bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms
Authors: Pennisi Manuela , Lanza Giuseppe , Falzone Luca , Fisicaro Francesco , Ferri Raffaele , Bella Rita
Published: August 2020

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.
A Structural Model for Bax∆2-Mediated Activation of Caspase 8-Dependent Apoptosis
Authors: Xie Bing , Yao Qi , Xiang Jialing , Minh David
Published: August 2020

Bax∆2 is a pro-apoptotic anti-tumor protein in the Bax family. While most of the Bax family causes cell death by targeting mitochondria, Bax∆2 forms cytosolic aggregates and activates caspase 8-dependent cell death. We previously showed that the Bax∆2 helix α9 is critical for caspase 8 recruitment. However, the interaction between these two proteins at the structural level is unknown. In this in silico study, we performed molecular dynamics (MD) simulations and protein–protein docking on Bax∆2 variants. The results suggest that the Bax∆2 variants have different stable states. Mutating the Baxα mitochondria-targeting signal [L26P/L27P] appears to introduce a kink into helix α1. Protein–protein docking suggests that helices α9 of both wild-type Bax∆2 and Bax∆2 caspase 8 binding-deficient mutant [L164P] can fit in the same caspase 8 binding site, but the mutant is unable to fit as well as wild-type Bax∆2. Together, these data point to a structural basis for explaining Bax∆2 function in caspase 8-dependent cell death.
Current Status and Future Perspectives of Checkpoint Inhibitor Immunotherapy for Prostate Cancer: A Comprehensive Review
Authors: Kim Tae Jin , Koo Kyo Chul
Published: August 2020

The clinical spectrum of prostate cancer (PCa) varies from castration-naive to metastatic castration-resistant disease. Despite the administration of androgen synthesis inhibitors and chemotherapy regimens for castration-resistant prostate cancer, the treatment options for this entity are limited. The utilization of the immune system against cancer cells shows potential as a therapeutic modality for various solid tumors and hematologic malignancies. With technological advances over the last decade, immunotherapy has become an integral treatment modality for advanced solid tumors. The feasibility of immunotherapy has shown promise for patients with PCa, and with advances in molecular diagnostic platforms and our understanding of immune mechanisms, immunotherapy is reemerging as a potential treatment modality for PCa. Various combinations of individualized immunotherapy and immune checkpoint blockers with androgen receptor-targeted therapies and conventional cytotoxic agents show promise. This article will review the current status of immunotherapy, including new discoveries and precision approaches to PCa, and discuss future directions in the continuously evolving landscape of immunotherapy.
Crosstalk between Tumor and Stromal Cells in Pancreatic Ductal Adenocarcinoma
Authors: Sperb Nadine , Tsesmelis Miltiadis , Wirth Thomas
Published: August 2020

Pancreatic ductal adenocarcinoma (PDAC) remains a lethal cancer. The poor prognosis calls for a more detailed understanding of disease biology in order to pave the way for the development of effective therapies. Typically, the pancreatic tumor is composed of a minority of malignant cells within an excessive tumor microenvironment (TME) consisting of extracellular matrix (ECM), fibroblasts, immune cells, and endothelial cells. Research conducted in recent years has particularly focused on cancer-associated fibroblasts (CAFs) which represent the most prominent cellular component of the desmoplastic stroma. Here, we review the complex crosstalk between CAFs, tumor cells, and other components of the TME, and illustrate how these interactions drive disease progression. We also discuss the emerging field of CAF heterogeneity, their tumor-supportive versus tumor-suppressive capacity, and the consequences for designing stroma-targeted therapies in the future.
Role of miR-96/EVI1/miR-449a Axis in the Nasopharyngeal Carcinoma Cell Migration and Tumor Sphere Formation
Authors: Chan Lai-Sheung , Lung Hong-Lok , Ngan Roger Kai-Cheong , Lee Anne Wing-Mui , Tsao Sai Wah , Lo Kwok-Wai , Kahn Michael , Lung Maria Li , Wieser Rotraud , Mak Nai-Ki
Published: August 2020

The Wnt signaling pathway is one of the major signaling pathways used by cancer stem cells (CSC). Ecotropic Viral Integration Site 1 (EVI1) has recently been shown to regulate oncogenic development of tumor cells by interacting with multiple signaling pathways, including the Wnt signaling. In the present study, we found that the Wnt modulator ICG-001 could inhibit the expression of EVI1 in nasopharyngeal carcinoma (NPC) cells. Results from loss-of-function and gain-of-function studies revealed that EVI1 expression positively regulated both NPC cell migration and growth of CSC-enriched tumor spheres. Subsequent studies indicated ICG-001 inhibited EVI1 expression via upregulated expression of miR-96. Results from EVI1 3′UTR luciferase reporter assay confirmed that EVI1 is a direct target of miR-96. Further mechanistic studies revealed that ICG-001, overexpression of miR-96, or knockdown of EVI1 expression could restore the expression of miR-449a. The suppressive effect of miR-449a on the cell migration and tumor sphere formation was confirmed in NPC cells. Taken together, the miR-96/EVI1/miR-449a axis is a novel pathway involved in ICG-001-mediated inhibition of NPC cell migration and growth of the tumor spheres.
Growing Old Too Early: Skeletal Muscle Single Fiber Biomechanics in Ageing R349P Desmin Knock-in Mice Using the MyoRobot Technology
Authors: Pollmann Charlotte , Haug Michael , Reischl Barbara , Prölß Gerhard , Pöschel Thorsten , Rupitsch Stefan J , Clemen Christoph S , Schröder Rolf , Friedrich Oliver
Published: August 2020

