bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Analysis of Metabolite Profiling of Momordica charantia Leaf and the Anti-Obesity Effect through Regulating Lipid Metabolism
Authors: Fan Meiqi , Lee Jae-In , Ryu Young-Bae , Choi Young-Jin , Tang Yujiao , Oh Mirae , Moon Sang-Ho , Lee Bokyung , Kim Eun-Kyung
Published: May 2021

This study investigated the effects of Momordica charantia (M. charantia) extract in obesity and abnormal lipid metabolism in mice fed high fat diet (HFD). Fruit, root, stem, and leaf extracts of M. charantia were obtained using distilled water, 70% ethanol and 95% hexane. M. charantia leaf distilled water extract (MCLW) showed the highest antioxidant activity in both 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity tests and reducing power. Metabolite profiles of M. charantia leaf extracts were analyzed for identification of bioactive compounds. HFD-fed mice were treated with MCLW (oral dose of 200 mg/kg/d) for 4 weeks. MCLW reduced lipid accumulation, body weight, organ weight, and adipose tissue volume and significantly improved glucose tolerance and insulin resistance in HFD mice. Furthermore, MCLW administration reduced serum total cholesterol and low-density lipoprotein cholesterol, and increased serum high-density lipoprotein cholesterol compared with HFD mice. Moreover, MCLW significantly reduced the levels of serum urea nitrogen, alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase; alleviated liver and kidney injury. MCLW decreases expression of genes that fatty acid synthesis; increase the expression of catabolic-related genes. These results indicate that MCLW has an inhibitory effect on obese induced by high fat diet intake, and the mechanism may be related to the regulation of abnormal lipid metabolism in liver and adipose tissue, suggesting that MCLW may be a suitable candidate for the treatment of obesity.
Factors Influencing Physical Activity Participation among Midlife Immigrant Women: A Systematic Review
Authors: Zou Ping , Kadri Zeest , Shao Jing , Wang Xiyi , Luo Yan , Zhang Hui , Banerjee Ananya
Published: May 2021

Immigrant women are less likely to be physically active and face many barriers to participation in physical activity. This systematic review aims to identify the influencing factors and adaption approaches of physical activity interventions among midlife immigrant women. A systematic literature search was performed using various databases, such as MEDLINE, PsycINFO, and CINAHL, in February 2021. Studies were included if they investigated midlife immigrant women participating in physical activity interventions and were published in an English peer-reviewed journal in or after 2000. Twenty-two papers were included in this review. Guided by the Ecosocial theory, thematic analysis was utilized for data analysis. Among midlife immigrant women, influencing factors associated with physical activity participation included individual factors (a lack of time, current health status, motivation, and a lack of proficiency in various life skills), familial factors (familial support and seasonality), and community factors (social support and neighbourhood environment). The appropriate adaptation of physical activity interventions included adjustments in language, physical activity intensity, physical activity duration, logistical intervention adjustments and other potential technology-based adjustments. The findings can inform community stakeholders, healthcare professionals and researchers to design appropriate physical activity interventions that meet the needs of midlife immigrant women and improve their health outcomes.
Effectiveness of Community Occupational Therapy Intervention in, with and from the Community in People with Disabilities in Azrou (Morocco)
Authors: González-Bernal Jerónimo J. , Eiguren-Munitis Leire , González-Santos Josefa , Santamaría-Peláez Mirian , Soto-Cámara Raúl , Rodríguez-Fernández Paula
Published: May 2021

In Morocco, the social and environmental context influences the volition and development of meaningful activities, creating physical, personal and social barriers to the occupational performance of people with disabilities. This study develops a community Occupational Therapy program in order to verify its effectiveness in the volition, quality of life and perceived self-stigma of people with disabilities in the Moroccan city of Azrou, and to reduce the stigma of the community towards people with disabilities in the city. Data were collected from people with disabilities who participated in the program (N = 52), using the Volitional Questionnaire (VQ), The World Health Organization Quality of Life scale (WHOQOL-BREF), the Stigma Awareness Questionnaire (SCQ) and an ad hoc interview. In addition, community stigma was assessed by the Attribution Questionnaire (AQ-27) in citizens without disabilities (N = 42). Results confirmed that this intervention favors the inclusion of people with disabilities in their closest environment, improving volition and quality of life and reducing self-stigma. Furthermore, the community’s stigma towards people with disabilities was also significantly reduced after the intervention.
The Effect of a Mixed Circuit of Aerobic and Resistance Training on Body Composition in Older Adults—Retrospective Study
Authors: Pieczyńska Anna , Zasadzka Ewa , Trzmiel Tomasz , Pyda Małgorzata , Pawlaczyk Mariola
Published: May 2021

Ageing is inevitably associated with body composition changes, such as loss of muscle mass, increase in the total fat mass, and unfavorable reduction of subcutaneous fat. Physical activity exerts significant effects on the body composition. The aim of the study was to investigate the effects of two different weekly doses of resistance-aerobic training on the body composition in older people. The study consisted in a retrospective data analysis of fitness club members aged ≥60. The trainees participated in resistance-aerobic training sessions two or three times/week for a minimum of two months. A body composition analysis was performed before and after the training sessions. Group 1 (36 subjects) and Group 2 (28 subjects) had two and three training sessions/week, respectively. A higher skeletal muscle mass was found in Group 1 and lower waist-hip-ratio indices were observed in Group 2. No statistically significant differences were found in the body mass, skeletal muscle mass, fat mass, total body water, lean mass, body mass index, visceral fat area between both groups. The number of training session/week proved to be statistically insignificant for all investigated variables. Resistance-aerobic training with two sessions/week may be as effective in maintaining proper body composition in older people as the same training at the dose of three sessions/week.
Divisive Faultlines and Knowledge Search in Technological Innovation Network: An Empirical Study of Global Biopharmaceutical Firms
Authors: Cheng Long , Wang Meng , Lou Xuming , Chen Zifeng , Yang Yang
Published: May 2021

