bluuebunny/crossref_metadata_2025 huggingface dataset:
A Role of Inflammation and Immunity in Essential Hypertension—Modeled and Analyzed Using Petri Nets
Authors: Formanowicz Dorota , Rybarczyk Agnieszka , Radom Marcin , Formanowicz Piotr
Published: May 2020

Recent studies have shown that the innate and adaptive immune system, together with low-grade inflammation, may play an important role in essential hypertension. In this work, to verify the importance of selected factors for the development of essential hypertension, we created a Petri net-based model and analyzed it. The analysis was based mainly on t-invariants, knockouts of selected fragments of the net and its simulations. The blockade of the renin-angiotensin (RAA) system revealed that the most significant effect on the emergence of essential hypertension has RAA activation. This blockade affects: (1) the formation of angiotensin II, (2) inflammatory process (by influencing C-reactive protein (CRP)), (3) the initiation of blood coagulation, (4) bradykinin generation via the kallikrein-kinin system, (5) activation of lymphocytes in hypertension, (6) the participation of TNF alpha in the activation of the acute phase response, and (7) activation of NADPH oxidase—a key enzyme of oxidative stress. On the other hand, we found that the blockade of the activation of the RAA system may not eliminate hypertension that can occur due to disturbances associated with the osmotically independent binding of Na in the interstitium. Moreover, we revealed that inflammation alone is not enough to trigger primary hypertension, but it can coexist with it. We believe that our research may contribute to a better understanding of the pathology of hypertension. It can help identify potential subprocesses, which blocking will allow better control of essential hypertension.
Influence of Innate Immunity on Cancer Cell Stemness
Authors: Pastò Anna , Consonni Francesca Maria , Sica Antonio
Published: May 2020

Even if cancer stem cells (CSCs) represent only a small proportion of the tumor mass, they significantly account for tumor maintenance, resistance to therapies, relapse and metastatic spread, due to their increased capacity of self-renewal, multipotency, tumorigenicity and quiescence. Emerging evidence suggests that the immune contexture within the tumor microenvironment (TME) determines both the response to therapy and the clinical outcome. In this context, CSCs acquire immune evasion skills by editing immune cell functions and sculpting the immunosuppressive landscape of TME. Reciprocally, infiltrating immune cells influence CSCs self-renewal, tumorigenicity and metastasis. In this review, we summarize the immunomodulatory properties of CSCs, as well as the impact of innate immune cells on cancer cells stemness in the different phases of cancer immunoediting process and neoplastic progression.
The Protective Role of Bark and Bark Fibers of the Giant Sequoia (Sequoiadendron giganteum) during High-Energy Impacts
Authors: Bold Georg , Langer Max , Börnert Laura , Speck Thomas
Published: May 2020

The influences of (1) a high fiber content, (2) the arrangement of fibers in fiber groups, and (3) a layered hierarchical composition of the bark of the giant sequoia (Sequoiadendron giganteum) on its energy dissipation capability are analyzed and discussed regarding the relevance for an application in bioinspired components in civil engineering. The giant sequoia is native to the Sierra Nevada (USA), a region with regular rockfalls. It is thus regularly exposed to high-energy impacts, with its bark playing a major protective role, as can be seen in the wild and has been proven in laboratory experiments. The authors quantify the fundamental biomechanical properties of the bark at various length scales, taking into account its hierarchical setup ranging from the integral level (whole bark) down to single bark fibers. Microtensile tests on single fibers and fiber pairs give insights into the properties of single fibers as well as the benefits of the strong longitudinal interconnection between single fibers arranged in pairs. Going beyond the level of single fibers or fiber pairs, towards the integral level, quasistatic compression tests and dynamic impact tests are performed on samples comprising the whole bark (inner and outer bark). These tests elucidate the deformation behavior under quasistatic compression and dynamic impact relevant for the high energy dissipation and impact-damping behavior of the bark. The remarkable energy dissipation capability of the bark at the abovementioned hierarchical levels are linked to the layered and fibrous structure of the bark structurally analyzed by thin sections and SEM and µCT scans.
Drought Stress Tolerance and Photosynthetic Activity of Alloplasmic Lines T. dicoccum x T. aestivum
Authors: Terletskaya Nina V. , Shcherban Andrey B. , Nesterov Michail A. , Perfil’ev Roman N. , Salina Elena A. , Altayeva Nazira A. , Blavachinskaya Irina V.
Published: May 2020

Tetraploid species T. dicoccum Shuebl is a potential source of drought tolerance for cultivated wheat, including common wheat. This paper describes the genotyping of nine stable allolines isolated in the offspring from crossing of T. dicoccum x T. aestivum L. using 21 microsatellite (simple sequence repeats—SSR) markers and two cytoplasmic mitochondrial markers to orf256, rps19-p genes; evaluation of drought tolerance of allolines at different stages of ontogenesis (growth parameters, relative water content, quantum efficiency of Photosystem II, electron transport rate, energy dissipated in Photosystem II); and the study of drought tolerance regulator gene Dreb-1 with allele-specific PCR (AS-MARKER) and partial sequence analysis. Most allolines differ in genomic composition and T. dicoccum introgressions. Four allolines—D-b-05, D-d-05, D-d-05b, and D-41-05—revealed signs of drought tolerance of varying degrees. The more drought tolerant D-41-05 line was also characterized by Dreb-B1 allele introgression from T. dicoccum. A number of non-specific patterns and significant differences in allolines in regulation of physiological parameters in drought conditions is identified. Changes in photosynthetic activity in stress-drought are shown to reflect the level of drought tolerance of the forms studied. The contribution of different combinations of nuclear/cytoplasmic genome and alleles of Dreb-1 gene in allolines to the formation of stress tolerance and photosynthetic activity is discussed.
Diagnostic and Prognostic Potential of Biomarkers CYFRA 21.1, ERCC1, p53, FGFR3 and TATI in Bladder Cancers
Authors: Matuszczak Milena , Salagierski Maciej
Published: May 2020