Muscle biomechanics relies on active motor protein assembly and passive strain transmission through cytoskeletal structures. The desmin filament network aligns myofibrils at the z-discs, provides nuclear–sarcolemmal anchorage and may also serve as memory for muscle repositioning following large strains. Our previous analyses of R349P desmin knock-in mice, an animal model for the human R350P desminopathy, already depicted pre-clinical changes in myofibrillar arrangement and increased fiber bundle stiffness. As the effect of R349P desmin on axial biomechanics in fully differentiated single muscle fibers is unknown, we used our MyoRobot to compare passive visco-elasticity and active contractile biomechanics in single fibers from fast- and slow-twitch muscles from adult to senile mice, hetero- or homozygous for the R349P desmin mutation with wild type littermates. We demonstrate that R349P desmin presence predominantly increased axial stiffness in both muscle types with a pre-aged phenotype over wild type fibers. Axial viscosity and Ca2+-mediated force were largely unaffected. Mutant single fibers showed tendencies towards faster unloaded shortening over wild type fibers. Effects of aging seen in the wild type appeared earlier in the mutant desmin fibers. Our single-fiber experiments, free of extracellular matrix, suggest that compromised muscle biomechanics is not exclusively attributed to fibrosis but also originates from an impaired intermediate filament network.
Rewiring of Lipid Metabolism in Adipose Tissue Macrophages in Obesity: Impact on Insulin Resistance and Type 2 Diabetes
Authors: Dahik Veronica D. , Frisdal Eric , Le Goff Wilfried
Published: August 2020

Obesity and its two major comorbidities, insulin resistance and type 2 diabetes, represent worldwide health issues whose incidence is predicted to steadily rise in the coming years. Obesity is characterized by an accumulation of fat in metabolic tissues resulting in chronic inflammation. It is now largely accepted that adipose tissue inflammation underlies the etiology of these disorders. Adipose tissue macrophages (ATMs) represent the most enriched immune fraction in hypertrophic, chronically inflamed adipose tissue, and these cells play a key role in diet-induced type 2 diabetes and insulin resistance. ATMs are triggered by the continuous influx of dietary lipids, among other stimuli; however, how these lipids metabolically activate ATM depends on their nature, composition and localization. This review will discuss the fate and molecular programs elicited within obese ATMs by both exogenous and endogenous lipids, as they mediate the inflammatory response and promote or hamper the development of obesity-associated insulin resistance and type 2 diabetes.
CDK19 as a Potential HPV-Independent Biomarker for Recurrent Disease in HNSCC
Authors: Paulsen Finn-Ole , Idel Christian , Ribbat-Idel Julika , Kuppler Patrick , Klapper Luise , Rades Dirk , Bruchhage Karl-Ludwig , Wollenberg Barbara , Brägelmann Johannes , Perner Sven , Offermann Anne
Published: August 2020

The Mediator complex is a central integrator of transcription and a hub for the regulation of gene expression. Cyclin dependent kinase (CDK) 19 and its paralog CDK8 are part of its kinase domain and contribute to cancer progression in different cancer entities. STAT1 is an important immune modulator and a downstream substrate of CDK8/CDK19 mediated phosphorylation. So far, little is known about CDK19’s role in head and neck squamous cell carcinoma (HNSCC) progression, its link to STAT1 activity, and related immune modulation. Immunohistochemistry for CDK19, activated pSTAT1, and PD-L1, known to be affected by STAT1, was conducted on samples of 130 primary tumors, 71 local recurrences, 32 lymph node metastases, and 25 distant metastases of HNSCC. Compared to primary tumors, CDK19 is overexpressed in local recurrences and distant metastases as well as in primary tumors that developed local recurrence after initial therapy. Patients with high-CDK19-expressing primary tumors have a significantly shorter disease-free survival. CDK19 expression correlates with pSTAT1 expression in primary tumors associated with recurrent disease, local recurrent tumors, lymph node metastases, and distant metastases. pSTAT1 expression correlates with PD-L1 expression in recurrent tumors. Our findings identify CDK19 as a potential biomarker in HNSCC to predict recurrent disease and support recent developments to target CDK19 and its paralog CDK8 in advanced cancer.
Antibody-Drug Conjugates: The New Frontier of Chemotherapy
Authors: Ponziani Sara , Di Vittorio Giulia , Pitari Giuseppina , Cimini Anna Maria , Ardini Matteo , Gentile Roberta , Iacobelli Stefano , Sala Gianluca , Capone Emily , Flavell David J. , Ippoliti Rodolfo , Giansanti Francesco
Published: August 2020

In recent years, antibody-drug conjugates (ADCs) have become promising antitumor agents to be used as one of the tools in personalized cancer medicine. ADCs are comprised of a drug with cytotoxic activity cross-linked to a monoclonal antibody, targeting antigens expressed at higher levels on tumor cells than on normal cells. By providing a selective targeting mechanism for cytotoxic drugs, ADCs improve the therapeutic index in clinical practice. In this review, the chemistry of ADC linker conjugation together with strategies adopted to improve antibody tolerability (by reducing antigenicity) are examined, with particular attention to ADCs approved by the regulatory agencies (the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA)) for treating cancer patients. Recent developments in engineering Immunoglobulin (Ig) genes and antibody humanization have greatly reduced some of the problems of the first generation of ADCs, beset by problems, such as random coupling of the payload and immunogenicity of the antibody. ADC development and clinical use is a fast, evolving area, and will likely prove an important modality for the treatment of cancer in the near future.
Ablation of Galectin-12 Inhibits Atherosclerosis through Enhancement of M2 Macrophage Polarization
Authors: Lin En-Shyh , Hsu Yu-An , Chang Ching-Yao , Lin Hui-Ju , Chen Chih Sheng , Wan Lei
Published: August 2020

