bluuebunny/crossref_metadata_2025 huggingface dataset:
Silver Nanoparticles Surface-Modified with Carbosilane Dendrons as Carriers of Anticancer siRNA
Authors: Pędziwiatr-Werbicka Elżbieta , Gorzkiewicz Michał , Horodecka Katarzyna , Abashkin Viktar , Klajnert-Maculewicz Barbara , Peña-González Cornelia E. , Sánchez-Nieves Javier , Gómez Rafael , de la Mata F. Javier , Bryszewska Maria
Published: June 2020

Gene therapy is a promising approach in cancer treatment; however, current methods have a number of limitations mainly due to the difficulty in delivering therapeutic nucleic acids to their sites of action. The application of non-viral carriers based on nanomaterials aims at protecting genetic material from degradation and enabling its effective intracellular transport. We proposed the use of silver nanoparticles (AgNPs) surface-modified with carbosilane dendrons as carriers of anticancer siRNA (siBcl-xl). Using gel electrophoresis, zeta potential and hydrodynamic diameter measurements, as well as transmission electron microscopy, we characterized AgNP:siRNA complexes and demonstrated the stability of nucleic acid in complexes in the presence of RNase. Hemolytic properties of free silver nanoparticles and complexes, their effect on lymphocyte proliferation and cytotoxic activity on HeLa cells were also examined. Confocal microscopy proved the effective cellular uptake of complexes, indicating the possible use of this type of silver nanoparticles as carriers of genetic material in gene therapy.
Aspirin Modifies Inflammatory Mediators and Metabolomic Profiles and Contributes to the Suppression of Obesity-Associated Breast Cancer Cell Growth
Authors: Hsieh Chia-Chien , Chiu Huai-Hsuan , Wang Chih-Hsuan , Kuo Ching-Hua
Published: June 2020

Breast cancer is the most common cancer among women. Adiposity generally accompanies immune cell infiltration and cytokine secretion, which is ideal for tumor development. Aspirin is a chemopreventive agent against several types of cancer. The aim of this study was to investigate whether aspirin inhibits the growth of 4T1 breast cancer cells by inhibiting the inflammatory response and regulating the metabolomic profile of 3T3-L1 adipocytes. 3T3-L1 adipocyte-conditioned medium (Ad-CM) was used to mimic the obese adipose tissue microenvironment in 4T1 cells. The results revealed that aspirin inhibited macrophage chemoattractant protein (MCP-1), interleukin (IL-6), IL-1β, and plasminogen activator inhibitor (PAI-1) production in 3T3-L1 adipocytes stimulated by tumor necrosis factor-alpha (TNF-α) and lipopolysaccharide (LPS). In the obesity-associated model, Ad-CM significantly promoted 4T1 cell growth and migration, which were attenuated after aspirin treatment. The results of metabolic analyses using Ad-CM showed that amino acid metabolites and oxidative stress were increased in mature 3T3-L1 adipocytes compared to those in fibroblasts. Aspirin treatment modified metabolites involved in suppressing lipogenesis, oxidative stress, and neoplastic formation. In the relative fatty acid quantitation analysis of Ad-CM, aspirin diminished fatty acid contents of C16:1, C18:1, C18:2, C20:4, and C24:1. This study is the first to show that aspirin modifies the metabolomics and fatty acid composition of 3T3-L1 adipocytes and inhibits obesity-associated inflammation that contributes to obesity-related breast cancer cell growth and migration.
Sugary Logistics Gone Wrong: Membrane Trafficking and Congenital Disorders of Glycosylation
Authors: Linders Peter T. A. , Peters Ella , ter Beest Martin , Lefeber Dirk J. , van den Bogaart Geert
Published: June 2020

Glycosylation is an important post-translational modification for both intracellular and secreted proteins. For glycosylation to occur, cargo must be transported after synthesis through the different compartments of the Golgi apparatus where distinct monosaccharides are sequentially bound and trimmed, resulting in increasingly complex branched glycan structures. Of utmost importance for this process is the intraorganellar environment of the Golgi. Each Golgi compartment has a distinct pH, which is maintained by the vacuolar H+-ATPase (V-ATPase). Moreover, tethering factors such as Golgins and the conserved oligomeric Golgi (COG) complex, in concert with coatomer (COPI) and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated membrane fusion, efficiently deliver glycosylation enzymes to the right Golgi compartment. Together, these factors maintain intra-Golgi trafficking of proteins involved in glycosylation and thereby enable proper glycosylation. However, pathogenic mutations in these factors can cause defective glycosylation and lead to diseases with a wide variety of symptoms such as liver dysfunction and skin and bone disorders. Collectively, this group of disorders is known as congenital disorders of glycosylation (CDG). Recent technological advances have enabled the robust identification of novel CDGs related to membrane trafficking components. In this review, we highlight differences and similarities between membrane trafficking-related CDGs.
Pharmacogenomics and Pharmacogenetics in Osteosarcoma: Translational Studies and Clinical Impact
Authors: Hattinger Claudia Maria , Patrizio Maria Pia , Luppi Silvia , Serra Massimo
Published: June 2020

