bluuebunny/crossref_metadata_2025 huggingface dataset:
A Global Cndp1-Knock-Out Selectively Increases Renal Carnosine and Anserine Concentrations in an Age- and Gender-Specific Manner in Mice
Authors: Weigand Tim , Colbatzky Florian , Pfeffer Tilman , Garbade Sven F. , Klingbeil Kristina , Colbatzky Florian , Becker Michael , Zemva Johanna , Bulkescher Ruben , Schürfeld Robin , Thiel Christian , Volk Nadine , Reuss David , Hoffmann Georg F. , Freichel Marc , Hecker Markus , Poth Tanja , Fleming Thomas , Poschet Gernot , Schmitt Claus P. , Peters Verena
Published: July 2020

Carnosinase 1 (CN1) is encoded by the Cndp1 gene and degrades carnosine and anserine, two natural histidine-containing dipeptides. In vitro and in vivo studies suggest carnosine- and anserine-mediated protection against long-term sequelae of reactive metabolites accumulating, e.g., in diabetes mellitus. We have characterized the metabolic impact of CN1 in 11- and 55-week-old Cndp1-knockout (Cndp1-KO) mice and litter-matched wildtypes (WT). In Cndp1-KO mice, renal carnosine and anserine concentrations were gender-specifically increased 2- to 9-fold, respectively in the kidney and both most abundant in the renal cortex, but remained unchanged in all other organs and in serum. Renal oxidized/reduced glutathione concentrations, renal morphology and function were unaltered. In Cndp1-KO mice at week 11, renal asparagine, serine and glutamine levels and at week 55, renal arginine concentration were reduced. Renal heat-shock-protein 70 (Hspa1a/b) mRNA declined with age in WT but not in Cndp1-KO mice, transcription factor heat-shock-factor 1 was higher in 55-week-old KO mice. Fasting blood glucose concentrations decreased with age in WT mice, but were unchanged in Cndp1-KO mice. Blood glucose response to intraperitoneal insulin was gender- but not genotype-dependent, the response to intraperitoneal glucose injection was similar in all groups. A global Cndp1-KO selectively, age- and gender-specifically, increases renal carnosine and anserine concentrations, alters renal amino acid- and HSP70 profile and modifies systemic glucose homeostasis. Increase of the natural occurring carnosine and anserine levels in the kidney by modulation of CN1 represents a promising therapeutic approach to mitigate or prevent chronic kidney diseases such as diabetic nephropathy.
Gradient Chitosan Hydrogels Modified with Graphene Derivatives and Hydroxyapatite: Physiochemical Properties and Initial Cytocompatibility Evaluation
Authors: Kosowska Karolina , Domalik-Pyzik Patrycja , Sekuła-Stryjewska Małgorzata , Noga Sylwia , Jagiełło Joanna , Baran Magdalena , Lipińska Ludwika , Zuba-Surma Ewa , Chłopek Jan
Published: July 2020

In this study, we investigated preparation of gradient chitosan-matrix hydrogels through a novel freezing–gelling–thawing method. The influence of three types of graphene family materials (GFM), i.e., graphene oxide (GO), reduced graphene oxide (rGO), and poly(ethylene glycol) grafted graphene oxide (GO-PEG), as well as hydroxyapatite (HAp) on the physicochemical and biological properties of the composite hydrogels was examined in view of their potential applicability as tissue engineering scaffolds. The substrates and the hydrogel samples were thoroughly characterized by X-ray photoelectron spectroscopy, X-ray diffractometry, infrared spectroscopy, digital and scanning electron microscopy, rheological and mechanical analysis, in vitro chemical stability and bioactivity assays, as well as initial cytocompatibility evaluation with human umbilical cord Wharton’s jelly mesenchymal stem cells (hUC-MSCs). We followed the green-chemistry approach and avoided toxic cross-linking agents, using instead specific interactions of our polymer matrix with tannic acid, non-toxic physical cross-linker, and graphene derivatives. It was shown that the most promising are the gradient hydrogels modified with GO-PEG and HAp.
Neuroprotective Effect of Bean Phosphatidylserine on TMT-Induced Memory Deficits in a Rat Model
Authors: Ye Minsook , Han Bong Hee , Kim Jin Su , Kim Kyungsoo , Shim Insop
Published: July 2020

Background: Trimethyltin (TMT) is a potent neurotoxin affecting various regions of the central nervous system, including the neocortex, the cerebellum, and the hippocampus. Phosphatidylserine (PS) is a membrane phospholipid, which is vital to brain cells. We analyzed the neuroprotective effects of soybean-derived phosphatidylserine (Bean-PS) on cognitive function, changes in the central cholinergic systems, and neural activity in TMT-induced memory deficits in a rat model. Methods: The rats were randomly divided into an untreated normal group, a TMT group (injected with TMT + vehicle), and a group injected with TMT + Bean-PS. The rats were treated with 10% hexane (TMT group) or TMT + Bean-PS (50 mg·kg−1, oral administration (p.o.)) daily for 21 days, following a single injection of TMT (8.0 mg/kg, intraperitoneally (i.p.)). The cognitive function of Bean-PS was assessed using the Morris water maze (MWM) test and a passive avoidance task (PAT). The expression of acetylcholine transferase (ChAT) and acetylcholinesterase (AchE) in the hippocampus was assessed via immunohistochemistry. A positron emission tomography (PET) scan was used to measure the glucose uptake in the rat brain. Results: Treatment with Bean-PS enhanced memory function in the Morris water maze (MWM) test. Consistent with the behavioral results, treatment with Bean-PS diminished the damage to cholinergic cells in the hippocampus, in contrast to those of the TMT group. The TMT+Bean-PS group showed elevated glucose uptake in the frontal lobe of the rat brain. Conclusion: These results demonstrate that Bean-PS protects against TMT-induced learning and memory impairment. As such, Bean-PS represents a potential treatment for neurodegenerative disorders, such as Alzheimer’s disease.
Polymorphic Forms of Valinomycin Investigated by NMR Crystallography
Authors: Czernek Jiří , Brus Jiří
Published: July 2020