The formation of foam cells, which are macrophages that have engulfed oxidized low-density lipoprotein (OxLDL), constitutes the first stage in the development of atherosclerosis. Previously, we found that knocking down galectin-12, a negative regulator of lipolysis, leads to reduced secretion of monocyte chemoattractant protein-1 (MCP-1), a chemokine that plays an important role in atherosclerosis. This prompted us to study the role of galectin-12 in atherosclerosis. With that aim, we examined foam cell formation in Gal12‒/‒ murine macrophages exposed to OxLDL and acetylated LDL (AcLDL). Then, we generated an LDL receptor and galectin-12 double knockout (DKO) mice and studied the effect of galectin-12 on macrophage function and atherosclerosis. Lastly, we evaluated the role of galectin-12 in human THP-1 macrophages using a doxycycline-inducible conditional knockdown system. Galectin-12 knockout significantly inhibited foam cell formation in murine macrophages through the downregulation of cluster of differentiation 36 (CD36), and the upregulation of ATP Binding Cassette Subfamily A Member 1 (ABCA1), ATP Binding Cassette Subfamily G Member 1 (ABCG1), and scavenger receptor class B type 1 (SRB1). Consistent with this, galectin-12 knockdown inhibited foam cell formation in human macrophages. In addition, the ablation of galectin-12 promoted M2 macrophage polarization in human and murine macrophages as evidenced by the upregulation of the M2 marker genes, CD206 and CD163, and downregulation of the M1 cytokines, tumor necrosis factor α (TNF- α), interleukin-6 (IL-6), and MCP-1. Moreover, the ablation of galectin-12 decreased atherosclerosis formation in DKO mice. Based on these results, we propose galectin-12 as a potential therapeutic target for atherosclerosis.
Indoleamine 2,3-Dioxygenase 2 Deficiency Exacerbates Imiquimod-Induced Psoriasis-Like Skin Inflammation
Authors: Fujii Kento , Yamamoto Yasuko , Mizutani Yoko , Saito Kuniaki , Seishima Mariko
Published: August 2020

Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme known to suppress immune responses, and several reports have showed that it is associated with psoriasis. IDO2 is an isoform of IDO1, recently identified as a catalytic enzyme in the tryptophan-kynurenine pathway, which is expressed in dendritic cells and monocytes. The expression of IDO2 in immune cells suggests that IDO2 may contribute to immune functions. However, the role of IDO2 in the pathogenesis of psoriasis remains unclear. In this study, to elucidate the role of IDO2 in psoriasis, we assessed imiquimod (IMQ)-induced psoriasis-like dermatitis in IDO2 knockout (KO) mice. Skin inflammation, evaluated by scoring erythema, scaling, and ear thickness, was significantly worse in the IDO2 KO mice than in the wild-type (WT) mice. The mRNA expression levels of TNF-α, IL-23p19, and IL-17A, key cytokines involved in the development of psoriasis, were also increased in the IDO2 KO mice. Furthermore, immunohistochemistry revealed that the number of Ki67-positive cells in the epidermis and CD4-, CD8-, and IL-17-positive lymphocytes infiltrating the dermis were significantly increased in the IDO2 KO mice. These results suggest that IDO2 might decrease IL-17 expression, thereby resulting in the suppression of skin inflammation in IMQ-induced psoriasis-like dermatitis.
A Small Molecule, 4-Phenylbutyric Acid, Suppresses HCV Replication via Epigenetically Induced Hepatic Hepcidin
Authors: Kim Kiyoon , Lee Young-seok , Jeong Suyun , Kim Daehong , Chon Suk , Pak Youngmi Kim , Kim Sungsoo , Ha Joohun , Kang Insug , Choe Wonchae
Published: August 2020

Hepatic hepcidin is a well-known major iron regulator and has been reported to be closely related to hepatitis C virus (HCV) replication. However, pharmacological targeting of the hepcidin in HCV replication has not been reported. A short-chain fatty acid, 4-Phenyl butyrate (4-PBA), is an acid chemical chaperone that acts as a histone deacetylase inhibitor (HDACi) to promote chromosomal histone acetylation. Here, we investigated the therapeutic effect of 4-PBA on hepcidin expression and HCV replication. We used HCV genotype 1b Huh 7.5-Con1 replicon cells and engraftment of NOD/SCID mice as in vitro and in vivo models to test the effect of 4-PBA. It was found that 4-PBA inhibited HCV replication in Huh7.5-Con1 replicon cells in a concentration- and time-dependent manner through the induction of hepcidin expression by epigenetic modification and subsequent upregulation of interferon-α signaling. HCV formed a membranous web composed of double-membrane vesicles and was utilized for RNA replication. Moreover, 4-PBA also disrupted the integrity of the membranous web and interfered with the molecular interactions critical for the assembly of the HCV replication complex. These findings suggest that 4-PBA is a key epigenetic inducer of anti-HCV hepatic hepcidin and might at least in part play a role in targeting host factors related to HCV infection as an attractive complement to current HCV therapies.
Inherited Metabolic Disorders Presenting with Ataxia
Authors: Silver Grace , Mercimek-Andrews Saadet
Published: August 2020