High-grade osteosarcoma (HGOS) is a very aggressive bone tumor which primarily affects adolescents and young adults. Although not advanced as is the case for other cancers, pharmacogenetic and pharmacogenomic studies applied to HGOS have been providing hope for an improved understanding of the biology and the identification of genetic biomarkers, which may impact on clinical care management. Recent developments of pharmacogenetics and pharmacogenomics in HGOS are expected to: i) highlight genetic events that trigger oncogenesis or which may act as drivers of disease; ii) validate research models that best predict clinical behavior; and iii) indicate genetic biomarkers associated with clinical outcome (in terms of treatment response, survival probability and susceptibility to chemotherapy-related toxicities). The generated body of information may be translated to clinical settings, in order to improve both effectiveness and safety of conventional chemotherapy trials as well as to indicate new tailored treatment strategies. Here, we review and summarize the current scientific evidence for each of the aforementioned issues in view of possible clinical applications.
Investigation of Cytotoxic T Lymphocyte Function during Allorejection in the Anterior Chamber of the Eye
Authors: Chang Hsin-Fang , Wirkner Marie-Louise , Krause Elmar , Rettig Jens
Published: June 2020

Cytotoxic T lymphocytes (CTL) are an essential part of our immune system by killing infected and malignant cells. To fully understand this process, it is necessary to study CTL function in the physiological setting of a living organism to account for their interplay with other immune cells like CD4+ T helper cells and macrophages. The anterior chamber of the eye (ACE), originally developed for diabetes research, is ideally suited for non-invasive and longitudinal in vivo imaging. We take advantage of the ACE window to observe immune responses, particularly allorejection of islets of Langerhans cells by CTLs. We follow the onset of the rejection after vascularization on islets until the end of the rejection process for about a month by repetitive two-photon microscopy. We find that CTLs show reduced migration on allogeneic islets in vivo compared to in vitro data, indicating CTL activation. Interestingly, the temporal infiltration pattern of T cells during rejection is precisely regulated, showing enrichment of CD4+ T helper cells on the islets before arrival of CD8+ CTLs. The adaptation of the ACE to immune responses enables the examination of the mechanism and regulation of CTL-mediated killing in vivo and to further investigate the killing in gene-deficient mice that resemble severe human immune diseases.
Chronic Sildenafil Treatment Improves Vasomotor Function in a Mouse Model of Accelerated Aging
Authors: Golshiri Keivan , Ataei Ataabadi Ehsan , Brandt Renata , van der Pluijm Ingrid , de Vries René , Danser A. H. Jan , Roks Anton
Published: June 2020

Aging leads to a loss of vasomotor control. Both vasodilation and vasoconstriction are affected. Decreased nitric oxide–cGMP-mediated relaxation is a hallmark of aging. It contributes to vascular disease, notably hypertension, infarction, and dementia. Decreased vasodilation can be caused by aging independently from cardiovascular risk factors. This process that can be mimicked in mice in an accelerated way by activation of the DNA damage response. Genetic deletion of the DNA repair enzyme ERCC1 endonuclease in mice, as in the case of Ercc1Δ/- mice, can be used as a tool to accelerate aging. Ercc1Δ/- mice develop age-dependent vasomotor dysfunction from two months after birth. In the present study we tested if chronic treatment with sildenafil, a phosphodiesterase 5 inhibitor that augments NO–cGMP signaling, can reduce the development of vasomotor dysfunction in Ercc1Δ/- mice. Ercc1Δ/- mice and wild-type littermates were treated with 10 mg/kg/d of sildenafil from the age of 6 to the age of 14 weeks. Blood pressure and in vivo and ex vivo vasomotor responses were measured at the end of the treatment period. Ercc1Δ/- mice developed decreased reactive hyperemia, and diminished NO–cGMP-dependent acetylcholine responses. The diminished acetylcholine response involved both endothelial and vascular smooth muscle cell signaling. Chronic sildenafil exclusively improved NO–cGMP signaling in VSMC, and had no effect on endothelium-derived hyperpolarization. Sildenafil also improved KCl hypocontractility in Ercc1Δ/- mice. All effects were blood pressure-independent. The findings might be of clinical importance for prevention of morbidities related to vascular aging as well as for progeria patients with a high risk of cardiovascular disease.
Body Composition Findings by Computed Tomography in SARS-CoV-2 Patients: Increased Risk of Muscle Wasting in Obesity
Authors: Gualtieri Paola , Falcone Carmela , Romano Lorenzo , Macheda Sebastiano , Correale Pierpaolo , Arciello Pietro , Polimeni Nicola , De Lorenzo Antonino
Published: June 2020

Obesity is a characteristic of COVID-19 patients and the risk of malnutrition can be underestimated due to excess of fat: a paradoxical danger. Long ICU hospitalization exposes patients to a high risk of wasting and loss of lean body mass. The complex management precludes the detection of anthropometric parameters for the definition and monitoring of the nutritional status. The use of imaging diagnostics for body composition could help to recognize and treat patients at increased risk of wasting with targeted pathways. COVID-19 patients admitted to the ICU underwent computed tomography within 24 h and about 20 days later, to evaluate the parameters of the body and liver composition. The main results were the loss of the lean mass index and a greater increase in liver attenuation in obese subjects. These could be co-caused by COVID-19, prolonged bed rest, the complex medical nutritional therapy, and the starting condition of low-grade inflammation of the obese. The assessment of nutritional status, with body composition applied to imaging diagnostics and metabolic profiles in COVID-19, will assist in prescribing appropriate medical nutritional therapy. This will reduce recovery times and complications caused by frailty.
LC–ESI–FT–MSn Metabolite Profiling of Symphytum officinale L. Roots Leads to Isolation of Comfreyn A, an Unusual Arylnaphthalene Lignan
Authors: D’Urso Gilda , Masullo Milena , Seigner Jacqueline , Holper-Schichl Yvonne M. , de Martin Rainer , Plaza Alberto , Piacente Sonia
Published: June 2020

