: Czarkwiani Anna , Taylor Jack , Oliveri Paola
Published: September 2022

Neural regeneration is very limited in humans but extremely efficient in echinoderms. The brittle star Amphiura filiformis can regenerate both components of its central nervous system as well as the peripheral system, and understanding the molecular mechanisms underlying this ability is key for evolutionary comparisons not only within the echinoderm group, but also wider within deuterostomes. Here we characterise the neural regeneration of this brittle star using a combination of immunohistochemistry, in situ hybridization and Nanostring nCounter to determine the spatial and temporal expression of evolutionary conserved neural genes. We find that key genes crucial for the embryonic development of the nervous system in sea urchins and other animals are also expressed in the regenerating nervous system of the adult brittle star in a hierarchic and spatio-temporally restricted manner.
Optimization of Ski Attitude for the In-Flight Aerodynamic Performance of Ski Jumping
Authors: Cao Lianzhong , Guo Youcai , Li Xiong , Chen Long , Wang Xin , Zhao Tianyu
Published: September 2022

The control and adjustment of in-flight attitudes are critical to enlarging the flight distance of ski jumping. As one of the most important gears, the skis provide sufficient lift and drag forces for the athletes, and thus their in-flight attitudes should be optimized to improve flight performance. Here, the lift-to-drag ratio of a ski jumping ski is optimized with/without a constraint of lift capacity. The ski attitude is defined by three Eulerian angles and the resulting aerodynamic characteristics are predicted by Kriging models, which are established based on computational fluid dynamics (CFD) data. The surrogated models are dynamically updated in the optimization process to ensure their accuracy. Our results find that the optimization of the lift-to-drag ratio should be constrained by a certain lift capacity to be more practical. The angle of attack of the ski dominates the optimal lift-to-drag ratio at different lift levels while the yaw and roll angles are almost independent of the constraint once the required lift coefficient surpasses 0.6. This thus suggests that the athletes should focus on the angle of attack when modifying the ski attitude in the flight, which may reduce the difficulties in their in-flight decision makings.
Phytohormones 2020
Authors: Kudoyarova Guzel
Published: September 2022

The hormonal system plays a decisive role in the control of plant growth and development [...]
Phytochemicals in Inhibition of Prostate Cancer: Evidence from Molecular Mechanisms Studies
Authors: Hao Qiongyu , Wu Yanyuan , Vadgama Jaydutt V. , Wang Piwen
Published: September 2022

Prostate cancer is one of the leading causes of death for men worldwide. The development of resistance, toxicity, and side effects of conventional therapies have made prostate cancer treatment become more intensive and aggressive. Many phytochemicals isolated from plants have shown to be tumor cytotoxic. In vitro laboratory studies have revealed that natural compounds can affect cancer cell proliferation by modulating many crucial cellular signaling pathways frequently dysregulated in prostate cancer. A multitude of natural compounds have been found to induce cell cycle arrest, promote apoptosis, inhibit cancer cell growth, and suppress angiogenesis. In addition, combinatorial use of natural compounds with hormone and/or chemotherapeutic drugs seems to be a promising strategy to enhance the therapeutic effect in a less toxic manner, as suggested by pre-clinical studies. In this context, we systematically reviewed the currently available literature of naturally occurring compounds isolated from vegetables, fruits, teas, and herbs, with their relevant mechanisms of action in prostate cancer. As there is increasing data on how phytochemicals interfere with diverse molecular pathways in prostate cancer, this review discusses and emphasizes the implicated molecular pathways of cell proliferation, cell cycle control, apoptosis, and autophagy as important processes that control tumor angiogenesis, invasion, and metastasis. In conclusion, the elucidation of the natural compounds’ chemical structure-based anti-cancer mechanisms will facilitate drug development and the optimization of drug combinations. Phytochemicals, as anti-cancer agents in the treatment of prostate cancer, can have significant health benefits for humans.
Ginsenoside and Its Therapeutic Potential for Cognitive Impairment
Authors: Feng Hui , Xue Mei , Deng Hao , Cheng Shiqi , Hu Yue , Zhou Chunxiang
Published: September 2022

Cognitive impairment (CI) is one of the major clinical features of many neurodegenerative diseases. It can be aging-related or even appear in non-central nerve system (CNS) diseases. CI has a wide spectrum that ranges from the cognitive complaint with normal screening tests to mild CI and, at its end, dementia. Ginsenosides, agents extracted from a key Chinese herbal medicine (ginseng), show great promise as a new therapeutic option for treating CI. This review covered both clinical trials and preclinical studies to summarize the possible mechanisms of how ginsenosides affect CI in different diseases. It shows that ginsenosides can modulate signaling pathways associated with oxidative stress, apoptosis, inflammation, synaptic plasticity, and neurogenesis. The involved signaling pathways mainly include the PI3K/Akt, CREB/BDNF, Keap1/Nrf2 signaling, and NF-κB/NLRP3 inflammasome pathways. We hope to provide a theoretical basis for the treatment of CI for related diseases by ginsenosides.
Phenolics from Defatted Black Cumin Seeds (Nigella sativa L.): Ultrasound-Assisted Extraction Optimization, Comparison, and Antioxidant Activity
Authors: Gueffai Abdelkrim , Gonzalez-Serrano Diego J. , Christodoulou Marios C. , Orellana-Palacios Jose C. , Ortega Maria Lopez S. , Ouldmoumna Aoumria , Kiari Fatima Zohra , Ioannou Georgia D. , Kapnissi-Christodoulou Constantina P. , Moreno Andres , Hadidi Milad
Published: September 2022