Ataxia is a common clinical feature in inherited metabolic disorders. There are more than 150 inherited metabolic disorders in patients presenting with ataxia in addition to global developmental delay, encephalopathy episodes, a history of developmental regression, coarse facial features, seizures, and other types of movement disorders. Seizures and a history of developmental regression especially are important clinical denominators to consider an underlying inherited metabolic disorder in a patient with ataxia. Some of the inherited metabolic disorders have disease specific treatments to improve outcomes or prevent early death. Early diagnosis and treatment affect positive neurodevelopmental outcomes, so it is important to think of inherited metabolic disorders in the differential diagnosis of ataxia.
Immune Landscape in Tumor Microenvironment: Implications for Biomarker Development and Immunotherapy
Authors: Pérez-Romero Karim , Rodríguez Ramón M. , Amedei Amedeo , Barceló-Coblijn Gwendolyn , Lopez Daniel H.
Published: August 2020

Integration of the tumor microenvironment as a fundamental part of the tumorigenic process has undoubtedly revolutionized our understanding of cancer biology. Increasing evidence indicates that neoplastic cells establish a dependency relationship with normal resident cells in the affected tissue and, furthermore, develop the ability to recruit new accessory cells that aid tumor development. In addition to normal stromal and tumor cells, this tumor ecosystem includes an infiltrated immune component that establishes complex interactions that have a critical effect during the natural history of the tumor. The process by which immune cells modulate tumor progression is known as immunoediting, a dynamic process that creates a selective pressure that finally leads to the generation of immune-resistant cells and the inability of the immune system to eradicate the tumor. In this context, the cellular and functional characterization of the immune compartment within the tumor microenvironment will help to understand tumor progression and, ultimately, will serve to create novel prognostic tools and improve patient stratification for cancer treatment. Here we review the impact of the immune system on tumor development, focusing particularly on its clinical implications and the current technologies used to analyze immune cell diversity within the tumor.
Anti-Epileptic Effects of FABP3 Ligand MF1 through the Benzodiazepine Recognition Site of the GABAA Receptor
Authors: Yabuki Yasushi , Liu Jiaqi , Kawahata Ichiro , Izumi Hisanao , Shinoda Yasuharu , Koga Kohei , Ueno Shinya , Shioda Norifumi , Fukunaga Kohji
Published: August 2020

Recently, we developed the fatty acid-binding protein 3 (FABP3) ligand MF1 (4-(2-(1-(2-chlorophenyl)-5-phenyl-1H-pyrazol-3-yl)phenoxy) butanoic acid) as a therapeutic candidate for α-synucleinopathies. MF1 shows affinity towards γ-aminobutyric acid type-A (GABAA) receptor, but its effect on the receptor remains unclear. Here, we investigate the pharmacological properties of MF1 on the GABAA receptor overexpressed in Neuro2A cells. While MF1 (1–100 μm) alone failed to evoke GABA currents, MF1 (1 μm) promoted GABA currents during GABA exposure (1 and 10 μm). MF1-promoted GABA currents were blocked by flumazenil (10 μm) treatment, suggesting that MF1 enhances receptor function via the benzodiazepine recognition site. Acute and chronic administration of MF1 (0.1, 0.3 and 1.0 mg/kg, p.o.) significantly attenuated status epilepticus (SE) and the mortality rate in pilocarpine (PILO: 300 mg/kg, i.p.)-treated mice, similar to diazepam (DZP: 5.0 mg/kg, i.p.). The anti-epileptic effects of DZP (5.0 mg/kg, i.p.) and MF1 (0.3 mg/kg, p.o.) were completely abolished by flumazenil (25 mg/kg, i.p.) treatment. Pentylenetetrazol (PTZ: 90 mg/kg, i.p.)-induced seizures in mice were suppressed by DZP (5.0 mg/kg, i.p.), but not MF1. Collectively, this suggests that MF1 is a mild enhancer of the GABAA receptor and exercises anti-epileptic effects through the receptor’s benzodiazepine recognition site in PILO-induced SE models.
Roles of Membrane Domains in Integrin-Mediated Cell Adhesion
Authors: Lietha Daniel , Izard Tina
Published: August 2020

The composition and organization of the plasma membrane play important functional and regulatory roles in integrin signaling, which direct many physiological and pathological processes, such as development, wound healing, immunity, thrombosis, and cancer metastasis. Membranes are comprised of regions that are thick or thin owing to spontaneous partitioning of long-chain saturated lipids from short-chain polyunsaturated lipids into domains defined as ordered and liquid-disorder domains, respectively. Liquid-ordered domains are typically 100 nm in diameter and sometimes referred to as lipid rafts. We posit that integrin β senses membrane thickness and that mechanical force on the membrane regulates integrin activation through membrane thinning. This review examines what we know about the nature and mechanism of the interaction of integrins with the plasma membrane and its effects on regulating integrins and its binding partners.
Identification of New Potential LncRNA Biomarkers in Hirschsprung Disease
Authors: Torroglosa Ana , Villalba-Benito Leticia , Fernández Raquel María , Luzón-Toro Berta , Moya-Jiménez María José , Antiñolo Guillermo , Borrego Salud
Published: August 2020

