bluuebunny/crossref_metadata_2025 huggingface dataset:
Umbilical Cord MSCs and Their Secretome in the Therapy of Arthritic Diseases: A Research and Industrial Perspective
Authors: Arrigoni Chiara , D’Arrigo Daniele , Rossella Valeria , Candrian Christian , Albertini Veronica , Moretti Matteo
Published: May 2020

The prevalence of arthritic diseases is increasing in developed countries, but effective treatments are currently lacking. The injection of mesenchymal stem cells (MSCs) represents a promising approach to counteract the degenerative and inflammatory environment characterizing those pathologies, such as osteoarthritis (OA). However, the majority of clinical approaches based on MSCs are used within an autologous paradigm, with important limitations. For this reason, allogeneic MSCs isolated from cord blood (cbMSCs) and Wharton’s jelly (wjMSCs) gained increasing interest, demonstrating promising results in this field. Moreover, recent evidences shows that MSCs beneficial effects can be related to their secretome rather than to the presence of cells themselves. Among the trophic factors secreted by MSCs, extracellular vesicles (EVs) are emerging as a promising candidate for the treatment of arthritic joints. In the present review, the application of umbilical cord MSCs and their secretome as innovative therapeutic approaches in the treatment of arthritic joints will be examined. With the prospective of routine clinical applications, umbilical cord MSCs and EVs will be discussed also within an industrial and regulatory perspective.
Deletion of Perilipin 5 Protects against Hepatic Injury in Nonalcoholic Fatty Liver Disease via Missing Inflammasome Activation
Authors: Asimakopoulou Anastasia , Engel Kathrin M. , Gassler Nikolaus , Bracht Thilo , Sitek Barbara , Buhl Eva M. , Kalampoka Stavroula , Pinoé-Schmidt Manuela , van Helden Josef , Schiller Jürgen , Weiskirchen Ralf
Published: May 2020

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver diseases with an increasing prevalence due to rising rates of obesity, metabolic syndrome and type II diabetes. Untreated NAFLD may progress to steatohepatitis (NASH) and ultimately liver cirrhosis. NAFLD is characterized by lipid accumulation, and when sufficient excess lipids are obtained, irreversible liver injury may follow. Perilipin 5 (PLIN5), a known lipid droplet coating protein and triglyceride metabolism regulator, is highly expressed in oxidatively modified tissues but it is still unclear how it affects NAFLD/NASH progress. We here studied how PLIN5 affects NAFLD development induced by a 30-week high-fat diet (HFD) administration in wild type and PLIN5 knock out (Plin5−/−) mice. The disruption of PLIN5 induced differences in lipid metabolism during HFD feeding and was associated with reduced hepatic fat accumulation. Surprisingly, Plin5−/− mice showed mitigated activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome, leading to minor hepatic damage. We conclude that PLIN5 is a pleiotropic regulator of hepatic homeostasis in NASH development. Targeting the PLIN5 expression appears critical for protecting the liver from inflammatory activation during chronic NAFLD.
Multiple Functions of Fubp1 in Cell Cycle Progression and Cell Survival
Authors: Kang Mingyu , Kim Hyeon Ji , Kim Tae-Jun , Byun Jin-Seok , Lee Jae-Ho , Lee Deok Heon , Kim Wanil , Kim Do-Yeon
Published: May 2020

The discovery of novel and critical genes implicated in malignant development is a topic of high interest in cancer research. Intriguingly, a group of genes named “double-agent” genes were reported to have both oncogenic and tumor-suppressive functions. To date, less than 100 “double-agent” genes have been documented. Fubp1 is a master transcriptional regulator of a subset of genes by interacting with a far upstream element (FUSE). Mounting evidence has collectively demonstrated both the oncogenic and tumor suppressive roles of Fubp1 and the debate regarding its roles in tumorigenesis has been around for several years. Therefore, the detailed molecular mechanisms of Fubp1 need to be determined in each context. In the present study, we showed that the Fubp1 protein level was enriched in the S phase and we identified that Fubp1 deficiency altered cell cycle progression, especially in the S phase, by downregulating the mRNA expression levels of Ccna genes encoding cyclin A. Although this Fubp1-cyclin A axis appears to exist in several types of tumors, Fubp1 showed heterogeneous expression patterns among various cancer tissues, suggesting it exhibits multiple and complicated functions in cancer development. In addition, we showed that Fubp1 deficiency confers survival advantages to cells against metabolic stress and anti-cancer drugs, suggesting that Fubp1 may play both positive and negative roles in malignant development.
Action Research to Enhance Inter-Organisational Coordination of Climate Change Adaptation in the Pacific
Authors: Gilfillan Daniel , Robinson Stacy-ann , Barrowman Hannah
Published: May 2020

Pacific regional organisations focusing on climate change have overlapping adaptation-related mandates. With the growing importance of regional organisations in supplying financial and technical resources for climate adaptation in small island developing states, it is important to understand how well these supranational organisations work together on these issues. In this paper, theories of regionalism and neofunctionalism, complex systems, and superordinate group identity are used to design an action research project that tests the level of coordination between Pacific regional organisations. It presents and discusses a pre-analysis plan for the project, the goal of which is to determine the ways in which virtual team structure can be used to enhance inter-organisational coordination of adaptation interventions across small, dispersed, resource-constrained country jurisdictions. The proposed study represents an important intermediary step in developing more robust climate-related organisational policies at the regional scale in the Pacific and beyond.
Soiling Losses: A Barrier for India’s Energy Security Dependency from Photovoltaic Power
Authors: Ghosh Aritra
Published: May 2020