Preparations of comfrey (Symphytum officinale L.) roots are used topically to reduce inflammation. Comfrey anti-inflammatory and analgesic properties have been proven in clinical studies. However, the bioactive compounds associated with these therapeutic activities are yet to be identified. An LC–ESI–Orbitrap–MSn metabolite profile of a hydroalcoholic extract of comfrey root guided the identification of 20 compounds, including a new arylnaphthalene lignan bearing a rare δ-lactone ring, named comfreyn A. Its structure was determined using extensive 2D NMR and ESI–MS experiments. Additionally, the occurrence of malaxinic acid, caffeic acid ethyl ester, along with the lignans ternifoliuslignan D, 3-carboxy-6,7-dihydroxy-1-(3′,4′-dihydroxyphenyl) -naphthalene, globoidnan A and B, and rabdosiin was reported in S. officinale for the first time. These results helped to redefine the metabolite profile of this medicinal plant. Finally, caffeic acid ethyl ester and comfreyn A were found to significantly inhibit E-selectin expression in IL-1β stimulated human umbilical vein endothelial cells (HUVEC), with EC values of 64 and 50 µM, respectively.
Wnt/β-Catenin Signaling in Oral Carcinogenesis
Authors: Reyes Montserrat , Flores Tania , Betancur Diego , Peña-Oyarzún Daniel , Torres Vicente A.
Published: June 2020

Oral carcinogenesis is a complex and multifactorial process that involves cumulative genetic and molecular alterations, leading to uncontrolled cell proliferation, impaired DNA repair and defective cell death. At the early stages, the onset of potentially malignant lesions in the oral mucosa, or oral dysplasia, is associated with higher rates of malignant progression towards carcinoma in situ and invasive carcinoma. Efforts have been made to get insights about signaling pathways that are deregulated in oral dysplasia, as these could be translated into novel markers and might represent promising therapeutic targets. In this context, recent evidence underscored the relevance of the Wnt/β-catenin signaling pathway in oral dysplasia, as this pathway is progressively “switched on” through the different grades of dysplasia (mild, moderate and severe dysplasia), with the consequent nuclear translocation of β-catenin and expression of target genes associated with the maintenance of representative traits of oral dysplasia, namely cell proliferation and viability. Intriguingly, recent studies provide an unanticipated connection between active β-catenin signaling and deregulated endosome trafficking in oral dysplasia, highlighting the relevance of endocytic components in oral carcinogenesis. This review summarizes evidence about the role of the Wnt/β-catenin signaling pathway and the underlying mechanisms that account for its aberrant activation in oral carcinogenesis.
The Structure of Amyloid Versus the Structure of Globular Proteins
Authors: Fabian Piotr , Banach Mateusz , Stapor Katarzyna , Konieczny Leszek , Ptak-Kaczor Magdalena , Roterman Irena
Published: June 2020

The issue of changing the structure of globular proteins into an amyloid form is in the focus of researchers' attention. Numerous experimental studies are carried out, and mathematical models to define the essence of amyloid transformation are sought. The present work focuses on the issue of the hydrophobic core structure in amyloids. The form of ordering the hydrophobic core in globular proteins is described by a 3D Gaussian distribution analog to the distribution of hydrophobicity in a spherical micelle. Amyloid fibril is a ribbon-like micelle made up of numerous individual chains, each representing a flat structure. The distribution of hydrophobicity within a single chain included in the fibril describes the 2D Gaussian distribution. Such a description expresses the location of polar residues on a circle with a center with a high level of hydrophobicity. The presence of this type of order in the amyloid forms available in Preotin Data Bank (PDB) (both in proto- and superfibrils) is demonstrated in the present work. In this system, it can be assumed that the amyloid transformation is a chain transition from 3D Gauss ordering to 2D Gauss ordering. This means changing the globular structure to a ribbon-like structure. This observation can provide a simple mathematical model for simulating the amyloid transformation of proteins.
Vasoactive Intestinal Polypeptide in the Carotid Body—A History of Forty Years of Research. A Mini Review
Authors: Gonkowski Slawomir
Published: June 2020

Vasoactive intestinal polypeptide (VIP) consists of 28 amino acid residues and is widespreadin many internal organs and systems. Its presence has also been found in the nervous structuressupplying the carotid body not only in mammals but also in birds and amphibians. The numberand distribution of VIP in the carotid body clearly depends on the animal species studied;however, among all the species, this neuropeptide is present in nerve fibers around blood vesselsand between glomus cell clusters. It is also known that the number of nerves containing VIP locatedin the carotid body may change under various pathological and physiological factors. The knowledgeconcerning the functioning of VIP in the carotid body is relatively limited. It is known that VIP mayimpact the glomus type I cells, causing changes in their spontaneous discharge, but the main impactof VIP on the carotid body is probably connected with the vasodilatory eects of this peptide and itsinfluence on blood flow and oxygen delivery. This review is a concise summary of forty years ofresearch concerning the distribution of VIP in the carotid body.
The Impact of Composition and Morphology on Ionic Conductivity of Silk/Cellulose Bio-Composites Fabricated from Ionic Liquid and Varying Percentages of Coagulation Agents
Authors: Blessing Bailey , Trout Cory , Morales Abneris , Rybacki Karleena , Love Stacy A. , Lamoureux Guillaume , O’Malley Sean M. , Hu Xiao , Salas-de la Cruz David
Published: June 2020