The high occurrence of bladder cancer and its tendency to recur in combination with a lifelong surveillance make the treatment of superficial bladder cancer one of the most expensive and time-consuming. Moreover, carcinoma in situ often leads to muscle invasion with an unfavorable prognosis. Currently, invasive methods including cystoscopy and cytology remain a gold standard. The aim of this study was to explore urine-based biomarkers to find the one with the best specificity and sensitivity, which would allow optimizing the treatment plan. In this review, we sum up the current knowledge about Cytokeratin fragments (CYFRA 21.1), Excision Repair Cross-Complementation 1 (ERCC1), Tumour Protein p53 (Tp53), Fibroblast Growth Factor Receptor 3 (FGFR3), Tumor-Associated Trypsin Inhibitor (TATI) and their potential applications in clinical practice.
Genome-Wide Association and Prediction of Traits Related to Salt Tolerance in Autotetraploid Alfalfa (Medicago sativa L.)
Authors: Medina Cesar Augusto , Hawkins Charles , Liu Xiang-Ping , Peel Michael , Yu Long-Xi
Published: May 2020

Soil salinity is a growing problem in world production agriculture. Continued improvement in crop salt tolerance will require the implementation of innovative breeding strategies such as marker-assisted selection (MAS) and genomic selection (GS). Genetic analyses for yield and vigor traits under salt stress in alfalfa breeding populations with three different phenotypic datasets was assessed. Genotype-by-sequencing (GBS) developed markers with allele dosage and phenotypic data were analyzed by genome-wide association studies (GWAS) and GS using different models. GWAS identified 27 single nucleotide polymorphism (SNP) markers associated with salt tolerance. Mapping SNPs markers against the Medicago truncatula reference genome revealed several putative candidate genes based on their roles in response to salt stress. Additionally, eight GS models were used to estimate breeding values of the training population under salt stress. Highest prediction accuracies and root mean square errors were used to determine the best prediction model. The machine learning methods (support vector machine and random forest) performance best with the prediction accuracy of 0.793 for yield. The marker loci and candidate genes identified, along with optimized GS prediction models, were shown to be useful in improvement of alfalfa with enhanced salt tolerance. DNA markers and the outcome of the GS will be made available to the alfalfa breeding community in efforts to accelerate genetic gains, in the development of biotic stress tolerant and more productive modern-day alfalfa cultivars.
Mitochondria Targeting as an Effective Strategy for Cancer Therapy
Authors: Ghosh Poorva , Vidal Chantal , Dey Sanchareeka , Zhang Li
Published: May 2020

Mitochondria are well known for their role in ATP production and biosynthesis of macromolecules. Importantly, increasing experimental evidence points to the roles of mitochondrial bioenergetics, dynamics, and signaling in tumorigenesis. Recent studies have shown that many types of cancer cells, including metastatic tumor cells, therapy-resistant tumor cells, and cancer stem cells, are reliant on mitochondrial respiration, and upregulate oxidative phosphorylation (OXPHOS) activity to fuel tumorigenesis. Mitochondrial metabolism is crucial for tumor proliferation, tumor survival, and metastasis. Mitochondrial OXPHOS dependency of cancer has been shown to underlie the development of resistance to chemotherapy and radiotherapy. Furthermore, recent studies have demonstrated that elevated heme synthesis and uptake leads to intensified mitochondrial respiration and ATP generation, thereby promoting tumorigenic functions in non-small cell lung cancer (NSCLC) cells. Also, lowering heme uptake/synthesis inhibits mitochondrial OXPHOS and effectively reduces oxygen consumption, thereby inhibiting cancer cell proliferation, migration, and tumor growth in NSCLC. Besides metabolic changes, mitochondrial dynamics such as fission and fusion are also altered in cancer cells. These alterations render mitochondria a vulnerable target for cancer therapy. This review summarizes recent advances in the understanding of mitochondrial alterations in cancer cells that contribute to tumorigenesis and the development of drug resistance. It highlights novel approaches involving mitochondria targeting in cancer therapy.
Gene Signatures of Early Response to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease
Authors: Salvador-Martín Sara , Raposo-Gutiérrez Irene , Navas-López Víctor Manuel , Gallego-Fernández Carmen , Moreno-Álvarez Ana , Solar-Boga Alfonso , Muñoz-Codoceo Rosana , Magallares Lorena , Martínez-Ojinaga Eva , Fobelo María J. , Millán-Jiménez Antonio , Rodriguez-Martinez Alejandro , Vayo Concepción A. , Sánchez Cesar , Tolin Mar , Bossacoma Ferrán , Pujol-Muncunill Gemma , González de Caldas Rafael , Loverdos Inés , Blanca-García José A. , Segarra Oscar , Eizaguirre Francisco J. , García-Romero Ruth , Merino-Bohórquez Vicente , Sanjurjo-Sáez María , López-Fernández Luis A.
Published: May 2020