A dodecadepsipeptide valinomycin (VLM) has been most recently reported to be a potential anti-coronavirus drug that could be efficiently produced on a large scale. It is thus of importance to study solid-phase forms of VLM in order to be able to ensure its polymorphic purity in drug formulations. The previously available solid-state NMR (SSNMR) data are combined with the plane-wave DFT computations in the NMR crystallography framework. Structural/spectroscopical predictions (the PBE functional/GIPAW method) are obtained to characterize four polymorphs of VLM. Interactions which confer a conformational stability to VLM molecules in these crystalline forms are described in detail. The way how various structural factors affect the values of SSNMR parameters is thoroughly analyzed, and several SSNMR markers of the respective VLM polymorphs are identified. The markers are connected to hydrogen bonding effects upon the corresponding (13C/15N/1H) isotropic chemical shifts of (CO, Namid, Hamid, Hα) VLM backbone nuclei. These results are expected to be crucial for polymorph control of VLM and in probing its interactions in dosage forms.
Viburnum opulus L. Juice Phenolic Compounds Influence Osteogenic Differentiation in Human Osteosarcoma Saos-2 Cells
Authors: Zakłos-Szyda Małgorzata , Nowak Adriana , Pietrzyk Nina , Podsędek Anna
Published: July 2020

Bone mass loss occurs with a decrease in osteoblast proliferation and differentiation, or the enhancement of bone resorption, which further leads to the impairment of bone mineral density and increase in bone fracture. Recent studies suggest that some phenolic compounds found in food play positive role in bone metabolism. High content of phenolic compounds with potential beneficial effects on bone metabolism have been identified in the Viburnum opulus fruit. The aim of the study was to determine the influence of V. opulus fresh juice (FJ) and juice purified by solid phase extraction (PJ) on osteogenesis processes with osteosarcoma Saos-2 cell lines. V. opulus purified juice revealed stronger potential as an inducer of Saos-2 osteogenic differentiation. Saos-2 cells matrix mineralization was evaluated with alkaline phosphatase (ALP) activity measurement and alizarin red S staining. Gene expression analysis showed the elevation of the mRNA levels of Runt-related transcription factor 2 (RUNX2), ALP, collagen type 1 and osteonectin, whereas the nuclear factor-κB ligand and osteoprotegerin ratio (RANKL/OPG) decreased. Furthermore, V. opulus was able to diminish the secretion of pro-inflammatory cytokines Il6 and TNFα, however had no effect on vascular endothelial growth factor (VEGF). It decreased intracellular oxidative stress and induced DNA repair, but had no effect on the growth inhibition of lactic acid beneficial microorganisms.
Gastrointestinal Disorders and Metabolic Syndrome: Dysbiosis as a Key Link and Common Bioactive Dietary Components Useful for their Treatment
Authors: De Filippis Anna , Ullah Hammad , Baldi Alessandra , Dacrema Marco , Esposito Cristina , Garzarella Emanuele Ugo , Santarcangelo Cristina , Tantipongpiradet Ariyawan , Daglia Maria
Published: July 2020

Gastrointestinal (GI) diseases, which include gastrointestinal reflux disease, gastric ulceration, inflammatory bowel disease, and other functional GI disorders, have become prevalent in a large part of the world population. Metabolic syndrome (MS) is cluster of disorders including obesity, hyperglycemia, hyperlipidemia, and hypertension, and is associated with high rate of morbidity and mortality. Gut dysbiosis is one of the contributing factors to the pathogenesis of both GI disorder and MS, and restoration of normal flora can provide a potential protective approach in both these conditions. Bioactive dietary components are known to play a significant role in the maintenance of health and wellness, as they have the potential to modify risk factors for a large number of serious disorders. Different classes of functional dietary components, such as dietary fibers, probiotics, prebiotics, polyunsaturated fatty acids, polyphenols, and spices, possess positive impacts on human health and can be useful as alternative treatments for GI disorders and metabolic dysregulation, as they can modify the risk factors associated with these pathologies. Their regular intake in sufficient amounts also aids in the restoration of normal intestinal flora, resulting in positive regulation of insulin signaling, metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. This review is designed to focus on the health benefits of bioactive dietary components, with the aim of preventing the development or halting the progression of GI disorders and MS through an improvement of the most important risk factors including gut dysbiosis.
Molecular Targets of Natural Products for Chondroprotection in Destructive Joint Diseases
Authors: Jayakumar Thanasekaran , Saravana Bhavan Periyakali , Sheu Joen-Rong
Published: July 2020