An ultrasound-assisted method was used for the extraction of phenolics from defatted black cumin seeds (Nigella sativa L.), and the effects of several extraction factors on the total phenolic content and DPPH radical scavenging activity were investigated. To improve the extraction efficiency of phenolics from black cumin seed by ultrasonic-assisted extraction, the optimal extraction conditions were determined as follows: ethanol concentration of 59.1%, extraction temperature of 44.6 °C and extraction time of 32.5 min. Under these conditions, the total phenolic content and DPPH radical scavenging activity increased by about 70% and 38%, respectively, compared with conventional extraction. Furthermore, a complementary quantitative analysis of individual phenolic compounds was carried out using the HPLC-UV technique. The phenolic composition revealed high amounts of epicatechin (1.88–2.37 mg/g) and rutin (0.96–1.21 mg/g) in the black cumin seed extracts. Ultrasonic-assisted extraction can be a useful extraction method for the recovery of polyphenols from defatted black cumin seeds.
Glycosylation—The Most Diverse Post-Translational Modification
Authors: Staudacher Erika , Van Damme Els J. M. , Smagghe Guy
Published: September 2022

This article is part of the Special Issue Glycosylation—The Most Diverse Post-Translational Modification [...]
Plasma Kallikrein-Activated TGF-β Is Prognostic for Poor Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma and Associates with Increased Fibrogenesis
Authors: Pedersen Rasmus S. , Nissen Neel I. , Jensen Christina , Thorlacius-Ussing Jeppe , Manon-Jensen Tina , Olesen Majken L. , Langholm Lasse L. , Diab Hadi M. H. , Jorgensen Lars N. , Hansen Carsten P. , Chen Inna M. , Johansen Julia S. , Karsdal Morten A. , Willumsen Nicholas
Published: September 2022

Pancreatic ductal adenocarcinoma (PDAC) is a hard-to-treat cancer due to the collagen-rich (fibrotic) and immune-suppressed microenvironment. A major driver of this phenomenon is transforming growth factor beta (TGF-β). TGF-β is produced in an inactive complex with a latency-associated protein (LAP) that can be cleaved by plasma kallikrein (PLK), hereby releasing active TGF-β. The aim of this study was to evaluate LAP cleaved by PLK as a non-invasive biomarker for PDAC and tumor fibrosis. An ELISA was developed for the quantification of PLK-cleaved LAP-TGF-β in the serum of 34 patients with PDAC (stage 1–4) and 20 healthy individuals. Biomarker levels were correlated with overall survival (OS) and compared to serum type III collagen (PRO-C3) and type VI collagen (PRO-C6) pro-peptides. PLK-cleaved LAP-TGF-β was higher in patients with PDAC compared to healthy individuals (p < 0.0001). High levels (>median) of PLK-cleaved LAP-TGF-β were associated with poor OS in patients with PDAC independent of age and stage (HR 2.57, 95% CI: 1.22–5.44, p = 0.0135). High levels of PLK-cleaved LAP-TGF-β were associated with high PRO-C3 and PRO-C6, indicating a relationship between the PLK-cleaved LAP-TGF-β fragment, TGF-β activity, and tumor fibrosis. If these preliminary results are validated, circulating PLK-cleaved LAP-TGF-β may be a biomarker for future clinical trials.
Expression of Major Lipid Raft Protein Raftlin in Chronic Rhinosinusitis with Nasal Polyps in Smoking and Non-Smoking Patients Correlated with Interleukin-17 and Tumor Necrosis Factor-α Levels
Authors: Lin Yu-Tsai , Tsai Ming-Hsien , Su Yan-Ye , Chen Wei-Chih , Huang Shun-Chen , Chien Chih-Yen
Published: September 2022

Raftlin, as an inflammatory biomarker, has been previously reported in chronic inflammatory diseases. This study investigates the expression of Raftlin in cigarette smokers and in chronic rhinosinusitis with nasal polyps (CRSwNP), as well as evaluating its correlation with interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) levels. A total of 30 CRSwNP non-smoking and 16 CRSwNP + SK (smoking) patients undergoing endoscopic sinus surgery were enrolled, while 20 middle turbinate tissue pieces were examined and performed as the control group. In nasal mucosa epithelial staining, Raftlin levels were elevated in the columnar cells and were stained much more intensely in the CRSwNP and CRSwNP + SK groups. Raftlin was located more closely to the apical region of the epithelium in the CRSwNP + SK group; however, the Raftlin levels from whole nasal tissue pieces, according to ELISA data, showed that there was no significant difference between the three different study groups. A positive relationship by Pearson correlation was found between IL-17 or TNF-α levels and Raftlin levels. Taken together, these data indicate that increasing Raftlin expression in columnar cells might involve nasal epithelial remodeling in smokers with CRSwNP.
The Paradoxical Role of Circulating Ketone Bodies in Glycemic Control of Individuals with Type 2 Diabetes: High Risk, High Reward?
Authors: van der Vaart Amarens , Knol Martine G. E. , de Borst Martin H. , Bakker Stephan J. L. , Connelly Margery A. , Garcia Erwin , Bilo Henk J. G. , van Dijk Peter R. , Dullaart Robin P. F.
Published: September 2022