Around a 20–30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2−∆∆Ct method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value < 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.
Zinc and Copper Enhance Cucumber Tolerance to Fusaric Acid by Mediating Its Distribution and Toxicity and Modifying the Antioxidant System
Authors: Wang Ruirui , Huang Jian , Liang Aichen , Wang Ying , Mur Luis Alejandro Jose , Wang Min , Guo Shiwei
Published: May 2020

Fusaric acid (FA), the fungal toxin produced by Fusarium oxysporum, plays a predominant role in the virulence and symptom development of Fusarium wilt disease. As mineral nutrients can be protective agents against Fusarium wilt, hydroponic experiments employing zinc (Zn) and copper (Cu) followed by FA treatment were conducted in a glasshouse. FA exhibited strong phytotoxicity on cucumber plants, which was reversed by the addition of Zn or Cu. Thus, Zn or Cu dramatically reduced the wilt index, alleviated the leaf or root cell membrane injury and mitigated against the FA inhibition of plant growth and photosynthesis. Cucumber plants grown with Zn exhibited decreased FA transportation to shoots and a 17% increase in toxicity mitigation and showed minimal hydrogen peroxide, lipid peroxidation level with the increased of antioxidant enzymes activity in both roots and leaves. Cucumber grown with additional Cu absorbed less FA but showed more toxicity mitigation at 20% compared to with additional Zn and exhibited decreased hydrogen peroxide level and increased antioxidant enzymes activity. Thus, adding Zn or Cu can decrease the toxicity of the FA by affecting the absorption or transportation of the FA in plants and mitigate toxicity possibly through chelation. Zn and Cu modify the antioxidant system to scavenge hydrogen peroxide for suppressing FA induction of oxidative damage. Our experiments could provide a theoretical basis for the direct application of micro-fertilizer as protective agents in farming.
Stability of Glutaraldehyde in Biocide Compositions
Authors: Matei Alina , Puscas Cristina , Patrascu Iulia , Lehene Maria , Ziebro Julia , Scurtu Florina , Baia Monica , Porumb Dan , Totos Robert , Silaghi-Dumitrescu Radu
Published: May 2020

Glutaraldehyde (GA) is used as biocide in hospitals. Recent public investigations on the chemical composition of biocides used in Romania have in some cases found GA, as a key ingredient, to be apparently diluted. However, these data did not explicitly consider the complex chemical equilibria inherent to GA. An investigation of experimental and theoretical data is reported here, assessing the stability of GA solutions relevant for biocide compositions. GA solutions of various chemical composition and under varying circumstances were analyzed using spectroscopy (UV-VIS, Raman, NMR) coupled with density functional theory (DFT) calculations, as well as chemically, such as via the formation of imines in reaction/titration with glycine monitored at 270 nm; using LC-MS; or using SDS-PAGE analysis with GA as reagent in the polymerization of two test proteins- hemoglobin and myoglobin. The spectral properties of GA changed significantly over time, in a temperature-dependent manner; titration with glycine confirmed the spectral data. SDS-PAGE experiments demonstrated a non-linear and apparently unpredictable change in the reactivity of GA over time. The results may be relevant for the determination of GA concentration in various settings such as biocide analysis, hospital wastewaters, and others.
Interplay between Cytokine Circuitry and Transcriptional Regulation Shaping Helper T Cell Pathogenicity and Plasticity in Inflammatory Bowel Disease
Authors: Fu Shin-Huei , Chien Ming-Wei , Hsu Chao-Yuan , Liu Yu-Wen , Sytwu Huey-Kang
Published: May 2020

Inflammatory bowel disease (IBD) is a chronic disorder manifested as Crohn’s disease (CD) and ulcerative colitis (UC) characterized by intestinal inflammation and involves a dysregulated immune response against commensal microbiota through the activation of CD4 T helper cells. T helper cell differentiation to effector or regulatory phenotypes is controlled by cytokine networks and transcriptional regulators. Distinct polarized T helper cells are able to alter their phenotypes to adapt to diverse and fluctuating physiological environments. T helper cells exhibit intrinsic instability and flexibility to express cytokines of other lineages or transdifferentiate from one T helper cell type to another in response to various perturbations from physiological cytokine milieu as a means of promoting local immunity in response to injury or ensure tissue homeostasis. Furthermore, functional plasticity and diversity of T helper cells are associated with pathogenicity and are critical for immune homeostasis and prevention of autoimmunity. In this review, we provide deeper insights into the combinatorial extrinsic and intrinsic signals that control plasticity and transdifferentiation of T helper cells and also highlight the potential of exploiting the genetic reprogramming plasticity of T helper cells in the treatment of IBD.
Characterization of FcXTH2, a Novel Xyloglucan Endotransglycosylase/Hydrolase Enzyme of Chilean Strawberry with Hydrolase Activity
Authors: Morales-Quintana Luis , Beltrán Dina , Mendez-Yañez Ángela , Valenzuela-Riffo Felipe , Herrera Raúl , Moya-León María Alejandra
Published: May 2020