Osteoarthritis (OA) is the most common type of arthritis that occurs in an aged population. It affects any joints in the body and degenerates the articular cartilage and the subchondral bone. Despite the pathophysiology of OA being different, cartilage resorption is still a symbol of osteoarthritis. Matrix metalloproteinases (MMPs) are important proteolytic enzymes that degrade extra-cellular matrix proteins (ECM) in the body. MMPs contribute to the turnover of cartilage and its break down; their levels have increased in the joint tissues of OA patients. Application of chondroprotective drugs neutralize the activities of MMPs. Natural products derived from herbs and plants developed as traditional medicine have been paid attention to, due to their potential biological effects. The therapeutic value of natural products in OA has increased in reputation due to their clinical impact and insignificant side effects. Several MMPs inhibitor have been used as therapeutic drugs, for a long time. Recently, different types of compounds were reviewed for their biological activities. In this review, we summarize numerous natural products for the development of MMPs inhibitors in arthritic diseases and describe the major signaling targets that were involved for the treatments of these destructive joint diseases.
Common Drug Pipelines for the Treatment of Diabetic Nephropathy and Hepatopathy: Can We Kill Two Birds with One Stone?
Authors: Sumida Yoshio , Yoneda Masashi , Toyoda Hidenori , Yasuda Satoshi , Tada Toshifumi , Hayashi Hideki , Nishigaki Yoichi , Suzuki Yusuke , Naiki Takafumi , Morishita Asahiro , Tobita Hiroshi , Sato Shuichi , Kawabe Naoto , Fukunishi Shinya , Ikegami Tadashi , Kessoku Takaomi , Ogawa Yuji , Honda Yasushi , Nakahara Takashi , Munekage Kensuke , Ochi Tsunehiro , Sawada Koji , Takahashi Atsushi , Arai Taeang , Kogiso Tomomi , Kimoto Satoshi , Tomita Kengo , Notsumata Kazuo , Nonaka Michihiro , Kawata Kazuhito , Takami Taro , Kumada Takashi , Tomita Eiichi , Okanoue Takeshi , Nakajima Atsushi ,   Japan Study Group of NAFLD (JSG-NAFLD)
Published: July 2020

Type 2 diabetes (T2D) is associated with diabetic nephropathy as well as nonalcoholic steatohepatitis (NASH), which can be called “diabetic hepatopathy or diabetic liver disease”. NASH, a severe form of nonalcoholic fatty disease (NAFLD), can sometimes progress to cirrhosis, hepatocellular carcinoma and hepatic failure. T2D patients are at higher risk for liver-related mortality compared with the nondiabetic population. NAFLD is closely associated with chronic kidney disease (CKD) or diabetic nephropathy according to cross-sectional and longitudinal studies. Simultaneous kidney liver transplantation (SKLT) is dramatically increasing in the United States, because NASH-related cirrhosis often complicates end-stage renal disease. Growing evidence suggests that NAFLD and CKD share common pathogenetic mechanisms and potential therapeutic targets. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH and diabetic nephropathy/CKD. There are no approved therapies for NASH, but a variety of drug pipelines are now under development. Several agents of them can also ameliorate diabetic nephropathy/CKD, including peroxisome proliferator-activated receptors agonists, apoptosis signaling kinase 1 inhibitor, nuclear factor-erythroid-2-related factor 2 activator, C-C chemokine receptor types 2/5 antagonist and nonsteroidal mineral corticoid receptor antagonist. This review focuses on common drug pipelines in the treatment of diabetic nephropathy and hepatopathy.
Significance of Autoantibodies in Autoimmune Encephalitis in Relation to Antigen Localization: An Outline of Frequently Reported Autoantibodies with a Non-Systematic Review
Authors: Tanaka Keiko , Kawamura Meiko , Sakimura Kenji , Kato Nobuo
Published: July 2020

Autoantibodies related to central nervous system (CNS) diseases propel research on paraneoplastic neurological syndrome (PNS). This syndrome develops autoantibodies in combination with certain neurological syndromes and cancers, such as anti-HuD antibodies in encephalomyelitis with small cell lung cancer and anti-Yo antibodies in cerebellar degeneration with gynecological cancer. These autoantibodies have roles in the diagnosis of neurological diseases and early detection of cancers that are usually occult. Most of these autoantibodies have no pathogenic roles in neuronal dysfunction directly. Instead, antigen-specific cytotoxic T lymphocytes are thought to have direct roles in neuronal damage. The recent discoveries of autoantibodies against neuronal synaptic receptors/channels produced in patients with autoimmune encephalomyelitis have highlighted insights into our understanding of the variable neurological symptoms in this disease. It has also improved our understanding of intractable epilepsy, atypical psychosis, and some demyelinating diseases that are ameliorated with immune therapies. The production and motility of these antibodies through the blood-brain barrier into the CNS remains unknown. Most of these recently identified autoantibodies bind to neuronal and glial cell surface synaptic receptors, potentially altering the synaptic signaling process. The clinical features differ among pathologies based on antibody targets. The investigation of these antibodies provides a deeper understanding of the background of neurological symptoms in addition to novel insights into their basic neuroscience.
From Inflammation to Cutaneous Repair: Topical Application of Lupeol Improves Skin Wound Healing in Rats by Modulating the Cytokine Levels, NF-κB, Ki-67, Growth Factor Expression, and Distribution of Collagen Fibers
Authors: Pereira Beserra Fernando , Sérgio Gushiken Lucas Fernando , Vieira Ana Júlia , Augusto Bérgamo Danilo , Luísa Bérgamo Patrícia , Oliveira de Souza Mariana , Alberto Hussni Carlos , Kiomi Takahira Regina , Henrique Nóbrega Rafael , Monteiro Martinez Emanuel Ricardo , John Jackson Christopher , Lemos de Azevedo Maia Gabriela , Leite Rozza Ariane , Helena Pellizzon Cláudia
Published: July 2020