Introduction: Fasting plasma ketone bodies (KB) are elevated in individuals with type 2 diabetes (T2D) and could affect glycemic control and disease progression. Prolonged KB exposure may result in adaptive beneficial responses, counteracting glycemic dysregulation. In the current proof-of-concept study in adults with T2D, we hypothesized that fasting plasma KB are cross-sectionally associated with poorer glycemic control but prospectively with better glycemic control. Materials and Methods: Fasting plasma KB were measured via nuclear magnetic resonance spectroscopy in patients with T2D treated in primary care (Zodiac cohort; The Netherlands). We analyzed the associations between KB and HbA1c at baseline using linear regression analyses and HbA1c changes over time using linear mixed models. We adjusted for potential confounders, including risk factors for poor glycemic control. Individuals with T2D participating in the general population-based PREVEND study were used as a replication cohort. Results: We included 271 individuals with T2D with a total of 859 HbA1c measurements during a follow-up period of 3.0 (2.0–3.2) years. At baseline, the total amount of fasting plasma KB was independently and positively associated with HbA1c levels (regression coefficient in the fully adjusted analysis = 0.31; 95% CI 0.06–0.57, per doubling of KB; p = 0.02). In contrast, in the longitudinal analyses, fasting plasma KB were associated with a yearly HbA1c (%) decrease of −0.10 (95% CI −0.19 to −0.00 per doubling baseline KB; p = 0.05). Results were replicated in 387 individuals with T2D from a general population cohort with a total of 1115 glucose measurements during a follow-up period of 7.5 (7.2–8.0) years. A yearly decrease in fasting plasma glucose (mmol/L) of 0.09 was found per doubling of baseline KB. Conclusions: This study is the first to suggest a paradoxical role of circulating KB on glycemic control in T2D: elevated KB are associated with cross-sectionally poorer glycemic control but longitudinally with better long-term glycemic control.
Role of circRNA in E3 Modification under Human Disease
Authors: Chen Zishuo , Song Minkai , Wang Ting , Gao Jiawen , Lin Fei , Dai Hui , Zhang Chao
Published: September 2022

Circular RNA (circRNA) is often regarded as a special kind of non-coding RNA, involved in the regulation mechanism of various diseases, such as tumors, neurological diseases, and inflammation. In a broad spectrum of biological processes, the modification of the 76-amino acid ubiquitin protein generates a large number of signals with different cellular results. Each modification may change the result of signal transduction and participate in the occurrence and development of diseases. Studies have found that circRNA-mediated ubiquitination plays an important role in a variety of diseases. This review first introduces the characteristics of circRNA and ubiquitination and summarizes the mechanism of circRNA in the regulation of ubiquitination in various diseases. It is hoped that the emergence of circRNA-mediated ubiquitination can broaden the diagnosis and prognosis of the disease.
Biphasic Response of Astrocytic Brain-Derived Neurotrophic Factor Expression following Corticosterone Stimulation
Authors: Tsimpolis Alexandros , Kokkali Maria , Logothetis Aris , Kalafatakis Konstantinos , Charalampopoulos Ioannis
Published: September 2022

Novel research studies indicate multivarious interactions of glucocorticoid hormones (GCs) with the brain-derived neurotrophic factor (BDNF), regulating important aspects of neuronal cell physiology. While there is recent evidence of the chronic effects of GC stimulation on BDNF levels, as well as of the role of BDNF stimulation in the type of genomic effects following activation of GC-sensitive receptors, no data exist concerning the acute effects of GC stimulation on BDNF/TrkB gene expression. To address this question, we conducted a chrono-pharmacological study on rodent glial cells, astrocytes, which express the BDNF receptor, TrkB, following corticosterone administration. mRNA levels of BDNF and TrkB were estimated 1, 6, 12 and 24 h post-treatment. Selective inhibitors for GC-sensitive receptors and TrkB were used to decipher the molecular pathways of the effects observed. Our data support a biphasic response of BDNF expression after corticosterone stimulation. This response is characterized by a rapid TrkB phosphorylation-dependent upregulation of BDNF mRNA within the first hour, followed by a glucocorticoid receptor (GR)-dependent downregulation of BDNF mRNA, evident at 6, 12 and 24 h, with a direct impact on the protein levels of mature BDNF. Finally, a second pulse of corticosterone administration 1 h prior to the 6, 12 or 24 h timepoints normalized BDNF expression for the corresponding timepoint (i.e., mRNA levels became indifferent from baseline). These results present for the first time a biphasic regulation of the neurotrophin system based on glucocorticoid rhythmicity, further indicating complex trophic responses to temporal hormonal mechanisms in the brain microenvironment.
Cardioprotective Role for Paraoxonase-1 in Chronic Kidney Disease
Authors: Dube Prabhatchandra , Khalaf Fatimah K. , DeRiso Armelle , Mohammed Chrysan J. , Connolly Jacob A. , Battepati Dhanushya , Lad Apurva , Breidenbach Joshua D. , Kleinhenz Andrew L. , Khatib-Shahidi Bella , Patel Mitra , Tassavvor Iman , Gohara Amira F. , Malhotra Deepak , Morgan Eric E. , Haller Steven T. , Kennedy David J.
Published: September 2022