Xyloglucan endotransglycosylase/hydrolases (XTHs) are cell wall enzymes with hydrolase (XEH) and/or endotransglycosylase (XET) activities. As they are involved in the modification of the xyloglucans, a type of hemicellulose present in the cell wall, they are believed to be very important in different processes, including growth, development, and fruit ripening. Previous studies suggest that XTHs might play a key role in development and ripening of Fragaria chiloensis fruit, and its characterization is pending. Therefore, in order to provide a biochemical characterization of the FcXTH2 enzyme to explain its possible role in strawberry development, the molecular cloning and the heterologous expression of FcXTH2 were performed. The recombinant FcXTH2 was active and displayed mainly XEH activity. The optimal pH and temperature are 5.5 and 37 °C, respectively. A KM value of 0.029 mg mL−1 was determined. Additionally, its protein structural model was built through comparative modeling methodology. The model showed a typically β-jelly-roll type folding in which the catalytic motif was oriented towards the FcXTH2 central cavity. Using molecular docking, protein-ligand interactions were explored, finding better interaction with xyloglucan than with cellulose. The data provided groundwork for understanding, at a molecular level, the enzymatic mechanism of FcXTH2, an important enzyme acting during the development of the Chilean strawberry.
Linear Ubiquitin Code: Its Writer, Erasers, Decoders, Inhibitors, and Implications in Disorders
Authors: Oikawa Daisuke , Sato Yusuke , Ito Hidefumi , Tokunaga Fuminori
Published: May 2020

The linear ubiquitin chain assembly complex (LUBAC) is a ubiquitin ligase composed of the Heme-oxidized IRP2 ubiquitin ligase-1L (HOIL-1L), HOIL-1L-interacting protein (HOIP), and Shank-associated RH domain interactor (SHARPIN) subunits. LUBAC specifically generates the N-terminal Met1-linked linear ubiquitin chain and regulates acquired and innate immune responses, such as the canonical nuclear factor-κB (NF-κB) and interferon antiviral pathways. Deubiquitinating enzymes, OTULIN and CYLD, physiologically bind to HOIP and control its function by hydrolyzing the linear ubiquitin chain. Moreover, proteins containing linear ubiquitin-specific binding domains, such as NF-κB-essential modulator (NEMO), optineurin, A20-binding inhibitors of NF-κB (ABINs), and A20, modulate the functions of LUBAC, and the dysregulation of the LUBAC-mediated linear ubiquitination pathway induces cancer and inflammatory, autoimmune, and neurodegenerative diseases. Therefore, inhibitors of LUBAC would be valuable to facilitate investigations of the molecular and cellular bases for LUBAC-mediated linear ubiquitination and signal transduction, and for potential therapeutic purposes. We identified and characterized α,β-unsaturated carbonyl-containing chemicals, named HOIPINs (HOIP inhibitors), as LUBAC inhibitors. We summarize recent advances in elucidations of the pathophysiological functions of LUBAC-mediated linear ubiquitination and identifications of its regulators, toward the development of LUBAC inhibitors.
Caviar Extract and Its Constituent DHA Inhibits UVB-Irradiated Skin Aging by Inducing Adiponectin Production
Authors: Lee Kyung-Eun , Nho Youn-Hwa , Yun Seok Kyun , Park Sung-Min , Kang Seunghyun , Yeo Hyeonju
Published: May 2020

In this study, caviar (sturgeon eggs) was used to elucidate its roles in adiponectin production and skin anti-aging. Recently, caviar has been largely used not only as a nutritional food, but also in cosmetic products. In particular, it has been reported that docosahexaenoic acid (DHA), as one of the main phospholipid components of caviar extract, induces intracellular lipid accumulation and the expression of adiponectin in adipocytes. Although adipocytes are well known to be associated with the skin dermis by secreting various factors (e.g., adiponectin), the effects of caviar extract and DHA on the skin are not well studied. Here, we demonstrate the effects of caviar extract and DHA on adipocyte differentiation and adiponectin production, resulting in a preventive role in UV-irradiated skin aging. Caviar extract and DHA enhanced adipocyte differentiation and promoted the synthesis of transcription factors controlling adipocyte differentiation and adiponectin. In addition, the mRNA expression levels of matrix metalloproteinase-1 (MMP-1) were decreased in UVB-irradiated Hs68 fibroblasts that were cultured in conditioned medium from caviar extract or DHA-treated differentiated adipocytes. Taken together, these results indicate that caviar extract and DHA induce adipocyte differentiation and adiponectin production, thereby inhibiting UVB-induced premature skin aging via the suppression of MMP-1 production.
Special Issue about Head and Neck Cancers: HPV Positive Cancers
Authors: Economopoulou Panagiota , Kotsantis Ioannis , Psyrri Amanda
Published: May 2020

The oropharynx has become the leading primary site for Human Papilloma Virus (HPV)-associated head and neck cancer. HPV positive oropharyngeal squamous cell carcinoma (HPV+ OSCC) has emerged as an epidemic not easily recognized by many physicians, resulting in delays in diagnosis and management. HPV+ OSCC traditionally refers to younger, healthier patients with high economic status and high-risk sexual behavior and is related to improved prognosis. De-intensification strategies are being evaluated in ongoing clinical trials and if validated, might help spare severe morbidity associated with current cisplatin-based chemoradiotherapy, which is the standard of care for all patients with locally advanced head and neck cancer. On the other hand, whether HPV status represents an important prognostic factor for non-oropharyngeal sites remains to be elucidated.
Regulation of Iron Homeostasis and Use in Chloroplasts
Authors: Kroh Gretchen E. , Pilon Marinus
Published: May 2020