Skin wound healing is a highly complex event that involves different mediators at the cellular and molecular level. Lupeol has been reported to possess different biological activities, such as anti-inflammatory, antioxidant, antidiabetic, and in vitro wound healing properties, which motivated us to proceed with in vivo studies. We aimed to investigate the wound healing effect of lupeol-based cream for 3, 7, and 14 days. Wound excisions were induced on the thoraco-lumbar region of rats and topically treated immediately after injury induction. Macroscopic, histopathological, and immunohistochemical analyses were performed. Cytokine levels were measured by ELISA and gene expression was evaluated by real-time RT-qPCR. Our results showed a strong wound-healing effect of lupeol-based cream after 7 and 14 days. Lupeol treatment caused a reduction in proinflammatory cytokines (TNF-a, IL-1β, and IL-6) and gene and protein NF-κB expression, and positively altered IL-10 levels, showing anti-inflammatory effects in the three treatment periods. Lupeol treatment showed involvement in the proliferative phase by stimulating the formation of new blood vessels, increasing the immunostaining of Ki-67 and gene expression, and immunolabeling of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), and increasing gene expression of transforming growth factor beta-1 (TGF-β1) after seven days of treatment. Lupeol was also involved in the tissue regeneration phase by increasing the synthesis of collagen fibers noted in the three treatment periods analyzed. Our findings suggest that lupeol may serve as a novel therapeutic option to treat cutaneous wounds by regulating mechanisms involved in the inflammatory, proliferative, and tissue-remodeling phases.
Activation of NOTCH1 by Shear Force Elicits Immediate Cytokine Expression in Human Chondrocytes
Authors: Cheng Hao-Jen , Hsu Wan-Ting , Chen Cheng-Nan , Li Chin
Published: July 2020

Osteoarthritis is caused by overloading of joints and is characterized by inflammation-induced disruption of cartilage structure. Current treatment strategy aims to relieve inflammation and prevent further deterioration of joint function. However, how mechanical force leads to inflammation and deterioration of chondrocyte function still remains incompletely understood. To explore the force-regulated molecular mechanism, an in vitro hydraulic shear force experiment to simulate the condition of force loading was required. The result demonstrated that multiple cytokines and immune regulators, including interleukin 8, interferon β, TRAF1 and TNFAIP3, were significantly increased by shear force within two hours of treatment. Moreover, JAG1 and HES1 were drastically upregulated as well, suggesting that NOTCH1 signaling is activated by shear force. Short-term expression of NOTCH1 intracellular domain activated a similar set of cytokines, indicating that NOTCH1 responds to shear force and activates downstream genes. When incubated under the medium conditioned by NOTCH1-activated chondrocyte, osteoblasts expressed higher levels of interferon β and interferon λ. Together, our results indicated that NOTCH1 functions as a force sensor and promotes expression of cytokines and immune regulators from shear-force bearing chondrocytes.
The Mitochondria: A Target of Polyphenols in the Treatment of Diabetic Cardiomyopathy
Authors: Bhagani Humna , Nasser Suzanne A. , Dakroub Ali , El-Yazbi Ahmed F. , Eid Assaad A. , Kobeissy Firas , Pintus Gianfranco , Eid Ali H.
Published: July 2020

Diabetic cardiomyopathy (DCM) is a constellation of symptoms consisting of ventricular dysfunction and cardiomyocyte disarray in the presence of diabetes. The exact cause of this type of cardiomyopathy is still unknown; however, several processes involving the mitochondria, such as lipid and glucose metabolism, reactive oxygen species (ROS) production, apoptosis, autophagy and mitochondrial biogenesis have been implicated. In addition, polyphenols have been shown to improve the progression of diabetes. In this review, we discuss some of the mechanisms by which polyphenols, particularly resveratrol, play a role in slowing the progression of DCM. The most important intermediates by which polyphenols exert their protective effect include Bcl-2, UCP2, SIRT-1, AMPK and JNK1. Bcl-2 acts to attenuate apoptosis, UCP2 decreases oxidative stress, SIRT-1 increases mitochondrial biogenesis and decreases oxidative stress, AMPK increases autophagy, and JNK1 decreases apoptosis and increases autophagy. Our dissection of these molecular players aims to provide potential therapeutic targets for the treatment of DCM.
Direct On-Chip Differentiation of Intestinal Tubules from Induced Pluripotent Stem Cells
Authors: Naumovska Elena , Aalderink Germaine , Wong Valencia Christian , Kosim Kinga , Nicolas Arnaud , Brown Stephen , Vulto Paul , Erdmann Kai S. , Kurek Dorota
Published: July 2020

Intestinal organoids have emerged as the new paradigm for modelling the healthy and diseased intestine with patient-relevant properties. In this study, we show directed differentiation of induced pluripotent stem cells towards intestinal-like phenotype within a microfluidic device. iPSCs are cultured against a gel in microfluidic chips of the OrganoPlate, in which they undergo stepwise differentiation. Cells form a tubular structure, lose their stem cell markers and start expressing mature intestinal markers, including markers for Paneth cells, enterocytes and neuroendocrine cells. Tubes develop barrier properties as confirmed by transepithelial electrical resistance (TEER). Lastly, we show that tubules respond to pro-inflammatory cytokine triggers. The whole procedure for differentiation lasts 14 days, making it an efficient process to make patient-specific organoid tubules. We anticipate the usage of the platform for disease modelling and drug candidate screening.
Lysosomal Storage Disorders Shed Light on Lysosomal Dysfunction in Parkinson’s Disease
Authors: Blumenreich Shani , Barav Or B. , Jenkins Bethan J. , Futerman Anthony H.
Published: July 2020