Paraoxonase-1 (PON-1) is a hydrolytic enzyme associated with HDL, contributing to its anti-inflammatory, antioxidant, and anti-atherogenic properties. Deficiencies in PON-1 activity result in oxidative stress and detrimental clinical outcomes in the context of chronic kidney disease (CKD). However, it is unclear if a decrease in PON-1 activity is mechanistically linked to adverse cardiovascular events in CKD. We investigated the hypothesis that PON-1 is cardioprotective in a Dahl salt-sensitive model of hypertensive renal disease. Experiments were performed on control Dahl salt-sensitive rats (SSMcwi, hereafter designated SS-WT rats) and mutant PON-1 rats (SS-Pon1em1Mcwi, hereafter designated SS-PON-1 KO rats) generated using CRISPR gene editing technology. Age-matched 10-week-old SS and SS-PON-1 KO male rats were maintained on high-salt diets (8% NaCl) for five weeks to induce hypertensive renal disease. Echocardiography showed that SS-PON-1 KO rats but not SS-WT rats developed compensated left ventricular hypertrophy after only 4 weeks on the high-salt diet. RT-PCR analysis demonstrated a significant increase in the expression of genes linked to cardiac hypertrophy, inflammation, and fibrosis, as well as a significant decrease in genes essential to left ventricular function in SS-PON-1 KO rats compared to SS-WT rats. A histological examination also revealed a significant increase in cardiac fibrosis and immune cell infiltration in SS-PON-1 KO rats, consistent with their cardiac hypertrophy phenotype. Our data suggest that a loss of PON-1 in the salt-sensitive hypertensive model of CKD leads to increased cardiac inflammation and fibrosis as well as a molecular and functional cardiac phenotype consistent with compensated left ventricular hypertrophy.
Granulocyte Colony-Stimulating Factor Ameliorates Endothelial Activation and Thrombotic Diathesis Biomarkers in a Murine Model of Hind Limb Ischemia
Authors: Valatsou Angeliki , Theofilis Panagiotis , Simantiris Spyridon , Vogiatzi Georgia , Briasoulis Alexandros , Sagris Marios , Oikonomou Evangelos , Antonopoulos Alexios S. , Pantopoulou Alkistis , Nasiri-Ansari Narjes , Fragopoulou Elizabeth , Perrea Despoina , Tsioufis Konstantinos , Tousoulis Dimitris
Published: September 2022

Novel therapies in peripheral arterial disease, such as granulocyte colony-stimulating factor (GCSF) administration, might result in anti-atherosclerotic effects. In this study, we used 10-week-old male ApoE−/− mice, which were fed an atherosclerosis-inducing diet for four weeks. At the end of the four weeks, hind limb ischemia was induced through left femoral artery ligation, the atherosclerosis-inducing diet was discontinued, and a normal diet was initiated. Mice were then randomized into a control group (intramuscular 0.4 mL normal saline 0.9% for 7 days) and a group in which GCSF was administrated intramuscularly in the left hind limb for 7 days (100 mg/kg). In the GCSF group, but not in the control group, we observed significant reductions in the soluble adhesion molecules (vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1)), sE-Selectin, and plasminogen activator inhibitor (PAI)-1 when they were measured through ELISA on the 1st and the 28th days after hind limb ischemia induction. Therefore, GCSF administration in an atherosclerotic mouse model of hind limb ischemia led to decreases in the biomarkers associated with endothelial activation and thrombosis. These findings warrant further validation in future preclinical studies.
Dynamic Regulation of NF-κB Response in Innate Immunity: The Case of the IMD Pathway in Drosophila
Authors: Cammarata-Mouchtouris Alexandre , Acker Adrian , Goto Akira , Chen Di , Matt Nicolas , Leclerc Vincent
Published: September 2022

Metazoans have developed strategies to protect themselves from pathogenic attack. These preserved mechanisms constitute the immune system, composed of innate and adaptive responses. Among the two kinds, the innate immune system involves the activation of a fast response. NF-κB signaling pathways are activated during infections and lead to the expression of timely-controlled immune response genes. However, activation of NF-κB pathways can be deleterious when uncontrolled. Their regulation is necessary to prevent the development of inflammatory diseases or cancers. The similarity of the NF-κB pathways mediating immune mechanisms in insects and mammals makes Drosophila melanogaster a suitable model for studying the innate immune response and learning general mechanisms that are also relevant for humans. In this review, we summarize what is known about the dynamic regulation of the central NF-κB-pathways and go into detail on the molecular level of the IMD pathway. We report on the role of the nuclear protein Akirin in the regulation of the NF-κB Relish immune response. The use of the Drosophila model allows the understanding of the fine-tuned regulation of this central NF-κB pathway.
Beneficial Effects of Table Grape Use on Serum Levels of Omega-3 Index and Liver Function: A Randomized Controlled Clinical Trial
Authors: Notarnicola Maria , De Nunzio Valentina , Lippolis Tamara , Tutino Valeria , Cisternino Anna , Iacovazzi Palma , Milella Rosa , Gasparro Marica , Negro Roberto , Polignano Maurizio , Caruso Maria
Published: September 2022