Hirschsprung disease (HSCR) is a neurocristopathy defined by intestinal aganglionosis due to alterations during the development of the Enteric Nervous System (ENS). A wide spectrum of molecules involved in different signaling pathways and mechanisms have been described in HSCR onset. Among them, epigenetic mechanisms are gaining increasing relevance. In an effort to better understand the epigenetic basis of HSCR, we have performed an analysis for the identification of long non-coding RNAs (lncRNAs) by qRT-PCR in enteric precursor cells (EPCs) from controls and HSCR patients. We aimed to test the presence of a set lncRNAs among 84 lncRNAs in human EPCs, which were previously related with crucial cellular processes for ENS development, as well as to identify the possible differences between HSCR patients and controls. As a result, we have determined a set of lncRNAs with positive expression in human EPCs that were screened for mutations using the exome data from our cohort of HSCR patients to identify possible variants related to this pathology. Interestingly, we identified three lncRNAs with different levels of their transcripts (SOCS2-AS, MEG3 and NEAT1) between HSCR patients and controls. We propose such lncRNAs as possible regulatory elements implicated in the onset of HSCR as well as potential biomarkers of this pathology.
Chrysin Inhibits High Glucose-Induced Migration on Chorioretinal Endothelial Cells via VEGF and VEGFR Down-Regulation
Authors: Liao Zhen-Yu , Liang I-Chia , Li Hsin-Ju , Wu Chia-Chun , Lo Huey-Ming , Chang Der-Chen , Hung Chi-Feng
Published: August 2020

Background: Diabetes mellitus (DM) is a chronic inflammatory disease, which causes multiple complications. Diabetic retinopathy (DR) is among these complications and is a dominant cause of vision loss for diabetic patients. Numerous studies have shown that chrysin, a flavonoid, has many biological activities such as anti-oxidation and anti-inflammation. However, it is rarely used in ocular diseases. In this study, we examined the inhibitory effects of flavonoid on high glucose induced migration of chorioretinal endothelial cells (RF/6A cells) and its mechanism. Materials and methods: The viability of RF/6A cells treated with chrysin was examined with a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The migration of RF/6A cells was assessed by the transwell migration and scratch wound assays. The expression of AKT, ERK, vascular endothelial growth factor (VEGF), HIF−1α and MMP-2 were determined by western blotting. To observe the mRNA expression of VEGF receptor (VEGFR), qRT-PCR, was utilized. Results: The results showed that chrysin can dose-dependently inhibit the RF/6A cell migration in vitro transwell and the scratch wound assays which are induced by high glucose. After pretreatment of RF/6A cells with different concentrations of chrysin, they did not produce any cytotoxicity in MTT assay. Moreover, chrysin down-regulated both phosphorylated AKT and ERK, as well as attenuated the expression levels of MMP-2. It also decreased the expression of the VEGF transcription factor and VEGF. Furthermore, it was shown that chrysin could suppress the protein and mRNA expression levels of VEGFR. Conclusion: The results indicate that chrysin could down-regulate the phosphorylation of AKT, ERK and MMP-2 and reduce the effects of VEGF and VEGFR in a high glucose environment. It further inhibits the high glucose-induced migration of RE/6A cells. Therefore, chrysin may have the potential for visual protection.
Dairy-Inspired Coatings for Bone Implants from Whey Protein Isolate-Derived Self-Assembled Fibrils
Authors: Rabe Rebecca , Hempel Ute , Martocq Laurine , Keppler Julia K. , Aveyard Jenny , Douglas Timothy E. L.
Published: August 2020

To improve the integration of a biomaterial with surrounding tissue, its surface properties may be modified by adsorption of biomacromolecules, e.g., fibrils. Whey protein isolate (WPI), a dairy industry by-product, supports osteoblastic cell growth. WPI’s main component, β-lactoglobulin, forms fibrils in acidic solutions. In this study, aiming to develop coatings for biomaterials for bone contact, substrates were coated with WPI fibrils obtained at pH 2 or 3.5. Importantly, WPI fibrils coatings withstood autoclave sterilization and appeared to promote spreading and differentiation of human bone marrow stromal cells (hBMSC). In the future, WPI fibrils coatings could facilitate immobilization of biomolecules with growth stimulating or antimicrobial properties.
Exploring the Mediators that Promote Carotid Body Dysfunction in Type 2 Diabetes and Obesity Related Syndromes
Authors: Sacramento Joana F. , Andrzejewski Kryspin , Melo Bernardete F. , Ribeiro Maria J. , Obeso Ana , Conde Silvia V.
Published: August 2020