The lysosome is a central player in the cell, acting as a clearing house for macromolecular degradation, but also plays a critical role in a variety of additional metabolic and regulatory processes. The lysosome has recently attracted the attention of neurobiologists and neurologists since a number of neurological diseases involve a lysosomal component. Among these is Parkinson’s disease (PD). While heterozygous and homozygous mutations in GBA1 are the highest genetic risk factor for PD, studies performed over the past decade have suggested that lysosomal loss of function is likely involved in PD pathology, since a significant percent of PD patients have a mutation in one or more genes that cause a lysosomal storage disease (LSD). Although the mechanistic connection between the lysosome and PD remains somewhat enigmatic, significant evidence is accumulating that lysosomal dysfunction plays a central role in PD pathophysiology. Thus, lysosomal dysfunction, resulting from mutations in lysosomal genes, may enhance the accumulation of α-synuclein in the brain, which may result in the earlier development of PD.
Research Tools for the Functional Genomics of Plant miRNAs During Zygotic and Somatic Embryogenesis
Authors: Wójcik Anna Maria
Published: July 2020

During early plant embryogenesis, some of the most fundamental decisions on fate and identity are taken making it a fascinating process to study. It is no surprise that higher plant embryogenesis was intensively analysed during the last century, while somatic embryogenesis is probably the most studied regeneration model. Encoded by the MIRNA, short, single-stranded, non-coding miRNAs, are commonly present in all Eukaryotic genomes and are involved in the regulation of the gene expression during the essential developmental processes such as plant morphogenesis, hormone signaling, and developmental phase transition. During the last few years dedicated to miRNAs, analytical methods and tools have been developed, which have afforded new opportunities in functional analyses of plant miRNAs, including (i) databases for in silico analysis; (ii) miRNAs detection and expression approaches; (iii) reporter and sensor lines for a spatio-temporal analysis of the miRNA-target interactions; (iv) in situ hybridisation protocols; (v) artificial miRNAs; (vi) MIM and STTM lines to inhibit miRNA activity, and (vii) the target genes resistant to miRNA. Here, we attempted to summarise the toolbox for functional analysis of miRNAs during plant embryogenesis. In addition to characterising the described tools/methods, examples of the applications have been presented.
P2 Purinergic Signaling in the Distal Lung in Health and Disease
Authors: Wirsching Eva , Fauler Michael , Fois Giorgio , Frick Manfred
Published: July 2020

The distal lung provides an intricate structure for gas exchange in mammalian lungs. Efficient gas exchange depends on the functional integrity of lung alveoli. The cells in the alveolar tissue serve various functions to maintain alveolar structure, integrity and homeostasis. Alveolar epithelial cells secrete pulmonary surfactant, regulate the alveolar surface liquid (ASL) volume and, together with resident and infiltrating immune cells, provide a powerful host-defense system against a multitude of particles, microbes and toxicants. It is well established that all of these cells express purinergic P2 receptors and that purinergic signaling plays important roles in maintaining alveolar homeostasis. Therefore, it is not surprising that purinergic signaling also contributes to development and progression of severe pathological conditions like pulmonary inflammation, acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and pulmonary fibrosis. Within this review we focus on the role of P2 purinergic signaling in the distal lung in health and disease. We recapitulate the expression of P2 receptors within the cells in the alveoli, the possible sources of ATP (adenosine triphosphate) within alveoli and the contribution of purinergic signaling to regulation of surfactant secretion, ASL volume and composition, as well as immune homeostasis. Finally, we summarize current knowledge of the role for P2 signaling in infectious pneumonia, ALI/ARDS and idiopathic pulmonary fibrosis (IPF).
De Novo Assembly of the Asian Citrus Psyllid Diaphorina citri (Hemiptera: Psyllidae) Transcriptome across Developmental Stages
Authors: Yang Chunxiao , Ou Da , Guo Wei , Lü Jing , Guo Changfei , Qiu Baoli , Pan Huipeng
Published: July 2020

Asian citrus psyllid Diaphorina citri Kuwayama is an important economic pest of citrus, as it transmits Candidatus Liberibacter asiaticus, the causative agent of huanglongbing. In this study, we used RNA-seq to identify novel genes and provide the first high-resolution view of the of D. citri transcriptome throughout development. The transcriptomes of D. citri during eight developmental stages, including the egg, five instars, and male and female adults were sequenced. In total, 115 million clean reads were obtained and assembled into 354,726 unigenes with an average length of 925.65 bp and an N50 length of 1733 bp. Clusters of Orthologous Groups, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to functionally annotate the genes. Differential expression analysis highlighted developmental stage-specific expression patterns. Furthermore, two trehalase genes were characterized with lower expression in adults compared to that in the other stages. The RNA interference (RNAi)-mediated suppression of the two trehalase genes resulted in significantly high D. citri mortality. This study enriched the genomic information regarding D. citri. Importantly, these data represent the most comprehensive transcriptomic resource currently available for D. citri and will facilitate functional genomics studies of this notorious pest.
Extraction Patterns to Derive Social Networks from Linked Open Data Using SPARQL
Authors: Ghawi Raji , Pfeffer Jürgen
Published: July 2020