This clinical trial was aimed to investigate the effects of fresh table grape intake on the serum levels of the Omega-3 index, defined as the sum of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) levels. Forty consecutive healthy subjects were randomly assigned to the control group, receiving only dietary recommendations, and the grape group receiving a daily dose of 5 g of fresh table grape per kg of body weight, for 21 days. Compared with baseline, the grape treatment produced no significant difference in the serum levels of glucose, liver transaminase, and triglycerides, with the exception of cholesterol value, which was significantly reduced in both control and grape group (180.5 ± 20.32 vs. 196.1 ± 30.0 and 181.4 ± 21.9 vs. 194.3 ± 37.5, respectively). After 4 weeks from the end of grape treatment, the analysis of single fatty acids showed a significant increase in oleic acid content (14.15 ± 1.8 vs. 12.85 ± 1.6, p < 0.05) and a significant induction of the Omega-3 index (8.23 ± 1.9 vs. 6.09 ± 1.2, p < 0.05), associated with increased serum levels of adiponectin (24.09 ± 1.08 vs. 8.8 ± 0.7, p < 0.001). In contrast, the expression of fibroblast growth factor 21 (FGF21), a molecule associated with metabolic syndrome and liver disease, was significantly reduced (37.9 ± 6.8 vs. 107.8 ± 10.1, p < 0.001). The data suggest that the intake of fresh grape improves the Omega-3 index in the serum and exerts beneficial effects on liver function through the overexpression of adiponectin and the reduction in FGF21 levels.
Identification of Hub Genes and Potential Biomarkers for Childhood Asthma by Utilizing an Established Bioinformatic Analysis Approach
Authors: Santri Ichtiarini Nurullita , Irham Lalu Muhammad , Djalilah Gina Noor , Perwitasari Dyah Aryani , Wardani Yuniar , Phiri Yohane Vincent Abero , Adikusuma Wirawan
Published: September 2022

Childhood asthma represents a heterogeneous disease resulting from the interaction between genetic factors and environmental exposures. Currently, finding reliable biomarkers is necessary for the clinical management of childhood asthma. However, only a few biomarkers are being used in clinical practice in the pediatric population. In the long run, new biomarkers for asthma in children are required and would help direct therapy approaches. This study aims to identify potential childhood asthma biomarkers using a genetic-driven biomarkers approach. Herein, childhood asthma-associated Single Nucleotide Polymorphisms (SNPs) were utilized from the GWAS database to drive and facilitate the biomarker of childhood asthma. We uncovered 466 childhood asthma-associated loci by extending to proximal SNPs based on r2 > 0.8 in Asian populations and utilizing HaploReg version 4.1 to determine 393 childhood asthma risk genes. Next, the functional roles of these genes were subsequently investigated using Gene Ontology (GO) term enrichment analysis, a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and a protein–protein interaction (PPI) network. MCODE and CytoHubba are two Cytoscape plugins utilized to find biomarker genes from functional networks created using childhood asthma risk genes. Intriguingly, 10 hub genes (IL6, IL4, IL2, IL13, PTPRC, IL5, IL33, TBX21, IL2RA, and STAT6) were successfully identified and may have been identified to play a potential role in the pathogenesis of childhood asthma. Among 10 hub genes, we strongly suggest IL6 and IL4 as prospective childhood asthma biomarkers since both of these biomarkers achieved a high systemic score in Cytohubba’s MCC algorithm. In summary, this study offers a valuable genetic-driven biomarker approach to facilitate the potential biomarkers for asthma in children.
Biodegradation of Dental Resin-Based Composite—A Potential Factor Affecting the Bonding Effect: A Narrative Review
Authors: Guo Xinwei , Yu Yiyan , Gao Shang , Zhang Zhimin , Zhao Hongyan
Published: September 2022

In recent years, although resin composite has played an important role in the restoration of tooth defects, it still has several disadvantages, including being biodegraded by saliva, bacteria and other enzymes in the oral cavity, which may result in repair failure. This factor is not conducive to the long-term survival of the prosthesis in the mouth. In this article, we review the causes, influencing factors and prevention methods of resin biodegradation. Biodegradation is mainly caused by esterase in saliva and bacteria, which breaks the ester bond in resin and causes the release of monomers. The mechanical properties of the prosthesis can then be affected. Meanwhile, cathepsin and MMPs are activated on the bonding surface, which may decompose the dentin collagen. In addition, neutrophils and residual water on the bonding surface can also aggravate biodegradation. Currently, the primary methods to prevent biodegradation involve adding antibacterial agents to resin, inhibiting the activity of MMPs and enhancing the crosslinking of collagen fibers. All of the above indicates that in the preparation and adhesion of resin materials, attention should be paid to the influence of biodegradation to improve the prosthesis’s service life in the complex environment of the oral cavity.
Choroidal and Retinal Thicknesses in Type 2 Diabetes Mellitus with Moderate Diabetic Retinopathy Measured by Swept Source OCT
Authors: Fernández-Espinosa Guisela , Orduna-Hospital Elvira , Boned-Murillo Ana , Diaz-Barreda Maria Dolores , Sanchez-Cano Ana , Sopeña-Pinilla María , Pinilla Isabel
Published: September 2022