Iron (Fe) is essential for life because of its role in protein cofactors. Photosynthesis, in particular photosynthetic electron transport, has a very high demand for Fe cofactors. Fe is commonly limiting in the environment, and therefore photosynthetic organisms must acclimate to Fe availability and avoid stress associated with Fe deficiency. In plants, adjustment of metabolism, of Fe utilization, and gene expression, is especially important in the chloroplasts during Fe limitation. In this review, we discuss Fe use, Fe transport, and mechanisms of acclimation to Fe limitation in photosynthetic lineages with a focus on the photosynthetic electron transport chain. We compare Fe homeostasis in Cyanobacteria, the evolutionary ancestors of chloroplasts, with Fe homeostasis in green algae and in land plants in order to provide a deeper understanding of how chloroplasts and photosynthesis may cope with Fe limitation.
Lysosome Dynamic Properties during Neuronal Stem Cell Differentiation Studied by Spatiotemporal Fluctuation Spectroscopy and Organelle Tracking
Authors: Durso William , Martins Manuella , Marchetti Laura , Cremisi Federico , Luin Stefano , Cardarelli Francesco
Published: May 2020

We investigated lysosome dynamics during neuronal stem cell (NSC) differentiation by two quantitative and complementary biophysical methods based on fluorescence: imaging-derived mean square displacement (iMSD) and single-particle tracking (SPT). The former extracts the average dynamics and size of the whole population of moving lysosomes directly from imaging, with no need to calculate single trajectories; the latter resolves the finest heterogeneities and dynamic features at the single-lysosome level, which are lost in the iMSD analysis. In brief, iMSD analysis reveals that, from a structural point of view, lysosomes decrement in size during NSC differentiation, from 1 μm average diameter in the embryonic cells to approximately 500 nm diameter in the fully differentiated cells. Concomitantly, iMSD analysis highlights modification of key dynamic parameters, such as the average local organelle diffusivity and anomalous coefficient, which may parallel cytoskeleton remodeling during the differentiation process. From average to local, SPT allows mapping heterogeneous dynamic responses of single lysosomes in different districts of the cells. For instance, a dramatic decrease of lysosomal transport in the soma is followed by a rapid increase of transport in the projections at specific time points during neuronal differentiation, an observation compatible with the hypothesis that lysosomal active mobilization shifts from the soma to the newborn projections. Our combined results provide new insight into the lysosome size and dynamics regulation throughout NSC differentiation, supporting new functions proposed for this organelle.
Bicalutamide Elicits Renal Damage by Causing Mitochondrial Dysfunction via ROS Damage and Upregulation of HIF-1
Authors: Chen Kuan-Chou , Chen Chang-Rong , Chen Chang-Yu , Tzou Kai-Yi , Peng Chiung-Chi , Peng Robert Y.
Published: May 2020

Combined androgen blockade using bicalutamide (Bic) is a therapeutic choice for treating prostate cancer (PCa). However, even at regular clinical dosages, Bic frequently shows adverse effects associated with cardiovascular and renal damage. Previously, we found that Bic selectively damaged mesangial cells compared to tubular cells and in an in vivo rat model, we also found renal damage caused by Bic. In the present study, a rat mesangial cell model was used to further the investigation. Results indicated that Bic enhanced lactate dehydrogenase release, reactive oxygen species (ROS) production, lysosome population and kidney injury molecule-1 and decreased N-cadherin. Bic elicited mitochondrial swelling and reduced the mitochondrial potential, resulting in severe suppression of the oxygen consumption rate (OCR), maximum respiration and ATP production. The hypoxia-inducible factor (HIF)-1 transcriptional activity and messenger RNA were significantly upregulated in dose-dependent manners. The HIF-1 protein reached a peak value at 24 h then rapidly decayed. BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 and cleaved caspase-3 were dose-dependently upregulated by Bic (60 M) and that eventually led to cell apoptosis. It is suggested that Bic induces renal damage via ROS and modulates HIF-1 pathway and clinically, some protective agents like antioxidants are recommended for co-treatment.
National Program for External Quality Assessment of Chinese Newborn Screening Laboratories
Authors: Du Yuxuan , Wang Wei , Liu Jiali , Zhang Zhixin , Zhao Zhen , He Falin , Yuan Shuai , Wang Zhiguo
Published: May 2020

Objectives: To analyze the coefficient of variation (CV) of external quality assessment (EQA) in Chinese newborn screening (NBS) laboratories. Method: EQA’s robust CV was analyzed by the Clinet-EQA evaluation system. Results: Participating laboratories of the EQA program increased annually. There was more than a 11-fold increase in phenylalanine (Phe) and thyroid stimulating hormone (TSH). It has shown a declining robust CV, which has tended to level off in recent years. The interquartile range (IQR) of Phe and TSH’s robust CV has decreased from 15.5% to 1.5% and from 22.8% to 1.8%, respectively. Compared to bacterial inhibition assay (BIA), the robust CV of Phe has been shown to be relatively reduced in the fluorescence assay and quantitative enzymatic assay (QEA). The robust CV by ELISA was relatively unstable compared to DELFIA and FEIA. In addition, the robust CVs of glucose-6-phosphate dehydrogenase (G6PD) and 17-alpha-hydroxy progesterone (17-OHP) by Genetic Screening Processor (GSP) were lower than other systems. The median of robust CV by non-derivatized MS/MS (Fenghua) in Phe and free carnitine were around 2.2–4.7% and 2.6–5.2%. Conclusion: Neonatal screening has developed rapidly in China and the majority of participant laboratories had satisfactory performance for the quantitative results.
Heuristic Analysis for In-Plane Non-Contact Calibration of Rulers Using Mask R-CNN
Authors: Telahun Michael , Sierra-Sossa Daniel , Elmaghraby Adel S.
Published: May 2020