Linked Open Data (LOD) refers to freely available data on the World Wide Web that are typically represented using the Resource Description Framework (RDF) and standards built on it. LOD is an invaluable resource of information due to its richness and openness, which create new opportunities for many areas of application. In this paper, we address the exploitation of LOD by utilizing SPARQL queries in order to extract social networks among entities. This enables the application of de-facto techniques from Social Network Analysis (SNA) to study social relations and interactions among entities, providing deep insights into their latent social structure.
Applying DevOps Practices of Continuous Automation for Machine Learning
Authors: Karamitsos Ioannis , Albarhami Saeed , Apostolopoulos Charalampos
Published: July 2020

This paper proposes DevOps practices for machine learning application, integrating both the development and operation environment seamlessly. The machine learning processes of development and deployment during the experimentation phase may seem easy. However, if not carefully designed, deploying and using such models may lead to a complex, time-consuming approaches which may require significant and costly efforts for maintenance, improvement, and monitoring. This paper presents how to apply continuous integration (CI) and continuous delivery (CD) principles, practices, and tools so as to minimize waste, support rapid feedback loops, explore the hidden technical debt, improve value delivery and maintenance, and improve operational functions for real-world machine learning applications.
In Vitro Evaluation of a Peptide-Mesoporous Silica Nanoparticle Drug Release System against HIV-1
Authors: Braun Katharina , Stürzel Christina M. , Kirchhoff Frank , Lindén Mika
Published: July 2020

It has been shown that the optimized VIR-576 derivative of the natural HIV-1 entry inhibitor targeting the viral gp41 fusion peptide is safe and effective in infected individuals. However, high doses of this peptide were required, and stability, as well as delivery, must be improved for clinical application. Here, we examined the loading and release of VIR-576 into/from mesoporous silica nanoparticles (MSNs) in vitro. We found that a moderately high peptide loading of 11.5 wt % could be achieved by adsorption from PBS buffer (pH 7.2), i.e., under mild, fully peptide-compatible conditions. The release rate of peptide into the same buffer was slow and the equilibrium concentration as indicated by the adsorption isotherm could not be reached even within 50 h at the particle concentrations studied. However, a faster release was observed at lower particle concentrations, indicating that partial particle dissolution had a positive influence on peptide release. To determine the antiviral activity of VIR-576-loaded MSNs, TZM-bl indicator cells were exposed to HIV-1 and the infection rates were followed as a function of time and VIR-576 concentration. The inhibitory activity observed for VIR-576 released from the MSNs was virtually identical to that of free VIR-576 at the 48 h time point, indicating that (a) VIR-576 was released in an active form from the MSNs, and (b) the release rate in the presence of serum proteins was clearly higher than that observed under protein-free conditions. These observations are discussed based on competitive peptide/protein adsorption, as well as potential influences of serum proteins on the dissolution-reprecipitation of silica under conditions where the total silica concentration is above the saturation level for dissolved silica. Our results highlight the need for studying drug release kinetics in the presence of serum proteins, in order to allow for a better extrapolation of in vitro data to in vivo conditions. Furthermore, due to the high peptide loadings that can be achieved using MSNs as carriers, such a formulation appears promising for local release applications. For systemic administration, however, peptides with a higher potency would be needed, due to their high molar masses limiting the drug loading in terms of moles per gram carrier.
Host Plant Species of Bemisia tabaci Affect Orientational Behavior of the Ladybeetle Serangium japonicum and Their Implication for the Biological Control Strategy of Whiteflies
Authors: Tian Mi , Xu Lili , Jiang Jun , Zhang Shize , Liu Tongxian , Xu Yongyu
Published: July 2020

Serangium japonicum Chapin (Coleoptera: Coccinellidae) is a predominant predator with a preference for Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). To date, the orientational behavior of S. japonicum toward B. tabaci-infested plants has seldom been reported. In this study, greenhouse cage experiments and bioassays with wind tunnels, a Y-tube olfactometer and B. tabaci-induced plant volatiles were executed to clarify this behavior. In greenhouse cage experiments, B. tabaci adults significantly preferred eggplant, cucumber and tobacco to cotton and tomato, whereas S. japonicum adults preferred B. tabaci-infested eggplant, cucumber and cotton to tobacco and tomato. In wind tunnel bioassays, B. tabaci showed a clear preference for eggplant, cucumber and tobacco. Compared with B. tabaci-infested eggplant, cucumber or cotton, B. tabaci-infested tobacco was rarely visited by S. japonicum. In Y-tube bioassays, S. japonicum did not distinguish between B. tabaci-infested and uninfested eggplant. Nine common plant volatiles were detected in different plant species, suggesting that these volatiles may play an important role in the process by which S. japonicum looks for prey. In light of the current results, we discuss the implications of our findings and put forward to a new strategy—i.e., an eggplant + B. tabaci + S. japonicum system—to control B. tabaci damage in the integrated management of whitefly.
Impact of Sacbrood Virus on Larval Microbiome of Apis mellifera and Apis cerana
Authors: Yongsawas Rujipas , Chaimanee Veeranan , Pettis Jeffery S. , Boncristiani Junior Humberto Freire , Lopez Dawn , In-on Ammarin , Chantawannakul Panuwan , Disayathanoowat Terd
Published: July 2020