Blended biocomposites created from the electrostatic and hydrophobic interactions between polysaccharides and structural proteins exhibit useful and unique properties. However, engineering these biopolymers into applicable forms is challenging due to the coupling of the material’s physicochemical properties to its morphology, and the undertaking that comes with controlling this. In this particular study, numerous properties of the Bombyx mori silk and microcrystalline cellulose biocomposites blended using ionic liquid and regenerated with various coagulation agents were investigated. Specifically, the relationship between the composition of polysaccharide-protein bio-electrolyte membranes and the resulting morphology and ionic conductivity is explored using numerous characterization techniques, including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray scattering, atomic force microscopy (AFM) based nanoindentation, and dielectric relaxation spectroscopy (DRS). The results revealed that when silk is the dominating component in the biocomposite, the ionic conductivity is higher, which also correlates with higher β-sheet content. However, when cellulose becomes the dominating component in the biocomposite, this relationship is not observed; instead, cellulose semicrystallinity and mechanical properties dominate the ionic conduction.
A Multi-Scale Study of Water Dynamics under Confinement, Exploiting Numerical Simulations in Relation to NMR Relaxometry, PGSE and NMR Micro-Imaging Experiments: An Application to the Clay/Water Interface
Authors: Porion Patrice , Delville Alfred
Published: June 2020

Water mobility within the porous network of dense clay sediments was investigated over a broad dynamical range by using 2H nuclear magnetic resonance spectroscopy. Multi-quanta 2H NMR spectroscopy and relaxation measurements were first performed to identify the contributions of the various relaxation mechanisms monitoring the time evolution of the nuclear magnetisation of the confined heavy water. Secondly, multi-quanta spin-locking NMR relaxation measurements were then performed over a broad frequency domain, probing the mobility of the confined water molecules on a time-scale varying between microseconds and milliseconds. Thirdly, 1H NMR pulsed-gradient spin-echo attenuation experiments were performed to quantify water mobility on a time-scale limited by the NMR transverse relaxation time of the confined NMR probe, typically a few milliseconds. Fourthly, the long living quantum state of the magnetisation of quadrupolar nuclei was exploited to probe a two-time correlation function at a time-scale reaching one second. Finally, magnetic resonance imaging measurements allow probing the same dynamical process on time-scales varying between seconds and several hours. In that context, multi-scale modelling is required to interpret these NMR measurements and extract information on the influences of the structural properties of the porous network on the apparent mobility of the diffusing water molecules. That dual experimental and numerical approach appears generalizable to a large variety of porous networks, including zeolites, micelles and synthetic or biological membranes.
An Overview on the Current Status and Future Perspectives of Smart Cars
Authors: Arena Fabio , Pau Giovanni , Severino Alessandro
Published: June 2020

In recent years, the smart car sector has been increasing enormously in the Internet of Things (IoT) market. Furthermore, the number of smart cars seems set to increase over the next few years. This goal will be achieved because the application of recent IoT technologies to the automotive sector opens up innovative opportunities for the mobility of the future, in which connected cars will be more and more prominent in smart cities. This paper aims to provide an overview of the current status and future perspectives of smart cars, taking into account technological, transport, and social features. An analysis concerning the approaches to making smart a generic car, the possible evolutions that could occur in the coming decades, the characteristics of 5G, ADAS (advanced driver assistance systems), and the power sources is carried out in this paper.
It Is Not All about Being Sweet: Differences in Floral Traits and Insect Visitation among Hybrid Carrot Cultivars
Authors: Gaffney Ann , Bohman Björn , Quarrell Stephen R. , Brown Philip H. , Allen Geoff R.
Published: June 2020

Cytoplasmically male-sterile (CMS) carrot cultivars suffer from low pollination rates. In this study, insect visitation varied more than eightfold between 17 CMS carrot cultivars in a field-based cultivar evaluation trial. The visitation rates of honey bees, nectar scarabs, muscoid flies, and wasps each significantly differed among these cultivars. No significant difference in visitation rates was observed among cultivars of different CMS type (brown-anther or petaloid) or flower colour, but cultivars of Berlicumer root type had significantly higher insect visitation rates than Nantes. Six cultivars were further compared in regard to selected umbel traits: as umbel diameter increased, so did the visitation of soldier beetles, while that of honey bees decreased. Finally, nectar of these six cultivars was analysed for sugar content, which revealed monosaccharides to be the most common sugars in all. There was high variation in the levels of sugars from individual umbellets but no significant difference in nectar sugar composition among cultivars, suggesting that nectar sugar composition is of minor importance regarding pollinator attraction to hybrid CMS carrot umbels.
Physical and Physiological Monitoring on Red Palm Weevil-Infested Oil Palms
Authors: Harith-Fadzilah Nazmi , Haris-Hussain Mohamad , Abd Ghani Idris , Zakaria Azlina , Amit Samsudin , Zainal Zamri , Azmi Wahizatul Afzan , Jalinas Johari , Hassan Maizom
Published: June 2020

The red palm weevil (RPW) is a stem boring Coleoptera that decimates host palm trees from within. The challenge of managing this pest is due to a lack of physical symptoms during the early stages of infestation. Investigating the physiological changes that occur within RPW-infested palm trees may be useful in establishing a new approach in RPW detection. In this study, the effects of RPW infestation were investigated in Elaeis guineensis by observing changes in physical and physiological parameters during the progress of infestation by visual inspection and the comparison of growth, gas exchange, stomatal conductance, and chlorophyll content between the non-infested control, physically wounded, and RPW-infested E. guineensis groups. During the study period, four distinct levels of physical infestation were observed and recorded. The RPW-infested group displayed significantly lower maximum photosynthesis activity (Amax) starting from the third week post-infestation. However, growth in terms of change in plant height and stem circumference, leaves’ stomatal conductance, and chlorophyll content were not significantly different between the three groups during the duration of the study. The significant drop in photosynthesis was observed one week before physical changes appeared. This suggests the promising utilisation of photosynthesis activity as a signal for detecting RPW infestation at the early stage of attacks, which could be useful for integration in integrated pest management (IPM).
18F-Fluorocholine PET and Multiphase CT Integrated in Dual Modality PET/4D-CT for Preoperative Evaluation of Primary Hyperparathyroidism
Authors: Pretet Valentin , Rotania Marianela , Helali Mehdi , Ignat Mihaela , Vix Michel , Imperiale Alessio
Published: June 2020