Determining an object measurement is a challenging task without having a well-defined reference. When a ruler is placed in the same plane of an object being measured it can serve as metric reference, thus a measurement system can be defined and calibrated to correlate actual dimensions with pixels contained in an image. This paper describes a system for non-contact object measurement by sensing and assessing the distinct spatial frequency of the graduations on a ruler. The approach presented leverages Deep Learning methods, specifically Mask Region proposal based Convolutional Neural Networks (R-CNN), for rulers’ recognition and segmentation, as well as several other computer vision (CV) methods such as adaptive thresholding and template matching. We developed a heuristic analytical method for calibrating an image by applying several filters to extract the spatial frequencies corresponding to the ticks on a given ruler. We propose an automated in-plane optical scaling calibration system for non-contact measurement.
Rare Nuclearities in Ni(II) Cluster Chemistry: An Unprecedented {Ni12} Nanosized Cage from the Use of N-Naphthalidene-2-Amino-5-Chlorobenzoic Acid
Authors: Perlepe Panagiota S. , Pantelis Konstantinos N. , Cunha-Silva Luís , Bekiari Vlasoula , Escuer Albert , Stamatatos Theocharis C.
Published: May 2020

The self-assembly reaction between NiI2, benzoic acid (PhCO2H) and the Schiff base chelate, N-naphthalidene-2-amino-5-chlorobenzoic acid (nacbH2), in the presence of the organic base triethylamine (NEt3), has resulted in the isolation and the structural, spectroscopic, and physicochemical characterization of the dodecanuclear [Ni12I2(OH)6(O2CPh)5(nacb)5(H2O)4(MeCN)4]I (1) cluster compound in ~30% yield. Complex 1 has a cage-like conformation, comprising twelve distorted, octahedral NiII ions that are bridged by five μ3-OH−, one μ-OH−, an I− in 55% occupancy, five PhCO2− groups (under the η1:η1:μ, η1:η2:μ3 and η2:η2:μ4 modes), and the naphthoxido and carboxylato O-atoms of five doubly deprotonated nacb2− groups. The overall {Ni12} cluster exhibits a nanosized structure with a diameter of ~2.5 nm and its metallic core can be conveniently described as a series of nine edge- or vertex-sharing {Ni3} triangular subunits. Complex 1 is the highest nuclearity coordination compound bearing the nacbH2 chelate, and a rare example of polynuclear NiII complex containing coordinating I− ions. Direct current (DC) magnetic susceptibility studies revealed the presence of predominant antiferromagnetic exchange interactions between the NiII ions, while photophysical studies of 1 in the solid-state showed a cyan-to-green centered emission at 520 nm, upon maximum excitation at 380 nm. The reported results demonstrate the rich coordination chemistry of the deprotonated nacb2− chelate in the presence of NiII metal ions, and the ability of this ligand to adopt a variety of different bridging modes, thus fostering the formation of high-nuclearity molecules with rare, nanosized dimensions and interesting physical (i.e., magnetic and optical) properties.
Airborne Pheromone Quantification in Treated Vineyards with Different Mating Disruption Dispensers against Lobesia botrana
Authors: Gavara Aitor , Vacas Sandra , Navarro Ismael , Primo Jaime , Navarro-Llopis Vicente
Published: May 2020

Mating disruption (MD) is widely used against the European grapevine moth (EGVM), Lobesia botrana (Denis and Schiffermüller; Lepidoptera: Tortricidae), by installing passive dispensers or aerosol devices. The present work reports a new sampling and quantification methodology to obtain absolute data about field airborne pheromone concentration based on air samplings and sensitive chromatographic-spectroscopic methods. Samplings were performed in fields treated with passive dispensers or aerosol devices at different moments throughout the crop cycle to study how they act and how the disruption is triggered. Moreover, pheromone adsorption and releasing capacity of vine leaves were studied to elucidate their role in the disruption. Although both types of dispensers were effective in limiting the damage inflicted by EGVM, they performed differently and provided different airborne pheromone concentration profiles. Results also proved that leaves were able to adsorb and release part of the airborne pheromone acting as subsequent and additional pheromone sources. This fact could explain the different concentration profiles. Moreover, our results suggest that lower pheromone emission than that of the current passive dispensers still could provide an adequate performance in the field. Competitive mechanisms involved in MD using both dispensers, the dynamics of the airborne pheromone throughout the time and the importance of the canopy are discussed.
Probing the Honey Bee Diet-Microbiota-Host Axis Using Pollen Restriction and Organic Acid Feeding
Authors: Ricigliano Vincent A. , Anderson Kirk E.
Published: May 2020