In this study, we examined the impact of Sacbrood virus (SBV), the cause of larval honeybee (Apis mellifera) death, producing a liquefied a larva sac, on the gut bacterial communities on two larval honeybee species, Apis mellifera and Apis cerana. SBV was added into a worker jelly food mixture and bee larvae were grafted into each of the treatment groups for 24 h before DNA/RNA extraction. Confirmation of SBV infection was achieved using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and visual symptomology. The 16S rDNA was sequenced by Illumina sequencing. The results showed the larvae were infected with SBV. The gut communities of infected A. cerana larvae exhibited a dramatic change compared with A. mellifera. In A. mellifera larvae, the Illumina sequencing revealed the proportion of Gilliamella, Snodgrassella and Fructobacillus was not significantly different, whereas in A. cerana, Gilliamella was significantly decreased (from 35.54% to 2.96%), however, with significant increase in Snodgrassella and Fructobacillus. The possibility of cross-infection should be further investigated.
Preliminary Design of a Smart Wristband Disinfectant to Help in Covid-19 Fight
Authors: El Majid Badre , Motahhir Saad , El Hammoumi Aboubakr , Lebbadi Ambar , El Ghzizal Abdelaziz
Published: July 2020

This concept paper describes a device consisting of a disinfectant wristband for the hands of the wearer and objects that the wearer intends to touch. This wristband can be powered automatically by the movement of the user’s hand or by solar cells or, if necessary, by a power outlet. It disinfects the surface of the hands and the objects in front of them using an ultraviolet (UV) lamp. Control and monitoring can be carried out automatically or manually, which guarantees complete and effective disinfection. The electronic control system, which is fully integrated into the UV emitter head, regulates the intensity and duration of the UV radiation and also manages the electrical energy. In addition, the wristband can be fitted with an optional watch to improve its decoration and ergonomics. The device in question has a compact, elegant, and practical shape. This hand sanitizing wristband can be an effective tool in the fight against the current COVID-19 pandemic and, in general, help to address the health challenges related to hygiene and disease prevention.
Prevention of Prosthetic Joint Infection: From Traditional Approaches towards Quality Improvement and Data Mining
Authors: Gallo Jiri , Nieslanikova Eva
Published: July 2020

A projected increased use of total joint arthroplasties will naturally result in a related increase in the number of prosthetic joint infections (PJIs). Suppression of the local peri-implant immune response counters efforts to eradicate bacteria, allowing the formation of biofilms and compromising preventive measures taken in the operating room. For these reasons, the prevention of PJI should focus concurrently on the following targets: (i) identifying at-risk patients; (ii) reducing “bacterial load” perioperatively; (iii) creating an antibacterial/antibiofilm environment at the site of surgery; and (iv) stimulating the local immune response. Despite considerable recent progress made in experimental and clinical research, a large discrepancy persists between proposed and clinically implemented preventative strategies. The ultimate anti-infective strategy lies in an optimal combination of all preventative approaches into a single “clinical pack”, applied rigorously in all settings involving prosthetic joint implantation. In addition, “anti-infective” implants might be a choice in patients who have an increased risk for PJI. However, further progress in the prevention of PJI is not imaginable without a close commitment to using quality improvement tools in combination with continual data mining, reflecting the efficacy of the preventative strategy in a particular clinical setting.
Short- and Long-Term Evaluation of Renal Function after Radical Cystectomy and Cutaneous Ureterostomy in High-Risk Patients
Authors: Creta Massimiliano , Fusco Ferdinando , La Rocca Roberto , Capece Marco , Celentano Giuseppe , Imbimbo Ciro , Imperatore Vittorio , Russo Luigi , Mangiapia Francesco , Mirone Vincenzo , Russo Domenico , Longo Nicola
Published: July 2020

Deterioration of renal function has been reported after radical cystectomy (RC) with urinary diversion. We investigated renal function changes in elderly bladder cancer (BCa) patients who underwent RC with cutaneous ureterostomy (CU) urinary diversion. We performed a retrospective, observational study. BCa patients aged ≥75 with an American Society of Anesthesiologists (ASA) class greater than II were included. Glomerular filtration rate (GFR) was the main outcome measure. GFR values were recorded preoperatively, at discharge, at 6-month follow-up, and yearly up to 60 months. A total of 70 patients with a median age of 78.0 years were identified. Median preoperative GFR was 74.3 mL/min/1.73 m2 and declined significantly to 54.6 mL/min/1.73 m2 after 6 months (p < 0.001). A gradual GFR decline was observed thereafter, reaching a median value of 46.2 after 60 months. Preoperative GFR and acute kidney injury were significant predictors of fast deterioration of GFR and of 25% deterioration of GFR after 12 months. Elderly BCa patients with high comorbidity rates undergoing RC with CU should be carefully informed about the risk of GFR deterioration and the need for adequate monitoring.
Pain Neuroscience Education Plus Usual Care Is More Effective than Usual Care Alone to Improve Self-Efficacy Beliefs in People with Chronic Musculoskeletal Pain: A Non-Randomized Controlled Trial
Authors: Rondon-Ramos Antonio , Martinez-Calderon Javier , Diaz-Cerrillo Juan Luis , Rivas-Ruiz Francisco , Ariza-Hurtado Gina Rocio , Clavero-Cano Susana , Luque-Suarez Alejandro
Published: July 2020