The present retrospective study evaluates the diagnostic value of integrated 18F-Fluorocholine positron emission tomography/four-dimensional contrast-enhanced computed tomography (18F-FCH PET/4D-CT) as second-line imaging in preoperative work-up of primary hyperparathyroidism (pHPT), and compares 18F-FCH PET with 4D-CT. Patients with pHPT and negative/discordant first-line imaging addressed for integrated 18F-FCH PET/4D-CT were retrospectively selected. Sensitivity and detection rate (DR%) of 18F-FCH PET/CT, 4D-CT, and PET/4D-CT were calculated according to the per patient and per lesion analyses, and afterwards compared. Histology associated with a decrease more than 50% of perioperative parathyroid hormone (PTH) blood level was used as a gold standard. Persistent high serum PTH and calcium levels during a 6-month follow-up was considered as presence of pHPT in both operated and non-operated patients. 50 patients (55 glands) were included. 44/50 patients (88%) were surgically treated. On a per patient analysis, sensitivity was 93%, 80%, and 95%, and DR% was 82%, 68%, and 84%, respectively for PET/CT, 4D-CT, and PET/4D-CT. PET/CT was more sensitive than 4D-CT (p = 0.046). PET/4D-CT performed better than 4D-CT (p = 0.013) but was equivalent to PET/CT alone. On a per gland analysis, sensitivity PET/CT, 4D-CT, and PET/4D-CT was 88%, 66%, and 92%, and DR% was 79%, 57%, and 83%, respectively. PET/CT and PET/4D-CT were more sensitive than 4D-CT alone (p = 0.01, p < 0.001, respectively). However, PET/CT and PET/4D-CT performed similarly. In conclusion, 18F-FCH PET provides better identification of hyperfunctioning parathyroids than 4D-CT and the combination of both did not significantly improve diagnostic sensitivity. Further investigations involving larger populations are necessary to define the role of 18F-FCH PET/4D-CT as a “one-stop shop” second-line imaging in preoperative work-up of pHPT, especially considering the additional patient radiation exposure due to multi-phase CT.
Genetic Study in Korean Pediatric Patients with Steroid-Resistant Nephrotic Syndrome or Focal Segmental Glomerulosclerosis
Authors: Park Eujin , Lee Chung , Kim Nayoung , Ahn Yo , Park Young , Lee Joo , Kim Seong , Cho Min , Cho Heeyeon , Yoo Kee , Shin Jae , Kang Hee , Ha Il-Soo , Park Woong-Yang , Cheong Hae
Published: June 2020

Steroid-resistant nephrotic syndrome (SRNS) is one of the major causes of end-stage renal disease (ESRD) in childhood and is mostly associated with focal segmental glomerulosclerosis (FSGS). More than 50 monogenic causes of SRNS or FSGS have been identified. Recently, the mutation detection rate in pediatric patients with SRNS has been reported to be approximately 30%. In this study, genotype-phenotype correlations in a cohort of 291 Korean pediatric patients with SRNS/FSGS were analyzed. The overall mutation detection rate was 43.6% (127 of 291 patients). WT1 was the most common causative gene (23.6%), followed by COQ6 (8.7%), NPHS1 (8.7%), NUP107 (7.1%), and COQ8B (6.3%). Mutations in COQ6, NUP107, and COQ8B were more frequently detected, and mutations in NPHS2 were less commonly detected in this cohort than in study cohorts from Western countries. The mutation detection rate was higher in patients with congenital onset, those who presented with proteinuria or chronic kidney disease/ESRD, and those who did not receive steroid treatment. Genetic diagnosis in patients with SRNS provides not only definitive diagnosis but also valuable information for decisions on treatment policy and prediction of prognosis. Therefore, further genotype-phenotype correlation studies are required.
Burden of Undiagnosed Type 2 Diabetes in Diabetic Kidney Disease: A Japanese Retrospective Cohort Study
Authors: Tanabe Hayato , Saito Haruka , Machii Noritaka , Kudo Akihiro , Tanaka Kenichi , Asahi Koichi , Kazama Junichiro James , Shimabukuro Michio
Published: June 2020