Microbial metabolites are considered important drivers of diet-based microbiota influence on the host, however, mechanistic models are confounded by interactions between diet, microbiota function, and host physiology. The honey bee harbors a simple microbiota that produces organic acids as fermentation products of dietary nectar and pollen, making it a model for gut microbiota research. Herein, we demonstrate that bacterial abundance in the honey bee gut is partially associated with the anterior rectum epithelium. We used dietary pollen restriction and organic acid feeding treatments to obtain information about the role of undigested pollen as a microbiota growth substrate and the impact of bacterial fermentation products on honey bee enteroendocrine signaling. Pollen restriction markedly reduced total and specific bacterial 16S rRNA abundance in the anterior rectum but not in the ileum. Anterior rectum expression levels of bacterial fermentative enzyme gene transcripts (acetate kinase, lactate dehydrogenase, and hydroxybutyryl-CoA dehydrogenase) were reduced in association with diet-induced microbiota shifts. To evaluate the effects of fermentative metabolites on host enteroendocrine function, pollen-restricted bees were fed an equimolar mixture of organic acid sodium salts (acetate, lactate, butyrate, formate, and succinate). Organic acid feeding significantly impacted hindgut enteroendocrine signaling gene expression, rescuing some effects of pollen restriction. This was specifically manifested by tissue-dependent expression patterns of neuropeptide F and allatostatin pathways, which are implicated in energy metabolism and feeding behaviors. Our findings provide new insights into the diet-microbiota-host axis in honey bees and may inform future efforts to improve bee health through diet-based microbiota manipulations.
From a Food Safety Prospective: The Role of Earthworms as Food and Feed in Assuring Food Security and in Valuing Food Waste
Authors: Tedesco Doriana Eurosia Angela , Castrica Marta , Tava Aldo , Panseri Sara , Balzaretti Claudia Maria
Published: May 2020

The Sustainable Development Goals are a set of global goals that provide a framework for shared action. These goals also include the reduction of food waste and the definition of sustainable solutions to achieve food security. In this context, the aim of the study was to describe all phases of a pilot earthworm rearing project started in September 2017 and concluded in December 2017, together with a risk analysis carried out in order to evaluate if earthworms can represent a safe and sustainable protein source for human consumption and/or animal nutrition. The conversion rate, that in this study is more appropriately identified as the “waste reduction efficiency,” was also calculated in order to define the extent to which earthworm rearing can contribute to the objective of reducing fruit and vegetable waste (FVW). The results showed that earthworms can bio-convert 3750 kg of FVW in three months producing 1050 kg of compost and 82 kg of fresh earthworms with minimal environmental impact showing good waste reduction efficiency. Moreover, the risk analysis conducted on earthworm rearing highlighted a microbiological hazard after the freeze-drying phase. The critical control point was therefore identified, and, in order to guarantee the total food safety of the finished product, corrective action was taken consisting in the implementation of heat treatment—sterilization at 121 °C for 20 min. The results of microbiological analyses carried out on the earthworm meal after the sterilization treatment showed that the treatment guarantees microbiological safety for the consumer and ensures a balanced approach in relation to two main topics—public health and food-borne diseases. In conclusion, earthworm meal is a concentrate of valuable nutrients useful for human and animal nutrition and can also transform fruit and vegetable waste into a resource.
Development, Reproduction, and Life Table Parameters of the Foxglove Aphid, Aulacorthum solani Kaltenbach (Hemiptera: Aphididae), on Soybean at Constant Temperatures
Authors: Seo Bo Yoon , Kim Eun Young , Ahn Jeong Joon , Kim Yonggyun , Kang Sungtaeg , Jung Jin Kyo
Published: May 2020

We investigated several characteristics of the development and reproduction of the aphid Aulacorthum solani raised on soybean (Glycine max) at 10 constant temperatures between 2.5 and 30 °C, and described the relationship between temperature and several critical biological characteristics using mathematical models. We found that A. solani could survive and reproduce on soybean at temperatures ranging from 5 to 27.5 °C. High fecundity was observed at temperatures from 12.5 to 20 °C. The lower developmental threshold and thermal constant for this species’ nymphal stages were estimated to be 5.02 °C and 131.2 degree-days, respectively, using a linear model. The upper developmental threshold was estimated to be 33.9 °C using the Lactin-2 model. The optimum temperature for nymphal development was estimated to be 26.9 °C. The maximum total fecundity was estimated as ca. 76.9 nymphs per adult at 18.1 °C. The daily fecundity sharply increased at earlier adult ages, and slowly decreased thereafter until final parthenogenesis occurred, over a range of temperatures from 12.5 to 25 °C. The maximum daily fecundity was estimated to be ca. 6.1 nymphs per adult per day for a 5.2 day old of adult at 21.3 °C using an age- and temperature-dependent model of adult fecundity. In terms of life table statistics, the intrinsic rates of increase and the finite rate of increase were both highest at 25 °C, while the net reproductive rate was highest at 20 °C.
Non-Vitamin K Antagonist Oral Anticoagulants and the Gastrointestinal Bleeding Risk in Real-World Studies
Authors: Anghel Larisa , Sascău Radu , Trifan Anca , Zota Ioana Mădălina , Stătescu Cristian
Published: May 2020

In the present study, we aimed to provide evidence from high-quality real world studies for a comprehensive and rigorous analysis on the gastrointestinal bleeding (GIB) risk for non-vitamin K antagonist oral anticoagulants (NOACs). We performed a systematic search of MEDLINE, EMBASE and PUBMED, and of 286 records screened, we included data from 11 high-quality real-world studies, coordinated by independent research groups over the last 3 years, that reported major GIB events in patients given NOACs or vitamin K antagonists for patients with nonvalvular atrial fibrillation. The lowest risk of gastrointestinal bleeding was with apixaban compared with warfarin (hazard ratio (HR) for GIB for apixaban ranging between 0.45 (95% confidence interval (CI) 0.34 to 0.59) and 1.13 (95% CI 0.79 to 1.63)). Apixaban was associated with a lower risk of GI bleeding than dabigatran ((HR ranging between 0.39 (95% CI 0.27 to 0.58) and 0.95 (95% CI 0.65 to 1.18)) or rivaroxaban ((HR ranging between 0.33 (95% CI 0.22 to 0.49) and 0.82 (95% CI 0.62 to 1.08)). The results of our study confirm a low or a similar risk for major GIB between patients receiving apixaban or dabigatran compared with warfarin, and apixaban appears to be associated with the lowest risk of GIB.
Diet and Nutritional Factors in Male (In)fertility—Underestimated Factors
Authors: Skoracka Kinga , Eder Piotr , Łykowska-Szuber Liliana , Dobrowolska Agnieszka , Krela-Kaźmierczak Iwona
Published: May 2020