Divisive faultlines caused by the uneven distribution of relationship strength play an essential role in knowledge search in the technological innovation network, which serves as an important requirement for the technological innovation network’s macro level to expand to the meso-subgroup level and promote its healthy development. Given that the biopharmaceutical industry, as a high-tech industry, plays a vital role in promoting healthy development, this paper uses the joint patent applications of global biopharmaceutical firms from 2003 to 2018 as a sample to construct a technological innovation network, to explore the relationship between divisive faultlines and knowledge search in the technological innovation network. We also study the moderating effect of structural holes in this relationship. The empirical results show that divisive faultlines significantly affect the depth of knowledge search in the technological innovation network. Divisive faultlines have an inverted U-shaped effect on the breadth of knowledge search in the technological innovation network. Structural holes positively moderate the relationship between divisive faultlines and depth of knowledge search but negatively moderate the inverted U-shaped relationship between divisive faultlines and breadth of knowledge search. This research reveals the relationship between divisive faultlines and the knowledge search in the technological innovation network. The research results provide a theoretical basis and management enlightenment to improve biopharmaceutical firms’ knowledge search ability and promote healthy and sustainable development.
Land Use Change Ontology and Traffic Prediction through Recurrent Neural Networks: A Case Study in Calgary, Canada
Authors: Azad Abul , Wang Xin
Published: May 2021

Land use and transportation planning have a significant impact on the performance of cities’ traffic conditions and the quality of people’s lives. The changing characteristics of land use will affect and challenge how a city is able to manage, organize, and plan for new developments and transportation. These challenges can be better addressed with effective methods of monitoring and predicting, which can enable optimal efficiency in how a growing city like Calgary, Canada, can perform. Using ontology in land use planning is a new initiative currently being researched and explored. In this regard, ontology incorporates relationships between the various entities of land use. The aim of this study is to present Land Use Change Ontology (LUCO) with a deep neural network for traffic prediction. We present a Land Use Change Ontology (LUCO) approach, using expressions of how the semantics of land use changes relate to the integration of temporal land use information. This study examines the City of Calgary’s land use data from the years 2001, 2010, and 2015. In applying the LUCO approach to test data, experimental outcomes indicated that from 2001 to 2015 residential land use increased by 30% and open space decreased by 40%. Forecasting traffic is increasingly essential for successful traffic modelling, operations, and management. However, traditional means for predicting traffic flow have largely assumed restrictive model architectures that have not controlled for the amounts of land use change. Inspired by deep learning methods and effective data mining computing capabilities, this paper introduces the deep learning Recurrent Neural Network (RNN) to predict traffic while considering the impact of land use change. The RNN was successful in learning the features of traffic flow under various land use change situations. Experimental results indicated that, with the consideration of LUCO, the deep learning predictors had better accuracy when compared with other existing models. Success of our modeling approach indicates that cities could apply this modeling approach to make land use transportation planning more efficient.
Exposure to the Methylselenol Precursor Dimethyldiselenide Induces a Reductive Endoplasmic Reticulum Stress in Saccharomyces cerevisiae
Authors: Dauplais Marc , Mahou Pierre , Plateau Pierre , Lazard Myriam
Published: May 2021

Methylselenol (MeSeH) is a major cytotoxic metabolite of selenium, causing apoptosis in cancer cells through mechanisms that remain to be fully established. Previously, we demonstrated that, in Saccharomyces cerevisiae, MeSeH toxicity was mediated by its metabolization into selenomethionine by O-acetylhomoserine (OAH)-sulfhydrylase, an enzyme that is absent in higher eukaryotes. In this report, we used a mutant met17 yeast strain, devoid of OAH- sulfhydrylase activity, to identify alternative targets of MeSeH. Exposure to dimethyldiselenide (DMDSe), a direct precursor of MeSeH, caused an endoplasmic reticulum (ER) stress, as evidenced by increased expression of the ER chaperone Kar2p. Mutant strains (∆ire1 and ∆hac1) unable to activate the unfolded protein response were hypersensitive to MeSeH precursors but not to selenomethionine. In contrast, deletion of YAP1 or SKN7, required to activate the oxidative stress response, did not affect cell growth in the presence of DMDSe. ER maturation of newly synthesized carboxypeptidase Y was impaired, indicating that MeSeH/DMDSe caused protein misfolding in the ER. Exposure to DMDSe resulted in induction of the expression of the ER oxidoreductase Ero1p with concomitant reduction of its regulatory disulfide bonds. These results suggest that MeSeH disturbs protein folding in the ER by generating a reductive stress in this compartment.
Biocompatibility Study of a New Dental Cement Based on Hydroxyapatite and Calcium Silicates: Focus on Liver, Kidney, and Spleen Tissue Effects
Authors: Paraš Smiljana , Trišić Dijana , Mitrović Ajtić Olivera , Antonijević Đorđe , Čolović Božana , Drobne Damjana , Jokanović Vukoman
Published: May 2021