The risk of developing diabetic kidney disease (DKD) in patients with undiagnosed diabetes mellitus (UD) has never been evaluated. We studied the burden of UD on the risk of developing DKD in the Japanese population in a single-center retrospective cohort study. The patients with type 2 diabetes mellitus, but without DKD (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or proteinuria), were recruited from January 2018 to January 2019; medical records were scrutinized retrospectively from January 2003 until May 2019. The individuals, with diabetes that could not be denied based on past and current records, comprised the undiagnosed diabetes (UD) group whereas those with confirmed diagnosis comprised the diagnosed diabetes (DD) group. The group differences were tested using a Kaplan–Meier curve and Cox proportional hazards model. Among the 408 participants, 164 (40.2%) and 244 (59.8%) comprised the DD and UD groups, respectively. The baseline parameters, including age, male gender, and BMI were comparable between the groups, but the plasma glucose, HbA1c levels, and diabetic retinopathy prevalence were higher in the UD group. The risk of developing DKD (log rank test, p < 0.001), an eGFR of < 60 mL/min/1.73 m2 (p = 0.001) and proteinuria (p = 0.007) were also higher in the UD group. The unadjusted and adjusted hazard ratios for DKD were 1.760 ((95% CI: 1.323–2.341), p < 0.001) and 1.566 ((95% CI: 1.159–2.115), p = 0.003), respectively, for the UD group. In conclusion, this is the first report showing that UD is a strong risk factor for DKD. The notion that a longer duration of untreated diabetes mellitus is involved strongly in the risk of developing DKD warrants the need for the identification and monitoring of UD patients.
Mathematical Model of Muscle Wasting in Cancer Cachexia
Authors: Farhang-Sardroodi Suzan , Wilkie Kathleen P.
Published: June 2020

Cancer cachexia is a debilitating condition characterized by an extreme loss of skeletal muscle mass, which negatively impacts patients’ quality of life, reduces their ability to sustain anti-cancer therapies, and increases the risk of mortality. Recent discoveries have identified the myostatin/activin A/ActRIIB pathway as critical to muscle wasting by inducing satellite cell quiescence and increasing muscle-specific ubiquitin ligases responsible for atrophy. Remarkably, pharmacological blockade of the ActRIIB pathway has been shown to reverse muscle wasting and prolong the survival time of tumor-bearing animals. To explore the implications of this signaling pathway and potential therapeutic targets in cachexia, we construct a novel mathematical model of muscle tissue subjected to tumor-derived cachectic factors. The model formulation tracks the intercellular interactions between cancer cell, satellite cell, and muscle cell populations. The model is parameterized by fitting to colon-26 mouse model data, and the analysis provides insight into tissue growth in healthy, cancerous, and post-cachexia treatment conditions. Model predictions suggest that cachexia fundamentally alters muscle tissue health, as measured by the stem cell ratio, and this is only partially recovered by anti-cachexia treatment. Our mathematical findings suggest that after blocking the myostatin/activin A pathway, partial recovery of cancer-induced muscle loss requires the activation and proliferation of the satellite cell compartment with a functional differentiation program.
The Role of Airways 17β-Estradiol as a Biomarker of Severity in Postmenopausal Asthma: A Pilot Study
Authors: Scioscia Giulia , Carpagnano Giovanna Elisiana , Lacedonia Donato , Soccio Piera , Quarato Carla Maria Irene , Trabace Luigia , Fuso Paolo , Foschino Barbaro Maria Pia
Published: June 2020

Background: Asthma severity differs according to gender; in adult women, there is higher prevalence and severity of asthma than in men, and it coincides with changes in sex hormones. Recently, a new phonotype of asthma has been identified that appears after menopause, and it may be associated with decreased estrogen levels. Our goal was to study the 17β-estradiol (E2) concentrations in the blood and airways of women affected by asthma onset after menopause, evaluating its possible role in the severity of the disease. Methods: We enrolled 33 consecutive women with a diagnosis of postmenopausal asthma, recruited from the outpatient pulmonary clinic: 18 with severe (SA) and 15 with mild-to-moderate (MMA) asthma. We also included 30 age-matched healthy menopausal women as controls (HS). All subjects enrolled underwent blood and sputum collection (IS), and E2 concentrations were determined in plasma and sputum supernatant samples using an enzyme-linked immunosorbent assay (ELISA) kit. Results: Significantly higher serum concentrations of E2 were found in postmenopausal SA compared to MMA and HS, respectively (33 ± 5.5 vs. 24 ± 6.63 vs. 7.79 ± 1.54 pg/mL, p < 0.05). Similar results were found in the IS: significantly higher levels of E2 were detected in patients with postmenopausal SA compared with MMA and HS, respectively (0.34 ± 0.17 vs. 0.26 ± 0.13 vs. 0.07 ± 0.06 pg/mL, p < 0.05). We found positive correlations between IS E2 concentrations and sputum neutrophil levels in SA group (ρ = 0.52, p < 0.05). Conclusions: Our findings showed the possibility to measure E2 in the airways, and it has increased in postmenopausal asthmatic patients, especially in those with SA. Airways E2 levels may serve as a suitable biomarker of postmenopausal SA to help to phenotype SA patients with neutrophil inflammation.
A Physiologic Approach to Hemodynamic Monitoring and Optimizing Oxygen Delivery in Shock Resuscitation
Authors: Russell Amy , Rivers Emanuel P. , Giri Paresh C. , Jaehne Anja K. , Nguyen H. Bryant
Published: June 2020

The approach to shock resuscitation focuses on all components of oxygen delivery, including preload, afterload, contractility, hemoglobin, and oxygen saturation. Resuscitation focused solely on preload and fluid responsiveness minimizes other key elements, resulting in suboptimal patient care. This review will provide a physiologic and practical approach for the optimization of oxygen delivery utilizing available hemodynamic monitoring technologies. Venous oxygen saturation (SvO2) and lactate will be discussed as indicators of shock states and endpoints of resuscitation within the framework of resolving oxygen deficit and oxygen debt.
Blood Levels of Free-Circulating Mitochondrial DNA in Septic Shock and Postsurgical Systemic Inflammation and Its Influence on Coagulation: A Secondary Analysis of a Prospective Observational Study
Authors: Schneck Emmanuel , Edinger Fabian , Hecker Matthias , Sommer Natascha , Pak Oleg , Weissmann Norbert , Hecker Andreas , Reichert Martin , Markmann Melanie , Sander Michael , Koch Christian
Published: June 2020