Worldwide photovoltaic power generation is affected by deposited dust on photovoltaic (PV) systems, which creates soiling losses. In this work, factors that have a detrimental influence on dust deposition and an impact on PV systems performance were reviewed. The different ways that dust deposition can be a barrier for India’s energy security plan involving PV were also discussed. Different available cleaning techniques were also introduced. The nature, size, and morphology of dust particles vary with geographical location. Any increase of the PV tilt angle, or high wind speed and heavy rain showers reduce dust deposition. Deposited dust reduces the incident transmitted light on the PV, which has an adverse impact on the reduction of short circuit current. However, the open-circuit voltage has a reduced effect due to dust deposition. The enhancement of temperature caused by dust-covered PVs is still a debatable area. A universal cleaning technique is required to eliminate the soiling losses from PV. India has a solar mission to generate 100 GW of PV power by 2022. However, India’s poor air quality can undermine efforts to achieve this target.
The Influence of Supplementation of Anthocyanins on Obesity-Associated Comorbidities: A Concise Review
Authors: Sivamaruthi Bhagavathi Sundaram , Kesika Periyanaina , Chaiyasut Chaiyavat
Published: May 2020

Anthocyanins are water-soluble plant pigments, and based on their chemical structure (nature, position, and the number of sugar moieties attached; the number of hydroxyl groups; acylation of sugars with acids) about 635 different anthocyanins have been identified and reported from plants. Cyanidin, peonidin, pelargonidin, petunidin, and malvidin are the commonly found anthocyanidins (aglycon forms of anthocyanins) in edible plants out of almost 25 anthocyanidins that are identified (based on the position of methoxyl and hydroxyl groups in the rings) in nature. Anthocyanins are known for numerous health benefits including anti-diabetes, anti-obesity, anti-inflammatory bowel disease, anti-cancer, etc. Obesity can be defined as excessive or abnormal adipose tissue and body mass, which increases the risk of developing chronic diseases such as diabetes, cardiovascular diseases, cancers, etc. The manuscript summarizes the recent updates in the effects of anthocyanins supplementation on the health status of obese subjects, and briefly the results of in vitro and in vivo studies. Several studies confirmed that the consumption of anthocyanins-rich food improved obesity-associated dysbiosis in gut microbiota and inflammation in adipose tissue. Anthocyanin consumption prevents obesity in healthy subjects, and aids in maintaining or reducing the body weight of obese subjects, also improving the metabolism and energy balance. Though preclinical studies proved the beneficial effects of anthocyanins such as the fact that daily intake of anthocyanin rich fruits and vegetables might aid weight maintenance in every healthy individual, Juҫara pulp might control the inflammatory status of obesity, Queen garnet plum juice reduced the blood pressure and risk factors associated with metabolic disorders, and highbush organic blueberries improved the metabolism of obese individuals, we don’t have an established treatment procedure to prevent or manage the over-weight condition and its comorbidities. Thus, further studies on the optimum dose, duration, and mode of supplementation of anthocyanins are required to develop an anthocyanins-based clinical procedure.
Can Manipulation of Durum Wheat Amylose Content Reduce the Glycaemic Index of Spaghetti?
Authors: Sissons Mike , Sestili Francesco , Botticella Ermelinda , Masci Stefania , Lafiandra Domenico
Published: May 2020

Resistant starch (RS) in foods has positive benefits for potentially alleviating lifestyle diseases. RS is correlated positively with starch amylose content. This study aimed to see what level of amylose in durum wheat is needed to lower pasta GI. The silencing of starch synthases IIa (SSIIa) and starch branching enzymes IIa (SBEIIa), key genes involved in starch biosynthesis, in durum wheat cultivar Svevo was performed and spaghetti was prepared and evaluated. The SSIIa and SBEIIa mutants have a 28% and 74% increase in amylose and a 2.8- and 35-fold increase in RS, respectively. Cooked pasta was softer, with higher cooking loss but lower stickiness compared to Svevo spaghetti, and with acceptable appearance and colour. In vitro starch digestion extent (area under the digestion curve) was decreased in both mutants, but much more in SBEIIa, while in vivo GI was only significantly reduced from 50 to 38 in SBEIIa. This is the first study of the glycaemic response of spaghetti prepared from SBEIIa and SSIIa durum wheat mutants. Overall pasta quality was acceptable in both mutants but the SBEIIa mutation provides a clear glycaemic benefit and would be much more appealing than wholemeal spaghetti. We suggest a minimum RS content in spaghetti of ~7% is needed to lower GI which corresponded to an amylose content of ~58%.
Transcriptome Analysis of Zebrafish Olfactory Epithelium Reveal Sexual Differences in Odorant Detection
Authors: Wang Ying , Jiang Haifeng , Yang Liandong
Published: May 2020