The effects of a new material based on hydroxyapatite and calcium silicates, named ALBO-MPCA, were investigated on the liver, kidney and spleen. The material was administrated orally for 120 days in an in vivo model in Wistar rats, and untreated animals served as a control. Hematological and biochemical blood parameters were analyzed. Qualitative histological analysis of tissues, change in mitotic activity of cells, and histological characteristics was conducted, as well as quantitative stereological analysis of parenchymal cells, blood sinusoids, and connective tissues. Additionally, the protein expressions of Ki67 and CD68 markers were evaluated. Histological analysis revealed no pathological changes after the tested period. It showed the preservation of the architecture of blood sinusoids and epithelial cells and the presence of mitosis. Additionally, the significantly increased number of the Ki67 in the presence of ALBO-MPCA confirmed the proliferative effect of the material noticed by stereological analysis, while immunoreactive CD68 positive cells did not differ between groups. The study showed non-toxicity of the tested material based on the effects on the hematological, biochemical, and observed histological parameters; in addition, it showed evidence of its biocompatibility. These results could be the basis for further steps toward the application of tested materials in endodontics.
Prenylated Flavonoids with Potential Antimicrobial Activity: Synthesis, Biological Activity, and In Silico Study
Authors: Osorio Mauricio , Carvajal Marcela , Vergara Alejandra , Butassi Estefania , Zacchino Susana , Mascayano Carolina , Montoya Margarita , Mejías Sophia , Martín Marcelo Cortez-San , Vásquez-Martínez Yesseny
Published: May 2021

Prenylated flavonoids are an important class of naturally occurring flavonoids with important biological activity, but their low abundance in nature limits their application in medicines. Here, we showed the hemisynthesis and the determination of various biological activities of seven prenylated flavonoids, named 7–13, with an emphasis on antimicrobial ones. Compounds 9, 11, and 12 showed inhibitory activity against human pathogenic fungi. Compounds 11, 12 (flavanones) and 13 (isoflavone) were the most active against clinical isolated Staphylococcus aureus MRSA, showing that structural requirements as prenylation at position C-6 or C-8 and OH at positions C-5, 7, and 4′ are key to the antibacterial activity. The combination of 11 or 12 with commercial antibiotics synergistically enhanced the antibacterial activity of vancomycin, ciprofloxacin, and methicillin in a factor of 10 to 100 times against drug-resistant bacteria. Compound 11 combined with ciprofloxacin was able to decrease the levels of ROS generated by ciprofloxacin. According to docking results of S enantiomer of 11 with ATP-binding cassette transporter showed the most favorable binding energy; however, more studies are needed to support this result.
The Effect of Platelet-Rich Plasma on the Intra-Articular Microenvironment in Knee Osteoarthritis
Authors: Szwedowski Dawid , Szczepanek Joanna , Paczesny Łukasz , Zabrzyński Jan , Gagat Maciej , Mobasheri Ali , Jeka Sławomir
Published: May 2021

Knee osteoarthritis (KOA) represents a clinical challenge due to poor potential for spontaneous healing of cartilage lesions. Several treatment options are available for KOA, including oral nonsteroidal anti-inflammatory drugs, physical therapy, braces, activity modification, and finally operative treatment. Intra-articular (IA) injections are usually used when the non-operative treatment is not effective, and when the surgery is not yet indicated. More and more studies suggesting that IA injections are as or even more efficient and safe than NSAIDs. Recently, research to improve intra-articular homeostasis has focused on biologic adjuncts, such as platelet-rich plasma (PRP). The catabolic and inflammatory intra-articular processes that exists in knee osteoarthritis (KOA) may be influenced by the administration of PRP and its derivatives. PRP can induce a regenerative response and lead to the improvement of metabolic functions of damaged structures. However, the positive effect on chondrogenesis and proliferation of mesenchymal stem cells (MSC) is still highly controversial. Recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, significant progress has been made in understanding the mechanism of PRP action. In this review, we will discuss mechanisms related to inflammation and chondrogenesis in cartilage repair and regenerative processes after PRP administration in in vitro and animal studies. Furthermore, we review clinical trials of PRP efficiency in changing the OA biomarkers in knee joint.
Immunopathology of Chronic Hepatitis B Infection: Role of Innate and Adaptive Immune Response in Disease Progression
Authors: Khanam Arshi , Chua Joel V. , Kottilil Shyam
Published: May 2021

More than 250 million people are living with chronic hepatitis B despite the availability of highly effective vaccines and oral antivirals. Although innate and adaptive immune cells play crucial roles in controlling hepatitis B virus (HBV) infection, they are also accountable for inflammation and subsequently cause liver pathologies. During the initial phase of HBV infection, innate immunity is triggered leading to antiviral cytokines production, followed by activation and intrahepatic recruitment of the adaptive immune system resulting in successful virus elimination. In chronic HBV infection, significant alterations in both innate and adaptive immunity including expansion of regulatory cells, overexpression of co-inhibitory receptors, presence of abundant inflammatory mediators, and modifications in immune cell derived exosome release and function occurs, which overpower antiviral response leading to persistent viral infection and subsequent immune pathologies associated with disease progression towards fibrosis, cirrhosis, and hepatocellular carcinoma. In this review, we discuss the current knowledge of innate and adaptive immune cells transformations that are associated with immunopathogenesis and disease outcome in CHB patients.
Multiplex Autoantibody Detection in Patients with Autoimmune Polyglandular Syndromes
Authors: Savvateeva Elena N. , Yukina Marina Yu. , Nuralieva Nurana F. , Filippova Marina A. , Gryadunov Dmitry A. , Troshina Ekaterina A.
Published: May 2021