Self-efficacy beliefs are associated with less physical impairment and pain intensity in people with chronic pain. Interventions that build self-efficacy beliefs may foster behavioral changes among this population. A non-randomized trial has been carried out to evaluate the effectiveness of pain neuroscience education (PNE) plus usual care in modifying self-efficacy beliefs, pain intensity, pain interference and analgesics consumption in people with chronic musculoskeletal pain. Participants were allocated to an experimental (PNE plus usual care, n = 49) and a control (usual care alone, n = 51) group. The primary outcome was self-efficacy beliefs (Chronic Pain Self-Efficacy Scale), and the secondary outcomes were pain intensity, pain interference (Graded Chronic Pain Scale) and analgesics consumption. The participant’s pain knowledge (revised Neurophysiology of Pain Questionnaire) after PNE intervention was also assessed to analyze its influence on every outcome measure. All the outcome measures were assessed at the baseline and at four-week and four-month follow-ups. PNE plus usual care was more effective than usual care alone to increase self-efficacy beliefs and decrease pain intensity and pain interference at all follow-up points. No differences between groups were found in terms of analgesics consumption. Knowledge of pain neurophysiology did not modify the effects of PNE plus usual care in any of the outcome measures. These results should be taken with caution because of the non-randomized nature of this design, the limited follow-ups and the uncertainty of the presence of clinical changes in self-efficacy for participants. Larger, methodological sound trials are needed.
Artificial Saliva in Diabetic Xerostomia (ASDIX): Double Blind Trial of Aldiamed® Versus Placebo
Authors: Sinjari Bruna , Feragalli Beatrice , Cornelli Umberto , Belcaro Giovanni , Vitacolonna Ester , Santilli Manlio , Rexhepi Imena , D’Addazio Gianmaria , Zuccari Francesca , Caputi Sergio
Published: July 2020

Xerostomia is a symptom frequently present in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). In the present trial, the activity of an artificial saliva (aldiamed® spray) in comparison to a placebo spray were used to evaluate the xerostomia and the saliva antioxidant capacity (SAT). Sixty patients of both genders with T1DM or T2DM were randomized into two groups of 30 subjects each. The experiment was a double-blind study approved by the Ethics Committee of the “G. d’Annunzio University” of Chieti and Pescara. Moreover, measurements of the stimulated saliva flow rate and the ultrasonography of the submandibular and parotid glands were performed at both the study time points. The results demonstrated statistically significant differences between the treatments in terms of the xerostomia average score. Specifically, the values were at baseline and after 30 days 2.9 ± 1.31 and 3.0 ± 1.44 and 1.4 ± 1.48 and 2.4 ± 0.99 for aldiamed® spray and the placebo, respectively. Meanwhile, no statistically significant differences were shown between the two groups for the other variables, such as the salivary flow rate, the antioxidant capacity of the saliva, and the ultrasonography of the major salivary glands.
Snake-Eye Myelopathy and Surgical Prognosis: Case Series and Systematic Literature Review
Authors: Fontanella Marco Maria , Zanin Luca , Bergomi Riccardo , Fazio Marco , Zattra Costanza Maria , Agosti Edoardo , Saraceno Giorgio , Schembari Silvia , De Maria Lucio , Quartini Luisa , Leggio Ugo , Filosto Massimiliano , Gasparotti Roberto , Locatelli Davide
Published: July 2020

The prognostic value of “snake-eyes” sign in spinal cord magnetic resonance imaging (MRI) is unclear and the correlation with different pathological conditions has not been completely elucidated. In addition, its influence on surgical outcome has not been investigated in depth. A literature review according to PRISMA (Preferred reporting items for systematic review and meta-analysis protocols) guidelines on the prognostic significance of “snake-eyes” sign in operated patients was performed. Clinical, neuroradiological, and surgical data of three institutional patients, were also retrospectively collected. The three patients, with radiological evidence of “snake-eyes” myelopathy, underwent appropriate surgical treatment for their condition, with no new post-operative neurological deficits and good outcome at follow-up. The literature review, however, reported conflicting results: the presence of “snake-eyes” sign seems a poor prognostic factor in degenerative cervical myelopathy, even if some cases can improve after surgery. “Snake-eyes” myelopathy represents a rare form of myelopathy; pathophysiology is still unclear. The frequency of this myelopathy may be greater than previously thought and according to our literature review it is mostly a negative prognostic factor. However, from our experience, prognosis might not be so dire, especially when tailored surgical intervention is performed; therefore, surgery should always be considered and based on the complete clinical, neurophysiological, and radiological data.
Medicine 4.0: New Technologies as Tools for a Society 5.0
Authors: Ioppolo Giuseppe , Vazquez Franck , Hennerici Michael G. , Andrès Emmanuel
Published: July 2020

Are new technologies in the medicine sector a driver to support the development of a society 5.0? Innovation pushes the artisan to become smart and lean, customer-oriented but within a standardized environment of production, maintaining and ensuring the quality of the product. An artisan is a user and innovator, as an essential part of the industrial chain. In the healthcare sector, the doctor is the industrial artisan, and medicine can be considered as an example of a smart tool, strongly tailored, that embeds the innovation of materials, nano-devices, and smart technology (e.g., sensors and controllers). But how much of society is ready to host smart technology “on board”, becoming “on life”, constantly connected with remote controls that allow us to monitor, gather data, and, in any case, act, with preventive healthcare solutions? After a short overview of the medicine sector, a preliminary, tentative link between technological innovation and the healthcare sector allows us to adopt several outlooks on how to change research, always more transdisciplinary, combining science with social science in order to remain human-centered.