Animals have evolved a large number of olfactory receptor genes in their genome to detect numerous odorants in their surrounding environments. However, we still know little about whether males and females possess the same abilities to sense odorants, especially in fish. In this study, we used deep RNA sequencing to examine the difference of transcriptome between male and female zebrafish olfactory epithelia. We found that the olfactory transcriptomes between males and females are highly similar. We also found evidence of some genes showing differential expression or alternative splicing, which may be associated with odorant-sensing between sexes. Most chemosensory receptor genes showed evidence of expression in the zebrafish olfactory epithelium, with a higher expression level in males than in females. Taken together, our results provide a comprehensive catalog of the genes mediating olfactory perception and pheromone-evoked behavior in fishes.
Association of NUDT15 c.415C>T and FPGS 2572C>T Variants with the Risk of Early Hematologic Toxicity During 6-MP and Low-Dose Methotrexate-Based Maintenance Therapy in Indian Patients with Acute Lymphoblastic Leukemia
Authors: Kodidela Sunitha , Dorababu Patchava , Thakkar Dimpal N. , Dubashi Biswajit , Sundaram Rajan , Muralidharan Niveditha , Nidanapu Ravi Prasad , Aribandi Anil , Pradhan Suresh Chandra , Uppugunduri Chakradhara Rao Satyanarayana
Published: May 2020

Genetic variants influencing the pharmacokinetics and/or pharmacodynamics of the chemotherapeutic drugs used in Acute Lymphoblastic Leukemia (ALL) therapy often contribute to the occurrence of treatment related toxicity (TRT). In this study, we explored the association of candidate genetic variants with early hematological TRT (grade 3–4) occurring within the first 100 days of low-dose methotrexate and 6-mercaptopurine based maintenance therapy (n = 73). Fourteen variants in the following candidate genes were genotyped using allele discrimination assay by real-time PCR: ABCB1, DHFR, GGH, FPGS, MTHFR, RFC1, SLCO1B1, TPMT, and NUDT15. Methotrexate polyglutamate (MTXPG3-5) levels in red blood cells were measured by LC-MS/MS. Early hematological TRT (grade 3–4) was seen in 54.9% of patients. The NUDT15c.415T allele was associated with early TRT occurrence [HR: 3.04 (95% CI: 1.5–6.1); p = 0.007]. Sensitivity of early TRT prediction improved (from 30.7% to 89.7%) by considering FPGS variant (rs1544105’T’) carrier status along with NUDT15c.415T allele [HR = 2.7 (1.5–4.7, p = 0.008)]. None of the considered genetic variants were associated with MTXPG3-5 levels, which in turn were not associated with early TRT. NUDT15c.415T allele carrier status could be used as a stratifying marker for Indian ALL patients to distinguish patients at high or low risk of developing early hematological TRT.
Hormonal Treatment Strategies Tailored to Non-Binary Transgender Individuals
Authors: Cocchetti Carlotta , Ristori Jiska , Romani Alessia , Maggi Mario , Fisher Alessandra Daphne
Published: May 2020

Introduction: To date no standardized hormonal treatment protocols for non-binary transgender individuals have been described in the literature and there is a lack of data regarding their efficacy and safety. Objectives: To suggest possible treatment strategies for non-binary transgender individuals with non-standardized requests and to emphasize the importance of a personalized clinical approach. Methods: A narrative review of pertinent literature on gender-affirming hormonal treatment in transgender persons was performed using PubMed. Results: New hormonal treatment regimens outside those reported in current guidelines should be considered for non-binary transgender individuals, in order to improve psychological well-being and quality of life. In the present review we suggested the use of hormonal and non-hormonal compounds, which—based on their mechanism of action—could be used in these cases depending on clients’ requests. Conclusion: Requests for an individualized hormonal treatment in non-binary transgender individuals represent a future challenge for professionals managing transgender health care. For each case, clinicians should balance the benefits and risks of a personalized non-standardized treatment, actively involving the person in decisions regarding hormonal treatment.
Hyperspectral Ophthalmoscope Images for the Diagnosis of Diabetic Retinopathy Stage
Authors: Yao Hsin-Yu , Tseng Kuang-Wen , Nguyen Hong-Thai , Kuo Chie-Tong , Wang Hsiang-Chen
Published: May 2020

A methodology that applies hyperspectral imaging (HSI) on ophthalmoscope images to identify diabetic retinopathy (DR) stage is demonstrated. First, an algorithm for HSI image analysis is applied to the average reflectance spectra of simulated arteries and veins in ophthalmoscope images. Second, the average simulated spectra are categorized by using a principal component analysis (PCA) score plot. Third, Beer-Lambert law is applied to calculate vessel oxygen saturation in the ophthalmoscope images, and oxygenation maps are obtained. The average reflectance spectra and PCA results indicate that average reflectance changes with the deterioration of DR. The G-channel gradually decreases because of vascular disease, whereas the R-channel gradually increases with oxygen saturation in the vessels. As DR deteriorates, the oxygen utilization of retinal tissues gradually decreases, and thus oxygen saturation in the veins gradually increases. The sensitivity of diagnosis is based on the severity of retinopathy due to diabetes. Normal, background DR (BDR), pre-proliferative DR (PPDR), and proliferative DR (PDR) are arranged in order of 90.00%, 81.13%, 87.75%, and 93.75%, respectively; the accuracy is 90%, 86%, 86%, 90%, respectively. The F1-scores are 90% (Normal), 83.49% (BDR), 86.86% (PPDR), and 91.83% (PDR), and the accuracy rates are 95%, 91.5%, 93.5%, and 96%, respectively.
UnReal? Investigating the Sense of Reality and Psychotic Symptoms with Virtual Reality
Authors: Drori Gad , Bar-Tal Paz , Stern Yonatan , Zvilichovsky Yair , Salomon Roy
Published: May 2020