The diagnosis of autoimmune polyglandular syndrome (APS) types 1/2 is difficult due to their rarity and nonspecific clinical manifestations. APS-1 development can be identified with assays for autoantibodies against cytokines, and APS-2 development with organ-specific antibodies. In this study, a microarray-based multiplex assay was proposed for simultaneous detection of both organ-specific (anti-21-OH, anti-GAD-65, anti-IA2, anti-ICA, anti-TG, and anti-TPO) and APS-1-specific (anti-IFN-ω, anti-IFN-α-2a, and anti-IL-22) autoantibodies. Herein, 206 serum samples from adult patients with APS-1, APS-2, isolated autoimmune endocrine pathologies or non-autoimmune endocrine pathologies and from healthy donors were analyzed. The prevalence of autoantibodies differed among the groups of healthy donors and patients with non-, mono- and multi-endocrine diseases. APS-1 patients were characterized by the presence of at least two specific autoantibodies (specificity 99.5%, sensitivity 100%). Furthermore, in 16 of the 18 patients, the APS-1 assay revealed triple positivity for autoantibodies against IFN-ω, IFN-α-2a and IL-22 (specificity 100%, sensitivity 88.9%). No anti-cytokine autoantibodies were found in the group of patients with non-APS-1 polyendocrine autoimmunity. The accuracy of the microarray-based assay compared to ELISA for organ-specific autoantibodies was 88.8–97.6%. This multiplex assay can be part of the strategy for diagnosing and predicting the development of APS.
The Effects of Insulin on Immortalized Rat Schwann Cells, IFRS1
Authors: Saiki Tomokazu , Nakamura Nobuhisa , Miyabe Megumi , Ito Mizuho , Minato Tomomi , Sango Kazunori , Matsubara Tatsuaki , Naruse Keiko
Published: May 2021

Schwann cells play an important role in peripheral nerve function, and their dysfunction has been implicated in the pathogenesis of diabetic neuropathy and other demyelinating diseases. The physiological functions of insulin in Schwann cells remain unclear and therefore define the aim of this study. By using immortalized adult Fischer rat Schwann cells (IFRS1), we investigated the mechanism of the stimulating effects of insulin on the cell proliferation and expression of myelin proteins (myelin protein zero (MPZ) and myelin basic protein (MBP). The application of insulin to IFRS1 cells increased the proliferative activity and induced phosphorylation of Akt and ERK, but not P38-MAPK. The proliferative potential of insulin-stimulated IFRS1 was significantly suppressed by the addition of LY294002, a PI3 kinase inhibitor. The insulin-stimulated increase in MPZ expression was significantly suppressed by the addition of PD98059, a MEK inhibitor. Furthermore, insulin-increased MBP expression was significantly suppressed by the addition of LY294002. These findings suggest that both PI3-K/Akt and ERK/MEK pathways are involved in insulin-induced cell growth and upregulation of MPZ and MBP in IFRS1 Schwann cells.
HNRNP A1 Promotes Lung Cancer Cell Proliferation by Modulating VRK1 Translation
Authors: Ryu Hye Guk , Jung Youngseob , Lee Namgyu , Seo Ji-Young , Kim Sung Wook , Lee Kyung-Ha , Kim Do-Yeon , Kim Kyong-Tai
Published: May 2021

THeterogeneous nuclear ribonucleoprotein (HNRNP) A1 is the most abundant and ubiquitously expressed member of the HNRNP protein family. In recent years, it has become more evident that HNRNP A1 contributes to the development of neurodegenerative diseases. However, little is known about the underlying role of HNRNP A1 in cancer development. Here, we report that HNRNP A1 expression is significantly increased in lung cancer tissues and is negatively correlated with the overall survival of patients with lung cancer. Additionally, HNRNP A1 positively regulates vaccinia-related kinase 1 (VRK1) translation via binding directly to the 3′ untranslated region (UTR) of VRK1 mRNA, thus increasing cyclin D1 (CCND1) expression by VRK1-mediated phosphorylation of the cAMP response element–binding protein (CREB). Furthermore, HNRNP A1 binding to the cis-acting region of the 3′UTR of VRK1 mRNA contributes to increased lung cancer cell proliferation. Thus, our study unveils a novel role of HNRNP A1 in lung carcinogenesis via post-transcriptional regulation of VRK1 expression and suggests its potential as a therapeutic target for patients with lung cancer.
Understanding the Intricate Web of Phytohormone Signalling in Modulating Root System Architecture
Authors: Sharma Manvi , Singh Dhriti , Saksena Harshita B. , Sharma Mohan , Tiwari Archna , Awasthi Prakhar , Botta Halidev Krishna , Shukla Brihaspati Narayan , Laxmi Ashverya
Published: May 2021