Major surgery is regularly associated with clinical signs of systemic inflammation, which potentially affects the rapid identification of sepsis. Therefore, this secondary analysis of an observational study aims to determine whether NADH dehydrogenase 1 (ND1) mitochondrial DNA (mtDNA) could be used as a potential biomarker for the discrimination between septic shock and postsurgical systemic inflammation. Overall, 80 patients were included (septic shock (n = 20), cardiac artery bypass grafting (CABG, n = 20), major abdominal surgery (MAS, n = 20), and matched controls (CTRL, n = 20)). Quantitative PCR was performed to measure ND1 mtDNA. Thromboelastography was used to analyze the coagulatory system. Free-circulating ND1 mtDNA levels were significantly higher in septic shock patients compared to patients suffering from post-surgical inflammation ({copies/µL}: CTRL: 1208 (668–2685); septic shock: 3823 (2170–7318); CABG: 1272 (417–2720); and MAS: 1356 (694–2845); CTRL vs. septic shock: p < 0.001; septic shock vs. CABG: p < 0.001; septic shock vs. MAS: p = 0.006; CABG vs. MAS: p = 0.01). ND1 mtDNA levels in CABG patients showed a strong positive correlation with fibrinogen (correlation coefficient [r]= 0.57, p < 0.001) and fibrinogen-dependent thromboelastographic assays (maximum clot firmness, EXTEM: r = 0.35, p = 0.01; INTEM: r = 0.31, p = 0.02; FIBTEM: r = 0.46, p < 0.001). In conclusion, plasma levels of free-circulating ND1 mtDNA were increased in septic shock patients and were discriminative between sepsis and surgery-induced inflammation. Furthermore, this study showed an association between ND1 mtDNA and a fibrinogen-dependent pro-coagulatory shift in cardiac surgical patients.
Tetracycline Photocatalytic Degradation under CdS Treatment
Authors: Nagamine Momoka , Osial Magdalena , Jackowska Krystyna , Krysinski Pawel , Widera-Kalinowska Justyna
Published: June 2020

Industrialization and the growing consumption of medicines leads to global aquatic contamination. One of the antibiotics widely used against bacterial infections in both human and veterinary medicine is tetracycline. Despite its positive antibiotic action, tetracycline is resistant against degradation, and therefore it accumulates in the environment, including the aquatic environment, creating great health hazards, possibly stimulating antibiotic resistance of pathogenic organisms. In this research, aqueous suspensions of semiconductor nanoparticles CdS were used for photocatalytic activity studies in the presence of methylene blue as a model compound, and finally, in the presence of tetracycline, a broad-spectrum antibiotic widely used against bacterial infections, as well as a live-stock food additive. The mechanism and kinetic rate constants of photocatalytic degradation processes of methylene blue and tetracycline were described in correlation with the energy diagram of CdS nanoparticles.
EQ-5D-3L for Assessing Quality of Life in Older Nursing Home Residents with Cognitive Impairment
Authors: Pérez-Ros Pilar , Martínez-Arnau Francisco M
Published: June 2020

Background: Quality of life (QoL) is recognized as an important patient-reported outcome measure. Assessing QoL in older people with cognitive impairment is a challenge due to discrepancies in the collection of data via proxies versus self-report. This study aimed to assess the psychometric properties of the self-reported EQ-5D (including the EQ index and EQ visual analog scale (VAS)) in nursing homes residents with cognitive impairment and to analyze its validity based on scales included in the comprehensive geriatric assessment. Methods: Cross-sectional, multicenter study analyzing the feasibility, acceptability, reliability, and validity of the EQ-5D based on 251 self-administered questionnaires in a sample of nursing home residents with cognitive impairment. Reference scales were those from the comprehensive geriatric assessment, equivalent to the five dimensions of the EuroQol. Results: The EQ index was 0.31 (0.37) and the EQ VAS was 35.96 (29.86), showing adequate acceptability and feasibility. Cronbach’s alpha was 0.723. The EQ index and EQ VAS, as outcome variables for multiple linear regression models including CGA titration scales, showed better validity for the EQ index than the EQ VAS. Conclusions: As a self-administered generic scale, the EQ-5D-3L could be a good tool for QoL assessment in nursing home residents with cognitive impairment.
Interaction of Oxidative Stress and Misfolded Proteins in the Mechanism of Neurodegeneration
Authors: Abramov Andrey Y. , Potapova Elena V. , Dremin Viktor V. , Dunaev Andrey V.
Published: June 2020

Aggregation of the misfolded proteins β-amyloid, tau, huntingtin, and α-synuclein is one of the most important steps in the pathology underlying a wide spectrum of neurodegenerative disorders, including the two most common ones—Alzheimer’s and Parkinson’s disease. Activity and toxicity of these proteins depends on the stage and form of aggregates. Excessive production of free radicals, including reactive oxygen species which lead to oxidative stress, is proven to be involved in the mechanism of pathology in most of neurodegenerative disorders. Both reactive oxygen species and misfolded proteins play a physiological role in the brain, and only deregulation in redox state and aggregation of the proteins leads to pathology. Here, we review the role of misfolded proteins in the activation of ROS production from various sources in neurons and glia. We discuss if free radicals can influence structural changes of the key toxic intermediates and describe the putative mechanisms by which oxidative stress and oligomers may cause neuronal death.
Friction Behavior of Pre-Damaged Wet-Running Multi-Plate Clutches in an Endurance Test
Authors: Schneider Thomas , Voelkel Katharina , Pflaum Hermann , Stahl Karsten
Published: June 2020