Distortions of reality, such as hallucinations, are common symptoms of many psychiatric conditions. Accordingly, sense of reality (SoR), the ability to discriminate between true and false perceptions, is a central criterion in the assessment of neurological and psychiatric health. Despite the critical role of the SoR in daily life, little is known about how this is formed in the mind. Here, we propose a novel theoretical and methodological framework to study the SoR and its relation to psychotic symptoms. In two experiments, we employed a specialized immersive virtual reality (VR) environment allowing for well-controlled manipulations of visual reality. We first tested the impact of manipulating visual reality on objective perceptual thresholds (just noticeable differences). In a second experiment, we tested how these manipulations affected subjective judgments of reality. The results revealed that the objective perceptual thresholds were robust and replicable, demonstrating that SoR is a stable psychometric property that can be measured experimentally. Furthermore, reality alterations reduced subjective reality judgments across all manipulated visual aspects. Finally, reduced sensitivity to changes in visual reality was related to self-reported prodromal psychotic symptoms. These results provide evidence for the relevance of SoR in the assessment of psychosis and other mental disorders in which reality is distorted.
Significance of NT-proBNP and High-Sensitivity Troponin in Friedreich Ataxia
Authors: Legrand Lise , Maupain Carole , Monin Marie-Lorraine , Ewenczyk Claire , Isnard Richard , Alkouri Rana , Durr Alexandra , Pousset Francoise
Published: May 2020

Background: Friedreich’s ataxia (FA) is a rare autosomal recessive mitochondrial disease resulting of a triplet repeat expansion guanine-adenine-adenine (GAA) in the frataxin (FXN) gene, exhibiting progressive cerebellar ataxia, diabetes and cardiomyopathy. We aimed to determine the relationship between cardiac biomarkers, serum N-terminal pro-brain natriuretic peptide (NT-proBNP), and serum cardiac high-sensitivity troponin (hsTnT) concentrations, and the extent of genetic abnormality and cardiac parameters. Methods: Between 2013 and 2015, 85 consecutive genetically confirmed FA adult patients were prospectively evaluated by measuring plasma hsTnT and NT-proBNP concentrations, electrocardiogram, and echocardiography. Results: The 85 FA patients (49% women) with a mean age of 39 ± 12 years, a mean disease onset of 17 ± 11 years had a mean SARA (Scale for the Assessment and Rating of Ataxia) score of 26 ± 10. The median hsTnT concentration was 10 ng/L (3 to 85 ng/L) and 34% had a significant elevated hsTnT ≥ 14 ng/L. Increased septal wall thickness was associated with increased hsTnT plasma levels (p < 0.001). The median NT-proBNP concentration was 31 ng/L (5 to 775 ng/L) and 14% had significant elevated NT-proBNP ≥ 125 ng/L. Markers of increased left ventricular filling pressure (trans mitral E/A and lateral E/E’ ratio) were associated with increased NT-proBNP plasma levels (p = 0.01 and p = 0.01). Length of GAA or the SARA score were not associated with hsTnT or NT-proBNP plasma levels. Conclusion: hsTnT was increased in 1/3 of the adult FA and associated with increased septal wall thickness. Increased NT-proBNP remained a marker of increased left ventricular filling pressure. This could be used to identify patients that should undergo a closer cardiac surveillance.
Effectiveness and Safety of Oral Anticoagulants among NVAF Patients with Obesity: Insights from the ARISTOPHANES Study
Authors: Deitelzweig Steve , Keshishian Allison , Kang Amiee , Dhamane Amol D. , Luo Xuemei , Li Xiaoyan , Balachander Neeraja , Rosenblatt Lisa , Mardekian Jack , Pan Xianying , Di Fusco Manuela , Garcia Reeves Alessandra B. , Yuce Huseyin , Lip Gregory Y. H.
Published: May 2020

This ARISTOPHANES analysis examined stroke/systemic embolism (SE) and major bleeding (MB) among a subgroup of nonvalvular atrial fibrillation (NVAF) patients with obesity prescribed warfarin or non-vitamin K antagonist oral anticoagulants (NOACs) in order to inform clinical decision making. A retrospective observational study was conducted among NVAF patients who were obese and initiated apixaban, dabigatran, rivaroxaban, or warfarin from 1 January 2013–30 September 2015, with data pooled from CMS Medicare and four US commercial claims databases. Propensity score matching was completed between NOACs and against warfarin in each database, and the results were pooled. Cox models were used to evaluate the risks of stroke/SE and MB. A total of 88,461 patients with obesity were included in the study. Apixaban and rivaroxaban were associated with a lower risk of stroke/SE vs. warfarin (HR: 0.63, 95% CI: 0.49–0.82 and HR: 0.84, 95% CI: 0.72–0.98). Dabigatran was associated with a similar risk of stroke/SE compared to warfarin. Compared with warfarin, apixaban and dabigatran had a lower risk of MB (HR: 0.54, 95% CI: 0.49–0.61 and HR: 0.75, 95% CI: 0.63–0.91). Rivaroxaban was associated with a similar risk of MB compared to warfarin. In this high-risk population with obesity, NOACs had a varying risk of stroke/SE and MB vs. warfarin.
Risk Stratification in Hypertrophic Cardiomyopathy. Insights from Genetic Analysis and Cardiopulmonary Exercise Testing
Authors: Magrì Damiano , Mastromarino Vittoria , Gallo Giovanna , Zachara Elisabetta , Re Federica , Agostoni Piergiuseppe , Giordano Dario , Rubattu Speranza , Forte Maurizio , Cotugno Maria , Torrisi Maria Rosaria , Petrucci Simona , Germani Aldo , Savio Camilla , Maruotti Antonello , Volpe Massimo , Autore Camillo , Piane Maria , Musumeci Beatrice
Published: May 2020