In up to 50% of cases, infertility issues stem solely from the male. According to some data, the quality of human semen has deteriorated by 50%–60% over the last 40 years. A high-fat diet and obesity, resulting from an unhealthy lifestyle, affects the structure of spermatozoa, but also the development of offspring and their health in later stages of life. In obese individuals, disorders on the hypothalamic-pituitary-gonadal axis are observed, as well as elevated oestrogen levels with a simultaneous decrease in testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels. Healthy dietary models clearly correlate with better sperm quality and a smaller risk of abnormalities in parameters such as sperm count, sperm concentration and motility, and lower sperm DNA fragmentation. Apart from mineral components such as zinc and selenium, the role of omega-3 fatty acids and antioxidant vitamins should be emphasized, since their action will be primarily based on the minimization of oxidative stress and the inflammation process. Additionally, the incorporation of carnitine supplements and coenzyme Q10 in therapeutic interventions also seems promising. Therefore, it is advisable to have a varied and balanced diet based on vegetables and fruit, fish and seafood, nuts, seeds, whole-grain products, poultry, and low-fat dairy products.
Association of Circulating microRNAs with Coronary Artery Disease and Usefulness for Reclassification of Healthy Individuals: The REGICOR Study
Authors: Dégano Irene R. , Camps-Vilaró Anna , Subirana Isaac , García-Mateo Nadia , Cidad Pilar , Muñoz-Aguayo Dani , Puigdecanet Eulàlia , Nonell Lara , Vila Joan , Crepaldi Felipe M. , de Gonzalo-Calvo David , Llorente-Cortés Vicenta , Pérez-García María Teresa , Elosua Roberto , Fitó Montserrat , Marrugat Jaume
Published: May 2020

Risk prediction tools cannot identify most individuals at high coronary artery disease (CAD) risk. Oxidized low-density lipoproteins (oxLDLs) and microRNAs are actively involved in atherosclerosis. Our aim was to examine the association of CAD and oxLDLs-induced microRNAs, and to assess the microRNAs predictive capacity of future CAD events. Human endothelial and vascular smooth muscle cells were treated with oxidized/native low-density lipoproteins, and microRNA expression was analyzed. Differentially expressed and CAD-related miRNAs were examined in serum samples from (1) a case-control study with 476 myocardial infarction (MI) patients and 487 controls, and (2) a case-cohort study with 105 incident CAD cases and 455 randomly-selected cohort participants. MicroRNA expression was analyzed with custom OpenArray plates, log rank tests and Cox regression models. Twenty-one microRNAs, two previously undescribed (hsa-miR-193b-5p and hsa-miR-1229-5p), were up- or down-regulated upon cell treatment with oxLDLs. One of the 21, hsa-miR-122-5p, was also upregulated in MI cases (fold change = 4.85). Of the 28 CAD-related microRNAs tested, 11 were upregulated in MI cases-1 previously undescribed (hsa-miR-16-5p)-, and 1/11 was also associated with CAD incidence (adjusted hazard ratio = 0.55 (0.35–0.88)) and improved CAD risk reclassification, hsa-miR-143-3p. We identified 2 novel microRNAs modulated by oxLDLs in endothelial cells, 1 novel microRNA upregulated in AMI cases compared to controls, and one circulating microRNA that improved CAD risk classification.
Safety Recommendations and Medical Liability in Ocular Surgery during the COVID-19 Pandemic: An Unsolved Dilemma
Authors: Napoli Pietro Emanuele , Nioi Matteo , d’Aloja Ernesto , Fossarello Maurizio
Published: May 2020

Ocular surgery is one of the most performed medical procedures in the world. Its limitation or suspension, recursively extended over time, could be associated with a significant increase in the number of blind people worldwide. Indeed, cataract causes more than half of all cases of visual impairment in those countries with limited availability of means for performing eye operations (e.g., Africa or India). In this scenario, the pandemic of coronavirus disease 2019 (COVID-19) quickly resulted in the suspension or sharp reduction of various ophthalmic activities considered non-urgent, including lens replacement surgery or some intraocular injections. Despite the imperative need to continuously practice eye operations to avoid the abovementioned problems, there are currently little-shared and vague recommendations among the various countries on safety in operating rooms (for health care workers and patients) and poor legal protection for surgeons (potentially transmitting the COVID-19 infectious agent). Herein, we individuated and discussed some critical points in safety recommendations and medical liability. A paradigm shift for ocular surgery during the COVID-19 era is now mandatory. While telemedicine has been able to solve some problems in clinical ophthalmology, the lack of adequate health and legal protection for surgeons and patients may result in an excessive reduction in the volume of surgical interventions during a pandemic era and the immediately following period, thus determining inability to ensure health care to all patients.