Background: To study choroidal thickness (CT) in type 2 diabetes mellitus (DM2) patients with moderate diabetic retinopathy (DR) and to correlate with changes in retinal thickness (RT) with swept-source OCT (SS-OCT) compared to healthy subjects. Methods: Fifty-four DM2 patients with moderate DR without diabetic macular edema (DME) and 73 age-matched healthy subjects were evaluated using SS-OCT to measure changes in total RT and CT in the nine areas of the Early Treatment Diabetic Retinopathy Study (ETDRS) macular grid. Results: The mean age was 64.06 ± 11.98 years and 60.79 ± 8.62 years in the diabetic and control groups, respectively. Total RT showed statistically significant differences in the temporal inner area, with higher values in the DM2 group (p = 0.010). CT did not show differences between the groups. There was a significant negative correlation between RT and age in all of the outer ETDRS areas and a positive significant correlation in the central area for the DM2 group. There was also a negative significant correlation between CT and age in all of the ETDRS areas except for the inferior inner area. In the DM2 group, a negative correlation was observed between RT and CT in the central area (p = 0.039) and in both horizontal parafoveal areas (temporal inner, p = 0.028; nasal inner, p= 0.003). Conclusion: DM2 patients with moderate DR have no changes with regard to CT. Both CT and RT decreased with age in DM2, showing a negative correlation between these factors in the central and horizontal parafoveal areas of the ETDRS grid.
Benzalkonium Chloride, Even at Low Concentrations, Deteriorates Intracellular Metabolic Capacity in Human Conjunctival Fibroblasts
Authors: Tsugeno Yuri , Sato Tatsuya , Watanabe Megumi , Furuhashi Masato , Umetsu Araya , Ida Yosuke , Hikage Fumihito , Ohguro Hiroshi
Published: September 2022

The objective of this study was to clarify the effects of benzalkonium chloride (BAC) on two-dimensional (2D) and three-dimensional (3D) cultures of human conjunctival fibroblast (HconF) cells, which are in vitro models replicating the epithelial barrier and the stromal supportive functions of the human conjunctiva. The cultured HconF cells were subjected to the following analyses in the absence and presence of 10−5% or 10−4% concentrations of BAC; (1) the barrier function of the 2D HconF monolayers, as determined by trans-endothelial electrical resistance (TEER) and FITC dextran permeability, (2) real-time metabolic analysis using an extracellular Seahorse flux analyzer, (3) the size and stiffness of 3D HconF spheroids, and (4) the mRNA expression of genes that encode for extracellular matrix (ECM) molecules including collagen (COL)1, 4 and 6, and fibronectin (FN), α-smooth muscle actin (α-SMA), ER stress related genes including the X-box binding protein-1 (XBP1), the spliced XBP1 (sXBP1) glucose regulator protein (GRP)78, GRP94, and the CCAAT/enhancer-binding protein homologous protein (CHOP), hypoxia inducible factor 1α (HIF1α), and Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α). In the presence of BAC, even at low concentrations at 10−5% or 10−4%, the maximal respiratory capacity, mitochondrial respiratory reserve, and glycolytic reserve of HconF cells were significantly decreased, although the barrier functions of 2D HconF monolayers, the physical properties of the 3D HconF spheroids, and the mRNA expression of the corresponding genes were not affected. The findings reported herein highlight the fact that BAC, even such low concentrations, may induce unfavorable adverse effects on the cellular metabolic capacity of the human conjunctiva.
Therapeutic Neuromodulation toward a Critical State May Serve as a General Treatment Strategy
Authors: Arvin Simon , Yonehara Keisuke , Glud Andreas Nørgaard
Published: September 2022

Brain disease has become one of this century’s biggest health challenges, urging the development of novel, more effective treatments. To this end, neuromodulation represents an excellent method to modulate the activity of distinct neuronal regions to alleviate disease. Recently, the medical indications for neuromodulation therapy have expanded through the adoption of the idea that neurological disorders emerge from deficits in systems-level structures, such as brain waves and neural topology. Connections between neuronal regions are thought to fluidly form and dissolve again based on the patterns by which neuronal populations synchronize. Akin to a fire that may spread or die out, the brain’s activity may similarly hyper-synchronize and ignite, such as seizures, or dwindle out and go stale, as in a state of coma. Remarkably, however, the healthy brain remains hedged in between these extremes in a critical state around which neuronal activity maneuvers local and global operational modes. While it has been suggested that perturbations of this criticality could underlie neuropathologies, such as vegetative states, epilepsy, and schizophrenia, a major translational impact is yet to be made. In this hypothesis article, we dissect recent computational findings demonstrating that a neural network’s short- and long-range connections have distinct and tractable roles in sustaining the critical regime. While short-range connections shape the dynamics of neuronal activity, long-range connections determine the scope of the neuronal processes. Thus, to facilitate translational progress, we introduce topological and dynamical system concepts within the framework of criticality and discuss the implications and possibilities for therapeutic neuromodulation guided by topological decompositions.
Effect of the Antimicrobial Agents Peppermint Essential Oil and Silver Nanoparticles on Bone Cement Properties
Authors: Robu Alina , Antoniac Aurora , Ciocoiu Robert , Grosu Elena , Rau Julietta V. , Fosca Marco , Krasnyuk Ivan I. , Pircalabioru Gratiela Gradisteanu , Manescu (Paltanea) Veronica , Antoniac Iulian , Gradinaru Sebastian
Published: September 2022