The role of genetic testing over the clinical and functional variables, including data from the cardiopulmonary exercise test (CPET), in the hypertrophic cardiomyopathy (HCM) risk stratification remains unclear. A retrospective genotype–phenotype correlation was performed to analyze possible differences between patients with and without likely pathogenic/pathogenic (LP/P) variants. A total of 371 HCM patients were screened at least for the main sarcomeric genes MYBPC3 (myosin binding protein C), MYH7 (β-myosin heavy chain), TNNI3 (cardiac troponin I) and TNNT2 (cardiac troponin T): 203 patients had at least an LP/P variant, 23 patients had a unique variant of uncertain significance (VUS) and 145 did not show any LP/P variant or VUS. During a median 5.4 years follow-up, 51 and 14 patients developed heart failure (HF) and sudden cardiac death (SCD) or SCD-equivalents events, respectively. The LP/P variant was associated with a more aggressive HCM phenotype. However, left atrial diameter (LAd), circulatory power (peak oxygen uptake*peak systolic blood pressure, CP%) and ventilatory efficiency (C-index = 0.839) were the only independent predictors of HF whereas only LAd and CP% were predictors of the SCD end-point (C-index = 0.738). The present study reaffirms the pivotal role of the clinical variables and, particularly of those CPET-derived, in the HCM risk stratification.
50 Years of Environmental Activism in Girona, Catalonia: From Case Advocacy to Regional Planning
Authors: Nuss-Girona Sergi , Vicente Rufí Joan , Canaleta Guillem
Published: May 2020

Environmental activism, with decades of relevant presence already, is a fundamental element for the preservation of natural and cultural values. Theories around their bases, protagonists, methods, instruments and results proliferate in a period of obliged ecological transition. Here, we present an investigation in the region of Girona (Catalunya, Spain), with the main objective of reflecting on environmental activism and its singular impact on the territorial reality of this area. The specific interest of this case resides in the longevity of the mobilizations (50 years) and the number of cases and actors; for its causes (a territory endowed with a very socialized narrative linking landscape to identity, and subject to multiple and powerful transformative pressures); and for its effective results. Through collaborative research and different data sources, we display map-based results about environmental movements and conflicts, and quantitative results about typologies of movements, conflict triggers, outcomes of the cases, and conversion rate to nature or heritage protection figures. The discussion, and by extension the conclusions, proposes answers to the exceptional nature of the case in the Catalan context, its relationship with NIMBY processes, and the notable incidence of these mobilizations in the landscape quality and land planning of Girona.
Non-Targeted Metabolite Profiles and Sensory Properties Elucidate Commonalities and Differences of Wines Made with the Same Variety but Different Cultivar Clones
Authors: Cuadros-Inostroza Álvaro , Verdugo-Alegría Claudio , Willmitzer Lothar , Moreno-Simunovic Yerko , Vallarino José G.
Published: May 2020

Grapes, one of the oldest agricultural crops, are cultivated to produce table fruits, dried fruits, juice, and wine. Grapevine variety is composed of clones that share common morphological traits. However, they can differ in minor genetic mutations which often result in not only notorious morphological changes but also in other non-visible sensorial distinctive attributes. In the present work, we identified three Vitis vinifera cv. Pinot noir clones grown under identical field conditions that showed different grape cluster types. Here, sensorial analysis together with non-targeted metabolite profiles by Ultra High performance Liquid Chromatography (UPLC) couples to Ultra High Resolution Mass Spectrometry (FT-ICR-MS) of wines elaborated from the three different grape cluster types was studied with the aim of (i) finding sensorial differences among these three types of wines, and, if there were, (ii) determining the molecular features (metabolites) associated with these sensorial attributes by a multivariate statistical approach.
Antiprotozoal Activity Against Entamoeba histolytica of Flavonoids Isolated from Lippia graveolens Kunth
Authors: Quintanilla-Licea Ramiro , Vargas-Villarreal Javier , Verde-Star María Julia , Rivas-Galindo Verónica Mayela , Torres-Hernández Ángel David
Published: May 2020

Amebiasis caused by Entamoeba histolytica is nowadays a serious public health problem worldwide, especially in developing countries. Annually, up to 100,000 deaths occur across the world. Due to the resistance that pathogenic protozoa exhibit against commercial antiprotozoal drugs, a growing emphasis has been placed on plants used in traditional medicine to discover new antiparasitics. Previously, we reported the in vitro antiamoebic activity of a methanolic extract of Lippia graveolens Kunth (Mexican oregano). In this study, we outline the isolation and structure elucidation of antiamoebic compounds occurring in this plant. The subsequent work-up of this methanol extract by bioguided isolation using several chromatographic techniques yielded the flavonoids pinocembrin (1), sakuranetin (2), cirsimaritin (3), and naringenin (4). Structural elucidation of the isolated compounds was achieved by spectroscopic/spectrometric analyses and comparing literature data. These compounds revealed significant antiprotozoal activity against E. histolytica trophozoites using in vitro tests, showing a 50% inhibitory concentration (IC50) ranging from 28 to 154 µg/mL. Amebicide activity of sakuranetin and cirsimaritin is reported for the first time in this study. These research data may help to corroborate the use of this plant in traditional Mexican medicine for the treatment of dyspepsia.
The Targeted Impact of Flavones on Obesity-Induced Inflammation and the Potential Synergistic Role in Cancer and the Gut Microbiota
Authors: Sudhakaran Meenakshi , Doseff Andrea I.
Published: May 2020