Carotid bodies (CBs) are peripheral chemoreceptors that sense changes in blood O2, CO2, and pH levels. Apart from ventilatory control, these organs are deeply involved in the homeostatic regulation of carbohydrates and lipid metabolism and inflammation. It has been described that CB dysfunction is involved in the genesis of metabolic diseases and that CB overactivation is present in animal models of metabolic disease and in prediabetes patients. Additionally, resection of the CB-sensitive nerve, the carotid sinus nerve (CSN), or CB ablation in animals prevents and reverses diet-induced insulin resistance and glucose intolerance as well as sympathoadrenal overactivity, meaning that the beneficial effects of decreasing CB activity on glucose homeostasis are modulated by target-related efferent sympathetic nerves, through a reflex initiated in the CBs. In agreement with our pre-clinical data, hyperbaric oxygen therapy, which reduces CB activity, improves glucose homeostasis in type 2 diabetes patients. Insulin, leptin, and pro-inflammatory cytokines activate the CB. In this manuscript, we review in a concise manner the putative pathways linking CB chemoreceptor deregulation with the pathogenesis of metabolic diseases and discuss and present new data that highlight the roles of hyperinsulinemia, hyperleptinemia, and chronic inflammation as major factors contributing to CB dysfunction in metabolic disorders.
Deciphering the Novel Role of AtMIN7 in Cuticle Formation and Defense against the Bacterial Pathogen Infection
Authors: Zhao Zhenzhen , Yang Xianpeng , Lü Shiyou , Fan Jiangbo , Opiyo Stephen , Yang Piao , Mangold Jack , Mackey David , Xia Ye
Published: August 2020

The cuticle is the outermost layer of plant aerial tissue that interacts with the environment and protects plants against water loss and various biotic and abiotic stresses. ADP ribosylation factor guanine nucleotide exchange factor proteins (ARF-GEFs) are key components of the vesicle trafficking system. Our study discovers that AtMIN7, an Arabidopsis ARF-GEF, is critical for cuticle formation and related leaf surface defense against the bacterial pathogen Pseudomonas syringae pathovar tomato (Pto). Our transmission electron microscopy and scanning electron microscopy studies indicate that the atmin7 mutant leaves have a thinner cuticular layer, defective stomata structure, and impaired cuticle ledge of stomata compared to the leaves of wild type plants. GC–MS analysis further revealed that the amount of cutin monomers was significantly reduced in atmin7 mutant plants. Furthermore, the exogenous application of either of three plant hormones—salicylic acid, jasmonic acid, or abscisic acid—enhanced the cuticle formation in atmin7 mutant leaves and the related defense responses to the bacterial Pto infection. Thus, transport of cutin-related components by AtMIN7 may contribute to its impact on cuticle formation and related defense function.
The LuxI/LuxR-Type Quorum Sensing System Regulates Degradation of Polycyclic Aromatic Hydrocarbons via Two Mechanisms
Authors: Yu Zhiliang , Hu Zeyu , Xu Qimiao , Zhang Mengting , Yuan Nate , Liu Jiongru , Meng Qiu , Yin Jianhua
Published: August 2020

Members of the Sphingomonadales are renowned for their ability to degrade polycyclic aromatic hydrocarbons (PAHs). However, little is known about the regulatory mechanisms of the degradative pathway. Using cross-feeding bioassay, a functional LuxI/LuxR-type acyl-homoserine lactone (AHL)-mediated quorum sensing (QS) system was identified from Croceicoccus naphthovorans PQ-2, a member of the order Sphingomonadales. Inactivation of the QS system resulted in a significant decrease in PAHs degradation. The QS system positively controlled the expression of three PAH-degrading genes (ahdA1e, xylE and xylG) and a regulatory gene ardR, which are located on the large plasmid. Interestingly, the transcription levels of these three PAH-degrading genes were significantly down-regulated in the ardR mutant. In addition, bacterial cell surface hydrophobicity and cell morphology were altered in the QS-deficient mutant. Therefore, the QS system in strain PQ-2 positively regulates PAH degradation via two mechanisms: (i) by induction of PAH-degrading genes directly and/or indirectly; and (ii) by an increase of bacterial cell surface hydrophobicity. The findings of this study improve our understanding of how the QS system influences the degradation of PAHs, therefore facilitating the development of new strategies for the bioremediation of PAHs.
How do the Employees’s Perceptions of Abusive Supervision Affect Customer Satisfaction in the Chain Restaurants? Employee-Customer Level Analysis
Authors: Jung Hyo Sun , Yoon Hye Hyun
Published: August 2020

The purpose of this study is to examine the effect of chain restaurant employees’ perception of abusive supervision on employee satisfaction and customer satisfaction. The sample for the survey was collected from 228 customers and 93 employees in a chain restaurant. The results showed a negative relationship between abusive supervision and employee satisfaction. However, abusive supervision did not have a significant, direct effect on customer satisfaction, but showed an indirect effect via employee satisfaction. In addition, employee satisfaction was positively associated with customer satisfaction.
Accuracy Comparison of Aerial Lidar, Mobile-Terrestrial Lidar, and UAV Photogrammetric Capture Data Elevations over Different Terrain Types
Authors: Khanal Mandar , Hasan Mahamudul , Sterbentz Nikolaus , Johnson Ryen , Weatherly Jesse
Published: August 2020

Lidar and other remotely sensed data such as UAV photogrammetric data capture are being collected and utilized for roadway design on an increasing basis. These methods are desirable over conventional survey due to their efficiency and cost-effectiveness over large areas. A high degree of relative accuracy is achievable through the establishment of survey control. In this case study, elevations (z-values) derived from mobile-terrestrial lidar, aerial lidar, and UAV photogrammetric capture collected with survey control were statistically compared to conventionally surveyed elevations. A cost comparison of the methods is also included. Each set of z-values corresponds to a discrete horizontal point originally part of the conventional survey, collected as cross-sections. These cross-sections were surveyed at three approximate tenth-mile sample locations along US-30 near Georgetown, Idaho. The cross-sections were collected as elevational accuracy verification, and each sample location was selected as an area where the mobile-terrestrial lidar in particular was expected to have more difficulty achieving accuracy off the road surface. Processing and analysis were performed in Esri ArcMap 10.6, and all data were obtained from the Idaho Transportation Department, District 5. Overall, the aerial lidar elevations were found to be closest to conventionally surveyed elevations; on road surface and level terrain, mobile-terrestrial and UAV photogrammetric capture elevations were closer to the conventionally measured elevations.
Arthropod Communities in Urban Agricultural Production Systems under Different Irrigation Sources in the Northern Region of Ghana
Authors: Amprako Louis , Stenchly Kathrin , Wiehle Martin , Nyarko George , Buerkert Andreas
Published: August 2020