The main problems directly linked with the use of PMMA bone cements in orthopedic surgery are the improper mechanical bond between cement and bone and the absence of antimicrobial properties. Recently, more research has been devoted to new bone cement with antimicrobial properties using mainly antibiotics or other innovative materials with antimicrobial properties. In this paper, we developed modified PMMA bone cement with antimicrobial properties proposing some experimental antimicrobial agents consisting of silver nanoparticles incorporated in ceramic glass and hydroxyapatite impregnated with peppermint oil. The impact of the addition of antimicrobial agents on the structure, mechanical properties, and biocompatibility of new PMMA bone cements was quantified. It has been shown that the addition of antimicrobial agents improves the flexural strength of the traditional PMMA bone cement, while the yield strength values show a decrease, most likely because this agent acts as a discontinuity inside the material rather than as a reinforcing agent. In the case of all samples, the addition of antimicrobial agents had no significant influence on the thermal stability. The new PMMA bone cement showed good biocompatibility and the possibility of osteoblast proliferation (MTT test) along with a low level of cytotoxicity (LDH test).
Language Development in Preschool Duchenne Muscular Dystrophy Boys
Authors: Chieffo Daniela Pia Rosaria , Moriconi Federica , Mastrilli Ludovica , Lino Federica , Brogna Claudia , Coratti Giorgia , Altobelli Michela , Massaroni Valentina , Norcia Giulia , Ferraroli Elisabetta , Lucibello Simona , Pane Marika , Mercuri Eugenio
Published: September 2022

Background: the present study aims to assess language in preschool-aged Duchenne muscular dystrophy (DMD) boys with normal cognitive quotients, and to establish whether language difficulties are related to attentional aspects or to the involvement of brain dystrophin isoforms. Methods: 20 children aged between 48 and 72 months were assessed with language and attention assessments for preschool children. Nine had a mutation upstream of exon 44, five between 44 and 51, four between 51 and 63, and two after exon 63. A control group comprising 20 age-matched boys with a speech language disorder and normal IQ were also used. Results: lexical and syntactic comprehension and denomination were normal in 90% of the boys with Duchenne, while the articulation and repetition of long words, and sentence repetition frequently showed abnormal results (80%). Abnormal results were also found in tests assessing selective and sustained auditory attention. Language difficulties were less frequent in patients with mutations not involving isoforms Dp140 and Dp71. The profile in Duchenne boys was different form the one observed in SLI with no cognitive impairment. Conclusion: The results of our observational cross-sectional study suggest that early language abilities are frequently abnormal in preschool Duchenne boys and should be assessed regardless of their global neurodevelopmental quotient.
Poor Spontaneous Recovery of Aphemia Accompanied by Damage to the Anterior Segment of the Left Arcuate Fasciculus: A Case Report
Authors: Yu Qiwei , Qian Wenjun
Published: September 2022

Aphemia is a rare and special type of speech disorder, and the mechanisms underlying the occurrence and recovery remain unclear. Here, we present a clinical case of poor spontaneous recovery of aphemia, with the anterior segment of the left arcuate fasciculus server damaged and the posterior segment intact, as detected by diffusion tensor imaging. Aphemia could be caused by the disruption of the cortical and subcortical language circuits. In particular, our data support the view that damage to the anterior segment of the left arcuate fasciculus may result in poor spontaneous recovery from speech production deficits and that an intact posterior segment seems to be crucial for supporting residual language comprehension ability in patients with post-stroke aphasia. Collectively, these data imply the importance of the left arcuate fasciculus during recovery from the language disorder in the subacute stage of stroke.
Staged Surgery for Intra-Extracranial Communicating Jugular Foramen Paraganglioma: A Case Report and Systematic Review
Authors: Li Qiang , Yu Yanbing , Zhang Li , Liu Jiang , Ren Hongxiang , Zhen Xueke
Published: September 2022