Obesity is an inflammatory disease that is approaching pandemic levels, affecting nearly 30% of the world’s total population. Obesity increases the risk of diabetes, cardiovascular disorders, and cancer, consequentially impacting the quality of life and imposing a serious socioeconomic burden. Hence, reducing obesity and related life-threatening conditions has become a paramount health challenge. The chronic systemic inflammation characteristic of obesity promotes adipose tissue remodeling and metabolic changes. Macrophages, the major culprits in obesity-induced inflammation, contribute to sustaining a dysregulated immune function, which creates a vicious adipocyte–macrophage crosstalk, leading to insulin resistance and metabolic disorders. Therefore, targeting regulatory inflammatory pathways has attracted great attention to overcome obesity and its related conditions. However, the lack of clinical efficacy and the undesirable side-effects of available therapeutic options for obesity provide compelling reasons for the need to identify additional approaches for the prevention and treatment of obesity-induced inflammation. Plant-based active metabolites or nutraceuticals and diets with an increased content of these compounds are emerging as subjects of intense scientific investigation, due to their ability to ameliorate inflammatory conditions and offer safe and cost-effective opportunities to improve health. Flavones are a class of flavonoids with anti-obesogenic, anti-inflammatory and anti-carcinogenic properties. Preclinical studies have laid foundations by establishing the potential role of flavones in suppressing adipogenesis, inducing browning, modulating immune responses in the adipose tissues, and hindering obesity-induced inflammation. Nonetheless, the understanding of the molecular mechanisms responsible for the anti-obesogenic activity of flavones remains scarce and requires further investigations. This review recapitulates the molecular aspects of obesity-induced inflammation and the crosstalk between adipocytes and macrophages, while focusing on the current evidence on the health benefits of flavones against obesity and chronic inflammation, which has been positively correlated with an enhanced cancer incidence. We conclude the review by highlighting the areas of research warranting a deeper investigation, with an emphasis on flavones and their potential impact on the crosstalk between adipocytes, the immune system, the gut microbiome, and their role in the regulation of obesity.
Solubility and Selectivity Effects of the Anion on the Adsorption of Different Heavy Metal Ions onto Chitosan
Authors: Weißpflog Janek , Gündel Alexander , Vehlow David , Steinbach Christine , Müller Martin , Boldt Regine , Schwarz Simona , Schwarz Dana
Published: May 2020

The biopolymer chitosan is a very efficient adsorber material for the removal of heavy metal ions from aqueous solutions. Due to the solubility properties of chitosan it can be used as both a liquid adsorber and a solid flocculant for water treatment reaching outstanding adsorption capacities for a number of heavy metal ions. However, the type of anion corresponding to the investigated heavy metal ions has a strong influence on the adsorption capacity and sorption mechanism on chitosan. In this work, the adsorption capacity of the heavy metal ions manganese, iron, cobalt, nickel, copper, and zinc were investigated in dependence on their corresponding anions sulfate, chloride, and nitrate by batch experiments. The selectivity of the different heavy metal ions was analyzed by column experiments.
Recent Strides in the Transition Metal-Free Cross-Coupling of Haloacetylenes with Electron-Rich Heterocycles in Solid Media
Authors: Sobenina Lyubov’ N. , Trofimov Boris A.
Published: May 2020

The publications covering new, transition metal-free cross-coupling reactions of pyrroles with electrophilic haloacetylenes in solid medium of metal oxides and salts to regioselectively afford 2-ethynylpyrroles are discussed. The reactions proceed at room temperature without catalyst and base under solvent-free conditions. These ethynylation reactions seem to be particularly important, since the common Sonogashira coupling does not allow ethynylpyrroles with strong electron-withdrawing substituents at the acetylenic fragments to be synthesized. The results on the behavior of furans, thiophenes, and pyrazoles under the conditions of these reactions are also provided. The reactivity and structural peculiarities of nucleophilic addition to the activated acetylene moiety of the novel C-ethynylpyrroles are considered.
Propionic Acid and Fasudil as Treatment against Rotenone Toxicity in an In Vitro Model of Parkinson’s Disease
Authors: Ostendorf Friederike , Metzdorf Judith , Gold Ralf , Haghikia Aiden , Tönges Lars
Published: May 2020

Parkinson’s disease (PD) is a multifactorial neurodegenerative disease. In recent years, several studies demonstrated that the gastroenteric system and intestinal microbiome influence central nervous system function. The pathological mechanisms triggered thereby change neuronal function in neurodegenerative diseases including dopaminergic neurons in Parkinson´s disease. In this study, we employed a model system for PD of cultured primary mesencephalic cells and used the pesticide rotenone to model dopaminergic cell damage. We examined neuroprotective effects of the Rho kinase inhibitor Fasudil and the short chain fatty acid (SCFA) propionic acid on primary neurons in cell morphological assays, cell survival, gene and protein expression. Fasudil application resulted in significantly enhanced neuritic outgrowth and increased cell survival of dopaminergic cells. The application of propionic acid primarily promoted cell survival of dopaminergic cells against rotenone toxicity and increased neurite outgrowth to a moderate extent. Interestingly, Fasudil augmented gene expression of synaptophysin whereas gene expression levels of tyrosine hydroxylase (TH) were substantially increased by propionic acid. Concerning protein expression propionic acid treatment increased STAT3 levels but did not lead to an increased phosphorylation indicative of pathway activation. Our findings indicate that both Fasudil and propionic acid treatment show beneficial potential in rotenone-lesioned primary mesencephalic cells.
Development of PLGA-PEG-PLGA Hydrogel Delivery System for Enhanced Immunoreaction and Efficacy of Newcastle Disease Virus DNA Vaccine
Authors: Gao Ying , Ji Hui , Peng Lin , Gao Xiuge , Jiang Shanxiang
Published: May 2020