Wet-running multi-plate clutches should be prevented from failing due to the often safety-relevant functions they fulfill in the drive train. In addition to long-term damage, spontaneous damage is of particular relevance for failures. This paper focuses on the influence of spontaneous damage on frictional behavior in the later life cycle. The aim of the experimental investigations is to initially cause spontaneous damage in wet-running multi-plate clutches with sintered friction linings. For this purpose, three clutches are first pre-damaged in stage tests with different intensities, so that the first spontaneous damage (local discoloration, sinter transfer) occurs. In the second step, an endurance test is carried out with the pre-damaged clutch packs and a non-pre-damaged reference clutch. The friction behavior of the clutches during the endurance test is compared and evaluated. It shows that local discoloration and sinter transfer are no longer visible after the endurance tests. At the beginning of the endurance test, the values of coefficient of friction are higher over the entire speed range of the heavily pre-damaged clutches than with the slightly pre-damaged clutch and the non-pre-damaged reference clutch. At the end of the endurance test, it can be observed that the greater the pre-damage to the clutches is, the greater the coefficient of friction increases with decreasing sliding speed.
Tribochemistry and Lubrication of Alkaline Glass Lubricants in Hot Steel Manufacturing
Authors: Ta Thi D. , Tran Bach H. , Tieu Kiet
Published: June 2020

Nowadays, the increasing demand to reduce energy consumption and improve process reliability requires an alternative lubricant with an effective tribological performance and environmentally friendly properties to replace traditional lubricants in hot steel manufacturing. The current work reviews recent comprehensive experimental and theoretical investigations in a new generation of alkaline-based glass lubricants, with phosphate, borate, and silicate being intensively researched. This class of lubricants showed an outstanding friction reduction, anti-wear, and anti-oxidation performance on coupled steel pairs over a wide range of temperatures (from 650 °C to 1000 °C). Each type had different tribochemical reactions within itself and with oxidized steel surfaces, which were largely determined by their chemical nature. In addition, the critical role of each structural component was also determined and corroborated by computational simulation. The theoretical studies at quantum and atomic levels reinforced our experimental findings by providing insights into the reaction mechanism using the static and dynamic simulations of the adsorption of lubricant molecules onto iron oxide surfaces. Additionally, the new reactive molecular dynamics (MD) model developed for alkali phosphate will need to be extended further to consider the realistic operating conditions of these lubricants at the atomic scale.
Recent Progress on Fullerene-Based Materials: Synthesis, Properties, Modifications, and Photocatalytic Applications
Authors: Yao Sai , Yuan Xingzhong , Jiang Longbo , Xiong Ting , Zhang Jin
Published: June 2020

Solar light is an inexpensive energy source making up for energy shortage and solving serious environmental problems. For efficient utilization of solar energy, photocatalytic materials have attracted extensive attention over the last decades. As zero-dimensional carbon nanomaterials, fullerenes (C60, C70, etc.) have been extensively investigated for photocatalytic applications. Due to their unique properties, fullerenes can be used with other semiconductors as photocatalyst enhancers, and also as novel photocatalysts after being dispersed on non-semiconductors. This review summarizes fullerene-based materials (including fullerene/semiconductors and fullerene/non-semiconductors) for photocatalytic applications, such as water splitting, Cr (VI) reduction, pollutant degradation and bacterial disinfection. Firstly, the optical and electronic properties of fullerene are presented. Then, recent advances in the synthesis and photocatalytic mechanisms of fullerene-based photocatalysts are summarized. Furthermore, the effective performances of fullerene-based photocatalysts are discussed, mainly concerning photocatalytic H2 generation and pollutant removal. Finally, the current challenges and prospects of fullerene-based photocatalysts are proposed. It is expected that this review could bring a better understanding of fullerene-based photocatalysts for water treatment and environmental protection.
Characterization of a Toothpaste Containing Bioactive Hydroxyapatites and In Vitro Evaluation of Its Efficacy to Remineralize Enamel and to Occlude Dentinal Tubules
Authors: Degli Esposti Lorenzo , Ionescu Andrei C. , Brambilla Eugenio , Tampieri Anna , Iafisco Michele
Published: June 2020

Demineralization of dental hard tissues is a well-known health issue and the primary mechanism responsible for caries and dentinal hypersensitivity. Remineralizing toothpastes are nowadays available to improve conventional oral care formulations regarding the prevention and repair of demineralization. In this paper, we analyzed the chemical-physical features of a commercial toothpaste (Biosmalto Caries Abrasion and Erosion, Curasept S.p.A., Saronno, Italy), with particular attention paid to the water-insoluble fraction which contains the remineralizing bioactive ingredients. Moreover, the efficacy of the toothpaste to induce enamel remineralization and to occlude dentinal tubules has been qualitatively and semiquantitatively tested in vitro on human dental tissues using scanning electron microscopy and X-ray microanalysis. Our results demonstrated that the water-insoluble fraction contained silica as well as chitosan and poorly crystalline biomimetic hydroxyapatite doped with carbonate, magnesium, strontium, and fluoride ions. The formulation showed excellent ability to restore demineralized enamel into its native structure by epitaxial deposition of a new crystalline phase in continuity with the native one. It was also able to occlude the dentinal tubules exposed completely by acid-etching. Overall, this study demonstrated that the tested toothpaste contained a biomimetic ionic-substituted hydroxyapatite-based active principle and that, within the in vitro conditions analyzed in this study, it was effective in dental hard tissue remineralization.