Staged surgery strategy was preferred for patients with intra-extracranial communicating jugular foramen paraganglioma (IECJFP). A female patient who presented mild tinnitus, headache, and dizziness, together with preoperative related imaging, was diagnosed with a left intra-extracranial communicating jugular foramen lesion in November 2015 and accepted an initial operation for the intracranial tumor by retrosigmoid approach. The pathologic report was paraganglioma. In November 2021, a subtotal resection of the extracranial tumor was conducted for prominent lower cranial nerves (LCNs) deficit and middle ear involvement by infratemporal approach. In patients with IECJFP accompanied by LCNs deficit and middle ear involvement, an initial surgery for extracranial lesion and a second procedure for intracranial tumor were appropriate. However, the first operation for the intracranial lesion was preferred in IECJFP cases without LCNs deficit and middle ear involvement, as it could remove compression to the neurovascular structure and brain stem, clarify a pathological diagnosis, avoid a CSF leak, and prevent a severe neurological disorder from extracranial lesion excision. Subtotal resection of the extracranial tumor would be performed when lesion became larger combined with obvious LCNs disorder and tympanic cavity involvement. Consideration of specific staged surgical strategy for IECJFP in accordance with preoperative LCNs deficit and tympanic cavity involvement could prevent critical postoperative neurological deficit and improve quality of life in the long term.
COVID-19 Long-Term Effects: Is There an Impact on the Simple Reaction Time and Alternative-Forced Choice on Recovered Patients?
Authors: Santoyo-Mora Mauro , Villaseñor-Mora Carlos , Cardona-Torres Luz M. , Martínez-Nolasco Juan J. , Barranco-Gutiérrez Alejandro I. , Padilla-Medina José A. , Bravo-Sánchez Micael Gerardo
Published: September 2022

A comparative single-evaluation cross-sectional study was performed to evaluate cognitive damage in post-COVID-19 patients. The psychophysics tests of Two-Alternative Forced Choice (2AFC) and Simple Reaction Time (SRT), under a designed virtual environment, were used to evaluate the cognitive processes of decision-making, visual attention, and information processing speed. The population under study consisted of 147 individuals, 38 controls, and 109 post-COVID patients. During the 2AFC test, an Emotiv EPOC+® headset was used to obtain EEG signals to evaluate their Focus, Interest, and Engagement metrics. Results indicate that compared to healthy patients or recovered patients from mild-moderate COVID-19 infection, patients who recovered from a severe-critical COVID infection showed a poor performance in different cognitive tests: decision-making tasks required higher visual sensitivity (p = 0.002), Focus (p = 0.01) and information processing speed (p < 0.001). These results signal that the damage caused by the coronavirus on the central nervous and visual systems significantly reduces the cognitive processes capabilities, resulting in a prevalent deficit of 42.42% in information processing speed for mild-moderate cases, 46.15% for decision-making based on visual sensitivity, and 62.16% in information processing speed for severe-critical cases. A psychological follow-up for patients recovering from COVID-19 is recommended based on our findings.
Enhanced Short-Term Memory Function in Older Adults with Dementia Following Music-Feedback Physical Training: A Pilot Study
Authors: Strong Jessica V. , Arnold Maria , Schneider Lydia , Perschl Johanna , Villringer Arno , Fritz Thomas Hans
Published: September 2022

Prior research demonstrates that music making, physical exercise, and social activity have unique, positive effects on cognition and mood. One intervention, “Jymmin®”, was developed incorporating these approaches and found effective for decreased pain perception and increased endurance, self-efficacy, mood, and muscle efficiency. Previously, Jymmin was not piloted with older adults with dementia. The current study is a randomized pilot study of the Jymmin® with an older adult population in a long-term care facility (n = 38), evaluated across dementia levels (mild, moderate, or severe). Results found significant improvements in scores on a confrontation naming task across all conditions (p = 0.047) and a significant interaction effect for short-term memory scores (p = 0.046), suggesting higher scores at Time 2 for the experimental group and at Time 3 for the control group. There were no significant changes in mood ratings. Findings are discussed in the context of neural activity and musical agency.
Clinico-Radiological Phenotype of UBTF c.628G>A Pathogenic Variant-Related Neurodegeneration in Childhood: A Case Report and Literature Review
Authors: Chi Ching-Shiang , Lee Hsiu-Fen , Tsai Chi-Ren
Published: September 2022

Background: This work aims to describe the clinico-radiological phenotype of UBTF c.628G>A (p.Glu210Lys) pathogenic variant-related neurodegeneration in childhood. Methods: We describe the progress of clinical and neuroimaging features in a male individual who had childhood-onset neuroregression and carried the heterozygous UBTF c.628G>A (p.Glu210Lys) pathogenic variant. Clinical cases reported in the literature are reviewed. Results: Fifteen individuals, from 14 reported cases and the index case, were noted. The median age at onset of neurodegeneration was 3 years. Clinical phenotype was consistent among the affected individuals, with progressive motor, speech, cognitive, and social–emotional regression together with ataxia and prominent pyramidal and extrapyramidal symptoms and signs in early to middle childhood. All individuals had the same brain MRI features in terms of symmetric and diffuse T2 high signal intensity over the bilateral subcortical, periventricular, and peritrigonal white matter and progressive cortical and subcortical supratentorial atrophy. Two individuals were reported to have bilateral thalamic involvement. All individuals had profound intellectual disability with loss of verbal and/or ambulatory functions during follow-up. Conclusions: Individuals with the heterozygous UBTF c.628G>A (p.Glu210Lys) pathogenic variant had consistent clinical progress and neuroimaging features. Familiarity with this clinico-radiological phenotype may allow earlier diagnosis of this rare disease.