Root system architecture (RSA) is an important developmental and agronomic trait that is regulated by various physical factors such as nutrients, water, microbes, gravity, and soil compaction as well as hormone-mediated pathways. Phytohormones act as internal mediators between soil and RSA to influence various events of root development, starting from organogenesis to the formation of higher order lateral roots (LRs) through diverse mechanisms. Apart from interaction with the external cues, root development also relies on the complex web of interaction among phytohormones to exhibit synergistic or antagonistic effects to improve crop performance. However, there are considerable gaps in understanding the interaction of these hormonal networks during various aspects of root development. In this review, we elucidate the role of different hormones to modulate a common phenotypic output, such as RSA in Arabidopsis and crop plants, and discuss future perspectives to channel vast information on root development to modulate RSA components.
Significance of Heme and Heme Degradation in the Pathogenesis of Acute Lung and Inflammatory Disorders
Authors: Ryter Stefan W.
Published: May 2021

The heme molecule serves as an essential prosthetic group for oxygen transport and storage proteins, as well for cellular metabolic enzyme activities, including those involved in mitochondrial respiration, xenobiotic metabolism, and antioxidant responses. Dysfunction in both heme synthesis and degradation pathways can promote human disease. Heme is a pro-oxidant via iron catalysis that can induce cytotoxicity and injury to the vascular endothelium. Additionally, heme can modulate inflammatory and immune system functions. Thus, the synthesis, utilization and turnover of heme are by necessity tightly regulated. The microsomal heme oxygenase (HO) system degrades heme to carbon monoxide (CO), iron, and biliverdin-IXα, that latter which is converted to bilirubin-IXα by biliverdin reductase. Heme degradation by heme oxygenase-1 (HO-1) is linked to cytoprotection via heme removal, as well as by activity-dependent end-product generation (i.e., bile pigments and CO), and other potential mechanisms. Therapeutic strategies targeting the heme/HO-1 pathway, including therapeutic modulation of heme levels, elevation (or inhibition) of HO-1 protein and activity, and application of CO donor compounds or gas show potential in inflammatory conditions including sepsis and pulmonary diseases.
DeepDISE: DNA Binding Site Prediction Using a Deep Learning Method
Authors: Hendrix Samuel Godfrey , Chang Kuan Y. , Ryu Zeezoo , Xie Zhong-Ru
Published: May 2021

It is essential for future research to develop a new, reliable prediction method of DNA binding sites because DNA binding sites on DNA-binding proteins provide critical clues about protein function and drug discovery. However, the current prediction methods of DNA binding sites have relatively poor accuracy. Using 3D coordinates and the atom-type of surface protein atom as the input, we trained and tested a deep learning model to predict how likely a voxel on the protein surface is to be a DNA-binding site. Based on three different evaluation datasets, the results show that our model not only outperforms several previous methods on two commonly used datasets, but also demonstrates its robust performance to be consistent among the three datasets. The visualized prediction outcomes show that the binding sites are also mostly located in correct regions. We successfully built a deep learning model to predict the DNA binding sites on target proteins. It demonstrates that 3D protein structures plus atom-type information on protein surfaces can be used to predict the potential binding sites on a protein. This approach should be further extended to develop the binding sites of other important biological molecules.
Sex-Specific Cannabidiol- and Iloperidone-Induced Neuronal Activity Changes in an In Vitro MAM Model System of Schizophrenia
Authors: Thériault Rachel-Karson , St-Denis Myles , Hewitt Tristen , Khokhar Jibran Y. , Lalonde Jasmin , Perreault Melissa L.
Published: May 2021

Cortical circuit dysfunction is thought to be an underlying mechanism of schizophrenia (SZ) pathophysiology with normalization of aberrant circuit activity proposed as a biomarker for antipsychotic efficacy. Cannabidiol (CBD) shows potential as an adjunctive antipsychotic therapy; however, potential sex effects in these drug interactions remain unknown. In the present study, we sought to elucidate sex effects of CBD coadministration with the atypical antipsychotic iloperidone (ILO) on the activity of primary cortical neuron cultures derived from the rat methylazoxymethanol acetate (MAM) model used for the study of SZ. Spontaneous network activity measurements were obtained using a multielectrode array at baseline and following administration of CBD or ILO alone, or combined. At baseline, MAM male neurons displayed increased bursting activity whereas MAM female neurons exhibited no difference in bursting activity compared to sex-matched controls. CBD administered alone showed a rapid but transient increase in neuronal activity in the MAM networks, an effect more pronounced in females. Furthermore, ILO had an additive effect on CBD-induced elevations in activity in the MAM male neurons. In the MAM female neurons, CBD or ILO administration resulted in time-dependent elevations in neuronal activity, but the short-term CBD-induced increases in activity were lost when CBD and ILO were combined. Our findings indicate that CBD induces rapid increases in cortical neuronal activity, with sex-specific drug interactions upon ILO coadministration. This suggests that sex should be a consideration when implementing adjunct therapy for treatment of SZ.
Metabolomic Biomarkers in Gestational Diabetes Mellitus: A Review of the Evidence
Authors: Alesi Simon , Ghelani Drishti , Rassie Kate , Mousa Aya
Published: May 2021