The highly contagious Newcastle disease virus (NDV) continues to threaten poultry all over the world. The NDV DNA vaccine is a promising solution to the current Newcastle disease (ND) challenges, and thus an efficient delivery system should be developed to facilitate the efficacy of DNA vaccines. In this study, we developed a DNA vaccine delivery system consisting of a triblock copolymer of poly(lactide co-glycolide acid) and polyethylene glycol (PLGA-PEG-PLGA) hydrogel in which the recombinant NDV hemagglutinin-neuraminidase (HN) plasmid was encapsulated. Its characteristics, security, immune responses, and efficacy against highly virulent NDV were detected. The results showed that the plasmids were gradually released in a sustained manner from the hydrogel, which improved the biological stability of the plasmids and demonstrated a high biocompatibility. The plasmids, when they were incorporated into the hydrogel delivery system, enhanced immune activation and provided 100% protection against the highly virulent NDV strain. Furthermore, we proved that this NDV DNA hydrogel vaccine could improve the lymphocyte proliferation and increase the immunological cytokine production via the PI3K/Akt pathway. These results indicate that the PLGA-PEG-PLGA thermosensitive hydrogel could be a promising delivery system for the NDV DNA vaccine in order to achieve a sustained supply of plasmids and induce potent immune responses.
Hydration and Barrier Potential of Cosmetic Matrices with Bee Products
Authors: Pavlačková Jana , Egner Pavlína , Slavík Roman , Mokrejš Pavel , Gál Robert
Published: May 2020

Honey, honey extracts, and bee products belong to traditionally used bioactive molecules in many areas. The aim of the study was primarily to evaluate the effect of cosmetic matrices containing honey and bee products on the skin. The study is complemented by a questionnaire survey on the knowledge and awareness of the effects and potential uses of bee products. The effect of bee molecules at various concentrations was observed by applying 12 formulations to the skin of the volar side of the forearm by non-invasive bioengineering methods on a set of 24 volunteers for 48 h. Very good moisturizing properties have been found in matrices with the glycerin extract of honey. Matrices containing forest honey had better moisturizing effects than those containing flower honey. Barrier properties were enhanced by gradual absorption, especially in formulations with both glycerin and aqueous honey extract. The observed organoleptic properties of the matrices assessed by sensory analysis through 12 evaluators did not show statistically significant differences except for color and spreadability. There are differences in the ability to hydrate the skin, reduce the loss of epidermal water, and affect the pH of the skin surface, including the organoleptic properties between honey and bee product matrices according to their type and concentration.
Sulfoximines-Assisted Rh(III)-Catalyzed C–H Activation and Intramolecular Annulation for the Synthesis of Fused Isochromeno-1,2-Benzothiazines Scaffolds under Room Temperature
Authors: Wang Bao , Han Xu , Li Jian , Li Chunpu , Liu Hong
Published: May 2020

A mild and facile Cp*Rh(III)-catalyzed C–H activation and intramolecular cascade annulation protocol has been proposed for the furnishing of highly fused isochromeno-1,2-benzothiazines scaffolds using S-phenylsulfoximides and 4-diazoisochroman-3-imine as substrates under room temperature. This method features diverse substituents and functional groups tolerance and relatively mild reaction conditions with moderate to excellent yields. Additionally, retentive configuration of sulfoximides in the conversion has been verified.
Influence of the Polymer Glass Transition Temperature and Molecular Weight on Drug Amorphization Kinetics Using Ball Milling
Authors: Asgreen Camilla , Knopp Matthias Manne , Skytte Jeppe , Löbmann Korbinian
Published: May 2020

In this study, the putative correlation between the molecular mobility of a polymer and the ball milling drug amorphization kinetics (i.e., time to reach full drug amorphization, ta) was studied using different grades of dextran (Dex) and polyvinylpyrrolidone (PVP) and the two model drugs indomethacin (IND) and chloramphenicol (CAP). In general, IND had lower ta values than CAP, indicating that IND amorphized faster than CAP in the presence of the polymers. In addition, an increase in polymer molecular weight (Mw) also led to an increase in ta for all systems investigated up to a critical Mw for each polymer, which was in line with an increase of the glass transition temperature (Tg) up to the critical Mw of each polymer. Hence, the increase in ta seemed to correlate well with the Tg/Mw of the polymers, which indicates that the polymers’ molecular mobility had an influence on the drug amorphization kinetics during ball milling.
Stigmasterol Causes Ovarian Cancer Cell Apoptosis by Inducing Endoplasmic Reticulum and Mitochondrial Dysfunction
Authors: Bae Hyocheol , Song Gwonhwa , Lim Whasun
Published: May 2020