Urban and peri-urban agricultural (UPA) production systems in West African countries do not only mitigate food and financial insecurity, they may also foster biodiversity of arthropods and partly compensate for structural losses of natural environments. However, management practices in UPA systems like irrigation may also contribute to disturbances in arthropod ecology. To fill knowledge gaps in the relationships between UPA management and arthropod populations, we compared arthropods species across different irrigation sources in Tamale. During a 72-h sampling period, 14,226 arthropods were caught with pitfall traps and pan traps from 36 fields. These specimens comprised 13 orders, 103 families, 264 genera, and 329 taxa (243 identified species, 86 unidentified species) and categorized into five feeding guilds (carnivores, decomposers, herbivores, omnivores, and pollinators). Species richness, species accumulation curves, and diversity functions (richness, evenness, and dispersion) were calculated to characterize the arthropod community. Non-metric multidimensional scaling was applied to examine structural similarity of arthropod communities among sites. To account for the effects of soil-related data, we furthermore applied a redundancy analysis. Arthropods grouped according to the irrigation water source, whereby the dipterans were most dominant under wastewater conditions. Here, particularly the eye gnat, Hippelates pusio, a disease-causing vector for humans, accounted for the dipterans. The occurrence of three alien ant species suggested community shifts through invasive species, while the occurrence of seven ant species (at least one ant species occurred under each water source) that form mutualistic relationships with aphids highlighted future risks of aphid pest outbreak. Future studies on these taxa should specifically target their ecological and economic effects and potential countermeasures.
In Vitro Protective Effect of Paste and Sauce Extract Made with Protaetia brevitarsis Larvae on HepG2 Cells Damaged by Ethanol
Authors: Hwang Dooseon , Goo Tae-Won , Yun Eun-Young
Published: August 2020

We made paste and sauce using protein-rich Protaetia brevitarsis larvae (PBL) and evaluated their fermentation levels. After pretreatment with the paste and sauce extracts, HepG2 cells were damaged with ethanol (EtOH), and then the effects of the paste and sauce were evaluated. As a result, we confirmed that the PBL paste and sauce extracts reduced the aspartate aminotransferase (AST) and alanine aminotransaminase (ALT) content in the medium as compared to soybean (Glycine max) sauce and paste extracts. In addition, the PBL paste and sauce extracts significantly lowered the level of tumor necrosis factor (TNF)-α and interleukin (IL)-6, which are biomarkers of inflammation, and significantly increased the inhibition rate of superoxide dismutase (SOD) and reduced glutathione (GSH), which are antioxidative indicators, in proportion to the amount of PBL added to the paste and sauce. These results suggest that an intake of PBL paste and sauce, a novel type of fermented food made from insects, may be effective for liver protection through anti-inflammatory and antioxidative effects against hepatocyte injury caused by EtOH.
Secondary Voltage Control Application in a Smart Grid with 100% Renewables
Authors: Abdalla Omar H. , Fayek Hady H. , Abdel Ghany A. M.
Published: August 2020

This paper presents secondary voltage control by extracting reactive power from renewable power technologies to control load buses voltage in a power system at different operating conditions. The study is performed on a 100% renewable 14-bus system. Active and reactive powers controls are considered based on grid codes of countries with high penetration levels of renewable energy technologies. A pilot bus is selected in order to implement the secondary voltage control. The selection is based on short-circuit calculation and sensitivity analysis. An optimal Proportional Integral Derivative (PID) voltage controller is designed using genetic algorithm. A comparison between system with and without secondary voltage control is presented in terms of voltage profile and total power losses. The optimal voltage magnitudes at busbars are calculated to achieve minimum power losses using optimal power flow. The optimal placement of Phasor Measurement Units (PMUs) is performed in order to measure the voltage magnitude of buses with minimum cost. Optimization and simulation processes are performed using DIgSILENT and MATLAB software applications.
Long-Term Outcomes and Risk Factors of Renal Failure Requiring Dialysis after Heart Transplantation: A Nationwide Cohort Study
Authors: Wang Tsai-Jung , Lin Ching-Heng , Wei Hao-Ji , Wu Ming-Ju
Published: August 2020