Gestational diabetes mellitus (GDM) is the fastest growing type of diabetes, affecting between 2 to 38% of pregnancies worldwide, varying considerably depending on diagnostic criteria used and sample population studied. Adverse obstetric outcomes include an increased risk of macrosomia, and higher rates of stillbirth, instrumental delivery, and birth trauma. Metabolomics, which is a platform used to analyse and characterise a large number of metabolites, is increasingly used to explore the pathophysiology of cardiometabolic conditions such as GDM. This review aims to summarise metabolomics studies in GDM (from inception to January 2021) in order to highlight prospective biomarkers for diagnosis, and to better understand the dysfunctional metabolic pathways underlying the condition. We found that the most commonly deranged pathways in GDM include amino acids (glutathione, alanine, valine, and serine), carbohydrates (2-hydroxybutyrate and 1,5-anhydroglucitol), and lipids (phosphatidylcholines and lysophosphatidylcholines). We also highlight the possibility of using certain metabolites as predictive markers for developing GDM, with the use of highly stratified modelling techniques. Limitations for metabolomic research are evaluated, and future directions for the field are suggested to aid in the integration of these findings into clinical practice.
Type IIa RPTPs and Glycans: Roles in Axon Regeneration and Synaptogenesis
Authors: Sakamoto Kazuma , Ozaki Tomoya , Suzuki Yuji , Kadomatsu Kenji
Published: May 2021

Type IIa receptor tyrosine phosphatases (RPTPs) play pivotal roles in neuronal network formation. It is emerging that the interactions of RPTPs with glycans, i.e., chondroitin sulfate (CS) and heparan sulfate (HS), are critical for their functions. We highlight here the significance of these interactions in axon regeneration and synaptogenesis. For example, PTPσ, a member of type IIa RPTPs, on axon terminals is monomerized and activated by the extracellular CS deposited in neural injuries, dephosphorylates cortactin, disrupts autophagy flux, and consequently inhibits axon regeneration. In contrast, HS induces PTPσ oligomerization, suppresses PTPσ phosphatase activity, and promotes axon regeneration. PTPσ also serves as an organizer of excitatory synapses. PTPσ and neurexin bind one another on presynapses and further bind to postsynaptic leucine-rich repeat transmembrane protein 4 (LRRTM4). Neurexin is now known as a heparan sulfate proteoglycan (HSPG), and its HS is essential for the binding between these three molecules. Another HSPG, glypican 4, binds to presynaptic PTPσ and postsynaptic LRRTM4 in an HS-dependent manner. Type IIa RPTPs are also involved in the formation of excitatory and inhibitory synapses by heterophilic binding to a variety of postsynaptic partners. We also discuss the important issue of possible mechanisms coordinating axon extension and synapse formation.
Correction: Pan et al. Genome-Wide Identification of M35 Family Metalloproteases in Rhizoctonia cerealis and Functional Analysis of RcMEP2 as a Virulence Factor during the Fungal Infection to Wheat. Int. J. Mol. Sci. 2020, 21, 2984
Authors: Pan Lijun , Wen Shengxian , Yu Jinfeng , Lu Lin , Zhu Xiuliang , Zhang Zengyan
Published: May 2021

In the original article, there was a mistake in Figure 8 as published [...]
Current State of CAR T-Cell Therapy in Chronic Lymphocytic Leukemia
Authors: Mancikova Veronika , Smida Michal
Published: May 2021

Chimeric antigen receptor (CAR) T-cell therapy has already achieved remarkable remissions in some difficult-to-treat patients with B-cell malignancies. Although the clinical experience in chronic lymphocytic leukemia (CLL) patients is limited, the proportion of remissions reached in this disease is clearly the lowest from the spectrum of B-cell tumors. In this review, we discuss the antigenic targets exploited in CLL CAR-T therapy, the determinants of favorable responses, as well as the mechanisms of treatment failure specific to this disease.
Comparative Antimicrobial Activity of Hp404 Peptide and Its Analogs against Acinetobacter baumannii
Authors: Hong Min Ji , Kim Min Kyung , Park Yoonkyung
Published: May 2021

An amphipathic α-helical peptide, Hp1404, was isolated from the venomous gland of the scorpion Heterometrus petersii. Hp1404 exhibits antimicrobial activity against methicillin-resistant Staphylococcus aureus but is cytotoxic. In this study, we designed antimicrobial peptides by substituting amino acids at the 14 C-terminal residues of Hp1404 to reduce toxicity and improve antibacterial activity. The analog peptides, which had an amphipathic α-helical structure, were active against gram-positive and gram-negative bacteria, particularly multidrug-resistant Acinetobacter baumannii, and showed lower cytotoxicity than Hp1404. N-phenyl-1-naphthylamine uptake and DisC3-5 assays demonstrated that the peptides kill bacteria by effectively permeating the outer and cytoplasmic membranes. Additionally, the analog peptides inhibited biofilm formation largely than Hp1404 at low concentrations. These results suggest that the analog peptides of Hp1404 can be used as therapeutic agents against A. baumannii infection.
Ancient Bacterial Class Alphaproteobacteria Cytochrome P450 Monooxygenases Can Be Found in Other Bacterial Species
Authors: Nzuza Nomfundo , Padayachee Tiara , Syed Puleng Rosinah , Kryś Justyna Dorota , Chen Wanping , Gront Dominik , Nelson David R. , Syed Khajamohiddin
Published: May 2021