Background: Phytosterols have physiological effects and are used as medicines or food supplements. Stigmasterol has shown anticancer effects against various cancers such as hepatoma, cholangiocarcinoma, gall bladder carcinoma, endometrial adenocarcinoma and skin, gastric, breast, prostate, and cervical cancer. However, there are no reports on stigmasterol’s effects on ovarian cancer. Methods: We investigated the effects of stigmasterol on proapoptotic signals, mitochondrial function, reactive oxygen species production, and the cytosolic and mitochondrial calcium levels in human ovarian cancer cells, to understand the mechanisms underlying the effects of stigmasterol on ovarian cancer cells. We also conducted migration assay to confirm whether that stigmasterol inhibits ovarian cancer cell migration. Results: Stigmasterol inhibited development of human ovarian cancer cells. However, it induced cell apoptosis, ROS production, and calcium overload in ES2 and OV90 cells. In addition, stigmasterol stimulated cell death by activating the ER-mitochondrial axis. We confirmed that stigmasterol suppressed cell migration and angiogenesis genes in human ovarian cancer cells. Conclusions: Our findings suggest that stigmasterol can be used as a new treatment for ovarian cancer.
Regulatory Potential of bHLH-Type Transcription Factors on the Road to Rubber Biosynthesis in Hevea brasiliensis
Authors: Yamaguchi Tomoko , Kurihara Yukio , Makita Yuko , Okubo-Kurihara Emiko , Kageyama Ami , Osada Emi , Shimada Setsuko , Tsuchida Hiroko , Shimada Hiroaki , Matsui Minami
Published: May 2020

Natural rubber is the main component of latex obtained from laticifer cells of Hevea brasiliensis. For improving rubber yield, it is essential to understand the genetic molecular mechanisms responsible for laticifer differentiation and rubber biosynthesis. Jasmonate enhances both secondary laticifer differentiation and rubber biosynthesis. Here, we carried out time-course RNA-seq analysis in suspension-cultured cells treated with methyljasmonic acid (MeJA) to characterize the gene expression profile. Gene Ontology (GO) analysis showed that the term “cell differentiation” was enriched in upregulated genes at 24 h after treatment, but inversely, the term was enriched in downregulated genes at 5 days, indicating that MeJA could induce cell differentiation at an early stage of the response. Jasmonate signaling is activated by MYC2, a basic helix–loop–helix (bHLH)-type transcription factor (TF). The aim of this work was to find any links between transcriptomic changes after MeJA application and regulation by TFs. Using an in vitro binding assay, we traced candidate genes throughout the whole genome that were targeted by four bHLH TFs: Hb_MYC2-1, Hb_MYC2-2, Hb_bHLH1, and Hb_bHLH2. The latter two are highly expressed in laticifer cells. Their physical binding sites were found in the promoter regions of a variety of other TF genes, which are differentially expressed upon MeJA exposure, and rubber biogenesis-related genes including SRPP1 and REF3. These studies suggest the possibilities that Hb_MYC2-1 and Hb_MYC2-2 regulate cell differentiation and that Hb_bHLH1 and Hb_bHLH2 promote rubber biosynthesis. We expect that our findings will help to increase natural rubber yield through genetic control in the future.
Effect of Microalgal Extracts from Chlorella vulgaris and Scenedesmus quadricauda on Germination of Beta vulgaris Seeds
Authors: Puglisi Ivana , Barone Valeria , Fragalà Ferdinando , Stevanato Piergiorgio , Baglieri Andrea , Vitale Alessandro
Published: May 2020

Sugar beet (Beta vulgaris subsp. vulgaris) is a commercially important biennial root crop, providing about 20% of the world’s annual sugar production. Seed quality is crucial for adequate plant growth and production. The productivity of sugar beet is often limited by heterogeneous germination in the field. In order to improve the sugar beet germination process, the effect of different concentrations of microalgal extracts from Chlorella vulgaris or Scenedesmus quadricauda was investigated by calculating several indices useful to evaluate the germination performance. Moreover, root morphological analysis was performed by using WinRHIZO software. B. vulgaris seeds were soaked with five different concentrations (from 0.1 to 10 mg Corg/L) of the microalgal extracts, considering the amount of organic carbon (Corg) in each extract. Our results show that these microalgal extracts exert a positive effect on sugar beet germination, by increasing efficiency and regularity of this critical process for B. vulgaris seeds. The best results, in terms of germination indices as well as root morphological traits, were reached by using C. vulgaris extract at the concentrations C2 (1 mg Corg/L) and C3 (2 mg Corg/L).
Evaluation of Nitrogen Nutrition in Diminishing Water Deficiency at Different Growth Stages of Maize by Chlorophyll Fluorescence Parameters
Authors: Simkó Attila , Gáspár Gáspár Soma , Kiss László , Makleit Péter , Veres Szilvia
Published: May 2020

Efficient nitrogen (N) nutrition has been reported to have the potential to alleviate the drought stress damages by maintaining metabolic activities even at low tissue water potential. The goal of our research was to find a correlation on the genotype level between the effect of different amounts of nitrogen nutrition and water supply at different growth stages. A small-plot experiment was established with three maize hybrids and three levels of nitrogen, and two different amounts of water supply were applied during the vegetation period of 2018 and 2019. Chlorophyll fluorescence parameters were detected, as well as potential and actual photochemical efficiency of PSII, at three growth stages: eight-leaf stage, tasseling, silking. At physiological maturity, the yield of hybrids was also measured. While only genotype differences were described among the investigated parameters in the V8 stage, treatment effects were also realized based on the measured chlorophyll fluorescence parameters during the tasseling and silking stages. Beyond the significant effect of irrigation, a similar impact was declared in the case of 80 kg ha−1 N treatment at the later growth stages. Pronounced correlation was described between chlorophyll fluorescence parameters and yield mainly under irrigated conditions. Our result suggested that lower N nutrition may be sufficient mainly under irrigated conditions, and in vivo chlorophyll fluorescence parameters are appropriate for detecting the effect of environmental factors in different growth stages.