Acute kidney injury and renal failure are common after heart transplantation. We retrospectively reviewed a national cohort and identified 1129 heart transplant patients. Patients receiving renal replacement therapy after heart transplantation were grouped into the dialysis cohort. The long-term survival and risk factors of dialysis were investigated. Patients who had undergone dialysis were stratified to early or late dialysis for subgroup analysis. The mean follow-up was five years, the incidence of dialysis was 28.4% (21% early dialysis and 7.4% late dialysis). The dialysis cohort had higher overall mortality compared with the non-dialysis cohort. The hazard ratios of mortality in patients with dialysis were 3.44 (95% confidence interval (CI), 2.73–4.33) for all dialysis patients, 3.58 (95% CI, 2.74–4.67) for early dialysis patients, and 3.27 (95% CI, 2.44–4.36; all p < 0.001) for late dialysis patients. Patients with diabetes mellitus, chronic kidney disease, acute kidney injury, and coronary artery disease were at higher risk of renal failure requiring dialysis. Cardiomyopathy, hepatitis B virus infection, and hyperlipidemia treated with statins were associated with a lower risk of renal dysfunction requiring early dialysis. The use of Sirolimus and Mycophenolate mofetil was associated with a lower incidence of late dialysis. Renal dysfunction requiring dialysis after heart transplantation is common in Taiwan. Early and late dialysis were both associated with an increased risk of mortality in heart transplant recipients.
The Relationship between Cognitive and Emotional Factors and Healthcare and Medication Use in People Experiencing Pain: A Systematic Review
Authors: Huysmans Eva , Leemans Lynn , Beckwée David , Nijs Jo , Ickmans Kelly , Moens Maarten , Goudman Lisa , Buyl Ronald , Putman Koen , Coppieters Iris
Published: August 2020

Pain conditions are among the leading causes of global disability, impacting on global healthcare utilization (HCU). Health seeking behavior might be influenced by cognitive and emotional factors (CEF), which can be tackled by specific therapies. The purpose of this study was to systematically review the evidence concerning associations between CEF and HCU in people experiencing pain. Three databases were consulted: PubMed, Web of Science and EconLit. Risk of bias was assessed using the Downs and Black Checklist (modified). A total of 90 publications (total sample n = 59,719) was included after double-blind screening. In people experiencing pain, positive associations between general anxiety symptoms, depressive symptoms and catastrophizing and pain medication use were found. Additionally, there appears to be a relationship between general anxiety and depressive symptoms and opioid use. Symptom-related anxiety and psychological distress were found to be positively related with consulting behavior. Last, a positive association between use of complementary and alternative medicine and level of perceived symptom control was confirmed in people with pain. For other relationships no evidence or inconsistent findings were found, or they were insufficiently studied to draw firm conclusions, indicating that more research on this topic is needed.
Cardiac Rehabilitation and Endothelial Function
Authors: Lanza Gaetano Antonio , Golino Michele , Villano Angelo , Lanza Oreste , Lamendola Priscilla , Fusco Augusto , Leggio Massimo
Published: August 2020

Endothelial dysfunction is an early abnormality in the process of atherosclerosis and cardiovascular disease and has been associated with worse clinical outcome. Cardiac rehabilitation (CR) has been reported to be helpful to reduce cardiovascular events in various types of cardiac disease, but the mechanisms of its beneficial effects remain only partially known. In this article, we review the studies that assessed the effect of CR on endothelial function in patients with various cardiac conditions. Available data show that CR significantly improves impaired endothelial function in these patients, which may contribute to the beneficial effects of CR on clinical outcome.
Psychological Profile and Distinct Salivary Cortisol Awake Response (CAR) in Two Different Study Populations with Obstructive Sleep Apnea (OSA) and Central Serous Chorioretinopathy (CSC)
Authors: Scarinci Fabio , Patacchioli Francesca Romana , Ghiciuc Cristina Mihaela , Pasquali Vittorio , Bercea Raluca Mihaela , Cozma Sebastian , Parravano Mariacristina
Published: August 2020

Obstructive sleep apnea (OSA) and central serous chorioretinopathy (CSC) are in terms of nosography different pathologies, however they share a stress-related physio-pathogenetic component, not yet explored in depth. Therefore, the aim of the present study was to ascertain whether OSA and CSC share a common profile, specifically in cortisol production focusing on the cortisol awake response (CAR), the area under curve (AUCCAR) and the SLOPECAR compared with healthy matched controls. Furthermore, standardized self-administered questionnaires were used to identify mental health status related to depression, anxiety and subjective stress perception levels in the study populations. The results showed hypothalamus-pituitary-adrenal (HPA) axis activity anomalies, represented by a flattening CAR in the OSA group and a statistically significant increase in cortisol production in CSC patients at awakening. This disarrangement of the HPA axis activity associated with elevated distress and mental health scores, and its presence in both patients with OSA and patients with CSC, might represent the shared path explaining the stress-related component in these diseases. Further research is needed to investigate the psycho-neuro-endocrinological aspects of OSA and CSC to determine whether psychoeducation on effective stress coping strategies might be of value in improving the quality of life of OSA and CSC patients.
Imaging in Primary Sjögren’s Syndrome
Authors: van Ginkel Martha S. , Glaudemans Andor W.J.M. , van der Vegt Bert , Mossel Esther , Kroese Frans G.M. , Bootsma Hendrika , Vissink Arjan
Published: August 2020

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by dysfunction and lymphocytic infiltration of the salivary and lacrimal glands. Besides the characteristic sicca complaints, pSS patients can present a spectrum of signs and symptoms, which challenges the diagnostic process. Various imaging techniques can be used to assist in the diagnostic work-up and follow-up of pSS patients. Developments in imaging techniques provide new opportunities and perspectives. In this descriptive review, we discuss imaging techniques that are used in pSS with a focus on the salivary glands. The emphasis is on the contribution of these techniques to the diagnosis of pSS, their potential in assessing disease activity and disease progression in pSS, and their contribution to diagnosing and staging of pSS-associated lymphomas. Imaging findings of the salivary glands will be linked to histopathological changes in the salivary glands of pSS patients.