Cytochrome P450 monooxygenases (CYPs/P450s), heme-thiolate proteins, are well-known players in the generation of chemicals valuable to humans and as a drug target against pathogens. Understanding the evolution of P450s in a bacterial population is gaining momentum. In this study, we report comprehensive analysis of P450s in the ancient group of the bacterial class Alphaproteobacteria. Genome data mining and annotation of P450s in 599 alphaproteobacterial species belonging to 164 genera revealed the presence of P450s in only 241 species belonging to 82 genera that are grouped into 143 P450 families and 214 P450 subfamilies, including 77 new P450 families. Alphaproteobacterial species have the highest average number of P450s compared to Firmicutes species and cyanobacterial species. The lowest percentage of alphaproteobacterial species P450s (2.4%) was found to be part of secondary metabolite biosynthetic gene clusters (BGCs), compared other bacterial species, indicating that during evolution large numbers of P450s became part of BGCs in other bacterial species. Our study identified that some of the P450 families found in alphaproteobacterial species were passed to other bacterial species. This is the first study to report on the identification of CYP125 P450, cholesterol and cholest-4-en-3-one hydroxylase in alphaproteobacterial species (Phenylobacterium zucineum) and to predict cholesterol side-chain oxidation capability (based on homolog proteins) by P. zucineum.
New Era in the Treatment of Iron Deficiency Anaemia Using Trimaltol Iron and Other Lipophilic Iron Chelator Complexes: Historical Perspectives of Discovery and Future Applications
Authors: Kontoghiorghes George , Kolnagou Annita , Demetriou Theodora , Neocleous Marina , Kontoghiorghe Christina
Published: May 2021

The trimaltol iron complex (International Non-proprietary Name: ferric maltol) was originally designed, synthesised, and screened in vitro and in vivo in 1980–1981 by Kontoghiorghes G.J. following his discovery of the novel alpha-ketohydroxyheteroaromatic (KHP) class of iron chelators (1978–1981), which were intended for clinical use, including the treatment of iron deficiency anaemia (IDA). Iron deficiency anaemia is a global health problem affecting about one-third of the world’s population. Many (and different) ferrous and ferric iron complex formulations are widely available and sold worldwide over the counter for the treatment of IDA. Almost all such complexes suffer from instability in the acidic environment of the stomach and competition from other dietary molecules or drugs. Natural and synthetic lipophilic KHP chelators, including maltol, have been shown in in vitro and in vivo studies to form stable iron complexes, to transfer iron across cell membranes, and to increase iron absorption in animals. Trimaltol iron, sold as Feraccru or Accrufer, was recently approved for clinical use in IDA patients in many countries, including the USA and in EU countries, and was shown to be effective and safe, with a better therapeutic index in comparison to other iron formulations. Similar properties of increased iron absorption were also shown by lipophilic iron complexes of 8-hydroxyquinoline, tropolone, 2-hydroxy-4-methoxypyridine-1-oxide, and related analogues. The interactions of the KHP iron complexes with natural chelators, drugs, metal ions, proteins, and other molecules appear to affect the pharmacological and metabolic effects of both iron and the KHP chelators. A new era in the treatment of IDA and other possible clinical applications, such as theranostic and anticancer formulations and metal radiotracers in diagnostic medicine, are envisaged from the introduction of maltol, KHP, and similar lipophilic chelators.
Hierarchical Action of Mulberry miR156 in the Vegetative Phase Transition
Authors: Li Hongshun , Luo Yiwei , Ma Bi , Hu Jianqiong , Lv Zhiyuan , Wei Wuqi , Hao Haiye , Yuan Jianglian , He Ningjia
Published: May 2021

The vegetative phase transition is a prerequisite for flowering in angiosperm plants. Mulberry miR156 has been confirmed to be a crucial factor in the vegetative phase transition in Arabidopsis thaliana. The over-expression of miR156 in transgenic Populus × canadensis dramatically prolongs the juvenile phase. Here, we find that the expression of mno-miR156 decreases with age in all tissues in mulberry, which led us to study the hierarchical action of miR156 in mulberry. Utilizing degradome sequencing and dual-luciferase reporter assays, nine MnSPLs were shown to be directly regulated by miR156. The results of yeast one-hybrid and dual-luciferase reporter assays also revealed that six MnSPLs could recognize the promoter sequences of mno-miR172 and activate its expression. Our results demonstrate that mno-miR156 performs its role by repressing MnSPL/mno-miR172 pathway expression in mulberry. This work uncovered a miR156/SPLs/miR172 regulation pathway in the development of mulberry and fills a gap in our knowledge about the molecular mechanism of vegetative phase transition in perennial woody plants.
Effects of Glymes on the Distribution of Mg(B10H10) and Mg(B12H12) from the Thermolysis of Mg(BH4)2
Authors: Tran Ba L. , Allen Tamara N. , Bowden Mark E. , Autrey Tom , Jensen Craig M.
Published: May 2021

We examined the effects of concentrations and identities of various glymes, from monoglyme up to tetraglyme, on H2 release from the thermolysis of Mg(BH4)2 at 160–200 °C for 8 h. 11B NMR analysis shows major products of Mg(B10H10) and Mg(B12H12); however, their relative ratio is highly dependent both on the identity and concentration of the glyme to Mg(BH4)2. Selective formation of Mg(B10H10) was observed with an equivalent of monoglyme and 0.25 equivalent of tetraglyme. However, thermolysis of Mg(BH4)2 in the presence of stoichiometric or greater equivalent of glymes can lead to unselective formation of Mg(B10H10) and Mg(B12H12) products or inhibition of H2 release.
On the Affinities and Systematic Position of Lachnaeus Schoenherr and Rhinocyllus Germar in the Tribe Lixini (Coleoptera: Curculionidae: Lixinae) Based on the Morphological Characters of the Immature Stages
Authors: Skuhrovec Jiří , Caldara Roberto , Gosik Rafał , Trnka Filip , Stejskal Robert
Published: May 2021

Mature larvae and pupae of Lachnaeus crinitus Schoenherr, 1826 and Rhinocyllus alpinus Gültekin, Diotti and Caldara, 2019 and pupae of R. conicus (Frölich, 1792), belonging to the Lixini (Curculionidae: Lixinae), are morphologically described for the first time. They possess all the characters considered distinctive in the immature stages of this tribe and are distinguishable from all the related genera by a combination of some characters (e.g., presence of endocarina, shape of premental sclerite; the number of pds on the abdominal segments; size and presence of urogomphi). It is emphasized that the controversial tribe Rhinocyllini is not supported by the characters of the larvae and pupae of Rhinocyllus and that the two subgenera of this genus, Rhinocyllus s. str. and Rhinolarinus, are separable from each other not only by characters of the adult but also distinctive characters of the larvae and pupae. These results confirm that the morphology of the immature stages, which is usually overlooked, can be very important for the purpose of identifying new characters that are useful for clarifying taxonomical and phylogenetic complex situations based only on the study of the imagoes.
The Importance of Implementing Cyber Physical Systems to Acquire Real-Time Data and Indicators
Authors: Morella Paula , Lambán María Pilar , Royo Jesús Antonio , Sánchez Juan Carlos
Published: May 2021

Among the new trends in technology that have emerged through the Industry 4.0, Cyber Physical Systems (CPS) and Internet of Things (IoT) are crucial for the real-time data acquisition. This data acquisition, together with its transformation in valuable information, are indispensable for the development of real-time indicators. Moreover, real-time indicators provide companies with a competitive advantage over the competition since they enhance the calculus and speed up the decision-making and failure detection. Our research highlights the advantages of real-time data acquisition for supply chains, developing indicators that would be impossible to achieve with traditional systems, improving the accuracy of the existing ones and enhancing the real-time decision-making. Moreover, it brings out the importance of integrating technologies 4.0 in industry, in this case, CPS and IoT, and establishes the main points for a future research agenda of this topic.
Predicting One-Year Deaths and Major Adverse Vascular Events with the Controlling Nutritional Status Score in Elderly Patients with Non–ST-Elevated Myocardial Infarction Undergoing Percutaneous Coronary Intervention
Authors: Kalyoncuoğlu Muhsin , Katkat Fahrettin , Biter Halil Ibrahim , Cakal Sinem , Tosu Aydin Rodi , Can Mehmet Mustafa
Published: May 2021

The prognostic value of malnutrition in elderly patients with non-ST-elevated myocardial infarction (NSTEMI) is not fully understood. Nutritional characteristics were evaluated by novel Controlling Nutritional status (CONUT), the prognostic nutritional index (PNI) and the geriatric nutritional risk index (GNRI) scores. The impact of these scores on major outcomes in 253 NSTEMI patients over 60 years and older were assessed. Compared to those with good nutritional status; malnourished patients had more major adverse cardiac and cerebrovascular events (MACCEs) at 1-year follow up. Multivariable cox regression analysis revealed that CONUT (hazard ratio = 1.372; p < 0.01) was independent predictor of MACCEs, whereas PNI (p = 0.44) and GNRI (p = 0.52) were not. The discriminating power of the CONUT (AUC: 0.79) was adequate and significantly superior to both the PNI (AUC: 0.68) and the GNRI (AUC: 0.60), with a p-value for both < 0.01. Patients with elevated CONUT exhibited the highest event rate for all-cause mortality and MACCEs in survival analysis (p < 0.01). We conclude that malnutrition is strongly associated with adverse outcomes in older patients with NSTEMI. In fact, the CONUT score adequately predicts one-year MACCEs among elderly NSTEMI patients who achieve complete revascularization after coronary intervention.
Micro-RNA Analysis of Pancreatic Cyst Fluid for Diagnosing Malignant Transformation of Intraductal Papillary Mucinous Neoplasm by Comparing Intraductal Papillary Mucinous Adenoma and Carcinoma
Authors: Shirakami Yohei , Iwashita Takuji , Uemura Shinya , Imai Hisashi , Murase Katsutoshi , Shimizu Masahito
Published: May 2021

Although intraductal papillary mucinous neoplasm (IPMN) is thought to be a precursor lesion of pancreatic cancer, diagnosing malignant transformation of IPMN using non-invasive diagnostic methods is difficult and complicated. Micro-RNAs (miRNAs) are currently recognized as biomarkers and molecular targets of various diseases, including malignancy. In this study, we investigated a potential diagnostic approach using miRNA in pancreatic cyst fluid as a marker for evaluating malignant alternation of IPMN. Cystic fluid was sampled mainly during surgical resection. The collected samples were evaluated by performing comprehensive analysis of miRNA using a highly sensitive DNA chip. miRNA expression was compared between IPM adenoma (IPMA) and IPM carcinoma (IPMC) to evaluate the related biomarkers for malignant transformation of IPMN. miRNA analysis revealed that six miRNAs (miR-711, miR-3679-5p, miR-6126, miR-6780b-5p, miR-6798-5p, and miR-6879-5p) in IPMC were significantly enriched compared to those in IPMA. The difference was validated using quantitative real-time PCR. Cyst fluid miRNA analysis might be useful for diagnosing malignant alteration of IPMN. Further evaluations of diagnostic capability as well as functional analysis using the identified miRNAs are required with larger cohorts to confirm its efficacy.